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Zhang Z, Cao M, Shang Z, Xu J, Chen X, Zhu Z, Wang W, Wei X, Zhou X, Bai Y, Zhang J. Research Progress on the Antibacterial Activity of Natural Flavonoids. Antibiotics (Basel) 2025; 14:334. [PMID: 40298463 PMCID: PMC12023951 DOI: 10.3390/antibiotics14040334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/18/2025] [Accepted: 03/19/2025] [Indexed: 04/30/2025] Open
Abstract
The use of antibiotics has greatly improved the treatment of bacterial infections; however, its abuse and misuse has led to a rapid rise in multidrug-resistant (MDR) bacteria. Therefore, the search for new antimicrobial strategies has become critical. Natural flavonoids, a class of widely existing phytochemicals, have gained significant research interest for their diverse biological activities and antibacterial effects on various drug-resistant bacteria. This review summarizes the latest research progress on flavonoids, with a particular focus on several flavonoids exhibiting certain antibacterial activity, and explores their antibacterial mechanisms, including disruption of cell membranes and cell walls, inhibition of proteins and nucleic acids, interference with signal transduction, suppression of efflux pump activity, and inhibition of biofilm formation and virulence factor production. Additionally, we have reviewed the synergistic combinations of flavonoids with antibiotics, such as the combination of quercetin with colistin or EGCG with tetracycline, which significantly enhance therapeutic efficacy.
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Affiliation(s)
- Zhijin Zhang
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- College of Life Science and Food Engineering, Hebei University of Engineering, Congtai District, Handan 056038, China; (M.C.); (Z.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Mingze Cao
- College of Life Science and Food Engineering, Hebei University of Engineering, Congtai District, Handan 056038, China; (M.C.); (Z.Z.)
| | - Zixuan Shang
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- College of Life Science and Food Engineering, Hebei University of Engineering, Congtai District, Handan 056038, China; (M.C.); (Z.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Jing Xu
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Xu Chen
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- College of Life Science and Food Engineering, Hebei University of Engineering, Congtai District, Handan 056038, China; (M.C.); (Z.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Zhen Zhu
- College of Life Science and Food Engineering, Hebei University of Engineering, Congtai District, Handan 056038, China; (M.C.); (Z.Z.)
| | - Weiwei Wang
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Xiaojuan Wei
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Xuzheng Zhou
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Yubin Bai
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Jiyu Zhang
- Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China; (Z.Z.); (Z.S.); (J.X.); (X.C.); (W.W.); (X.W.); (X.Z.)
- Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
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Alwanian WM. Fisetin Mitigates Chronic Lung Injury Induced by Benzo(a)Pyrene by Regulation of Inflammation and Oxidative Stress. Curr Issues Mol Biol 2025; 47:209. [PMID: 40136463 PMCID: PMC11941139 DOI: 10.3390/cimb47030209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/16/2025] [Accepted: 03/18/2025] [Indexed: 03/27/2025] Open
Abstract
Background: Polycyclic aromatic hydrocarbons such as Benzo(a)Pyrene, which are produced by smoking or present in air pollution, greatly contribute to lung diseases. B(a)P has been found to induce inflammation and eventually lung cancer. Fisetin, a polyphenol, abundant in many fruits and vegetables, has an appealing therapeutic potential in many disorders, including inflammation and cancer. Objectives: This study aimed to investigate the importance of fisetin in the regulation of chronic lung inflammation and oxidative stress resulting from exposure to Benzo(a)Pyrene. Methods: The effect of fisetin on rats at a concentration of 50 mg/kg was evaluated by ELISA to measure oxidative stress and inflammatory markers. The tissue architecture was also investigated using hematoxylin and eosin (H&E) staining. The expression pattern of IL-6 in lung tissues was assayed using immunohistochemistry. Fibrosis was evaluated in lung tissues using Masson Trischrome and Sirius red stains. Cell apoptosis in lung tissues was studied using a TUNEL assay. Results: After exposure to Benzo(a)Pyrene for eight weeks, the data indicated that fisetin led to a significant reduction in oxidative stress, evidenced by the reduction of SOD, MDA, NO, GPH, and GPx. Moreover, IL-6, TNF-α, and CRP levels were also decreased, indicating a reduction in inflammation. Apoptosis was reduced upon fisetin treatment. Furthermore, a significant decrease in fibrosis was also observed. Conclusions: This study reveals the importance of fisetin as a natural product in the management of chronic lung injury by protecting lung tissues from inflammation, and its use suggests better prognosis in diseases caused by exposure to B(a)P.
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Affiliation(s)
- Wanian M Alwanian
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
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Elghonemy MM, Sharaf El-Din MG, Aboelsoued D, Abdelhameed MF, El-Saied MA, Toaleb NI, Farag MA, Elshamy AI, Elgamal AM. Anticryptosporidial action mechanisms of Launaea spinosa extracts in Cryptosporidium parvum experimentally infected mice in relation to its UHPLC-MS metabolite profile and biochemometric tools. PLoS One 2025; 20:e0317497. [PMID: 40029925 PMCID: PMC11875388 DOI: 10.1371/journal.pone.0317497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 12/30/2024] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Cryptosporidium parvum, a leading cause of diarrhea, is responsible for millions of food and waterborne illnesses in humans and animals worldwide. Launaea spinosa (Asteraceae family) is a common herb found in the desert of the Mediterranean region, encompassing the peninsula of Sinai. Traditionally, it has been utilized for managing gastrointestinal issues and inflammation. METHODS AND FINDINGS The present study aimed to assess Launaea spinosa (LS) extracts viz. ethyl acetate (LS-EtOAc), ethanol (LS-EtOH), and n-butanol (LS-BuOH), of different polarities against C. parvum in experimentally infected mice based on immunological, biochemical, histo- and immunohistochemical assays. Extracts were characterized via UHPLC-ESI-LIT-Orbitrap-MS and metabolite profiles were subjected to correlation modeling with bioactivities via supervised Partial Least Square (PLS) to identify active agents. Most L. spinosa extracts reduced fecal C. parvum oocyst count and mucosal burden (P < 0.05) than untreated infected mice, with LS-BuOH (200 mg/kg) exerting the highest reduction percentage (97%). These extracts increased immunoglobulin G (IgG) levels in infected and treated mice at all examined days post treatment. Also, the highest Interferon-Gamma (IFN-γ) and Interleukin-15 (IL-15) levels were obtained after 10 days of post inoculation (dPI), which were restored to a healthy state after 21 days, concurrent with a decrease in Tumor Necrosis Factor-Alpha (TNF-α) (P < 0.001). The increased liver enzyme (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) levels with infection were likewise reduced with extract administration. The LS extracts caused a significant increase in antioxidant glutathione peroxidase (GSH-Px) and catalase (P < 0.001). Examination of colon tissue revealed that infected-treated mice with LS extracts exhibited a reduction in the expression of cleaved caspase-3, damage score, and degenerative changes. Metabolite profiling of different L. spinosa extracts led to the identification of 86 components, primarily phenolic acids, flavonoids, triterpenoid saponins, and fatty acids, with the first report of sulfated triterpenoid saponins in Launaea genus. PLS regression analysis revealed that bioeffects were significantly positioned close to LS-BuOH extract (R2: 0.9) mostly attributed to triterpenoid saponins and flavonoid glycosides. CONCLUSIONS This study demonstrated potential anti-cryptosporidial effects of LS extracts, especially LS-BuOH, suggesting its potential for inclusion in future nutraceuticals aimed at C. parvum treatment.
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Affiliation(s)
- Mai M. Elghonemy
- Department of Natural Compounds Chemistry, National Research Centre, Giza, Egypt
| | | | - Dina Aboelsoued
- Parasitology and Animal Diseases Department, Veterinary Research Institute, National Research Centre, Giza, Egypt
| | - Mohamed F. Abdelhameed
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
| | - Mohamed A. El-Saied
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Nagwa I. Toaleb
- Parasitology and Animal Diseases Department, Veterinary Research Institute, National Research Centre, Giza, Egypt
| | - Mohamed A. Farag
- Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | | | - Abdelbaset M. Elgamal
- Department of Chemistry of Microbial and Natural Products, National Research Centre, Giza, Egypt
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Garcia‐Merino JA, Carrabs V, Ferrini F, Salucci S, Battistelli M, Burattini S, Luchetti F, Nasoni MG, Annibalini G, Micucci M, Gianfanti F, Sestili P, Larrosa M, Barbieri E. Revitalizing Muscle Regeneration: Cocoa Polyphenols Shield Mitochondrial Integrity and Boost Myogenesis Under Oxidative Stress. Microsc Res Tech 2025; 88:905-912. [PMID: 39614764 PMCID: PMC11842948 DOI: 10.1002/jemt.24755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 10/13/2024] [Accepted: 11/14/2024] [Indexed: 02/22/2025]
Abstract
In this study, we describe the effect of cocoa polyphenol extract (CPE, from flavanols-rich cocoa) on myogenic differentiation in murine myoblasts (C2C12 cells) exposed to H2O2. The myogenic program was monitored using morphological, ultrastructural, and molecular approaches. Treatment with 100 μM of H2O2 for 1 h decreased cell viability. C2C12 (D1) exposed to H2O2 shows more apoptotic and necrotic cells, and mitochondria appear emptied, with cristae heavily damaged. To evaluate the effect of CPE on myoblast viability and myotube formation, 10 μg/mL of CPE were added 24 h prior to H2O2 treatment and cells were supplemented with fresh CPE every 24 h during differentiation. Supplementation with CPE protected C2C12 myoblasts from H2O2-induced oxidative damage both at early (D1) and late (D6) phases of differentiation, preventing cell death and mitochondrial damage. The number of mitochondria (per area of cell surface) increased 2-fold in both control and in CPE-supplemented and mitochondria in myotubes D6 showed a greater extension of mitochondrial cristae than mitochondria in D1. At D1 and D6 the monolayers showed surface and inner cell features relatively comparable to the untreated control suggesting that CPE supplementation significantly mitigated the effect of H2O2. Preliminary data obtained by the myogenic index (Giemsa staining) suggested that CPE-supplemented cells were partially protected from H2O2-induced myogenesis inhibition. The CPE supplementation seems to preserve the mitochondrial integrity and the myogenic differentiation ability of oxidatively injured C2C12 ensuing further nutraceutical perspectives.
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Affiliation(s)
- Jose Angel Garcia‐Merino
- Faculty of Health SciencesUniversidad Europea de CanariasLa OrotavaSpain
- MAS Microbiota Group, Faculty of Biomedical and Health SciencesUniversidad Europea de MadridVillaviciosa de OdónSpain
| | - Vittoria Carrabs
- Departamento de Farmacia, Facultad de Ciencias de la SaludUniversidad CEU Cardenal HerreraValenciaSpain
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Fabio Ferrini
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Sara Salucci
- Institute of Oncology ResearchBellinzonaSwitzerland
| | | | - Sabrina Burattini
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Francesca Luchetti
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Maria Gemma Nasoni
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Giosuè Annibalini
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Matteo Micucci
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Federico Gianfanti
- Università della Svizzera ItalianaLuganoSwitzerland
- Department of Biomedical and NeuroMotor Sciences (DIBINEM)University of BolognaBolognaItaly
| | - Piero Sestili
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | - Mar Larrosa
- MAS Microbiota Group, Faculty of Biomedical and Health SciencesUniversidad Europea de MadridVillaviciosa de OdónSpain
| | - Elena Barbieri
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
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Micucci M, Gianfanti F, Donati Zeppa S, Annibalini G, Canonico B, Fanelli F, Saltarelli R, Osman R, Montanari M, Lopez D, Nasoni G, Panza G, Bargagni E, Luchetti F, Retini M, Mari M, Zappia G, Stocchi V, Bartolacci A, Burattini S, Battistelli M. Q-Der: a next-generation CoQ10 analogue supercharging neuroprotection by combating oxidative stress and enhancing mitochondrial function. Front Mol Biosci 2025; 12:1525103. [PMID: 40070687 PMCID: PMC11893404 DOI: 10.3389/fmolb.2025.1525103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/30/2025] [Indexed: 03/14/2025] Open
Abstract
Background Mitochondrial dysfunction and oxidative stress are central mechanisms in the progression of neurodegenerative diseases. This study first evaluated the toxicity of Q-Der (Q10-diacetate), a derivative of Coenzyme Q10, in HT22 hippocampal neurons under normal and oxidative stress conditions. Methods HT22 cells were treated with Q-Der at 2.5, 5 and 10 µM with and without rotenone. Mitochondrial superoxide production (Mitosox), gene expression (via qRT-PCR), and protein levels (via Western blot) were measured. Morphological analyses were performed using transmission (TEM) and scanning (SEM) electron microscopes. Results Q-Der significantly reduced mitochondrial superoxide levels, particularly at 5 μM, and upregulated key mitochondrial biogenesis genes, including PGC-1α and TFAM. Additionally, it restored the expression of MT-ND1 and MT-COI, which were downregulated by rotenone. Western blot results showed a significant recovery in CV-ATP5A (complex V) expression (p < 0.05), preserving mitochondrial ATP production. Morphological analyses further confirmed Q-Der's ability to maintain cellular and mitochondrial structure under stress conditions. Conclusion These findings suggest that Q-Der is non-toxic under normal conditions and protects against oxidative stress, supporting its potential as a therapeutic agent for neurodegenerative diseases.
