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Jomova K, Alomar SY, Valko R, Liska J, Nepovimova E, Kuca K, Valko M. Flavonoids and their role in oxidative stress, inflammation, and human diseases. Chem Biol Interact 2025; 413:111489. [PMID: 40147618 DOI: 10.1016/j.cbi.2025.111489] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 02/23/2025] [Accepted: 03/24/2025] [Indexed: 03/29/2025]
Abstract
Oxidative stress and chronic inflammation are important drivers in the pathogenesis and progression of many chronic diseases, such as cancers of the breast, kidney, lung, and others, autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (hypertension, atherosclerosis, arrhythmia), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal disorders (inflammatory bowel disease, colorectal cancer), and other disorders. With the increasing demand for less toxic and more tolerable therapies, flavonoids have the potential to effectively modulate the responsiveness to conventional therapy and radiotherapy. Flavonoids are polyphenolic compounds found in fruits, vegetables, grains, and plant-derived beverages. Six of the twelve structurally different flavonoid subgroups are of dietary significance and include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols (e.g. epicatechin, epigallocatechin), flavonols (e.g. quercetin, kaempferol), flavones (e.g. luteolin, baicalein), flavanones (e.g. hesperetin, naringenin), and isoflavones (daidzein, genistein). The health benefits of flavonoids are related to their structural characteristics, such as the number and position of hydroxyl groups and the presence of C2C3 double bonds, which predetermine their ability to chelate metal ions, terminate ROS (e.g. hydroxyl radicals formed by the Fenton reaction), and interact with biological targets to trigger a biological response. Based on these structural characteristics, flavonoids can exert both antioxidant or prooxidant properties, modulate the activity of ROS-scavenging enzymes and the expression and activation of proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), induce apoptosis and autophagy, and target key signaling pathways, such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family of proteins. This review aims to briefly discuss the mutually interconnected aspects of oxidative and inflammatory mechanisms, such as lipid peroxidation, protein oxidation, DNA damage, and the mechanism and resolution of inflammation. The major part of this article discusses the role of flavonoids in alleviating oxidative stress and inflammation, two common components of many human diseases. The results of epidemiological studies on flavonoids are also presented.
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Affiliation(s)
- Klaudia Jomova
- Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University in Nitra, Nitra, 949 74, Slovakia
| | - Suliman Y Alomar
- Zoology Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Richard Valko
- Zoology Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Jan Liska
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University, 811 08, Bratislava, Slovakia
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Sciences, University of Hradec Kralove, 50003, Hradec Kralove, Czech Republic; Center of Advanced Innovation Technologies, VSB-Technical University of Ostrava, Ostrava-Poruba, 708 00, Czech Republic
| | - Kamil Kuca
- Center of Advanced Innovation Technologies, VSB-Technical University of Ostrava, Ostrava-Poruba, 708 00, Czech Republic; Biomedical Research Center, University Hospital Hradec Kralove, 5005, Hradec Kralove, Czech Republic
| | - Marian Valko
- Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37, Bratislava, Slovakia.
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Ding F, Yu Y, Zhang Y, Wei S, Han JH, Li Z, Jiang HB, Ryu D, Park W, Ha KT, Geng L. Harnessing nutrients and natural products for sustainable drug development against aging. Front Pharmacol 2025; 16:1579266. [PMID: 40356992 PMCID: PMC12066681 DOI: 10.3389/fphar.2025.1579266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 04/04/2025] [Indexed: 05/15/2025] Open
Abstract
Developing treatments for age-related diseases requires cost-effective and efficient approaches. Nutrients and natural metabolites offer safer alternatives to synthetic drugs. Aging increases the need for solutions that protect health and repair cells. Recent studies show that nutrients and natural products reduce oxidative stress, regulate metabolism, and influence longevity-related genes. This review focuses on vitamins, minerals, antioxidants, and natural products that improve healthspan and combat aging. It also discusses challenges such as standardization, clinical validation, and regulatory approval. Finally, emerging trends, such as personalized nutrition and advanced delivery systems, highlight the potential of these metabolites for addressing aging.
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Affiliation(s)
- Fuan Ding
- Department of Vascular Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Ying Yu
- Department of Surgery, Changchun University of Chinese Medicine, Changchun, China
| | - Yan Zhang
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Shibo Wei
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Jung Ho Han
- Korean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of Korea
| | - Zhuo Li
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Hong-Bo Jiang
- Department of Dermatology, Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, Shandong, China
| | - Dongryeol Ryu
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Wonyoung Park
- Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea
- Research Institute for Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea
| | - Ki-Tae Ha
- Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea
- Research Institute for Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea
| | - Li Geng
- Department of Vascular Surgery, The Second Hospital of Jilin University, Changchun, China
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Mehta PA, Nelson A, Loveless S, Lane A, Fukuda T, Teusink-Cross A, Elder D, Lagory D, Miller E, Cancelas JA, Howell J, Zhao J, Mizuno K, Myers KC, Lake K, McIntosh K, Setchell KDR, Luebbering N, Edwards S, Chihanga T, Wells SI, Davies SM. Phase 1 study of quercetin, a natural antioxidant for children and young adults with Fanconi anemia. Blood Adv 2025; 9:1927-1939. [PMID: 39820512 PMCID: PMC12008688 DOI: 10.1182/bloodadvances.2024015053] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 12/04/2024] [Accepted: 12/24/2024] [Indexed: 01/19/2025] Open
Abstract
ABSTRACT Fanconi anemia (FA) is a rare inherited disorder characterized by progressive bone marrow failure (BMF) and a predisposition to malignancy. Systemic reactive oxygen species (ROS) and increased sensitivity of FA hematopoietic progenitors to ROS play a key role in the pathogenesis of BMF. Treatment with antioxidants improve hematopoietic function in Fancc-/- mice. We report the safety, tolerability, and pharmacokinetics of quercetin, a naturally occurring antioxidant in the first dose-finding phase 1 study for patients with FA. Twelve patients (median age, 7 years [range, 3-21]) received oral quercetin twice daily for 4 months. Quercetin was well tolerated at all dose levels. Allometrically bodyweight-adjusted dose with a maximum adult daily dose of 4000 mg/d was established as the recommended dose of quercetin. Patients in an expansion cohort (n = 18) were treated using this recommended dose for 6 months. A subset of patients showed reduced ROS levels in the peripheral blood (PB) and bone marrow stem cell compartment. Patients in the analysis cohort treated with the recommended dose of quercetin achieved an a priori-defined optimal response of 25% reduction in the PB ROS level compared with baseline. Platelet counts remained stable to slightly improved over the study period (P = .06). Absolute neutrophil counts (P = .01) and hemoglobin levels gradually declined (P = .001). In those with evidence of BMF at baseline, 8 of 15 patients (53%) had a hematological response at some point after quercetin treatment. Fluctuations in counts are common in patients with FA, limiting accurate assessment of the impact of quercetin use in FA. This trial was registered at www.ClinicalTrials.gov as #NCT01720147.
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Affiliation(s)
- Parinda A. Mehta
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Adam Nelson
- Bone Marrow Transplant MDT, Kids Cancer Centre, Sydney Children's Hospital Randwick, Australia
| | - Sara Loveless
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Adam Lane
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Tsuyoshi Fukuda
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Ashley Teusink-Cross
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Deborah Elder
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Denise Lagory
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Clinical Pharmacology, Investigational Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Erica Miller
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Jose A. Cancelas
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Hoxworth Blood Center Academic Unit, University of Cincinnati College of Medicine, Cincinnati, OH
- Reilly and O’Connell Families Cell Manipulation Core Facility and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
| | - Jonathan Howell
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Junfang Zhao
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Kana Mizuno
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Kasiani C. Myers
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Kelly Lake
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Kelly McIntosh
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Kenneth D. R. Setchell
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Nathan Luebbering
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Stephanie Edwards
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Tafadzwa Chihanga
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Susanne I. Wells
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
- Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Stella M. Davies
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
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Le HT, Nguyen TD, Do AK, Nguyen TP, Ngo TMD, Nguyen THT, Bui XH, Sichaem J, Duong TH, Nguyen NH. Alpha-Glucosidase and Nitric Oxide Inhibitors from Paramignya trimera Leaves and Dicranopteris linearis Spores: In Silico and In Vitro Aspects. Chem Biodivers 2025:e202500588. [PMID: 40223452 DOI: 10.1002/cbdv.202500588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/07/2025] [Accepted: 04/11/2025] [Indexed: 04/15/2025]
Abstract
Dicranopteris linearis and Paramignya trimera, widely utilized plants in traditional Vietnamese medicine, lack comprehensive chemical and biological data pertaining to their composition. The crude extracts of these biosources showed remarkable alpha-glucosidase and nitric oxide (NO) inhibition. Bioguided isolation based on alpha-glucosidase inhibition and anti-inflammatory activity was applied to P. trimera and D. linearis, providing 14 metabolites. Upon evaluating the alpha-glucosidase activity of compounds 1-14, it was observed that all tested compounds exhibited significant activity, with IC50 values ranging from 22.5 to 157.7 µM. Notably, compound 14 was identified as a new compound. Compounds 6-8 exhibited potent NO inhibitory effect in LPS-induced RAW264.7 macrophage cells, with IC50 values ranging from 26.65 to 28.79 µg/mL.
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Affiliation(s)
- Huong Thuy Le
- Research Group in Pharmaceutical and Biomedical Sciences, Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam
| | - Tuan-Dat Nguyen
- Department of Chemistry, Ho Chi Minh City University of Education, Ho Chi Minh City, Vietnam
| | - Anh-Ky Do
- Department of Chemistry, Ho Chi Minh City University of Education, Ho Chi Minh City, Vietnam
| | - Thi-Phuong Nguyen
- NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam
| | - Thi-My-Duyen Ngo
- Research Group in Pharmaceutical and Biomedical Sciences, Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam
| | - Thi-Hoai-Thu Nguyen
- Faculty of Fundamental Sciences, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Xuan-Hao Bui
- Department of Chemistry, Ho Chi Minh City University of Education, Ho Chi Minh City, Vietnam
| | - Jirapast Sichaem
- Research Unit in Natural Products Chemistry and Bioactivities, Faculty of Science and Technology, Thammasat University Lampang Campus, Lampang, Thailand
| | - Thuc-Huy Duong
- Department of Chemistry, Ho Chi Minh City University of Education, Ho Chi Minh City, Vietnam
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Khanna S, Kumar S, Sharma P, Daksh R, Nandakumar K, Shenoy RR. Flavonoids regulating NLRP3 inflammasome: a promising approach in alleviating diabetic peripheral neuropathy. Inflammopharmacology 2025:10.1007/s10787-025-01729-7. [PMID: 40205269 DOI: 10.1007/s10787-025-01729-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 01/25/2025] [Indexed: 04/11/2025]
Abstract
A common and serious side effect of diabetes is diabetic peripheral neuropathy (DPN), which is characterised by gradual nerve damage brought on by oxidative stress, chronic inflammation, and prolonged hyperglycemia. Studies identify NLRP3 inflammasome as a key mediator in the pathogenesis of DPN, connecting neuroinflammation and neuronal damage to metabolic failure. Because of their strong anti-inflammatory and antioxidant qualities, flavonoids, a broad class of naturally occurring polyphenols, have drawn interest as potential treatments for DPN. The various ways that flavonoids affect the NLRP3 inflammasome and their potential as a treatment for DPN are examined in this review. It has been demonstrated that flavonoids prevent NLRP3 activation, which lowers the release of pro-inflammatory cytokines including IL-1β and IL-18 and causes neuroinflammation. Flavonoids work mechanistically by reducing oxidative stress, altering important signalling pathways, and blocking the activities of NF-κB and caspase-1, which are both essential for the activation of the NLRP3 inflammasome. Preclinical research has shown that flavonoids have strong neuroprotective benefits, and few clinical evidence also points to the potential of flavonoids to improve nerve function and lessen neuropathic pain in diabetic patients. The current review emphasises how flavonoids may be used as a treatment strategy to target inflammation in DPN caused by the NLRP3 inflammasome. By targeting important inflammatory pathways, flavonoids provide a new way to slow the progression of this debilitating illness. Further investigation into the mechanisms, clinical translation, and novel drug delivery techniques could enhance the therapeutic efficacy of diabetic peripheral neuropathy.
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Affiliation(s)
- Saumya Khanna
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Sachindra Kumar
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Pratyasha Sharma
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Rajni Daksh
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Krishnadas Nandakumar
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Rekha Raghuveer Shenoy
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104.
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Plazas E, Sierra-Marquez L, Olivero-Verbel J. Bioactive Molecules from Tropical American Plants: Potential Anti-Inflammatory Agents for Cytokine Storm Management. Molecules 2025; 30:1486. [PMID: 40286093 PMCID: PMC11990702 DOI: 10.3390/molecules30071486] [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: 01/15/2025] [Revised: 03/15/2025] [Accepted: 03/17/2025] [Indexed: 04/29/2025] Open
Abstract
The cytokine storm, a hyperinflammatory response characterized by the excessive release of pro-inflammatory mediators such as TNFα, INFγ, IL-1β, IL-6, and GM-CSF, has been identified as a critical factor in the progression and severity of acute inflammatory conditions. Regulating these pathways is essential for mitigating systemic damage and improving outcomes. Natural products from tropical American plants have shown significant potential in modulating these hyperinflammatory responses. Key polyphenols, like quercetin and luteolin, found in plants such as Achyrocline satureioides and Mangifera indica demonstrate the downregulation of NF-κB and inhibition of pro-inflammatory cytokines. Alkaloids, such as berberine and mitraphylline, isolated from Berberis species and Uncaria tomentosa, respectively, have shown potent effects in suppressing nitric oxide production and regulating inflammasomes. Terpenoids, including parthenolide from Tanacetum parthenium and curcumol from Curcuma longa, exhibit multitarget activity, reducing cytokine levels and inhibiting key inflammatory enzymes like COX-2 and iNOS. These findings highlight the immense potential of bioactive compounds from tropical American plants as modulators of immune-inflammatory pathways, providing a foundation for developing effective therapeutic agents to counteract the severe effects of cytokine storms.
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Affiliation(s)
| | | | - Jesus Olivero-Verbel
- Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, University of Cartagena, Cartagena 130014, Colombia; (E.P.); (L.S.-M.)
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de Angelis M, Amicucci C, Banchelli M, D'Andrea C, Gori A, Agati G, Brunetti C, Matteini P. Rapid determination of phenolic composition in chamomile (Matricaria recutita L.) using surface-enhanced Raman spectroscopy. Food Chem 2025; 463:141084. [PMID: 39241429 DOI: 10.1016/j.foodchem.2024.141084] [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: 07/08/2024] [Revised: 08/18/2024] [Accepted: 08/29/2024] [Indexed: 09/09/2024]
Abstract
Flavonoids and hydroxycinnamic acids are the main responsible of the antioxidant activity of chamomile (Matricaria recutita L.). Traditional methods for the analysis of the phenolic content in vegetables often suffer from limitations such as being expensive, time-consuming, and complex. In this study, we propose, for the first time, the use of surface-enhanced Raman spectroscopy (SERS) for the rapid determination of the main components of the polyphenolic fraction in chamomile. Results demonstrate that SERS can serve as an alternative or complementary technique to main analytical strategies for qualitative and quantitative determination of polyphenol compounds in plant extracts. The method can be proposed for quasi real-time analysis of herbal teas and infusions, facilitating rapid screening of their main antioxidant components.