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Affiliation(s)
- Matteo Micucci
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Federico Gianfanti
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Sabrina Donati Zeppa
- Department of Human Sciences and Promotion of the Quality of Life, University of San Raffaele, Roma, Italy
| | - Giosuè Annibalini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Barbara Canonico
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Fabiana Fanelli
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Roberta Saltarelli
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Riham Osman
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Mariele Montanari
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Daniele Lopez
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Gemma Nasoni
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Giovanna Panza
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Erik Bargagni
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Francesca Luchetti
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Michele Retini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Michele Mari
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Giovanni Zappia
- Department of Human Sciences and Promotion of the Quality of Life, University of San Raffaele, Roma, Italy
- Umolsystem Srl, Tecnopolo Roma-Castel Romano, Roma, Italy
| | - Vilberto Stocchi
- Department of Human Sciences and Promotion of the Quality of Life, University of San Raffaele, Roma, Italy
| | - Alessia Bartolacci
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Sabrina Burattini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Michela Battistelli
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
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Oliveira AMS, Santos AM, Nascimento Júnior JAC, Júnior CCS, Brito JRLR, dos Santos JS, Shanmugam S, dos Passos Menezes P, Frank LA, Serafini MR. Pharmaceutical technological trends containing flavonoids: a patent review. Future Med Chem 2025; 17:363-379. [PMID: 39835701 PMCID: PMC11792795 DOI: 10.1080/17568919.2025.2453408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 01/06/2025] [Indexed: 01/22/2025] Open
Abstract
Flavonoids such as silibinin, hesperetin, and phloretin exhibit well-documented biological activities, including anti-inflammatory, cytoprotective, anticarcinogenic, and antioxidant effects. However, their clinical application remains limited due to challenges such as poor aqueous solubility, low bioavailability, and restricted intestinal absorption, which can significantly reduce their pharmacological efficacy. This review analyzed patents related to innovative pharmaceutical technologies for flavonoids. The analysis used databases from the World Intellectual Property Organization and the European Patent Office. Following a comprehensive screening process, 38 patents were selected for detailed examination. These patents highlighted numerous studies on novel formulations, characterizations, and proprietary conditions. This review highlights technologies, such as nanocapsules, nanoemulsions, solid dispersions, phospholipid carriers, inclusion complexes, microemulsions, and other advanced systems, which enhance bioactive molecules' water solubility and stability. Consequently, these technologies improve permeability and absorption through the intended administration route, demonstrating the potential of flavonoids as promising candidates for various treatments, particularly when integrated into pharmaceutical technologies.
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Affiliation(s)
- Ana Maria Santos Oliveira
- Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, São Cristóvão, Brazil
| | | | | | | | | | | | - Saravanan Shanmugam
- Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, São Cristóvão, Brazil
| | | | - Luiza Abrahão Frank
- Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
- Núcleo de Terapias Nanotecnológicas (NTnano), Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Mairim Russo Serafini
- Postgraduate Program in Pharmaceutical Sciences, Federal University of Sergipe, São Cristóvão, Brazil
- Postgraduate Program in Health Sciences, Federal University of Sergipe, Aracaju, Brazil
- Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Brazil
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Yu M, Wang S, Lin D. Mechanism and Application of Biomaterials Targeting Reactive Oxygen Species and Macrophages in Inflammation. Int J Mol Sci 2024; 26:245. [PMID: 39796102 PMCID: PMC11720555 DOI: 10.3390/ijms26010245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/22/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Inflammation, an adaptive reaction to harmful stimuli, is a necessary immune system response and can be either acute or chronic. Since acute inflammation tends to eliminate harmful stimuli and restore equilibrium, it is generally advantageous to the organism. Chronic inflammation, however, is caused by either increased inflammatory signaling or decreased pro-anti-inflammatory signaling. According to current studies, inflammation is thought to be a major factor in a number of chronic diseases, including diabetes, cancer, arthritis, inflammatory bowel disease, and obesity. Consequently, reducing inflammation is essential for both preventing and delaying diseases. The application of biomaterials in the treatment of inflammatory illnesses has grown in recent years. A variety of biomaterials can be implanted either by themselves or in conjunction with other bioactive ingredients and therapeutic agents. The mechanisms of action and therapeutic applications of well-known anti-inflammatory biomaterials are the main topics of this article.
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Daniele-Silva A, Lucas Tenório CJ, Roberto da Costa Rodrigues J, Torres-Rêgo M, Cavalcanti FF, de Sousa Ferreira S, Pontes da Silva D, Assunção Ferreira MR, de Freitas Fernandes-Pedrosa M, Lira Soares LA. Anti-inflammatory and antiophidic effects of extract of Hymenaea eriogyne benth and structure-activity relationship prediction of the major markers in silico. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118619. [PMID: 39053713 DOI: 10.1016/j.jep.2024.118619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 07/19/2024] [Accepted: 07/22/2024] [Indexed: 07/27/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hymenaea eriogyne Benth (Fabaceae) is popularly known as "Jatobá". Despite its use in folk medicine to treat inflammatory disorders, there are no descriptions that show its anti-inflammatory potential. AIM OF THE STUDY In this sense, this study aimed to evaluate the anti-inflammatory and antivenom action of bark and leaves extract of H. eriogyne. MATERIALS AND METHODS The in vivo anti-inflammatory activity was conducted by carrageenan-induced paw edema and zymosan-induced air pouch models, evaluating the edematogenic effect, leukocyte migration, protein concentration, levels of pro-inflammatory cytokines, malondialdehyde (MDA) and myeloperoxidase (MPO) activity. The antivenom potential was investigated in vitro on the enzymatic action (proteolytic, phospholipase and hyaluronidase) of Bothrops brazili and B. leucurus venom, as well as in vivo on the paw edema model induced by B. leucurus. Furthermore, the influence of its markers (astilbin and rutin) on MPO activity was investigated in silico. For molecular docking, AutodockVina, Biovia Discovery Studio, and Chimera 1.16 software were used. RESULTS The extracts and bark and leaves of H. eriogyne revealed a high anti-inflammatory effect, with a reduction in all inflammatory parameters evaluated. The bark extract showed superior results when compared to the leaf extract, suggesting the influence of the astilbin concentration, higher in the bark, on the anti-inflammatory action. In addition, only the H. eriogyne bark extract was able to reduce MDA, indicating an associated antioxidant effect. Regarding the in vitro antivenom action, the extracts (bark and leaves) revealed the ability to inhibit the proteolytic, phospholipase and hyaluronidase action of both bothropic venom, with a greater effect against B. leucurus venom. In vivo, extracts from the bark and leaves of H. eriogyne (50-200 mg/kg) showed antiedematogenic activity, reducing the release of MPO and pro-inflammatory cytokines, indicating the presence of bioactive components useful in controlling the inflammatory process induced by the venom. In the in silico assays, astilbin and rutin showed reversible interactions of 9 possible positions and orientations towards MPO, with affinities of -9.5 and -10.4 kcal/mol and interactions with Phe407, Gln91, His95 and Arg239, important active pockets of MPO. Rutin demonstrated more effective types of interactions with MPO. CONCLUSION This approach reveals for the first time the anti-inflammatory action of H. eriogyne bark and leaf extracts in vivo, as well as its antiophidic potential. Moreover, the distinct effect of pharmacogens as antioxidant agents and distinct effect of astilbin and rutin under MPO sheds light on the different anti-inflammatory mechanisms of bioactive compounds present in H. eriogyne extracts, with high potential for the prospection of new pharmacological agents.
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Affiliation(s)
- Alessandra Daniele-Silva
- Laboratory of Pharmacognosy, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Brazil; Laboratory of Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Federal University of Rio Grande Do Norte, Brazil
| | - Camylla Janiele Lucas Tenório
- Laboratory of Pharmacognosy, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Brazil; Graduate Program of Therapeutic Innovation, Center for Biosciences, Federal University of Pernambuco, Brazil
| | | | - Manoela Torres-Rêgo
- Graduate Program of Chemistry, Chemistry Institute, Federal University of Rio Grande Do Norte, Brazil
| | - Felipe França Cavalcanti
- Graduate Program of Chemistry, Chemistry Institute, Federal University of Rio Grande Do Norte, Brazil
| | - Sarah de Sousa Ferreira
- Laboratory of Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Federal University of Rio Grande Do Norte, Brazil
| | - Diana Pontes da Silva
- Laboratory of Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Federal University of Rio Grande Do Norte, Brazil
| | | | | | - Luiz Alberto Lira Soares
- Laboratory of Pharmacognosy, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Brazil.
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Liu Y, Fang M, Tu X, Mo X, Zhang L, Yang B, Wang F, Kim YB, Huang C, Chen L, Fan S. Dietary Polyphenols as Anti-Aging Agents: Targeting the Hallmarks of Aging. Nutrients 2024; 16:3305. [PMID: 39408272 PMCID: PMC11478989 DOI: 10.3390/nu16193305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/20/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Aging is a natural biological process influenced by multiple factors and is a significant contributor to various chronic diseases. Slowing down the aging process and extending health span have been pursuits of the scientific field. Methods: Examination of the effects of dietary polyphenols on hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Results: Polyphenols, abundant in nature, exhibit numerous biological activities, including antioxidant effects, free radical scavenging, neuroprotection, and anti-aging properties. These compounds are generally safe and effective in potentially slowing aging and preventing age-related disorders. Conclusions: The review encourages the development of novel therapeutic strategies using dietary polyphenols to create holistic anti-aging therapies and nutritional supplements.
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Affiliation(s)
- Ying Liu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Minglv Fang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Xiaohui Tu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Xueying Mo
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Lu Zhang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Binrui Yang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Feijie Wang
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Young-Bum Kim
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Cheng Huang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
| | - Liang Chen
- Nutrilite Health Institute, Amway (Shanghai) Innovation and Science Co., Ltd., Shanghai 201203, China
| | - Shengjie Fan
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (Y.L.); (C.H.)
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10
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Khatun MM, Bhuia MS, Chowdhury R, Sheikh S, Ajmee A, Mollah F, Al Hasan MS, Coutinho HDM, Islam MT. Potential utilization of ferulic acid and its derivatives in the management of metabolic diseases and disorders: An insight into mechanisms. Cell Signal 2024; 121:111291. [PMID: 38986730 DOI: 10.1016/j.cellsig.2024.111291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 06/28/2024] [Accepted: 07/05/2024] [Indexed: 07/12/2024]
Abstract
Metabolic diseases are abnormal conditions that impair the normal metabolic process, which involves converting food into energy at a cellular level, and cause difficulties like obesity and diabetes. The study aimed to investigate how ferulic acid (FA) and its derivatives could prevent different metabolic diseases and disorders and to understand the specific molecular mechanisms responsible for their therapeutic effects. Information regarding FA associations with metabolic diseases and disorders was compiled from different scientific search engines, including Science Direct, Wiley Online, PubMed, Scopus, Web of Science, Springer Link, and Google Scholar. This review revealed that FA exerts protective effects against metabolic diseases such as diabetes, diabetic retinopathy, neuropathy, nephropathy, cardiomyopathy, obesity, and diabetic hypertension, with beneficial effects on pancreatic cancer. Findings also indicated that FA improves insulin secretion by increasing Ca2+ influx through the L-type Ca2+ channel, thus aiding in diabetes management. Furthermore, FA regulates the activity of inflammatory cytokines (TNF-α, IL-18, and IL-1β) and antioxidant enzymes (CAT, SOD, and GSH-Px) and reduces oxidative stress and inflammation, which are common features of metabolic diseases. FA also affects various signaling pathways, including the MAPK/NF-κB pathways, which play an important role in the progression of diabetic neuropathy and other metabolic disorders. Additionally, FA regulates apoptosis markers (Bcl-2, Bax, and caspase-3) and exerts its protective effects on cellular destruction. In conclusion, FA and its derivatives may act as potential medications for the management of metabolic diseases.
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Affiliation(s)
- Mst Muslima Khatun
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj 8100, Dhaka, Bangladesh
| | - Md Shimul Bhuia
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj 8100, Dhaka, Bangladesh
| | - Raihan Chowdhury
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj 8100, Dhaka, Bangladesh
| | - Salehin Sheikh
- Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj 8100, Dhaka, Bangladesh
| | - Afiya Ajmee
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Faysal Mollah
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Md Sakib Al Hasan
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Henrique D M Coutinho
- Department of Biological Chemistry, Regional University of Cariri, Crato, CE 63105-000, Brazil.
| | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj 8100, Dhaka, Bangladesh; Pharmacy Discipline, Khulna University, Khulna 9208, Bangladesh.
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11
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Wang Y, Wang H, Gao A, Wei L, Yu J. A comprehensive study of Chuanwang Xiaoyan capsule based on characterization of chemical constituents in vitro and in vivo using ultra-high-performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry and pharmacokinetic study of multiple components in rats using ultra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry. Biomed Chromatogr 2024; 38:e5930. [PMID: 38881164 DOI: 10.1002/bmc.5930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/14/2024] [Accepted: 05/27/2024] [Indexed: 06/18/2024]
Abstract
Chuanwang Xiaoyan (CWXY) capsule is primarily used to treat a variety of acute and chronic inflammations, including acute and chronic pharyngitis and tonsillitis. However, a systematic study of its chemical constituents is still not available. This study evaluated the chemical constituents in vitro and metabolite profiles in vivo of CWXY using ultra-high-performance liquid chromatography (UHPLC) coupled with Q-Exactive Orbitrap mass spectrometry, and the pharmacokinetic behaviors of the nine main components in rats were detected using ultra-high-performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-QQQ-MS/MS). A total of 92 chemical constituents in CWXY were preliminarily identified in vitro. After oral administration to rats, 56 prototype components and 128 metabolites of CWXY were detected in the biological samples of rat plasma, urine, bile, and feces. Of these prototype components and metabolites, seven new compounds, namely M15, M16, M25, M30, M31, M71, and M128, were detected for the first time. The quantitation method of nine components in rat plasma was developed using a pharmacokinetic study. To the best of our knowledge, this study was the first to investigate the pharmacokinetic behavior of triumbelletin.
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Affiliation(s)
- Yufeng Wang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Hongjin Wang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Aichun Gao
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Lan Wei
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Jia Yu
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
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12
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Munteanu C, Schwartz B. Interactions between Dietary Antioxidants, Dietary Fiber and the Gut Microbiome: Their Putative Role in Inflammation and Cancer. Int J Mol Sci 2024; 25:8250. [PMID: 39125822 PMCID: PMC11311432 DOI: 10.3390/ijms25158250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/19/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
The intricate relationship between the gastrointestinal (GI) microbiome and the progression of chronic non-communicable diseases underscores the significance of developing strategies to modulate the GI microbiota for promoting human health. The administration of probiotics and prebiotics represents a good strategy that enhances the population of beneficial bacteria in the intestinal lumen post-consumption, which has a positive impact on human health. In addition, dietary fibers serve as a significant energy source for bacteria inhabiting the cecum and colon. Research articles and reviews sourced from various global databases were systematically analyzed using specific phrases and keywords to investigate these relationships. There is a clear association between dietary fiber intake and improved colon function, gut motility, and reduced colorectal cancer (CRC) risk. Moreover, the state of health is reflected in the reciprocal and bidirectional relationships among food, dietary antioxidants, inflammation, and body composition. They are known for their antioxidant properties and their ability to inhibit angiogenesis, metastasis, and cell proliferation. Additionally, they promote cell survival, modulate immune and inflammatory responses, and inactivate pro-carcinogens. These actions collectively contribute to their role in cancer prevention. In different investigations, antioxidant supplements containing vitamins have been shown to lower the risk of specific cancer types. In contrast, some evidence suggests that taking antioxidant supplements can increase the risk of developing cancer. Ultimately, collaborative efforts among immunologists, clinicians, nutritionists, and dietitians are imperative for designing well-structured nutritional trials to corroborate the clinical efficacy of dietary therapy in managing inflammation and preventing carcinogenesis. This review seeks to explore the interrelationships among dietary antioxidants, dietary fiber, and the gut microbiome, with a particular focus on their potential implications in inflammation and cancer.
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Affiliation(s)
- Camelia Munteanu
- Department of Plant Culture, Faculty of Agriculture, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Betty Schwartz
- The Institute of Biochemistry, Food Science and Nutrition, The School of Nutritional Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel
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13
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Scarpa ES, Antonelli A, Balercia G, Sabatelli S, Maggi F, Caprioli G, Giacchetti G, Micucci M. Antioxidant, Anti-Inflammatory, Anti-Diabetic, and Pro-Osteogenic Activities of Polyphenols for the Treatment of Two Different Chronic Diseases: Type 2 Diabetes Mellitus and Osteoporosis. Biomolecules 2024; 14:836. [PMID: 39062550 PMCID: PMC11275061 DOI: 10.3390/biom14070836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/27/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Polyphenols are natural bioactives occurring in medicinal and aromatic plants and food and beverages of plant origin. Compared with conventional therapies, plant-derived phytochemicals are more affordable and accessible and have no toxic side effects. Thus, pharmaceutical research is increasingly inclined to discover and study new and innovative natural molecules for the treatment of several chronic human diseases, like type 2 diabetes mellitus (T2DM) and osteoporosis. These pathological conditions are characterized by a chronic inflammatory state and persistent oxidative stress, which are interconnected and lead to the development and worsening of these two health disorders. Oral nano delivery strategies have been used to improve the bioavailability of polyphenols and to allow these natural molecules to exert their antioxidant, anti-inflammatory, anti-diabetic, and pro-osteogenic biological activities in in vivo experimental models and in patients. Polyphenols are commonly used in the formulations of nutraceuticals, which can counteract the detrimental effects of T2DM and osteoporosis pathologies. This review describes the polyphenols that can exert protective effects against T2DM and osteoporosis through the modulation of specific molecular markers and pathways. These bioactives could be used as adjuvants, in combination with synthetic drugs, in the future to develop innovative therapeutic strategies for the treatment of T2DM and osteoporosis.
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Affiliation(s)
| | - Antonella Antonelli
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (A.A.); (M.M.)
| | - Giancarlo Balercia
- Division of Endocrinology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy;
| | - Sofia Sabatelli
- Clinic of Endocrinology and Metabolic Diseases, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy; (S.S.); (G.G.)
| | - Filippo Maggi
- Chemistry Interdisciplinary Project (CHIP) Research Center, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; (F.M.); (G.C.)
| | - Giovanni Caprioli
- Chemistry Interdisciplinary Project (CHIP) Research Center, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; (F.M.); (G.C.)
| | - Gilberta Giacchetti
- Clinic of Endocrinology and Metabolic Diseases, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60126 Ancona, Italy; (S.S.); (G.G.)
| | - Matteo Micucci
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; (A.A.); (M.M.)
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14
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Niu W, Feng Y, Peng M, Cai J. A narrative review on the mechanism of natural flavonoids in improving glucolipid metabolism disorders. Phytother Res 2024. [PMID: 38924256 DOI: 10.1002/ptr.8276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/29/2024] [Accepted: 06/07/2024] [Indexed: 06/28/2024]
Abstract
Glucolipid metabolism disorder (GLMD) is a complex chronic disease characterized by glucose and lipid metabolism disorders with a complex and diverse etiology and rapidly increasing incidence. Many studies have identified the role of flavonoids in ameliorating GLMD, with mechanisms related to peroxisome proliferator-activated receptors, nuclear factor kappa-B, AMP-activated protein kinase, nuclear factor (erythroid-derived 2)-like 2, glucose transporter type 4, and phosphatidylinositol-3-kinase/protein kinase B pathway. However, a comprehensive summary of the flavonoid effects on GLMD is lacking. This study reviewed the roles and mechanisms of natural flavonoids with different structures in the treatment of GLMD reported globally in the past 5 years and provides a reference for developing flavonoids as drugs for treating GLMD.
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Affiliation(s)
- Wenjing Niu
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Yongshi Feng
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Minwen Peng
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Jinyan Cai
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
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15
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Micucci M, Gioacchini S, Baggieri M, Fioravanti R, Bucci P, Giuseppetti R, Saleem SS, Maulud SQ, Abdullah FO, Ismael BQ, Ahmed JQ, D'Ugo E, Marchi A, Okeke UJ, Magurano F. Review from host and guest approach to new frontiers nutraceuticals in the era of COVID-19. FUTURE FOODS 2024; 9:100303. [DOI: 10.1016/j.fufo.2024.100303] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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16
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Adarthaiya S, Sehgal A. Moringa oleifera Lam. as a potential plant for alleviation of the metabolic syndrome-A narrative review based on in vivo and clinical studies. Phytother Res 2024; 38:755-775. [PMID: 38015048 DOI: 10.1002/ptr.8079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 11/29/2023]
Abstract
The metabolic syndrome (MetS) refers to the co-occurrence of risk factors, including hyperglycaemia, increased body weight, hypertension and dyslipidemia, which eventually lead to diabetes and cardiovascular disease, a common health problem worldwide. Recently, there has been an increasing interest in the use of plant-based products for the management of MetS, because of their less detrimental and more beneficial effects. Moringa oleifera (Moringaceae), commonly known as drumstick, is cultivated worldwide for its nutritional and medicinal properties. This review focuses on the in vivo and human studies concerning the potential of M. oleifera in the alleviation of MetS and its comorbidities. The search for relevant articles was carried out in PubMed and Google Scholar databases. Randomised controlled and clinical trials from the PubMed database were included in this review. The results suggested that the administration of M. oleifera, in vivo, shows clear signs of improvement in MetS indices. Despite fewer human studies, the existing data documented convincing results that uphold the potential of M. oleifera against MetS. Therefore, future research discussing the probable mechanism of action is much needed which could further assure the usage of M. oleifera in the treatment regimen of MetS.
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Affiliation(s)
- Saikrupa Adarthaiya
- Department of Zoology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, India
| | - Amit Sehgal
- Department of Zoology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, India
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17
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Saher F, Ijaz MU, Hamza A, Ain QU, Hayat MF, Afsar T, Almajwal A, Shafique H, Razak S. Mitigative potential of rhoifolin against cisplatin prompted testicular toxicity: biochemical, spermatogenic and histological based analysis. Toxicol Res (Camb) 2023; 12:814-823. [PMID: 37915485 PMCID: PMC10615821 DOI: 10.1093/toxres/tfad073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 07/26/2023] [Accepted: 08/05/2023] [Indexed: 11/03/2023] Open
Abstract
Rhoifolin (ROF) is a naturally occurring flavonoid compound with diverse pharmacological and therapeutic benefits. The current investigation was designed to evaluate the curative potential of Rhoifolin (ROF) against Cisplatin (CP) induced testicular damage. Mature male albino rats (n = 48) were randomly distributed into 4 equal groups: control, CP (10 mg/kg), CP + ROF (10 mg/kg + 20 mg/kg) and ROF (20 mg/kg) supplemented group. Following 56 days of the trial, biochemical, inflammatory markers, spermatogenic, steroidogenic, hormonal, apoptotic, anti-apoptotic, and histopathological parameters were evaluated. The exposure to CP markedly (p < 0.05) lowered the activities of anti-oxidant enzymes, glutathione reductase (GSR), catalase (CAT), and glutathione peroxidase (GPx) as well as superoxide dismutase (SOD) in testicular tissues of male albino rats. Besides the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were considerably augmented in CP exposed rats. The administration of CP also increased the level of inflammatory cytokines i.e. IL-6, TNF-α, 1L-1β and NF-κβ as well as COX-2 activity. Additionally, a notable (p < 0.05) upsurge was observed in dead sperms count, abnormality in the tail, midpiece as well as head of sperms along with a notable decline in sperm motility in CP treated rats. Moreover, the expressions of steroidogenic enzymes were also lowered in CP administered group. The levels of follicle stimulating hormone (FSH) and plasma testosterone as well as luteinizing hormone (LH) were decreased in CP treated group. Moreover, the expression of Bax as well as Caspase-3 (apoptotic markers) were increased. On the other hand, Bcl-2 expression (anti-apoptotic marker) was reduced. Furthermore, the histopathological analysis showed that CP considerably (p < 0.05) damaged the testicular tissues. However, the administration of ROF significantly reduced the damaging effects of CP in testicular tissues. The results of our study suggested that ROF can potentially alleviate CP-induced testicular damages due to its androgenic, anti-oxidant and anti-inflammatory as well as anti-apoptotic nature.
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Affiliation(s)
- Faria Saher
- Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan
| | - Muhammad Umar Ijaz
- Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan
| | - Ali Hamza
- Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan
| | - Qurat Ul Ain
- Department of Zoology, Government College Women University, Sialkot 51040, Pakistan
| | - Muhammad Faisal Hayat
- Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan
| | - Tayyaba Afsar
- Department of Community Health Sciences, College of Applied Medical Sciences, 11433, King Saud University, Riyadh, Saudi Arabia
| | - Ali Almajwal
- Department of Community Health Sciences, College of Applied Medical Sciences, 11433, King Saud University, Riyadh, Saudi Arabia
| | - Huma Shafique
- Institute of Cellular Medicine, Newcastle University Medical School, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
| | - Suhail Razak
- Department of Community Health Sciences, College of Applied Medical Sciences, 11433, King Saud University, Riyadh, Saudi Arabia
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18
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Farag FSAA, Anwar HM, Aboushousha T, Mohammed HS, Ismail LDM. Ameliorative Effects of Thunbergia erecta L. Leaves Against the Initiation of Hepatocarcinogenesis Induced by Diethylnitrosamine in the Rat Model. Appl Biochem Biotechnol 2023; 195:5881-5902. [PMID: 36708488 PMCID: PMC10511368 DOI: 10.1007/s12010-022-04292-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2022] [Indexed: 01/29/2023]
Abstract
Thunbergia erecta L. contains cytotoxic and liver-protective compounds. Thunbergia erecta L. leaves were macerated in 70% aqueous ethanol, then fractionated with ethyl acetate (9.3 g) and butanol (12.7 g), and attenuated Den-induced liver cancer in a Wistar rat experimental model. Ethyl acetate and butanol fractions were chromatographed using column chromatography and solid-phase extraction (SPE); Vicenin-II (1), kaempferol (2), biochanin A, sissotrin 7-O-β-glucopyranoside (3), gentianose (4), acacetin 7-O-β-glucopyranoside (5), apigenin 7-O-β-glucopyranoside (6), and rosmarinic acid (7) were extracted, and their structures were determined using NMR spectroscopy and ESI-mass spectrometry. Sixty rats were divided into six groups (ten each): control group, Den group, doxorubicin/Den-treated group, butanol fraction/Den-treated group, and isolated acacetin 7-O-β-glucopyranoside/Den-treated group. The liver enzymes and proinflammatory biomarkers were used to estimate the liver function. In addition, liver tissues were collected for analysis of oxidative stress markers, gene expression, and histopathology. There is a significant increase in the levels of liver enzymes, AFP, and TNF-ἁ. This was conveyed by a significant increase of IL-1 and caspase-3, elevation of MDA and reduction of GSH, and suppression of Bcl2 and elevation of Bax expression. All parameters in butanol, ethyl acetate fractions, and isolated acacetin 7-O-β-glucopyranoside (major constituents) of T. erecta L. were significantly improved to values close to those of the control group.