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Affiliation(s)
- Marella de Angelis
- National Research Council of Italy, "Nello Carrara" Institute of Applied Physics (IFAC), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy.
| | - Chiara Amicucci
- National Research Council of Italy, "Nello Carrara" Institute of Applied Physics (IFAC), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy
| | - Martina Banchelli
- National Research Council of Italy, "Nello Carrara" Institute of Applied Physics (IFAC), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy
| | - Cristiano D'Andrea
- National Research Council of Italy, "Nello Carrara" Institute of Applied Physics (IFAC), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy
| | - Antonella Gori
- University of Florence, Department of Agri-Food Production and Environmental Sciences (DAGRI), via delle Idee 30, 50019, Sesto Fiorentino (Florence), Italy; National Research Council of Italy, Institute for Sustainable Plant Protection (IPSP), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy
| | - Giovanni Agati
- National Research Council of Italy, "Nello Carrara" Institute of Applied Physics (IFAC), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy
| | - Cecilia Brunetti
- University of Florence, Department of Agri-Food Production and Environmental Sciences (DAGRI), via delle Idee 30, 50019, Sesto Fiorentino (Florence), Italy; National Research Council of Italy, Institute for Sustainable Plant Protection (IPSP), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy
| | - Paolo Matteini
- National Research Council of Italy, "Nello Carrara" Institute of Applied Physics (IFAC), via Madonna del Piano 10, 50019, Sesto Fiorentino (Florence), Italy.
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Rezgui A, Tachour RA, Layaida H, Derguine R, Hab FZ, Benmanseur A, Matougui B, Agred R, Sobhi W. Doxorubicin inhibits SIRT2 and NF-kB p65 phosphorylation in Brest cell-line cancer. Biochem Biophys Res Commun 2025; 743:151162. [PMID: 39689645 DOI: 10.1016/j.bbrc.2024.151162] [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: 09/04/2024] [Revised: 12/04/2024] [Accepted: 12/09/2024] [Indexed: 12/19/2024]
Abstract
Doxorubicin (DOXO) is a widely used anti-cancer agent, yet the precise mechanism underlying the induction of tumor cell death remains unclear. This study aimed to elucidate new mechanisms by which doxorubicin induces apoptosis in the EMT6 mouse breast carcinoma cell line. The role of doxorubicin was assessed using the XTT assay. The assessment of oxidative stress markers, alongside the analysis of SIRT2 and NF-κB p65 (RelA) phosphorylation inhibition, was conducted. In silico studies, including density functional theory (DFT) calculations and molecular docking simulations, were employed to characterize the molecular interactions between doxorubicin and SIRT2. Additionally, doxorubicin was assessed for its capacity to modulate gene expression and associated pathways using multiple bioinformatics tools and web-based platforms. Our finding indicates that Doxorubicin induced apoptosis in EMT6 cells with an IC50 of 8,32 μM. At lower concentrations, doxorubicin enhances the oxidative balance and promotes cell viability. At high concentrations, doxorubicin inhibits SIRT2. Furthermore, an experimental investigation revealed that doxorubicin inhibits RelA phosphorylation. The results also showed that doxorubicin modulated the expression of 19 genes involved in different pathways and several transcription factors. The results of implementing the gene set with SIRT2 and RELA consolidated the experimental results. In conclusion, Doxorubicin was observed to induce EMT6 apoptosis through the inhibition of SIRT2 and RelA proteins. The outcomes of both experimental and bioinformatic studies provide a novel perspective on the biological effects of doxorubicin and underscore the potential of inhibiting the SIRT2-RelA axis as a promising biological target for cancer therapy.
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Affiliation(s)
- Abdelmalek Rezgui
- Biotechnology Research Center (CRBt), Ali Mendjli, Constantine, 25000, Algeria
| | - Rechda Amel Tachour
- Laboratory of Plant Biotechnology and Ethnobotany, Faculty of Nature and Life Sciences, University of Bejaia, Bejaia, 6000, Algeria
| | - Houdhaifa Layaida
- Laboratoire d'Electrochimie des Matériaux Moléulaires et des Complexes (LEMMC), Faculté de Technologie, Université Ferhat Abbas- Sétif 1, Setif, Algeria
| | - Rania Derguine
- Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University of Ferhat Abbas Setif-1, Setif, 19000, Algeria
| | - Fatma Zahra Hab
- Laboratory of Plant Biotechnology and Ethnobotany, Faculty of Nature and Life Sciences, University of Bejaia, Bejaia, 6000, Algeria
| | - Anfel Benmanseur
- Laboratory of Plant Biotechnology and Ethnobotany, Faculty of Nature and Life Sciences, University of Bejaia, Bejaia, 6000, Algeria
| | - Brahim Matougui
- Biotechnology Research Center (CRBt), Ali Mendjli, Constantine, 25000, Algeria
| | - Rym Agred
- Biotechnology Research Center (CRBt), Ali Mendjli, Constantine, 25000, Algeria
| | - Widad Sobhi
- Biotechnology Research Center (CRBt), Ali Mendjli, Constantine, 25000, Algeria.
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Medini F, Ksouri R, Msaada K, Legault J. Phenolic compounds from Limonium densiflorum: a multifaceted approach to antioxidant, anti-inflammatory, anticancer, and anti-influenza activities. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2025; 35:94-104. [PMID: 38656221 DOI: 10.1080/09603123.2024.2342572] [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: 10/18/2023] [Accepted: 04/09/2024] [Indexed: 04/26/2024]
Abstract
Exploration of the hydroethanolic extracts from the halophyte Limonium densiflorum, led to the isolation of seven phenolic compounds: gallic acid, epigallocatechin gallate (EGCG), quercitrin, a mixture of myricetin 3-O-α-rhamnopyranoside + myricetin 3-O-L-arabinofuranoside, dihydrokaempferol, pinoresinol, and trans-N-ferulolyl tyramine. These compounds were assessed for anticancer, anti-influenza A virus, antioxidant, and anti-inflammatory properties. The results indicated that these compounds do not exhibit toxicity towards healthy cells (WS-1 and MDCK). Furthermore, they displayed strong antioxidant properties. Among these compounds, gallic acid, the mixture of myricetin 3-O-α-rhamnopyranoside + myricetin 3-O-L-arabinofuranoside, dihydrokaempferol, and pinoresinol, showed significant cytotoxicity against colon cancer cells (IC50: 1-39 µg/mL). EGCG, gallic acid, dihydrokaempferol, pinoresinol, and trans-N-ferulolyl tyramine demonstrated potent anti-inflammatory activity by reducing nitric oxide (NO) production and also inhibited the replication of the influenza A virus. Biological activities varied based on compound structure, with phenolic acids and flavonoid aglycones showing stronger effects than glycosylated compounds and lignans.
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Affiliation(s)
- Faten Medini
- Laboratory of Aromatic and Medicinal Plants (LPAM), Center of Biotechnology of Borj-Cedria, Hammam-Lif, Tunisia
| | - Riadh Ksouri
- Laboratory of Aromatic and Medicinal Plants (LPAM), Center of Biotechnology of Borj-Cedria, Hammam-Lif, Tunisia
| | - Kamel Msaada
- Laboratory of Aromatic and Medicinal Plants (LPAM), Center of Biotechnology of Borj-Cedria, Hammam-Lif, Tunisia
| | - Jean Legault
- LASEVE Laboratory, Quebec University at Chicoutimi, 555 Boulvard of the University, Chicoutimi, Quebec, Canada
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Antar A, Abdel-Rehiem ES, Al-Khalaf AA, Abuelsaad ASA, Abdel-Gabbar M, Shehab GMG, Abdel-Aziz AM. Therapeutic Efficacy of Lavandula dentata's Oil and Ethanol Extract in Regulation of the Neuroinflammation, Histopathological Alterations, Oxidative Stress, and Restoring Balance Treg Cells Expressing FoxP3+ in a Rat Model of Epilepsy. Pharmaceuticals (Basel) 2024; 18:35. [PMID: 39861097 PMCID: PMC11768170 DOI: 10.3390/ph18010035] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 12/26/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.g., Lavandula dentata L., are rich in phenolic compounds and may provide neuroprotective and anti-inflammatory benefits. However, limited research evaluates their effectiveness in modulating neuroinflammation and histopathological changes in epilepsy models. Therefore, the current study hypothesized that treating Lavandula dentata L. extract or essential oils may reduce neuroinflammatory responses and mitigate histopathological changes in the brain, providing a natural alternative or adjunct therapy for epilepsy management. Methods: Five groups of male Wistar rats were used: control, pilocarpine-treated epileptic, valproic acid (VPA-treated epileptic), L. dentata extract, and essential oils. Numerous electrolyte levels, monoamine levels, neurotransmitter levels, and the mRNA expression of specific gate channel subtypes were evaluated in homogenate brain tissue. Additionally, histological changes in various brain regions were investigated. Results: The investigation revealed that the extract and essential oils obtained from L. dentata L. exhibited the ability to improve the modulation of electrolytes and ions across voltage- and ligand-gated ion channels. Furthermore, it was revealed that they could decrease neuronal excitability by facilitating repolarization. Moreover, L. dentata's oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusions: The present work confirms that the extract and essential oils of L. dentata L. have different activities to ameliorate the progression of histopathological alterations. Therefore, when used in conjunction with other AEDs, the extract and essential oils of L. dentata can slow the progression of epileptogenesis.
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Affiliation(s)
- Aziza Antar
- Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt; (A.A.); (M.A.-G.)
| | - Eman S. Abdel-Rehiem
- Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt;
| | - Areej A. Al-Khalaf
- Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Abdelaziz S. A. Abuelsaad
- Immunology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt
| | - Mohamed Abdel-Gabbar
- Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt; (A.A.); (M.A.-G.)
| | - Gaber M. G. Shehab
- Department of Biochemistry, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Ayman M. Abdel-Aziz
- Zoology Department, Faculty of Science, Fayoum University, Fayoum 63514, Egypt;
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Jiang C, Luo J, Shao Y. Evaluating the relationship between dietary flavonoids intake and constipation incidence in the general US population. BMC Gastroenterol 2024; 24:455. [PMID: 39696041 DOI: 10.1186/s12876-024-03551-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Dietary adjustment has consistently been regarded as an effective and health way for both the prevention and treatment of constipation. Several researches suggest a significant correlation between dietary flavonoids intake and gut microbiota, while the relationship between dietary flavonoids and constipation has not been reported. The objective of this study is to investigate the relationship between flavonoids intake and constipation. METHODS This cross-sectional analysis was based on data from the National Health and Nutrition Examination Survey (NHANES) collected from 2007 to 2010. The dietary flavonoid and subclasses intake value were obtained from the United States Department of Food and Nutrient Database for Dietary Studies (FNDDS), while constipation was defined using the stool consistency or frequency. Relationships between total and six main flavonoid subclasses intake constipation were investigated using weighted logistic regression approach. RESULTS The study revealed a negative association between isoflavones, anthocyanidins, flavanones, flavones, flavonols, and total flavonoid intake and constipation, with significant p-trends of < 0.05. Following multivariate adjustment, decreased odds of constipation could still be observed in the highest quartiles of anthocyanidins compared with those in the reference quartiles (p-value = 0.03). Ln-transformed anthocyanidins exhibited a statistically significant nonlinear association with constipation, displaying an inverted U-shaped pattern. When anthocyanidins intake exceeded 0.92 mg, the rate of constipation trended downward with increases in anthocyanidins intake. CONCLUSIONS Our study demonstrated that higher dietary flavonoids intake can reduce the incidence of constipation in the adult US population. In addition, the negative association between anthocyanin intake and constipation was more stable compared to other subclasses.
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Affiliation(s)
- Chenyu Jiang
- Department of Geriatric, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, 318000, China
| | - Jingyao Luo
- Department of Oncology Rehabilitation, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 318000, China
| | - Yaojian Shao
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, 318000, China.
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12
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Meng X, Xia C, Wu H, Gu Q, Li P. Metabolism of quercitrin in the colon and its beneficial regulatory effects on gut microbiota. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:9255-9264. [PMID: 39043159 DOI: 10.1002/jsfa.13747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 06/11/2024] [Accepted: 06/30/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND Quercitrin is a dietary flavonoid widely found in plants with various physiological activities. However, whether quercitrin alters gut microbiota in vivo is not well understood. The aim of this study was to investigate metabolism of quercitrin in the colon and its regulation on gut microbiota in mice. RESULTS Herein, 22 flavonoids related to quercitrin metabolism were identified based on ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Gas chromatography and 16S rDNA gene sequencing were used to investigate short-chain fatty acid (SCFA) content and diversity of composition of gut microbiota, respectively. The results showed that quercitrin significantly alters the beta-diversity of the gut microbiota, probiotics such as Akkermansia and Lactococcus were significantly increased, and the production of propanoate, isovalerate and hexanoate of the quercitrin group were enhanced significantly. The Spearman's association analysis provided evidence that Gardnerella and Akkermansia have obvious correlations with most of quercitrin metabolites and SCFAs. CONCLUSION Quercitrin and its metabolites in the colon altered the structure of the mice gut microbiota and increased the content of SCFAs. Our experiments provide valuable insights into quercitrin research and application. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Xia Meng
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Chenlan Xia
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Hongchen Wu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
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Sendani AA, Farmani M, Kazemifard N, Ghavami SB, Sadeghi A. Molecular mechanisms and therapeutic effects of natural products in inflammatory bowel disease. CLINICAL NUTRITION OPEN SCIENCE 2024; 58:21-42. [DOI: 10.1016/j.nutos.2024.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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14
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Beigoli S, Boskabady MH. The molecular basis of the immunomodulatory effects of natural products: A comprehensive review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156028. [PMID: 39276685 DOI: 10.1016/j.phymed.2024.156028] [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: 01/29/2024] [Revised: 07/21/2024] [Accepted: 09/02/2024] [Indexed: 09/17/2024]
Abstract
BACKGROUND Natural products (NPs) have long been recognized for their potential to modulate the immune system, offering a natural and holistic approach to enhancing immune function. In recent years, the immunomodulation effects of various natural products have attained significant attention. PURPOSE This article provides an overview of the role of natural products in immunomodulation, exploring their mechanisms of action, common types of NPs with immunomodulation properties, clinical applications, as well as considerations for their safety and efficacy. METHODS Extensive research has been conducted to compile important discoveries on the immunomodulatory properties of NPs through thorough searches of multiple databases such as PubMed, Science Direct, and Scopus up until January 2024. RESULTS By decreasing the levels of Th2 cytokines and pro-inflammatory cytokines, the results suggested that NPs have the ability to modulate the immune system. Therefore, NPs alleviate inflammation in various disorders such as asthma and cancer. Furthermore, the observed increase in CD4 cells and IFN-ɣ/IL4 levels, along with an increased IFN-c/IL4 ratio, indicates a stimulatory effect of NPs on Th1 activity in various inflammatory conditions. Therefore, NPs regulate the immune system by inhibiting T-cells and decreasing the growth of young B-cell lymphoma cells. CONCLUSION Reviewing studies indicated that NPs have the potential to serve as immunomodulatory candidates for treating disorders characterized by immune dysregulation. However, additional experimental and clinical studies are necessary before these agents can be implemented in clinical settings.