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Affiliation(s)
- Fatma Sayed Abdel-Aal Farag
- Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11651, Egypt.
| | - Hend Mohamed Anwar
- Department of Biochemistry, National Organization for Drug Control & Research, Cairo, Egypt
| | - Tarek Aboushousha
- Department of Pathology, Theodor Bilharz Research Institute, Kornaish El-Nile, Warrak El-Hadar, P.O. 30 Imbaba, Giza, 12411, Egypt
| | - Hala Sh Mohammed
- Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11651, Egypt
| | - Lotfi Diab Mousa Ismail
- Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11651, Egypt
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19
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Yang J, Zhang L, Ding Q, Zhang S, Sun S, Liu W, Liu J, Han X, Ding C. Flavonoid-Loaded Biomaterials in Bone Defect Repair. Molecules 2023; 28:6888. [PMID: 37836731 PMCID: PMC10574214 DOI: 10.3390/molecules28196888] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/25/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Skeletons play an important role in the human body, and can form gaps of varying sizes once damaged. Bone defect healing involves a series of complex physiological processes and requires ideal bone defect implants to accelerate bone defect healing. Traditional grafts are often accompanied by issues such as insufficient donors and disease transmission, while some bone defect implants are made of natural and synthetic polymers, which have characteristics such as good porosity, mechanical properties, high drug loading efficiency, biocompatibility and biodegradability. However, their antibacterial, antioxidant, anti-inflammatory and bone repair promoting abilities are limited. Flavonoids are natural compounds with various biological activities, such as antitumor, anti-inflammatory and analgesic. Their good anti-inflammatory, antibacterial and antioxidant activities make them beneficial for the treatment of bone defects. Several researchers have designed different types of flavonoid-loaded polymer implants for bone defects. These implants have good biocompatibility, and they can effectively promote the expression of angiogenesis factors such as VEGF and CD31, promote angiogenesis, regulate signaling pathways such as Wnt, p38, AKT, Erk and increase the levels of osteogenesis-related factors such as Runx-2, OCN, OPN significantly to accelerate the process of bone defect healing. This article reviews the effectiveness and mechanism of biomaterials loaded with flavonoids in the treatment of bone defects. Flavonoid-loaded biomaterials can effectively promote bone defect repair, but we still need to improve the overall performance of flavonoid-loaded bone repair biomaterials to improve the bioavailability of flavonoids and provide more possibilities for bone defect repair.
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Affiliation(s)
- Jiali Yang
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (J.Y.); (L.Z.); (Q.D.); (S.Z.); (S.S.); (W.L.)
- Jilin Agriculture Science and Technology College, Jilin 132101, China
| | - Lifeng Zhang
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (J.Y.); (L.Z.); (Q.D.); (S.Z.); (S.S.); (W.L.)
- Jilin Agriculture Science and Technology College, Jilin 132101, China
| | - Qiteng Ding
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (J.Y.); (L.Z.); (Q.D.); (S.Z.); (S.S.); (W.L.)
| | - Shuai Zhang
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (J.Y.); (L.Z.); (Q.D.); (S.Z.); (S.S.); (W.L.)
| | - Shuwen Sun
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (J.Y.); (L.Z.); (Q.D.); (S.Z.); (S.S.); (W.L.)
| | - Wencong Liu
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (J.Y.); (L.Z.); (Q.D.); (S.Z.); (S.S.); (W.L.)
- School of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543002, China
| | - Jinhui Liu
- Huashikang (Shenyang) Health Industrial Group Corporation, Shenyang 110031, China;
| | - Xiao Han
- Looking Up Starry Sky Medical Research Center, Siping 136001, China;
| | - Chuanbo Ding
- Jilin Agriculture Science and Technology College, Jilin 132101, China
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20
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Kumar S, Senapati S, Bhattacharya N, Bhattacharya A, Maurya SK, Husain H, Bhatti JS, Pandey AK. Mechanism and recent updates on insulin-related disorders. World J Clin Cases 2023; 11:5840-5856. [PMID: 37727490 PMCID: PMC10506040 DOI: 10.12998/wjcc.v11.i25.5840] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 07/06/2023] [Accepted: 08/07/2023] [Indexed: 09/01/2023] Open
Abstract
Insulin, a small protein with 51 amino acids synthesized by pancreatic β-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.
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Affiliation(s)
- Shashank Kumar
- Department of Biochemistry, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Sabyasachi Senapati
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Neetu Bhattacharya
- Department of Zoology, Dyal Singh College, University of Delhi, New Delhi 110003, India
| | - Amit Bhattacharya
- Department of Zoology, Ramjas College, University of Delhi, New Delhi 110007, India
| | | | - Hadiya Husain
- Department of Zoology, University of Lucknow, Lucknow 226007, India
| | - Jasvinder Singh Bhatti
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
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21
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Saeidi A, Saei MA, Mohammadi B, Zarei HRA, Vafaei M, Mohammadi AS, Barati M, Montazer M, Razi O, Kiyumi MHA, Laher I, Gholami M, Weiss K, Knechtle B, Zouhal H. Supplementation with spinach-derived thylakoid augments the benefits of high intensity training on adipokines, insulin resistance and lipid profiles in males with obesity. Front Endocrinol (Lausanne) 2023; 14:1141796. [PMID: 37576981 PMCID: PMC10422041 DOI: 10.3389/fendo.2023.1141796] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 06/23/2023] [Indexed: 08/15/2023] Open
Abstract
Introduction This study investigated the effects of 12 weeks of high-intensity functional training (HIFT) combined with spinach-derived thylakoid supplementation on some selected Adipokines and insulin resistance in males with obesity. Method Sixty-eight participants (mean age: 27.6 ± 8.4 yrs.; mean height: 168.4 ± 2.6 cm; mean weight: 95.7 ± 3.8 kg, mean BMI: 32.6 ± 2.6 kg/m2) were randomly divided into four groups of 17 per group: Control group (CG), Supplement group (SG), Training group (TG), and Training + supplement group (TSG). Following baseline measurements, the two training groups (TG and TSG) started the 12 weeks of exercise training program (3 sessions per week). A total of 36 sessions lasting up to 60 min were included in the HIFT program using the CrossFit program. The eligible participants received 5 g/day of thylakoid-rich spinach extract or matching placebo as 5 g/day of raw corn starch (one sachet, 30 min before lunch) for 12 weeks. Baseline assessments were obtained 48 hours before the start of the training protocols and 48 hours after the last training session in all groups. Results There were significant interactions (p<0.001 for all) between exercise and time for adiponectin (ES:0.48), leptin (ES:0.46), resistin (ES:0.3), omentin (ES:0.65), vaspin (ES:0.46), visfatin (ES:0.62), apelin (ES:0.42), RBP4 (ES:0.63), chemrin (0.36) and semaphorin3c (ES: 0.5). Plasma levels of semaphorin3c were significantly correlated (p<0.05) with body weight (r= 0.57), BMI (r= 0.43), FFM (r= -0.612), FAT (r= 0.768), VO2peak (r=-0.53), insulin (r= 0.756), glucose (r= 0.623), and HOMA-IR (r= 0.727). There were also significant group differences in insulin (ES: 0.77), glucose (ES: 0.21), and HOM-IR (ES: 0.44) (p<0.05). Discussion Our findings indicate that 12 weeks of HIFT supplemented with spinach-derived thylakoid reduced levels of leptin, resistin, vaspin, visfatin, apelin, RBP4, chemrin, semaphorin3c and insulin resistance while increasing adiponectin and omentin levels in men with obesity.
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Affiliation(s)
- Ayoub Saeidi
- Department of Physical Education and Sport Sciences, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Iran
| | - Mohammad Amin Saei
- Department of Sports Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran
| | - Behnam Mohammadi
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Hamid Reza Akbarzadeh Zarei
- Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Morvarid Vafaei
- Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Amir Shayan Mohammadi
- Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Masoumeh Barati
- Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mona Montazer
- Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Omid Razi
- Department of Exercise Physiology, Faculty of Physical Education and Sports Science, Razi University, Kermanshah, Iran
| | - Maisa Hamed Al Kiyumi
- Department of Family Medicine and Public Health, Sultan Qaboos University, Sultan Qaboos University Hospital, Muscat, Oman
| | - Ismail Laher
- Department of 87 Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC, Canada
| | - Mandana Gholami
- Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Katja Weiss
- Institute of Primary Care, University of Zurich, Zurich, Switzerland
| | - Beat Knechtle
- Institute of Primary Care, University of Zurich, Zurich, Switzerland
- Medbase St. Gallen Am Vadianplatz, St. Gallen, Switzerland
| | - Hassane Zouhal
- Univ Rennes, M2S (Laboratoire Mouvement, Sport, Santé), Rennes, France
- Institut International des Sciences du Sport (2I2S), Irodouer, France
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22
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Singh SV, Ganguly R, Jaiswal K, Yadav AK, Kumar R, Pandey AK. Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review. World J Clin Cases 2023; 11:4458-4476. [PMID: 37469740 PMCID: PMC10353503 DOI: 10.12998/wjcc.v11.i19.4458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 05/09/2023] [Accepted: 06/06/2023] [Indexed: 06/30/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.
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Affiliation(s)
- Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Kritika Jaiswal
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Aditya Kumar Yadav
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
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23
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Anwar F, Naqvi S, Shams S, Sheikh RA, Al-Abbasi FA, Asseri AH, Baig MR, Kumar V. Nanomedicines: intervention in inflammatory pathways of cancer. Inflammopharmacology 2023; 31:1199-1221. [PMID: 37060398 PMCID: PMC10105366 DOI: 10.1007/s10787-023-01217-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 03/29/2023] [Indexed: 04/16/2023]
Abstract
Inflammation is a complex defense process that maintains tissue homeostasis. However, this complex cascade, if lasts long, may contribute to pathogenesis of several diseases. Chronic inflammation has been exhaustively studied in the last few decades, for its contribution in development and progression of cancer. The intrinsic limitations of conventional anti-inflammatory and anti-cancer therapies triggered the development of nanomedicines for more effective and safer therapies. Targeting inflammation and tumor cells by nanoparticles, encapsulated with active therapeutic agents, offers a promising outcome with patient survival. Considerable technological success has been achieved in this field through exploitation of tumor microenvironment, and recognition of molecules overexpressed on endothelial cells or macrophages, through enhanced vascular permeability, or by rendering biomimetic approach to nanoparticles. This review focusses on the inflammatory pathways in progression of a tumor, and advancement in nanotechnologies targeting these pathways. We also aim to identify the gaps that hinder the successful clinical translation of nanotherapeutics with further clinical studies that will allow oncologist to precisely identify the patients who may be benefited from nanotherapy at time when promotion or progression of tumor initiates. It is postulated that the nanomedicines, in near future, will shift the paradigm of cancer treatment and improve patient survival.
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Affiliation(s)
- Firoz Anwar
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
| | - Salma Naqvi
- Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, United Arab Emirates
| | - Saiba Shams
- School of Pharmaceutical Education & Research, (Deemed to be University), New Delhi, 110062, India
| | - Ryan Adnan Sheikh
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Fahad A Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Amer H Asseri
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Mirza Rafi Baig
- Department of Clinical Pharmacy & Pharmacotherapeutics. Dubai Pharmacy College for Girls, Po Box 19099, Dubai, United Arab Emirates
| | - Vikas Kumar
- Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India.
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24
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Prasad S, Kumar V, Singh C, Singh A. Crosstalk between phytochemicals and inflammatory signaling pathways. Inflammopharmacology 2023; 31:1117-1147. [PMID: 37022574 DOI: 10.1007/s10787-023-01206-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 03/21/2023] [Indexed: 04/07/2023]
Abstract
Novel bioactive constituents from natural sources are actively being investigated. The phytochemicals in these phenolic compounds are believed to have a variety of beneficial effects on human health. Several phenolic compounds have been found in plants. The antioxidant potential of phenols has been discussed in numerous studies along with their anti-inflammatory effects on pro-inflammatory cytokine, inducible cyclooxygenase-2, and nitric oxide synthase. Through current study, an attempt is made to outline and highlight a wide variety of inflammation-associated signaling pathways that have been modified by several natural compounds. These signaling pathways include nuclear factor-kappa B (NF-кB), activator protein (AP)-1, protein tyrosine kinases (PTKs), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors, tyrosine phosphatidylinositol 3-kinase (PI3K)/AKT, and the ubiquitin-proteasome system. In light of the influence of natural substances on signaling pathways, their impact on the production of inflammatory mediator is highlighted in this review.
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Affiliation(s)
- Sonima Prasad
- Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India
| | - Vishal Kumar
- Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India
| | - Charan Singh
- Department of Pharmaceutical Sciences, School of Pharmacy, H.N.B. Garhwal University, Srinagar, Garhwal, 246174, Uttarakhand, India
| | - Arti Singh
- Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
- Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India.
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25
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Mechanism Repositioning Based on Integrative Pharmacology: Anti-Inflammatory Effect of Safflower in Myocardial Ischemia–Reperfusion Injury. Int J Mol Sci 2023; 24:ijms24065313. [PMID: 36982389 PMCID: PMC10048972 DOI: 10.3390/ijms24065313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 02/21/2023] [Accepted: 02/28/2023] [Indexed: 03/12/2023] Open
Abstract
Safflower (Carthamus tinctorius. L) possesses anti-tumor, anti-thrombotic, anti-oxidative, immunoregulatory, and cardio-cerebral protective effects. It is used clinically for the treatment of cardio-cerebrovascular disease in China. This study aimed to investigate the effects and mechanisms of action of safflower extract on myocardial ischemia–reperfusion (MIR) injury in a left anterior descending (LAD)-ligated model based on integrative pharmacology study and ultra-performance liquid chromatography–quadrupole time-of-flight-tandem mass spectrometer (UPLC-QTOF-MS/MS). Safflower (62.5, 125, 250 mg/kg) was administered immediately before reperfusion. Triphenyl tetrazolium chloride (TTC)/Evans blue, echocardiography, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, lactate dehydrogenase (LDH) ability, and superoxide dismutase (SOD) levels were determined after 24 h of reperfusion. Chemical components were obtained using UPLC-QTOF-MS/MS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to analyze mRNA and protein levels, respectively. Safflower dose-dependently reduced myocardial infarct size, improved cardiac function, decreased LDH levels, and increased SOD levels in C57/BL6 mice. A total of 11 key components and 31 hub targets were filtered based on the network analysis. Comprehensive analysis indicated that safflower alleviated inflammatory effects by downregulating the expression of NFκB1, IL-6, IL-1β, IL-18, TNFα, and MCP-1 and upregulating NFκBia, and markedly increased the expression of phosphorylated PI3K, AKT, PKC, and ERK/2, HIF1α, VEGFA, and BCL2, and decreased the level of BAX and phosphorylated p65. Safflower shows a significant cardioprotective effect by activating multiple inflammation-related signaling pathways, including the NFκB, HIF-1α, MAPK, TNF, and PI3K/AKT signaling pathways. These findings provide valuable insights into the clinical applications of safflower.