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Affiliation(s)
- Sima Beigoli
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Hossein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Apaza Ticona L, Sánchez Sánchez-Corral J, Montoto Lozano N, Prieto Ramos P, Sánchez ÁR. Study of Pentacyclic Triterpenes from Lyophilised Aguaje: Anti-Inflammatory and Antioxidant Properties. Int J Mol Sci 2024; 25:9615. [PMID: 39273562 PMCID: PMC11395096 DOI: 10.3390/ijms25179615] [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: 08/19/2024] [Revised: 09/01/2024] [Accepted: 09/04/2024] [Indexed: 09/15/2024] Open
Abstract
Mauritia flexuosa (M. flexuosa), commonly known as Aguaje or Moriche palm, is traditionally recognised in South America for its medicinal properties, particularly for its anti-inflammatory and antioxidant effects. However, the bioactive compounds responsible for these effects have not been thoroughly investigated. This study aims to isolate and characterise pentacyclic triterpenoid compounds from M. flexuosa and to evaluate their therapeutic potential. Using various chromatographic and spectroscopic techniques including Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS), three pentacyclic triterpenoid compounds were successfully isolated. Among them, compound 1 (3,11-dioxours-12-en-28-oic acid) exhibited notable bioactivity, significantly inhibiting the activation of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) (IC50 = 7.39-8.11 μM) and of Nitric Oxide (NO) (IC50 = 4.75-6.59 μM), both of which are key processes in inflammation. Additionally, compound 1 demonstrated potent antioxidant properties by activating the antioxidant enzyme Superoxide Dismutase (SOD) (EC50 = 1.87 μM) and the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) (EC50 = 243-547.59 nM), thus showing its potential in combating oxidative stress. This study is the first to isolate and characterise the three compounds from M. flexuosa, suggesting that compound 1 could be a promising candidate for the development of safer and more effective therapies for inflammatory and oxidative stress-related diseases.
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Affiliation(s)
- Luis Apaza Ticona
- Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ramón y Cajal s/n, 28040 Madrid, Spain
- Department of Organic Chemistry, Faculty of Sciences, University Autónoma of Madrid, Cantoblanco, 28049 Madrid, Spain
| | - Javier Sánchez Sánchez-Corral
- Department of Organic Chemistry, Faculty of Sciences, University Autónoma of Madrid, Cantoblanco, 28049 Madrid, Spain
| | - Natalia Montoto Lozano
- Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ramón y Cajal s/n, 28040 Madrid, Spain
| | - Pablo Prieto Ramos
- Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ramón y Cajal s/n, 28040 Madrid, Spain
| | - Ángel Rumbero Sánchez
- Department of Organic Chemistry, Faculty of Sciences, University Autónoma of Madrid, Cantoblanco, 28049 Madrid, Spain
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Manoharan RR, Zachová K, Buzáš M, Pospíšil P, Křupka M, Prasad A. NADPH oxidase-dependent free radical generation and protein adduct formation in neutrophils. RSC Adv 2024; 14:24765-24780. [PMID: 39114440 PMCID: PMC11305404 DOI: 10.1039/d4ra02739f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 07/31/2024] [Indexed: 08/10/2024] Open
Abstract
Neutrophils mediate the early innate immune response through extracellular traps comprising intracellular protein and DNA. These traps play a pivotal role in both immunity against invading pathogens and the development of immunopathological reactions through the production of reactive oxygen species (ROS). Proteins serve as the main target for ROS, resulting in the formation of protein adducts. Herein, we report that the superoxide anion radical (O2˙-) plays a vital role in neutrophil function through sequential events involving 5-lipoxygenase (5-LOX) and NADPH oxidase (NOX). More specifically, differences in NOX homologs expression were observed post-stimulation with PMA and LPS. Differentiation conditions and O2˙- generation were confirmed using flow cytometry. Immunoblotting analysis confirmed the time-dependent expression of NOX underlying its requirement and 5-LOX-mediated lipid peroxidation events in neutrophil function. Protein-malondialdehyde (MDA) adducts formed were detected using immunoblotting, and quercetin was evaluated for its ability to scavenge free radicals through electron paramagnetic resonance (EPR) spin-trapping spectroscopy and results were confirmed with blotting analysis. Free radical-mediated protein oxidation events influence neutrophil function and protein adducts formed serve as markers of neutrophil activation upon infection and inflammation. The study warrants further corroboration and the study of specific proteins involved in neutrophil activation and their role in inflammation.
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Affiliation(s)
- Renuka Ramalingam Manoharan
- Department of Biophysics, Faculty of Science, Palacký University Šlechtitelů 27 783 71 Olomouc Czech Republic +420 585225737 +420 585634752
| | - Kateřina Zachová
- Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Hněvotínská 3 775 15 Olomouc Czech Republic
| | - Marek Buzáš
- Department of Biophysics, Faculty of Science, Palacký University Šlechtitelů 27 783 71 Olomouc Czech Republic +420 585225737 +420 585634752
| | - Pavel Pospíšil
- Department of Biophysics, Faculty of Science, Palacký University Šlechtitelů 27 783 71 Olomouc Czech Republic +420 585225737 +420 585634752
| | - Michal Křupka
- Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Hněvotínská 3 775 15 Olomouc Czech Republic
| | - Ankush Prasad
- Department of Biophysics, Faculty of Science, Palacký University Šlechtitelů 27 783 71 Olomouc Czech Republic +420 585225737 +420 585634752
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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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Nelson VK, Nuli MV, Ausali S, Gupta S, Sanga V, Mishra R, Jaini PK, Madhuri Kallam SD, Sudhan HH, Mayasa V, Abomughaid MM, Almutary AG, Pullaiah CP, Mitta R, Jha NK. Dietary anti-inflammatory and anti-bacterial medicinal plants and its compounds in bovine mastitis associated impact on human life. Microb Pathog 2024; 192:106687. [PMID: 38750773 DOI: 10.1016/j.micpath.2024.106687] [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: 02/15/2024] [Revised: 04/25/2024] [Accepted: 05/12/2024] [Indexed: 05/31/2024]
Abstract
Bovine mastitis (BM) is the most common bacterial mediated inflammatory disease in the dairy cattle that causes huge economic loss to the dairy industry due to decreased milk quality and quantity. Milk is the essential food in the human diet, and rich in crucial nutrients that helps in lowering the risk of diseases like hypertension, cardiovascular diseases and type 2 diabetes. The main causative agents of the disease include various gram negative, and positive bacteria, along with other risk factors such as udder shape, age, genetic, and environmental factors also contributes much for the disease. Currently, antibiotics, immunotherapy, probiotics, dry cow, and lactation therapy are commonly recommended for BM. However, these treatments can only decrease the rise of new cases but can't eliminate the causative agents, and they also exhibit several limitations. Hence, there is an urgent need of a potential source that can generate a typical and ideal treatment to overcome the limitations and eliminate the pathogens. Among the various sources, medicinal plants and its derived products always play a significant role in drug discovery against several diseases. In addition, they are also known for its low toxicity and minimum resistance features. Therefore, plants and its compounds that possess anti-inflammatory and anti-bacterial properties can serve better in bovine mastitis. In addition, the plants that are serving as a food source and possessing pharmacological properties can act even better in bovine mastitis. Hence, in this evidence-based study, we particularly review the dietary medicinal plants and derived products that are proven for anti-inflammatory and anti-bacterial effects. Moreover, the role of each dietary plant and its compounds along with possible role in the management of bovine mastitis are delineated. In this way, this article serves as a standalone source for the researchers working in this area to help in the management of BM.
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Affiliation(s)
- Vinod Kumar Nelson
- Center for global health research, saveetha medical college, saveetha institute of medical and technical sciences, India.
| | - Mohana Vamsi Nuli
- Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, India
| | - Saijyothi Ausali
- College of Pharmacy, MNR higher education and research academy campus, MNR Nagar, Sangareddy, 502294, India
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura, Uttar Pradesh, India
| | - Vaishnavi Sanga
- Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, India
| | - Richa Mishra
- Department of Computer Engineering, Faculty of Engineering and Technology, Parul University, Vadodara, 391760, Gujrat, India
| | - Pavan Kumar Jaini
- Department of Pharmaceutics, Raffles University, Neemrana, Rajasthan, India
| | - Sudha Divya Madhuri Kallam
- Department of Pharmaceutical Sciences, Vignan's Foundation for Science, Technology & Research (Deemed to be University), Guntur, Vadlamudi, Andhra Pradesh, 522213, India
| | - Hari Hara Sudhan
- Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, India
| | - Vinyas Mayasa
- GITAM School of Pharmacy, GITAM University Hyderabad Campus, Rudraram, India
| | - Mosleh Mohammad Abomughaid
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha, 61922, Saudi Arabia
| | - Abdulmajeed G Almutary
- Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, P.O. Box, 59911, United Arab Emirates
| | - Chitikela P Pullaiah
- Department of Chemistry, Siddha Central Research Institute, Chennai, Tamil Nadu, 60016, India
| | - Raghavendra Mitta
- Department of Pharmaceutical Sciences, Vignan's Foundation for Science, Technology & Research (Deemed to be University), Vadlamudi, Guntur, 522213, Andhra Pradesh, India
| | - Niraj Kumar Jha
- Department of Biotechnology, Sharda School of Engineering & Technology (SSET), Sharda University, Greater Noida, India; School of Bioengineering & Biosciences, Lovely Professional University, Phagwara, 144411, India; Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, 248007, India.
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Rao MR, Gaikwad P, Misal P, Gandhi SV. Phyto-cosmeceutical gel containing curcumin and quercetin loaded mixed micelles for improved anti-oxidant and photoprotective activity. Colloids Surf B Biointerfaces 2024; 237:113837. [PMID: 38508086 DOI: 10.1016/j.colsurfb.2024.113837] [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: 01/03/2024] [Revised: 03/05/2024] [Accepted: 03/08/2024] [Indexed: 03/22/2024]
Abstract
Ultra Violet radiations induced skin damage and associated skin disorders are a widespread concern. The consequences of sun exposure include a plethora of dermal conditions like aging, solar urticaria, albinism and cancer. Sunscreens provide effective protection to skin from these damages. Besides FDA approved physical and chemical UV filters, phytoconstituents with their multi functionalities are emerging as frontrunners in Therapy of skin disorders. Objective of this study was to develop novel phyto-dermal gel (PDG) with dual action of sun protection and antioxidant potential using polymeric mixed micelles (PMMs) are nanocarriers. PMMs of Pluronic F127 and Pluronic F68 loaded with curcumin and quercetin were optimized by 32 factorial designs. Responses studied were vesicle size, SPF, entrapment efficiency of curcumin and quercetin and antioxidant activity. Droplet size ranged from 300 to 500 nm with PDI in between 0.248 and 0.584. Combination of curcumin and quercetin showed enhanced sun protection and antioxidant activity. Pluronics played a significant positive role in various parameters. In present studies vesicle size of factorial batches was found to be between 387 and 527 nm, and SPF was found to be between 18.86 and 28.32. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into Carbopol 940. Optimized PDG was evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and skin retention. Hysteresis loop in the rheogram suggested thixotropy of PDG. Syneresis for gels from day 0-30 days was found to be between 0% and 12.46% w/w. SPF of optimized PDG was 27±0.5. Optimized PDG showed no signs of erythema and edema on Wistar rats. PMMs thus effectively enhanced antioxidant and skin protective effect of curcumin and quercetin.
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Affiliation(s)
- Monica Rp Rao
- Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune, Maharashtra 411001, India
| | - Pranjali Gaikwad
- Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune, Maharashtra 411001, India
| | - Poonam Misal
- Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune, Maharashtra 411001, India
| | - Santosh V Gandhi
- Department of Quality Assurance, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune, Maharashtra 411001, India
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Wang L, Li M, Gu Y, Shi J, Yan J, Wang X, Li B, Wang B, Zhong W, Cao H. Dietary flavonoids-microbiota crosstalk in intestinal inflammation and carcinogenesis. J Nutr Biochem 2024; 125:109494. [PMID: 37866426 DOI: 10.1016/j.jnutbio.2023.109494] [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: 09/27/2022] [Revised: 02/20/2023] [Accepted: 10/17/2023] [Indexed: 10/24/2023]
Abstract
Colorectal cancer (CRC) is currently the third leading cancer and commonly develops from chronic intestinal inflammation. A strong association was found between gut microbiota and intestinal inflammation and carcinogenic risk. Flavonoids, which are abundant in vegetables and fruits, can inhibit inflammation, regulate gut microbiota, protect gut barrier integrity, and modulate immune cell function, thereby attenuating colitis and preventing carcinogenesis. Upon digestion, about 90% of flavonoids are transported to the colon without being absorbed in the small intestine. This phenomenon increases the abundance of beneficial bacteria and enhances the production of short-chain fatty acids. The gut microbe further metabolizes these flavonoids. Interestingly, some metabolites of flavonoids play crucial roles in anti-inflammation and anti-tumor effects. This review summarizes the modulatory effect of flavonoids on gut microbiota and their metabolism by intestinal microbe under disease conditions, including inflammatory bowel disease, colitis-associated cancer (CAC), and CRC. We focus on dietary flavonoids and microbial interactions in intestinal mucosal barriers as well as intestinal immune cells. Results provide novel insights to better understand the crosstalk between dietary flavonoids and gut microbiota and support the standpoint that dietary flavonoids prevent intestinal inflammation and carcinogenesis.
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Affiliation(s)
- Lei Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China; Department of Gastroenterology and Hepatology, The Affiliated Hospital of Chengde Medical College, Hebei, China
| | - Mengfan Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yu Gu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Junli Shi
- Department of Gastroenterology and Hepatology, The Affiliated Hospital of Chengde Medical College, Hebei, China
| | - Jing Yan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China; Department of Nutrition, the Second Affiliated Hospital, Air Force Medical University, Xi'an, China
| | - Xin Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Bingqing Li
- Department of Gastroenterology and Hepatology, The Affiliated Hospital of Chengde Medical College, Hebei, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Weilong Zhong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
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Qi J, Pan Z, Wang X, Zhang N, He G, Jiang X. Research advances of Zanthoxylum bungeanum Maxim. polyphenols in inflammatory diseases. Front Immunol 2024; 15:1305886. [PMID: 38343532 PMCID: PMC10853423 DOI: 10.3389/fimmu.2024.1305886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 01/08/2024] [Indexed: 02/15/2024] Open
Abstract
Zanthoxylum bungeanum Maxim., commonly known as Chinese prickly ash, is a well-known spice and traditional Chinese medicine ingredient with a rich history of use in treating inflammatory conditions. This review provides a comprehensive overview of the botanical classification, traditional applications, and anti-inflammatory effects of Z. bungeanum, with a specific focus on its polyphenolic components. These polyphenols have exhibited considerable promise, as evidenced by preclinical studies in animal models, suggesting their therapeutic potential in human inflammatory diseases such as ulcerative colitis, arthritis, asthma, chronic obstructive pulmonary disease, cardiovascular disease, and neurodegenerative conditions. This positions them as a promising class of natural compounds with the potential to enhance human well-being. However, further research is necessary to fully elucidate their mechanisms of action and develop safe and effective therapeutic applications.
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Affiliation(s)
- Jinxin Qi
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Zhaoping Pan
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoyun Wang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Nan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Hospital of Chengdu University of Traditional Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Gu He
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Xian Jiang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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Lokes K, Kiptilyi A, Skikevych M, Steblovskyi D, Lychman V, Bilokon S, Avetikov D. Microbiological substantiation of the effectiveness of quercitin and its combination with ethylmethylhydroxypyridine succinate in the complex treatment of odontogenic phlegmon and maxillofacial abscesses. FRONTIERS IN ORAL HEALTH 2024; 5:1338258. [PMID: 38314105 PMCID: PMC10834767 DOI: 10.3389/froh.2024.1338258] [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: 11/14/2023] [Accepted: 01/09/2024] [Indexed: 02/06/2024] Open
Abstract
Odontogenic infections can become life-threatening. The aim of the study was to determine the effectiveness of quercitin and its combination with ethylmethylhydroxypyridine succinate in the complex treatment of odontogenic infections by assessing the microbial population of the infection site. Materials and methods The cross-sectional study included 75 patients. Purulent exudate was collected from the infection site. The number of colony-forming units was counted using the standard plate method. Results The microbiological examination of purulent exudate obtained from the patients revealed the general prevalence of Gram-positive cocci. On the seventh day of treatment, the total number of microorganisms in the purulent exudate of patients in group I, whose treatment included a combination of the standard protocol with quercitin, significantly decreased compared to the first day of the same group. The results of treatment of patients in group II, which included the standard protocol in combination with quercitin and 2-ethyl-6-methyl-3-hydroxypyridine succinate, demonstrate a significant decrease in the total number of bacteria in the infection focus on the fifth day of treatment compared to this indicator of the group at the beginning of the study. Conclusions When quercitin was used as part of complex treatment, the total treatment period was reduced by 1.4 days. However, the combined use of quercitin and ethylmethylhydroxypyridine succinate against the background of standard treatment of patients with odontogenic infection contributed to a reduction in hospital stay by 2 days.