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26
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Magurano F, Micucci M, Nuzzo D, Baggieri M, Picone P, Gioacchini S, Fioravanti R, Bucci P, Kojouri M, Mari M, Retini M, Budriesi R, Mattioli LB, Corazza I, Di Liberto V, Todaro L, Giuseppetti R, D’Ugo E, Marchi A, Mecca M, D’Auria M. A potential host and virus targeting tool against COVID-19: Chemical characterization, antiviral, cytoprotective, antioxidant, respiratory smooth muscle relaxant effects of Paulownia tomentosa Steud. Biomed Pharmacother 2023; 158:114083. [PMID: 36495668 PMCID: PMC9721285 DOI: 10.1016/j.biopha.2022.114083] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/23/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
COronaVIrus Disease 2019 (COVID-19) is a newly emerging infectious disease that spread across the world, caused by the novel coronavirus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Despite the advancements in science that led to the creation of the vaccine, there is still an urgent need for new antiviral drugs effective against SARS-CoV-2. This study aimed to investigate the antiviral effect of Paulownia tomentosa Steud extract against SARS-CoV-2 and to evaluate its antioxidant properties, including respiratory smooth muscle relaxant effects. Our results showed that P. tomentosa extract can inhibit viral replication by directly interacting with both the 3-chymotrypsin-like protease and spike protein. In addition, the phyto complex does not reduce lung epithelial cell viability and exerts a protective action in those cells damaged by tert-butyl hydroperoxide , a toxic agent able to alter cells' functions via increased oxidative stress. These data suggest the potential role of P. tomentosa extract in COVID-19 treatment, since this extract is able to act both as an antiviral and a cytoprotective agent in vitro.
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Affiliation(s)
- Fabio Magurano
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
| | - Matteo Micucci
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza Rinascimento 6, 61029 Urbino, PU, Italy
| | - Domenico Nuzzo
- Istituto per la Ricerca e l’Innovazione Biomedica, CNR, via U. La Malfa 153, 90146 Palermo, Italy
| | - Melissa Baggieri
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Pasquale Picone
- Istituto per la Ricerca e l’Innovazione Biomedica, CNR, via U. La Malfa 153, 90146 Palermo, Italy
| | - Silvia Gioacchini
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Raoul Fioravanti
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Paola Bucci
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Maedeh Kojouri
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Michele Mari
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza Rinascimento 6, 61029 Urbino, PU, Italy
| | - Michele Retini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza Rinascimento 6, 61029 Urbino, PU, Italy
| | - Roberta Budriesi
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy
| | - Laura Beatrice Mattioli
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy
| | - Ivan Corazza
- Department of Specialistic, Diagnostic and Experimental Medicine (DIMES), University of Bologna, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Valentina Di Liberto
- Department of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, 90128 Palermo, Italy
| | - Luigi Todaro
- Scuola di Scienze Agrarie, Forestali, Alimentari ed Ambientali, Università della Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, Italy
| | - Roberto Giuseppetti
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Emilio D’Ugo
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Antonella Marchi
- Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Marisabel Mecca
- Dipartimento di Scienze, Università della Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, Italy
| | - Maurizio D’Auria
- Dipartimento di Scienze, Università della Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, Italy
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27
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Bullón-Vela V, Xu Y, Razquin C, Abete I, Zulet MA, Martínez-González MA, Buil-Corsiales P, Vitelli-Storelli F, Martín Sánchez V, Vazquez-Ruíz Z, Sayón-Orea C, Domínguez-Fernández M, Cid C, Estruch R, Lamuela-Raventós RM, Fitó M, Blanchart G, Babio N, Salas-Salvadó J, Tinahones FJ, Tur JA, Romaguera D, Konieczna J, Pintó X, Daimiel L, Rodriguez-Mateos A, Martínez JA. Health associations of liver enzymes and inflammatory scores with urinary citrus flavonoid metabolites. Food Funct 2023; 14:1011-1023. [PMID: 36562455 PMCID: PMC9870039 DOI: 10.1039/d2fo02846h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 11/17/2022] [Indexed: 12/24/2022]
Abstract
Background: Dietary flavonoid intake is associated with a reduced risk of some cardiometabolic disorders, attributed in part to their claimed anti-inflammatory activity. Our aim was to investigate the potential association between specific urine flavonoid metabolites, liver enzymes, and inflammatory status in individuals with metabolic syndrome (MetS). Methods: In this cross-sectional study, clinical and dietary data from 267 participants, aged 55 to 75 years, participating in the PREDIMED Plus study (PREvención con DIeta MEDiterránea) were analyzed. At the baseline, spot urine samples were collected and seven urinary flavonoid metabolites were quantified using ultra-performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS). Liver enzymes, inflammatory scores, and urinary flavonoid concentrations were inverse normally transformed. Results: Adjusted linear regression models showed an inverse association between urinary citrus flavanone concentrations and gamma-glutamyl transferase (GGT) (all p-values <0.05). Naringenin 7'-GlcUA was significantly associated with a lower aggregate index of systemic inflammation (AISI) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.025) and systemic inflammation index (SII) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.028). To investigate the relationship between flavanone subclasses and GGT levels, we fitted a score of citrus-flavanones, and subjects were stratified into quartiles. The highest values of the citrus-flavanone score (per 1-SD increase) were associated with lower GGT levels (Bper 1SD = -0.41; 95% CI: -0.74 to -0.07), exhibiting a linear trend across quartiles (p-trend = 0.015). Conclusion: This cross-sectional study showed that higher urinary excretion of citrus-flavanone metabolites was associated with lower GGT levels in subjects diagnosed with MetS and obesity.
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Affiliation(s)
- Vanessa Bullón-Vela
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
| | - Yifan Xu
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
| | - Cristina Razquin
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Itziar Abete
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Center for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Maria Angeles Zulet
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Center for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Miguel A Martínez-González
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Pilar Buil-Corsiales
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | | | - Vicente Martín Sánchez
- Institute of Biomedicine (IBIOMED), University of León, León, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Zenaida Vazquez-Ruíz
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Carmen Sayón-Orea
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Maite Domínguez-Fernández
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Center for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Concepción Cid
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Center for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Ramon Estruch
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Internal Medicine, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Rosa María Lamuela-Raventós
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA-UB, School of Pharmacy and Food Sciences, Nutrition and Food Safety Research Institute, University of Barcelona, Barcelona, Spain
| | - Montserrat Fitó
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - Gemma Blanchart
- Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - Nancy Babio
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Tarragona, Spain
- Institut d'Investigació Pere Virgili (IISPV), Hospital Universitari Sant Joan de Reus, Reus, Spain
| | - Jordi Salas-Salvadó
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Tarragona, Spain
- Institut d'Investigació Pere Virgili (IISPV), Hospital Universitari Sant Joan de Reus, Reus, Spain
| | - Francisco J Tinahones
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Endocrinology, Instituto de Investigación Biomédica de Málaga-IBIMA, University of Málaga, Virgen de la Victoria Hospital, Málaga, Spain
| | - Josep A Tur
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands-IUNICS, Palma de Mallorca, Spain
| | - Dora Romaguera
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology (NUTRECOR), Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases (HUSE), Palma de Mallorca, Spain
| | - Jadwiga Konieczna
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology (NUTRECOR), Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases (HUSE), Palma de Mallorca, Spain
| | - Xavier Pintó
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | - Lidia Daimiel
- Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, CEI UAM+ CSIC, Madrid, Spain
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
| | - José Alfredo Martínez
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Center for Nutrition Research, University of Navarra, Pamplona, Spain
- Cardiometabolic Nutrition Group, Precision Nutrition and Cardiovascular Health Program, IMDEA Food, CEI UAM+ CSIC, Madrid, Spain
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Kassouri C, Rodriguez Torres S, Gonzalez Suarez N, Duhamel S, Annabi B. EGCG Prevents the Transcriptional Reprogramming of an Inflammatory and Immune-Suppressive Molecular Signature in Macrophage-like Differentiated Human HL60 Promyelocytic Leukemia Cells. Cancers (Basel) 2022; 14:5065. [PMID: 36291849 PMCID: PMC9599716 DOI: 10.3390/cancers14205065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/07/2022] [Accepted: 10/13/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The promyelocytic leukemia cell differentiation process enables recapitulation of the polarized M1 or M2 macrophage-like phenotype with inflammatory and immune-suppressive properties. While evidence supports the anti-inflammatory effect of dietary-derived epigallocatechin-3-gallate (EGCG), its impact on the onset of immune phenotype molecular signature remains unclear. METHODS Human HL60 promyelocytic cells grown in suspension were differentiated into CD11bHigh/CD14Low adherent macrophages with phorbol 12-myristate 13-acetate (PMA). Gelatin zymography was used to assess the levels of matrix metalloproteinase (MMP)-9, and total RNA was isolated for RNAseq and RT-qPCR assessment of differentially expressed gene levels involved in inflammation and immunity. Protein lysates were used to assess the phosphorylation status of signaling intermediates involved in macrophage-like cell differentiation. RESULTS Cell adhesion and induction of MMP-9 were indicative of HL60 cell differentiation into a macrophage-like phenotype. The extracellular signal-regulated kinase (ERK), glycogen synthase kinase (GSK)-3, p90 ribosomal S6 kinases (RSK), and cAMP-response-element-binding protein (CREB) were all phosphorylated, and EGCG reduced such phosphorylation status. Increases in inflammation and immunity genes included, among others, CCL22, CSF1, CSF2, IL1B, and TNF, which inductions were prevented by EGCG. This was corroborated by unbiased transcriptomic analysis which further highlighted the capacity of EGCG to downregulate the hematopoietic stem cell regulator CBFA2T3. CONCLUSION EGCG inhibits inflammatory signaling crosstalk and prevents the onset of an immune phenotype in macrophage-like differentiated cells.
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Affiliation(s)
- Celia Kassouri
- Laboratoire d’Oncologie Moléculaire, Département de Chimie, and CERMO-FC, Université du Québec à Montréal, Montreal, QC H2X 2J6, Canada
| | - Sahily Rodriguez Torres
- Laboratoire d’Oncologie Moléculaire, Département de Chimie, and CERMO-FC, Université du Québec à Montréal, Montreal, QC H2X 2J6, Canada
| | - Narjara Gonzalez Suarez
- Laboratoire d’Oncologie Moléculaire, Département de Chimie, and CERMO-FC, Université du Québec à Montréal, Montreal, QC H2X 2J6, Canada
| | - Stéphanie Duhamel
- Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada
| | - Borhane Annabi
- Laboratoire d’Oncologie Moléculaire, Département de Chimie, and CERMO-FC, Université du Québec à Montréal, Montreal, QC H2X 2J6, Canada
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Chen M, Xiao J, El-Seedi HR, Woźniak KS, Daglia M, Little PJ, Weng J, Xu S. Kaempferol and atherosclerosis: From mechanism to medicine. Crit Rev Food Sci Nutr 2022; 64:2157-2175. [PMID: 36099317 DOI: 10.1080/10408398.2022.2121261] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Natural products possess pleiotropic cardiovascular protective effects owing to their anti-oxidation, anti-inflammation and anti-thrombotic properties. Kaempferol, (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), is a kind of naturally occurring flavonoid existing in many common fruits and vegetables (e.g., onions, broccoli, strawberries and grapes) and particularly in traditional Chinese medicine as exemplified by Ginkgo biloba. Epidemiological, preclinical and clinical studies have revealed an inverse association between the consumption of kaempferol-containing foods and medicines and the risk of developing cardiovascular diseases. Numerous translational studies in experimental animal models and cultured cells have demonstrated a wide range of pharmacological activities of kaempferol. In this article, we reviewed the antioxidant, anti-inflammatory and cardio-protective activities of kaempferol and elucidated the potential molecular basis of the therapeutic capacity of kaempferol by focusing on its anti-atherosclerotic effects. Overall, the review presents the health benefits of kaempferol-containing plants and medicines and reflects on the potential of kaempferol as a possible drug candidate to prevent and treat atherosclerosis, the underlying pathology of most cardiovascular diseases.
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Affiliation(s)
- Meijie Chen
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, Anhui, China
| | - Jianbo Xiao
- Department of Analytical Chemistry and Food Science, University of Vigo, Vigo, Spain
| | - Hesham R El-Seedi
- Pharmacognosy Group, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
| | | | - Maria Daglia
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
- Department of Pharmacy, University of Napoli Federico II, Naples, Italy
| | - Peter J Little
- School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, QLD, Australia
| | - Jianping Weng
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, Anhui, China
| | - Suowen Xu
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, Anhui, China
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Peraza-Labrador A, Buitrago DM, Coy-Barrera E, Perdomo-Lara SJ. Antiproliferative and Pro-Apoptotic Effects of a Phenolic-Rich Extract from Lycium barbarum Fruits on Human Papillomavirus (HPV) 16-Positive Head Cancer Cell Lines. Molecules 2022; 27:molecules27113568. [PMID: 35684505 PMCID: PMC9182172 DOI: 10.3390/molecules27113568] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 11/16/2022] Open
Abstract
The in vitro antiproliferative activity of a phenolic-rich extract from Lycium barbarum fruits against head and neck HPV16 squamous cell carcinoma (OSCC) has been demonstrated, indicating for the first time that L. barbarum extract inhibits human papillomavirus (HPV) type 16 cell lines. Ethanol extract of L. barbarum was used for cell viability evaluation on SCC090, CAL27, and HGnF cell lines. After 24 and 48 h, the cell cycle effect of L. barbarum extract (at 1.0, 10, and 100 µg/mL) was measured via flow cytometry. In addition, the mRNA expression on E6/E7 and p53 via RT-PCR and the expression of p16, p53, Ki-67, and Bcl-2 via immunohistochemistry were also determined. Untreated cells, 20 µM cisplatin, and a Camellia sinensis-derived extract were used as negative and positive controls, respectively. We demonstrated that the studied L. barbarum extract resulted in G0/G1 arrest and S phase accumulation in SCC090 at 1.0 and 10 μg/mL. A reduction in mRNA levels of E6/E7 oncogenes (p < 0.05) with p53 overexpression was also observed through PCR, while immunohistochemical analyses indicated p16 overexpression (p > 0.05) and a decrease in p53 overexpression. The observed effects were associated with anticancer and immunomodulatory phenolics, such as flavonols/flavan-3-ols and tyramine-conjugated hydroxycinnamic acid amides, identified in the studied extract. These findings revealed that the phenolic-rich extract of L. barbarum fruits has promising properties to be considered further for developing new therapies against oral and oropharyngeal HPV lesions.