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Affiliation(s)
- Kateryna Lokes
- Department of Oral and Maxillofacial Surgery, Poltava State Medical University, Poltava, Ukraine
| | - Anatolii Kiptilyi
- Department of Oral and Maxillofacial Surgery, Poltava State Medical University, Poltava, Ukraine
| | - Margaryta Skikevych
- Department of Oral and Maxillofacial Surgery, Poltava State Medical University, Poltava, Ukraine
| | - Dmytro Steblovskyi
- Department of Oral and Maxillofacial Surgery, Poltava State Medical University, Poltava, Ukraine
| | - Vitaliy Lychman
- Department of Oral and Maxillofacial Surgery, Poltava State Medical University, Poltava, Ukraine
| | - Serhii Bilokon
- Department of Pediatric Oral Surgery, Poltava State Medical University, Poltava, Ukraine
| | - David Avetikov
- Department of Oral and Maxillofacial Surgery, Poltava State Medical University, Poltava, Ukraine
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Li MT, Ke J, Guo SF, Shan LL, Gong JH, Qiao TC, Tian HY, Wu Y, Peng ZY, Zeng XQ, Han Y. Huzhangqingmaiyin protected vascular endothelial cells against cerebral small vessel disease through inhibiting inflammation. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:116905. [PMID: 37442491 DOI: 10.1016/j.jep.2023.116905] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/09/2023] [Accepted: 07/10/2023] [Indexed: 07/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Huzhangqingmaiyin (HZQMY) is a Chinese medicine formula used to treat small vessel disease, but the mechanism is unclear. AIM OF THE STUDY This study aimed to reveal the protective effects of HZQMY on human brain microvascular endothelial cells (HBMECs) and explore the potential targets and mechanistic pathways using network pharmacology on treating cerebral small vessel disease (CSVD). MATERIALS AND METHODS HBMECs were cultured in vitro and an endothelial cell injury model was constructed by hypoxia for 12 h followed by reoxygenation for 8 h (H/R). Cell viability was measured by CCK-8 assay, migration ability of cells was detected by scratch assay, angiogenesis ability of endothelial cells was detected by tubulogenesis assay. Meanwhile, JC-1 staining was employed to determine the alteration of mitochondrial membrane potential, and finally, cell apoptosis was assessed by flow cytometry. To further explore the mechanism of action of HZQMY, the target proteins of a candidate active compound was first collected from the traditional Chinese medicine systems pharmacology database with analytical platform and Swiss target prediction database (www.swisstargetprediction.ch) by HPLC/MS determination of its main active components. CSVD associated targets were retrieved from four disease associated targets databases, OMIM, DisGenNET, GeneCards and GeneCLip, respectively. Using the website String, the genes overlapped between HZQMY and CSVD were imported into the database, PPI network plots were drawn using Cytoscape software. GO and KEGG analyses were performed to explore the possible pathways and targets of HZQMY. Its most probable targets were further explored with molecular docking and verified. RESULTS HZQMY at 0.5-2 μg/mL concentration range could promote cell proliferation, cell migration, angiogenesis, reduce mitochondrial membrane potential damage as well as inhibit apoptosis. Besides that, 29 active compounds were detected from HZQMY, including key components such as quercetin, polydatin, kaempferol, isorhamnetin and resveratrol. Core targets that might include IL-1β、ICAM-1、VCAM-1 and VEGF and so on. CONCLUSIONS HZQMY could regulate the levels of key targets such as IL-1β、ICAM-1、VCAM-1 and VEGF, so as to achieve the purpose of treating CSVD.
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Affiliation(s)
- Meng-Ting Li
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Jia Ke
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Shu-Fen Guo
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Li-Li Shan
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Jia-Hao Gong
- Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Tian-Ci Qiao
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Hao-Yu Tian
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Yang Wu
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Zheng-Yu Peng
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Xue-Qian Zeng
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Yan Han
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
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Almeida Silva VE, de Freitas Pereira ET, Ferreira JA, Magno Teixeira A, Borges RM, da Silva LCRP. Bioactive Compounds in Citrus Species with Potential for the Treatment of Chronic Venous Disease: A Review. Curr Pharm Des 2024; 30:2835-2849. [PMID: 39108121 DOI: 10.2174/0113816128314974240724045220] [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: 03/08/2024] [Accepted: 06/10/2024] [Indexed: 10/22/2024]
Abstract
Chronic venous disease (CVD) significantly impacts global health, presenting a complex challenge in medical management. Despite its prevalence and the burden it places on healthcare systems, CVD remains underdiagnosed and undertreated. This review aims to provide a comprehensive analysis of the bioactive compounds in the Citrus genus, exploring their therapeutic potential in CVD treatment and addressing the gap in current treatment modalities. A narrative review methodology was adopted, focusing on the pharmacological effects of Citrus-derived bioactive compounds, including flavonoids and terpenes. Additionally, the review introduced the DBsimilarity method for analyzing the chemical space and structural similarities among Citrus compounds. The review highlights the Citrus genus as a rich source of pharmacologically active compounds, notably flavonoids and terpenes, which exhibit significant anti-inflammatory, antioxidant, and veno-protective properties. Some of these compounds have been integrated into existing therapies, underscoring their potential for CVD management. The DBsimilarity analysis further identified many clusters of compounds with more than 85% structural similarity. Citrus-derived bioactive compounds offer promising therapeutic potential for managing CVD, showcasing significant anti-inflammatory, antioxidant, and veno-protective effects. The need for further comparative studies, as well as safety and efficacy investigations specific to CVD treatment, is evident. This review underlines the importance of advancing our understanding of these natural compounds and encouraging the development of novel treatments and formulations for effective CVD management. The DBsimilarity method's introduction provides a novel approach to exploring the chemical diversity within the Citrus genus, opening new pathways for pharmacological research.
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Affiliation(s)
| | | | | | - Andrew Magno Teixeira
- Instituto de Pesquisas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ricardo Moreira Borges
- Instituto de Pesquisas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Khil NHS, Sharma S, Sharma PK, Alam MA. Neoteric Role of Quercetin in Visual Disorders. Curr Drug Res Rev 2024; 16:164-174. [PMID: 37608659 DOI: 10.2174/2589977515666230822114324] [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: 01/19/2023] [Revised: 06/25/2023] [Accepted: 07/18/2023] [Indexed: 08/24/2023]
Abstract
Flavonoids are a family of secondary metabolites found in plants and fungi that exhibit strong antioxidant properties and low toxicity, making them potential candidates for medicinal use. Quercetin, a flavonoid present in various plant-based foods, has gained attention for its numerous biological benefits, including anti-inflammatory, anti-fibrosis, and antioxidant properties. The ocular surface research community has recently focused on quercetin's therapeutic potential for managing ocular diseases, such as dry eye, keratoconus, corneal inflammation, and neovascularization. In this paper, we discuss the role of quercetin for ocular disease prevention, highlighting its fundamental characteristics, common biological properties, and recent applications. By reviewing the latest research conducted in the last 10 years which was focused on novel herbal formulations for ocular diseases, we aim to provide insights into the role of quercetin in managing ocular diseases and offer perspectives on its potential as a therapeutic agent.