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Affiliation(s)
- Alberto Peraza-Labrador
- Unit of Basic Oral Investigation-UIBO, School of Dentistry, Universidad El Bosque, Bogotá 110121, Colombia; (A.P.-L.); (D.M.B.)
- Cellular and Molecular Immunology Group-INMUBO, School of Dentistry, Universidad El Bosque, Bogotá 110121, Colombia
| | - Diana Marcela Buitrago
- Unit of Basic Oral Investigation-UIBO, School of Dentistry, Universidad El Bosque, Bogotá 110121, Colombia; (A.P.-L.); (D.M.B.)
| | - Ericsson Coy-Barrera
- Bioorganic Chemistry Laboratory, Department of Chemistry, Universidad Militar Nueva Granada, Cajicá 250247, Colombia;
| | - Sandra J. Perdomo-Lara
- Cellular and Molecular Immunology Group-INMUBO, School of Dentistry, Universidad El Bosque, Bogotá 110121, Colombia
- Correspondence: ; Tel.: +57-164-89000
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Zhou T, Zheng A, Zhang W, Lu X, Chen H, Tan H. Concise total syntheses of two flavans and structure revision assisted by quantum NMR calculations. Org Biomol Chem 2022; 20:4096-4100. [PMID: 35522925 DOI: 10.1039/d2ob00634k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A two-step protecting-group-free protocol for the synthesis of 3'-hydroxy-5,7-dimethoxy-4-O-2'-cycloflavan (1) and concise total synthesis of 4'-hydroxy-5,7-dimethoxy-4-O-2'-cycloflavan (8) enabled by a PTSA triggered bioinspired olefin isomerization/hemiacetalization/dehydration/[3 + 3]-type cycloaddition cascade reaction are reported. The successful synthesis of cycloflavan 8 along with GIAO 13C NMR calculations of flavan-4-ol 9 and cycloflavan 8 indicated the misassignment of the flavonoid isolated previously and realized the revision of its actual structure.
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Affiliation(s)
- Tingting Zhou
- Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People's Republic of China. .,School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, People's Republic of China
| | - Anquan Zheng
- Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People's Republic of China. .,School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, People's Republic of China
| | - Wenge Zhang
- Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People's Republic of China.
| | - Xiuxiang Lu
- Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People's Republic of China.
| | - Huiyu Chen
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, People's Republic of China.,School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, People's Republic of China
| | - Haibo Tan
- Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People's Republic of China. .,Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University, Haikou, 571158, People's Republic of China
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Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules 2022; 27:molecules27092901. [PMID: 35566252 PMCID: PMC9100260 DOI: 10.3390/molecules27092901] [Citation(s) in RCA: 335] [Impact Index Per Article: 111.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 04/27/2022] [Accepted: 04/28/2022] [Indexed: 12/22/2022] Open
Abstract
Hydroxylated polyphenols, also called flavonoids, are richly present in vegetables, fruits, cereals, nuts, herbs, seeds, stems, and flowers of numerous plants. They possess numerous medicinal properties such as antioxidant, anti-cancer, anti-microbial, neuroprotective, and anti-inflammation. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect. They inhibit the secretions of enzymes such as lysozymes and β-glucuronidase and inhibit the secretion of arachidonic acid, which reduces inflammatory reactions. Flavonoids such as quercetin, genistein, apigenin, kaempferol, and epigallocatechin 3-gallate modulate the expression and activation of a cytokine such as interleukin-1beta (IL-1β), Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8); regulate the gene expression of many pro-inflammatory molecules such s nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM), and E-selectins; and also inhibits inducible nitric oxide (NO) synthase, cyclooxygenase-2, and lipoxygenase, which are pro-inflammatory enzymes. Understanding the anti-inflammatory action of flavonoids provides better treatment options, including coronavirus disease 2019 (COVID-19)-induced inflammation, inflammatory bowel disease, obstructive pulmonary disorder, arthritis, Alzheimer’s disease, cardiovascular disease, atherosclerosis, and cancer. This review highlights the sources, biochemical activities, and role of flavonoids in enhancing human health.
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Ganguly R, Kumar R, Pandey AK. Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation. World J Hepatol 2022; 14:729-743. [PMID: 35646277 PMCID: PMC9099103 DOI: 10.4254/wjh.v14.i4.729] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 09/17/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.
AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.
METHODS Male albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.
RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.
CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.
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Affiliation(s)
- Risha Ganguly
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, India
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Xiang Z, Wang Y, Liu S. The chemical and metabolite profiles of Gualou-Xiebai-Banxia decoction, a classical traditional Chinese medicine formula, by using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and in-house software. JOURNAL OF ETHNOPHARMACOLOGY 2022; 288:114994. [PMID: 35033623 DOI: 10.1016/j.jep.2022.114994] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 12/14/2021] [Accepted: 01/10/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gualou-Xiebai-Banxia decoction (GXBD) was a classical traditional Chinese medicine formula for the treatment of coronary heart disease. However, the current study on the chemical and metabolite profiles of GXBD did not follow the ancient prescription and extraction method, which hindered the discovery of effective compounds and quality control. MATERIALS AND METHODS In this study, we prepared GXBD by ancient prescription and extraction methods, and then analysed the chemical components and xenobiotics of GXBD in vivo using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and in-house software. RESULTS 49 chemical constituents were preliminarily identified, including 7 terpenoids, 6 flavonoids, 5 alkaloids, 17 organic acids, 8 steroids and steroidal saponins, 2 nucleosides and 4 other types of compounds, of which 10 constituents were confirmed unambiguously with authentic standards. Moreover, 129 metabolites were tentatively identified, including 83 metabolites in plasma, 39 metabolites in urine, 25 metabolites in bile and 9 metabolites in feces. Our study speculated that luteolin, adenosine, vanillic acid and curbitacin B might be possible effective components of GXBD for the treatment of coronary heart disease. Dehydration, deglycosylation, dehydrogenation, acetylation and taurine regulation were the main biotransformation reactions of GXBD. CONCLUSION Our results provided an important basis for the discovery of effective compounds and quality control of GXBD. In addition, in-house software was an useful tool for identifcation of metabolites.
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Affiliation(s)
- Zheng Xiang
- Medical School, Zhejiang University City College, Hangzhou, 310015, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
| | - Yuzhen Wang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China
| | - Shundi Liu
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China
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Zheng B, Zheng Y, Zhang N, Zhang Y, Zheng B. Rhoifolin from Plumula Nelumbinis exhibits anti-cancer effects in pancreatic cancer via AKT/JNK signaling pathways. Sci Rep 2022; 12:5654. [PMID: 35383226 PMCID: PMC8983741 DOI: 10.1038/s41598-022-09581-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 03/25/2022] [Indexed: 02/07/2023] Open
Abstract
This study aimed to evaluate the anti-pancreatic cancer effects of flavonoids in Plumula Nelumbinis. High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry showed that apiin, rhoifolin, and vitexin were three principal components in total flavonoids derived from Plumula Nelumbinis, with vitexin being the most abundant component. Cell viability assay revealed that apiin, rhoifolin, and vitexin could inhibit proliferation of PANC-1 and ASPC-1, with rhoifolin showing the maximum inhibitory effect. Rhoifolin inhibited cell proliferation and promoted apoptosis of pancreatic cancer cells, which was associated with up-regulated JNK and p-JNK as well as down-regulated p-AKT. Rhoifolin also inhibited cell migration and invasion, and increased the antioxidant capacity in PANC-1 and ASPC-1. Besides, AKT activator (SC79) or JNK inhibitor (SP600125) effectively reversed the anticancer effects of rhoifolin in pancreatic cancer. Quantitative proteomics analysis showed that rhoifolin altered proteomic profiles in pancreatic cancer cells. Western blot analysis showed that rhoifolin down-regulated transforming growth factor beta 2 (TGF-β2), the regulator of proteoglycan synthesis, with the concomitant down-regulation of phosphorylated SMAD family member 2 (SMAD2), the downstream effector of TGF-β2. In conclusion, rhoifolin regulates the AKT/JNK/caspase-3 and TGF-β2/SMAD2 signaling pathways, which may contribute to its anti-pancreatic cancer effects.
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Affiliation(s)
- Bingxin Zheng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, People's Republic of China
| | - Yixin Zheng
- Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fuzhou, 350002, Fujian, People's Republic of China
| | - Ningning Zhang
- Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fuzhou, 350002, Fujian, People's Republic of China
| | - Yi Zhang
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, People's Republic of China.
| | - Baodong Zheng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, People's Republic of China.
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Curci F, Corbo F, Clodoveo ML, Salvagno L, Rosato A, Corazza I, Budriesi R, Micucci M, Mattioli LB. Polyphenols from Olive-Mill Wastewater and Biological Activity: Focus on Irritable Bowel Syndrome. Nutrients 2022; 14:nu14061264. [PMID: 35334922 PMCID: PMC8952826 DOI: 10.3390/nu14061264] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 02/04/2023] Open
Abstract
Waste represents a cost for companies, in particular for agro-food companies, which can become a resource as a secondary material. In this work, we examine three products of olive-oil waste water, named MOMAST® (Plus30, PW25, and HY100). Based on the chemical composition, obtained with different methods, we hypothesized a possible application as food supplements in irritable bowel syndrome (IBS). We therefore studied MOMASTs on some targets linked to this pathology: antioxidant action and spontaneous and induced intestinal contractility of the ileum and colon. Plus30, which showed a more promising biological of activity also for its oleuropein content, was characterized by an interesting action against some microorganisms. The results highlighted the ability of Plus30 to modulate spontaneous and induced contractility, to exert a good antioxidant action, and to significantly act on various microorganisms. These effects are synergistic in the presence of antibiotics. In conclusion, we can confirm that Plus30 could be a great candidate as a food supplement in patients with IBS.
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Affiliation(s)
- Francesca Curci
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Filomena Corbo
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Maria Lisa Clodoveo
- Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Lara Salvagno
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Antonio Rosato
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Ivan Corazza
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy;
| | - Roberta Budriesi
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;
- Correspondence: ; Tel.: +39-051-209-9721
| | - Matteo Micucci
- Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, 61029 Urbino, Italy;
- UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant’Alessandro, 800131 Rome, Italy
| | - Laura Beatrice Mattioli
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;
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Dumić J, Cvetko A, Abramović I, Šupraha Goreta S, Perović A, Njire Bratičević M, Kifer D, Sinčić N, Gornik O, Žarak M. Changes in Specific Biomarkers Indicate Cardiac Adaptive and Anti-inflammatory Response of Repeated Recreational SCUBA Diving. Front Cardiovasc Med 2022; 9:855682. [PMID: 35360010 PMCID: PMC8964121 DOI: 10.3389/fcvm.2022.855682] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 02/21/2022] [Indexed: 11/13/2022] Open
Abstract
ObjectiveRecreational SCUBA (rSCUBA) diving has become a highly popular and widespread sport. Yet, information on molecular events underlying (patho)physiological events that follow exposure to the specific environmental conditions (hyperbaric conditions, coldness, immersion, and elevated breathing pressure), in which rSCUBA diving is performed, remain largely unknown. Our previous study suggested that repeated rSCUBA diving triggers an adaptive response of cardiovascular and immune system. To elucidate further molecular events underlying cardiac and immune system adaptation and to exclude possible adverse effects we measured blood levels of specific cardiac and inflammation markers.MethodsThis longitudinal intervention study included fourteen recreational divers who performed five dives, one per week, on the depth 20–30 m that lasted 30 min, after the non-dive period of 5 months. Blood samples were taken immediately before and after the first, third, and fifth dives. Copeptin, immunoglobulins A, G and M, complement components C3 and C4, and differential blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) were determined using standard laboratory methods. Cell-free DNA was measured by qPCR analysis and N-glycans released from IgG and total plasma proteins (TPP), were analyzed by hydrophilic interaction ultra-performance liquid chromatography.ResultsCopeptin level increased after the first dive but decreased after the third and fifth dive. Increases in immunoglobulins level after every dive and during whole studied period were observed, but no changes in C3, C4, and cfDNA level were detected. NLR increased only after the first dive. IgG and TPP N-glycosylation alterations toward anti-inflammatory status over whole studied period were manifested as an increase in monogalyctosylated and core-fucosylated IgG N-glycans and decrease in agalactosylated TPP N-glycans.ConclusionrSCUBA diving practiced on a regular basis promotes anti-inflammatory status thus contributing cardioprotection and conferring multiple health benefits.
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Affiliation(s)
- Jerka Dumić
- Department of Biochemistry and Molecular Biology, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Ana Cvetko
- Department of Biochemistry and Molecular Biology, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Irena Abramović
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Sandra Šupraha Goreta
- Department of Biochemistry and Molecular Biology, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Antonija Perović
- Department of Laboratory Diagnostics, Dubrovnik General Hospital, Dubrovnik, Croatia
| | | | - Domagoj Kifer
- Department of Biophysics, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Nino Sinčić
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Olga Gornik
- Department of Biochemistry and Molecular Biology, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Marko Žarak
- Clinical Department of Laboratory Diagnostics, Dubrava University Hospital, Zagreb, Croatia
- *Correspondence: Marko Žarak,
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Ying P, Chen J, Ye Y, Ye J, Cai W. Adipose tissue is a predictor of 30-days mortality in patients with bloodstream infection caused by carbapenem-resistant Klebsiella pneumoniae. BMC Infect Dis 2022; 22:173. [PMID: 35189823 PMCID: PMC8860278 DOI: 10.1186/s12879-022-07108-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 01/29/2022] [Indexed: 11/23/2022] Open
Abstract
Background Prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection with high mortality has attached physicians' attention. High visceral adipose tissue (VAT) and high subcutaneous adipose tissue (SAT) were confirmed by previous studies that were closely related to increased pneumonia severity, more complications, and higher mortality in COVID-19. Thus, we speculate that CT-quantified body composition may also be connected to all-cause mortality and bacterial clearance in patients with CRKP bloodstream infection (BSI). Methods We investigated the associations of CT-quantified body composition with the mortality of CRKP bloodstream infectious patients. All CT images were obtained at the level of the L3/4 spinal level. The prognostic value of the body composition was analyzed using the Cox regression model, and precise clinical nomograms were established. Results 72 eligible patients both suffered from CRKP bloodstream infection and performed abdominopelvic CT were included. Factors associated with 30-day all-in hospital mortality included total adipose tissue (TAT) [adjusted hazard ratio (HR) = 1.028, 95% confidence interval (CI), 1.003–1.053; P = 0.025], age [HR = 1.030, 95% CI, 1.000–1.061; P = 0.047] and SOFA scores [HR = 1.138, 95% CI 1.049–1.263; P = 0.002]. Compared with low-VAT, patients with high-VAT show a strikingly poor prognosis in both 30-day all-cause mortality (P = 0.0108, Fig. 2A) and 30-day CRKP BSI mortality (P = 0.0049, Fig. 2C). The results of TAT were similar to VAT. Conclusions Our study suggested that CT-derived body composition could be a credible and effective alternative to assess the prognosis of patients with BSI owing to CRKP. CT-quantified TAT, age, and SOFA scores were independently associated with 30-day all-cause mortality in these severe infectious patients, while skeletal muscle did not have obvious statistical significance.
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Affiliation(s)
- Piaopiao Ying
- Department of General Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China
| | - Jiajing Chen
- Department of Pneumology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yinchai Ye
- Department of General Medicine, The Health Center of Eryuan Town, Wencheng County, Wenzhou, China
| | - Jianzhong Ye
- Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
| | - Weiyang Cai
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
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Handono K, Sunarti S, Pratama MZ, Hidayat S, Solikhin MB, Sermoati IA, Yuniati MG. The Mango’s Mistletoe Leaves Extract Ameliorates Lupus by Inhibiting the Anti-dsDNA Antibody Production, the Percentages of CD8+CD28− and CD4+CD28− T Cells. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.8093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: In SLE patients, repeated antigen stimulations induce a progressive reduction in CD28 expression on the surface of T cells and the chronic inflammation condition. Mango’s mistletoe is a parasitic plant that has anti-inflammation, antiproliferation, and immunomodulatory activities.
AIM: This study aimed to investigate the effect of mango’s mistletoe leaves extract (MLE) in inhibiting anti-dsDNA antibodies and ameliorating the percentages of CD8+CD28− and CD4+CD28− T cells in a pristane-induced lupus mice model.
METHODS: Lupus induction was undertaken by an injection of pristane 0.5 ml intraperitoneally in 6–8-week-old female balb/c mice. Mice with lupus signs were grouped randomly into the treatment groups which received MLE at doses of 150, 300, and 600 mg/kgbw/d for 28 days, respectively, and the positive control group without MLE. On day 29, anti-dsDNA antibody levels were analyzed using an ELISA. One of the immunosenescence markers (CD28− T cells) was investigated using a flow cytometer. ANOVA test was used for statistical analysis.
RESULTS: The mango’s mistletoe leaves extract (MLE) significantly decreased the number of anti-dsDNA antibodies (*p < 0.05), the percentages of CD8+CD28− T cells (*p < 0.05) and CD4+CD28− T cells (*p < 0.05).
CONCLUSION: We resume that the mango’s mistletoe leaves can ameliorate lupus by inhibiting anti-dsDNA antibody production and the percentages of CD8+CD28− and CD4+CD28− T cells.
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Zheng X, Jiang W, Zhang L, Abasubong KP, Zhang D, Li X, Jiang G, Chi C, Liu W. Protective effects of dietary icariin on lipopolysaccharide-induced acute oxidative stress and hepatopancreas injury in Chinese mitten crab, Eriocheir sinensis. Comp Biochem Physiol C Toxicol Pharmacol 2022; 251:109192. [PMID: 34597777 DOI: 10.1016/j.cbpc.2021.109192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/04/2021] [Accepted: 09/20/2021] [Indexed: 11/25/2022]
Abstract
To investigate the effects of dietary icariin (ICA) supplementation on acute oxidative stress and hepatopancreatic injury induced by lipopolysaccharide (LPS) injection in Eriocheir sinensis, an 8-week feeding trial of crabs was conducted using 4 diets with different supplementation levels of ICA (0, 50, 100, and 200 mg/kg diet weight, respectively), and then challenged with LPS of 400 μg/kg body weight for 6 h. Results showed that 100 mg/kg ICA supplementation increased the antioxidant capacity, reduced the stress-related indicators in haemolymph, strengthen the mitochondrial membrane potential, and reduce apoptosis compared to the single LPS-treated crabs. The expressions of apoptosis-related genes and proteins were also evaluated to further understand the effects of dietary ICA pretreatment on LPS-induced cell apoptosis. As a result, dietary 100 mg/kg diet weight ICA pre-addition significantly down-regulated the expression of HSP60, HSP70, Caspase 3c, Caspase 8, Caspase 3, Caspase 9, P38, and Bax (P < 0.05), and alleviated the suppressed expression of PI3K, AKT, MEK, and Bcl-2 (P < 0.05) in crabs challenged with LPS. Overall, this research reveals that ICA supplementation of 100 mg/kg diet weight could enhance the resistance to oxidative damage and apoptosis in E. sinensis facing LPS challenge.
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Affiliation(s)
- Xiaochuan Zheng
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Weibo Jiang
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Ling Zhang
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Kenneth P Abasubong
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Dingdong Zhang
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Xiangfei Li
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Guangzhen Jiang
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Cheng Chi
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China
| | - Wenbin Liu
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, Jiangsu Province, People's Republic of China.
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Kasali FM, Kadima JN, Peter EL, Mtewa AG, Ajayi CO, Tusiimire J, Tolo CU, Ogwang PE, Weisheit A, Agaba AG. Antidiabetic Medicinal Plants Used in Democratic Republic of Congo: A Critical Review of Ethnopharmacology and Bioactivity Data. Front Pharmacol 2021; 12:757090. [PMID: 34776975 PMCID: PMC8579071 DOI: 10.3389/fphar.2021.757090] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 10/08/2021] [Indexed: 12/14/2022] Open
Abstract
Several studies have been conducted and published on medicinal plants used to manage Diabetes Mellitus worldwide. It is of great interest to review available studies from a country or a region to resort to similarities/discrepancies and data quality. Here, we examined data related to ethnopharmacology and bioactivity of antidiabetic plants used in the Democratic Republic of Congo. Data were extracted from Google Scholar, Medline/PubMed, Scopus, ScienceDirect, the Wiley Online Library, Web of Science, and other documents focusing on ethnopharmacology, pharmacology, and phytochemistry antidiabetic plants used in the Democratic Republic of Congo from 2005 to September 2021. The Kew Botanic Royal Garden and Plants of the World Online web databases were consulted to verify the taxonomic information. CAMARADES checklist was used to assess the quality of animal studies and Jadad scores for clinical trials. In total, 213 plant species belonging to 72 botanical families were reported. Only one plant, Droogmansia munamensis, is typically native to the DRC flora; 117 species are growing in the DRC and neighboring countries; 31 species are either introduced from other regions, and 64 are not specified. Alongside the treatment of Diabetes, about 78.13% of plants have multiple therapeutic uses, depending on the study sites. Experimental studies explored the antidiabetic activity of 133 plants, mainly in mice, rats, guinea pigs, and rabbits. Several chemical classes of antidiabetic compounds isolated from 67 plant species have been documented. Rare phase II clinical trials have been conducted. Critical issues included poor quality methodological protocols, author name incorrectly written (16.16%) or absent (14.25%) or confused with a synonym (4.69%), family name revised (17.26%) or missing (1.10%), voucher number not available 336(92.05%), ecological information not reported (49.59%). Most plant species have been identified and authenticated (89.32%). Hundreds of plants are used to treat Diabetes by traditional healers in DRC. However, most plants are not exclusively native to the local flora and have multiple therapeutic uses. The analysis showed the scarcity or absence of high-quality, in-depth pharmacological studies. There is a need to conduct further studies of locally specific species to fill the gap before their introduction into the national pharmacopeia.
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Affiliation(s)
- Félicien Mushagalusa Kasali
- Pharm-Bio Technology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda
- Department of Pharmacy, Faculty of Pharmaceutical Sciences and Public Health, Official University of Bukavu, Bukavu, Democratic Republic of Congo
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Justin Ntokamunda Kadima
- Department of Pharmacy, Faculty of Pharmaceutical Sciences and Public Health, Official University of Bukavu, Bukavu, Democratic Republic of Congo
- Department of Pharmacology, School of Medicine and Pharmacy, University of Rwanda, Huye, Rwanda
| | - Emanuel L. Peter
- Pharm-Bio Technology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
- Department of Innovation, Technology Transfer and Commercialization, National Institute for Medical Research, Dar es Salaam, Tanzania
| | - Andrew G. Mtewa
- Pharm-Bio Technology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
- Chemistry Section, Department of Applied Studies, Institute of Technology, Malawi University of Science and Technology, Limbe, Malawi
| | - Clement Olusoji Ajayi
- Pharm-Bio Technology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
- Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Jonans Tusiimire
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Casim Umba Tolo
- Pharm-Bio Technology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Patrick Engeu Ogwang
- Pharm-Bio Technology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda
- Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Anke Weisheit
- Pharm-Bio Technology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Amon Ganafa Agaba
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
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Wong ILK, Zhu X, Chan KF, Liu Z, Chan CF, Chow TS, Chong TC, Law MC, Cui J, Chow LMC, Chan TH. Flavonoid Monomers as Potent, Nontoxic, and Selective Modulators of the Breast Cancer Resistance Protein (ABCG2). J Med Chem 2021; 64:14311-14331. [PMID: 34606270 DOI: 10.1021/acs.jmedchem.1c00779] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
We synthesize various substituted triazole-containing flavonoids and identify potent, nontoxic, and highly selective BCRP inhibitors. Ac18Az8, Ac32Az19, and Ac36Az9 possess m-methoxycarbonylbenzyloxy substitution at C-3 of the flavone moiety and substituted triazole at C-4' of the B-ring. They show low toxicity (IC50 toward L929 > 100 μM), potent BCRP-inhibitory activity (EC50 = 1-15 nM), and high BCRP selectivity (BCRP selectivity over MRP1 and P-gp > 67-714). They inhibit the efflux activity of BCRP, elevate the intracellular drug accumulation, and restore the drug sensitivity of BCRP-overexpressing cells. Like Ko143, Ac32Az19 remarkably exhibits a 100% 5D3 shift, indicating that it can bind and cause a conformational change of BCRP. Moreover, it significantly reduces the abundance of functional BCRP dimers/oligomers by half to retain more mitoxantrone in the BCRP-overexpressing cell line and that may account for its inhibitory activity. They are promising candidates to be developed into combination therapy to overcome MDR cancers with BCRP overexpression.
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Affiliation(s)
- Iris L K Wong
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Xuezhen Zhu
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Kin-Fai Chan
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Zhen Liu
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Chin-Fung Chan
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Tsun Sing Chow
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Tsz Cheung Chong
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Man Chun Law
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Jiahua Cui
- School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Larry M C Chow
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
| | - Tak Hang Chan
- Department of Applied Biology and Chemical Technology and State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong Polytechnic University, Hong Kong SAR 999077, China.,Department of Chemistry, McGill University, Montreal, Quebec H3A 2K6, Canada
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Vargas-Arana G, Merino-Zegarra C, Riquelme-Penaherrera M, Nonato-Ramirez L, Delgado-Wong H, Pertino MW, Parra C, Simirgiotis MJ. Antihyperlipidemic and Antioxidant Capacities, Nutritional Analysis and UHPLC-PDA-MS Characterization of Cocona Fruits ( Solanum sessiliflorum Dunal) from the Peruvian Amazon. Antioxidants (Basel) 2021; 10:1566. [PMID: 34679701 PMCID: PMC8533405 DOI: 10.3390/antiox10101566] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022] Open
Abstract
Cocona fruits are a popular food and medicinal fruit used mainly in the Amazon and several countries of South America for the preparation of several food products such as drinks, jams and milk shakes. In this study five ecotypes of cocona native to Peru have been studied regarding their nutritional and antioxidants values plus antihyperlipidemic activities. Seventy bioactive compounds have been detected in Peruvian cocona ecotypes including several phenolic acids, aminoacids and flavonoids; of those six were spermidines, (peaks 1, 2, 25, 26, 38 and 39), thirteen were aminoacids, (peaks 3-9, 11-13, 16, 17, 22-24), eighteen flavonoids (peaks 28, 30-32 45,46, 48-53 56, 57, 61 and 64-66), twelve were phenolics (peaks 19, 21, 27, 29, 34, 35, 36, 42, 43, 44, 54, and 59), two carotenoids, (peak 62 and 63), eight were lipid derivatives (peaks 37, 55, 58, 60 and 67-70), one sugar (peak 47), four terpenes (peaks 33, 40, 41 and 47), two amides, (peaks 10 and 18), one aldehyde, (peak 15), and three saturated organic acids, (peaks 4, 5 and 20). Hypercholesterolemic rats administered with pulp of the ecotypes CTR and SRN9 showed the lowest cholesterol and triglyceride levels after treatment (126.74 ± 6.63; 102.11 ± 9.47; 58.16 ± 6.64; 61.05 ± 4.00 mg/dL, for cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein respectively, for the group treated with SRN9 pulp, and 130.09 ± 8.55; 108.51 ± 10.04; 57.30 ± 5.72; and 65.41 ± 7.68 mg/dL, for cholesterol, triglycerides, HDL and LDL lipoproteins respectively for the group treated with CTR pulp). The ecotypes proved to be good sources of natural antioxidants and their consumption represent an alternative for the prevention of atherosclerosis.
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Affiliation(s)
- Gabriel Vargas-Arana
- Laboratorio de Química de Productos Naturales, Instituto de Investigaciones de la Amazonía Peruana, Av. Abelardo Quiñones km 2.5, Iquitos 16001, Peru;
| | - Claudia Merino-Zegarra
- Laboratorio de Química de Productos Naturales, Instituto de Investigaciones de la Amazonía Peruana, Av. Abelardo Quiñones km 2.5, Iquitos 16001, Peru;
| | - Marcos Riquelme-Penaherrera
- Facultad de Farmacia y Bioquímica, Universidad Nacional de la Amazonía Peruana, Iquitos 16001, Peru; (M.R.-P.); (L.N.-R.); (H.D.-W.)
| | - Luis Nonato-Ramirez
- Facultad de Farmacia y Bioquímica, Universidad Nacional de la Amazonía Peruana, Iquitos 16001, Peru; (M.R.-P.); (L.N.-R.); (H.D.-W.)
| | - Henry Delgado-Wong
- Facultad de Farmacia y Bioquímica, Universidad Nacional de la Amazonía Peruana, Iquitos 16001, Peru; (M.R.-P.); (L.N.-R.); (H.D.-W.)
| | - Mariano Walter Pertino
- Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca 3460000, Chile;
| | - Claudio Parra
- Laboratorio de Química Orgánica y Productos Naturales, Facultad de Ciencias Agronómicas, Universidad de Tarapacá, Av. General Velásquez 1775, Arica 1000000, Chile;
| | - Mario J. Simirgiotis
- Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 509000, Chile
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Duan J, Guo H, Fang Y, Zhou G. The mechanisms of wine phenolic compounds for preclinical anticancer therapeutics. Food Nutr Res 2021; 65:6507. [PMID: 34512232 PMCID: PMC8396239 DOI: 10.29219/fnr.v65.6507] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 03/24/2021] [Accepted: 05/02/2021] [Indexed: 11/20/2022] Open
Abstract
Background Wine is one of the oldest and most popular drinks worldwide, which is rich in phenolic compounds. Epidemiological studies show that moderate consumption of wine can reduce the risk of certain diseases, and this effect is attributed to its phenolic compounds. Objective The objective of this review was to elaborate the effects of wine-derived phenolic compounds for preclinical anticancer therapeutics and their major mechanisms. Methods In this review, we discuss the classification and content of common phenolic compounds in wine and summarize previous studies that have evaluated the anticancer properties of wine-derived phenolic compounds and their mechanisms. Results Wine-derived phenolic compounds have been proven to participate in several mechanisms against cancers, including deoxyribonucleic acid damage, oxidative stress, cell proliferation, cell cycle arrest, cell apoptosis, autophagy, cell invasion and metastasis, immunity and metabolism, regulation of multiple signaling molecules, and gene expression. However, the exact anticancer mechanisms of the phenolic compounds in wine need to be further investigated. Conclusion Wine-derived phenolic compounds are promising chemoprotective and chemotherapeutic agents for cancer.
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Affiliation(s)
- Jing Duan
- College of Enology, Northwest A&F University, Yangling, China
| | - Hua Guo
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yulin Fang
- College of Enology, Northwest A&F University, Yangling, China
| | - Guangbiao Zhou
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Flavonoid-Modifying Capabilities of the Human Gut Microbiome-An In Silico Study. Nutrients 2021; 13:nu13082688. [PMID: 34444848 PMCID: PMC8398226 DOI: 10.3390/nu13082688] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/26/2021] [Accepted: 07/26/2021] [Indexed: 02/06/2023] Open
Abstract
Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.
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Md Idris MH, Mohd Amin SN, Mohd Amin SN, Wibowo A, Zakaria ZA, Shaameri Z, Hamzah AS, Selvaraj M, Teh LK, Salleh MZ. Discovery of polymethoxyflavones as potential cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and phosphodiesterase 4B (PDE4B) inhibitors. J Recept Signal Transduct Res 2021; 42:325-337. [PMID: 34323638 DOI: 10.1080/10799893.2021.1951756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed to treat inflammatory-related diseases, pain and fever. However, the prolong use of traditional NSAIDs leads to undesirable side effects such as gastric, ulceration, and renal toxicity due to lack of selectivity toward respective targets for COX-2, 5-LOX, and PDE4B. Thus, targeting multiple sites can reduce these adverse effects of the drugs and increase its potency. A series of methoxyflavones (F1-F5) were synthesized and investigated for their anti-inflammatory properties through molecular docking and inhibition assays. Among these flavones, only F2 exhibited selectivity toward COX-2 (Selectivity Index, SI: 3.90, COX-2 inhibition: 98.96 ± 1.47%) in comparison with celecoxib (SI: 7.54, COX-2 inhibition: 98.20 ± 2.55%). For PDEs, F3 possessed better selectivity to PDE4B (SI: 4.67) than rolipram (SI: 0.78). F5 had the best 5-LOX inhibitory activity among the flavones (33.65 ± 4.74%) but less than zileuton (90.81 ± 0.19%). Docking analysis indicated that the position of methoxy group and the substitution of halogen play role in determining the bioactivities of flavones. Interestingly, F1-F5 displayed favorable pharmacokinetic profiles and acceptable range of toxicity (IC50>70 µM) in cell lines with the exception for F1 (IC50: 16.02 ± 1.165 µM). This study generated valuable insight in designing new anti-inflammatory drug based on flavone scaffold. The newly synthesized flavones can be further developed as future therapeutic agents against inflammation.
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Affiliation(s)
- Muhd Hanis Md Idris
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia
| | - Siti Norhidayah Mohd Amin
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia
| | - Siti Norhidayu Mohd Amin
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia
| | - Agustono Wibowo
- Faculty of Applied Science, Universiti Teknologi MARA (UiTM) Pahang Branch, Jengka Campus, Pahang, Malaysia
| | - Zainul Amiruddin Zakaria
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang, Malaysia
| | - Zurina Shaameri
- Organic Synthesis Laboratory, Institute of Science (IOS), Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia
| | - Ahmad Sazali Hamzah
- Organic Synthesis Laboratory, Institute of Science (IOS), Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia
| | - Manikandan Selvaraj
- School of Engineering, Monash University (Malaysia Campus), Bandar Sunway, Malaysia
| | - Lay Kek Teh
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia
| | - Mohd Zaki Salleh
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia
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Kozłowska A, Dzierżanowski T. Targeting Inflammation by Anthocyanins as the Novel Therapeutic Potential for Chronic Diseases: An Update. Molecules 2021; 26:4380. [PMID: 34299655 PMCID: PMC8304181 DOI: 10.3390/molecules26144380] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/14/2021] [Accepted: 07/15/2021] [Indexed: 02/07/2023] Open
Abstract
Low-grade chronic inflammation (LGCI) and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases. Polyphenols, including anthocyanins, are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Anthocyanins' effects on inflammatory markers are promising and may have the potential to exert an anti-inflammatory effect in vitro and in vivo. Therefore, translating these research findings into clinical practice would effectively contribute to the prevention and treatment of chronic disease. The present narrative review summarizes the results of clinical studies from the last 5 years in the context of the anti-inflammatory and anti-oxidative role of anthocyanins in both health and disease. There is evidence to indicate that anthocyanins supplementation in the regulation of pro-inflammatory markers among the healthy and chronic disease population. Although the inconsistencies between the result of randomized control trials (RCTs) and meta-analyses were also observed. Regarding anthocyanins' effects on inflammatory markers, there is a need for long-term clinical trials allowing for the quantifiable progression of inflammation. The present review can help clinicians and other health care professionals understand the importance of anthocyanins use in patients with chronic diseases.
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Affiliation(s)
| | - Tomasz Dzierżanowski
- Department of Social Medicine and Public Health, Medical University of Warsaw, 02-776 Warsaw, Poland;
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Mödinger Y, Schön C, Wilhelm M, Pickel C, Grothe T. A Food Supplement with Antioxidative Santa Herba Extract Modulates Energy Metabolism and Contributes to Weight Management. J Med Food 2021; 24:1235-1242. [PMID: 34255555 DOI: 10.1089/jmf.2021.0016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The plant Santa herba (Eriodictyon californicum) contains high flavonoids, thus potentially exerting beneficial effects in context of obesity, often accompanied by inflammation and metabolic imbalance. The study assessed the impact of Santa herba on oxidative stress, energy metabolism, weight reduction, and eating behavior, combining in vitro models with clinical data. Santa herba binding of the adenosine receptor A2A (ADORA2A) was assessed using a radioligand binding assay. A Caenorhabditis elegans model was used to determine mobility boosting effects, and Santa herba oxygen radical absorbance capacity (ORAC) values were determined in comparison to antioxidative plants. Clinical data, that is, body weight and appetite-related parameters, were obtained from overweight and obese women receiving either Santa herba or placebo for 12 weeks. Results showed that Santa herba extract binds to ADORA2A, stimulates C. elegans motility (+7.5%) and locomotion, and yields high antioxidative capacities (ORAC: 819 trolox equivalent). Clinical data, obtained from 24 overweight and 25 obese women (mean: 47.5 years), demonstrated a reduced body weight (P = .042) and body fat (P = .044), and by trend reduced leptin levels (P = .065) in women with obesity after Santa herba consumption compared to placebo. In conclusion, Santa herba extract has energizing and antioxidative properties and may aid in weight management of people with obesity. ClinicalTrials.gov Identifier: NCT03853603.
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Affiliation(s)
| | | | - Manfred Wilhelm
- Department of Mathematics, Natural and Economic Sciences, Ulm University of Applied Sciences, Baden-Württemberg, Germany
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Rong X, Xu J, Jiang Y, Li F, Chen Y, Dou QP, Li D. Citrus peel flavonoid nobiletin alleviates lipopolysaccharide-induced inflammation by activating IL-6/STAT3/FOXO3a-mediated autophagy. Food Funct 2021; 12:1305-1317. [PMID: 33439200 DOI: 10.1039/d0fo02141e] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nobiletin, a polymethoxyflavone widely present in the peel of citrus fruits, has significant anti-inflammatory activity. Autophagy plays a critical role in maintaining cell homeostasis by promoting the degradation of intracellular structures in response to various stress. Recent research suggests the involvement of autophagy in the inflammatory process and therefore some inflammation-related diseases. However, the "cross-talk" between autophagy and nobiletin's anti-inflammation response remains not well elucidated. Therefore, this study was initiated with the aim of investigating the role of autophagy in nobiletin's protective effect against inflammation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results showed that nobiletin significantly (P < 0.05) inhibited the release of nitric oxide (NO) and decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Moreover, nobiletin significantly (P < 0.05) promoted autophagy as evidenced by the appearance of more autophagosomes, up-regulated LC3II protein, low-regulated p62 protein, and increased autophagy-related (Atg) genes' expression compared with the control treated with LPS alone. Addition of chloroquine, an autophagy inhibitor, alleviated nobiletin's anti-inflammatory effect, further supporting the requirement of an active autophagy process for the citrus peel flavonoid's biological activity. Mechanistically, we found that nobiletin treatment leads to activation of the IL-6/STAT3/FOXO3a signal pathway through the down-regulation of IL-6 and STAT3 phosphorylation and the upregulation of FOXO3a phosphorylation in the cell nucleus, which is responsible for induction of macrophage autophagy. Taken together, our study provides evidence that nobiletin suppresses inflammatory response through enhancing autophagy through activating the IL-6/STAT3/FOXO3a pathway in macrophage cells.
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Affiliation(s)
- Xue Rong
- Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China.
| | - Jie Xu
- Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China.
| | - Yang Jiang
- Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China.
| | - Feng Li
- Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China.
| | - Yilun Chen
- Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China.
| | - Q Ping Dou
- Barbara Ann Karmanos Cancer Institute and Departments of Oncology, Pharmacology and Pathology, Wayne State University School of Medicine, Wayne State University, Detroit, MI 48201, USA
| | - Dapeng Li
- Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China.
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Diet-Derived Antioxidants and Their Role in Inflammation, Obesity and Gut Microbiota Modulation. Antioxidants (Basel) 2021; 10:antiox10050708. [PMID: 33946864 PMCID: PMC8146040 DOI: 10.3390/antiox10050708] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/23/2021] [Accepted: 04/25/2021] [Indexed: 12/12/2022] Open
Abstract
It is generally accepted that gut microbiota, inflammation and obesity are linked to the development of cardiovascular diseases and other chronic/non-communicable pathological conditions, including cancer, neurodegenerative diseases and ageing-related disorders. In this scenario, oxidative stress plays a pivotal role. Evidence suggests that the global dietary patterns may represent a tool in counteracting oxidative stress, thus preventing the onset of diseases related to oxidative stress. More specifically, dietary patterns based on the regular consumption of fruits and vegetables (i.e., Mediterranean diet) have been licensed by various national nutritional guidelines in many countries for their health-promoting effects. Such patterns, indeed, result in being rich in specific components, such as fiber, minerals, vitamins and antioxidants, whose beneficial effects on human health have been widely reported. This suggests a potential nutraceutical power of specific dietary components. In this manuscript, we summarize the most relevant evidence reporting the impact of dietary antioxidants on gut microbiota composition, inflammation and obesity, and we underline that antioxidants are implicated in a complex interplay between gut microbiota, inflammation and obesity, thus suggesting their possible role in the development and modulation of chronic diseases related to oxidative stress and in the maintenance of wellness. Do all roads lead to Rome?
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