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Affiliation(s)
- Noor Hassan Sulaiman Khil
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Shaweta Sharma
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Pramod Kumar Sharma
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Md Aftab Alam
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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Huang CY, Ng MY, Lin T, Liao YW, Huang WS, Hsieh CW, Yu CC, Chen CJ. Quercetin ameliorates advanced glycation end product-induced wound healing impairment and inflammaging in human gingival fibroblasts. J Dent Sci 2024; 19:268-275. [PMID: 38303825 PMCID: PMC10829550 DOI: 10.1016/j.jds.2023.04.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/15/2023] [Indexed: 02/03/2024] Open
Abstract
Background/purpose Diabetes mellitus (DM) and periodontal disease are both prevalent and chronic inflammatory disorders that have significant health impact. Many studies have pointed out that advanced glycation end-products (AGEs) in DM induces inflammaging, which is a pre-aging and hyperinflammatory condition, and it has been linked to a greater likelihood in developing periodontitis. Inflammaging in DM has been shown to be driven by AGEs-induced cell senescence, inflammatory cytokines, and oxidative stress, resulting in the degradation of periodontium. Quercetin has shown abilities to decrease inflammation and oxidative stress in a variety of tissues, however, the effect in diabetic periodontitis remains uncertain. Thus, the aim of this study was to investigate its impacts on inflammaging in diabetic periodontitis. Materials and methods We examined cell proliferation in human gingival fibroblasts (HGF), wound healing, IL-6 and IL-8 secretions, cellular senescence expression, and the formation of reactive oxygen species (ROS) in response to AGE stimulation with and without Quercetin intervention. Following that, we looked into NF-κβ activity to see if Quercetin mediate its effects via this pro-inflammatory signaling. Results Quercetin at 20 μM and below did not have any impact on HGFs' cell proliferation rate. Quercetin intervention improved the AGEs-impaired wound healing, in addition to the attenuation of AGEs-induced ROS in a dose-dependent pattern. Moreover, Quercetin therapy dose-dependently inhibited AGEs-induced cell senescence activity along with its senescence associated secretion phenotype (SASP) secretions such as IL-6 and IL-8. Western blot analysis indicated that Quercetin was able to reverse the phosphorylation of p65 and Iκβ in AGEs-stimulated HGFs, demonstrating it can modulate NF-κβ pathway. Conclusion Accumulation of AGEs can elicit inflammaging in HGFs, as seen by increased pro-inflammatory cytokines, cell senescence expression and oxidative stress. The results proposed that Quercetin is able to ameliorate inflammaging in diabetic periodontitis and improve wound healing via the suppression of NF-κβ pathway and hence, may be a promising approach for treatment of diabetes-associated periodontitis.
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Affiliation(s)
- Chao-Yen Huang
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Min Yee Ng
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
| | - Taichen Lin
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yi-Wen Liao
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Wei-Shiuan Huang
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
| | - Chang-Wei Hsieh
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan
| | - Cheng-Chia Yu
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chun-Jung Chen
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Division of Periodontics, Department of Dentistry, Chi Mei Medical Center, Tainan, Taiwan
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Vezza T, Molina-Tijeras JA, Rodríguez-Nogales A, Garrido-Mesa J, Cádiz-Gurrea MDLL, Segura-Carretero A, González-Tejero MR, Rodríguez-Cabezas ME, Gálvez J, Algieri F. The Antioxidant Properties of Salvia verbenaca Extract Contribute to Its Intestinal Antiinflammatory Effects in Experimental Colitis in Rats. Antioxidants (Basel) 2023; 12:2071. [PMID: 38136191 PMCID: PMC10741154 DOI: 10.3390/antiox12122071] [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: 10/24/2023] [Revised: 11/25/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammation with unpredictable symptom fluctuations. While there is no effective cure for IBD, various treatments aim to manage symptoms and improve the quality of life for affected individuals. In recent years, there has been growing interest in the potential benefits of certain natural plants and herbs in the management of IBD. In this regard, this study aimed to evaluate the immunomodulatory and anti-inflammatory effects of a well-characterized extract of Salvia verbenaca (S. verbenaca) in an experimental model of colitis in rats. Interestingly, the daily administration of S. verbenaca (10 and 25 mg/kg) effectively alleviated colitis symptoms, as evidenced by reduced weight/length ratio and colonic damage. Moreover, it reduced oxidative stress markers (MPO and GSH), decreased pro-inflammatory cytokine expression (Il-6, Il-12a, Il-1β, Il-23, Icam-1, Mcp-1, Cinc-1), and preserved the integrity of the intestinal barrier (Villin, Muc-2, Muc-3). These effects suggest S. verbenaca extract could represent a potential complementary candidate to treat gastrointestinal disorders. Its beneficial actions can be related to its antioxidant properties as well as the downregulation of the immune response, which can result in the improvement in the intestine epithelial barrier.
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Affiliation(s)
- Teresa Vezza
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; (T.V.); (J.A.M.-T.); (J.G.-M.); (J.G.); (F.A.)
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), 18012 Granada, Spain
- Servicio de Digestivo, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain
| | - Jose Alberto Molina-Tijeras
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; (T.V.); (J.A.M.-T.); (J.G.-M.); (J.G.); (F.A.)
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), 18012 Granada, Spain
| | - Alba Rodríguez-Nogales
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; (T.V.); (J.A.M.-T.); (J.G.-M.); (J.G.); (F.A.)
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), 18012 Granada, Spain
| | - Jose Garrido-Mesa
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; (T.V.); (J.A.M.-T.); (J.G.-M.); (J.G.); (F.A.)
| | - María de la Luz Cádiz-Gurrea
- Department of Analytical Chemistry, Faculty of Science, University of Granada, 18071 Granada, Spain; (M.d.l.L.C.-G.); (A.S.-C.)
| | - Antonio Segura-Carretero
- Department of Analytical Chemistry, Faculty of Science, University of Granada, 18071 Granada, Spain; (M.d.l.L.C.-G.); (A.S.-C.)
| | | | - María Elena Rodríguez-Cabezas
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; (T.V.); (J.A.M.-T.); (J.G.-M.); (J.G.); (F.A.)
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), 18012 Granada, Spain
| | - Julio Gálvez
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; (T.V.); (J.A.M.-T.); (J.G.-M.); (J.G.); (F.A.)
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), 18012 Granada, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Francesca Algieri
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain; (T.V.); (J.A.M.-T.); (J.G.-M.); (J.G.); (F.A.)
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), 18012 Granada, Spain
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Jeje TO, Bando H, Azad MTA, Fukuda Y, Oluwafemi IE, Kato K. Antiplasmodial and interferon-gamma-modulating activities of the aqueous extract of stone breaker (Phyllanthus niruri Linn.) in malaria infection. Parasitol Int 2023; 97:102789. [PMID: 37473798 DOI: 10.1016/j.parint.2023.102789] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 07/14/2023] [Accepted: 07/15/2023] [Indexed: 07/22/2023]
Abstract
Plasmodium falciparum parasites are the primary cause of malaria across Africa. The problem of drug resistance to malaria is ever growing and novel therapeutic strategies need to be developed, particularly those targeting the parasite and also the host or host-pathogen interaction. Previous studies have shown that the development of cerebral malaria (CM) is related to dysregulation of the immune system in a murine malaria model of experimental cerebral malaria. It involves a complex interaction of events and interferon-gamma seems to be the unifying factor. Therefore, the antiplasmodial activity targeting the parasite and immunomodulatory strategies that reduce overall host inflammation, with IFN-γ in focus, could delay CM onset and prove beneficial in malaria infection therapy. Phyllanthus niruri is used to treat fever and other symptoms of malaria in Nigeria. Its modes of action as an anti-malarial remedy have not been exhaustively investigated. This study therefore examined the aqueous extract of P. niruri (PE) for its antiplasmodial activity in vitro using the Plasmodium falciparum HB3 strain. Furthermore, in vivo murine malaria model using the Plasmodium berghei ANKA strain was used to investigate its anti-malarial effects. We showed that PE has multiple anti-malarial effects, including anti-parasitic and host immunomodulatory activities. Co-culture of P. falciparum with PE and some of its phytoconstituents drastically reduced parasite number. PE also decreased parasitemia, and increased the survival of infected mice. We also observed that the integrity of the blood-brain barrier was maintained in the PE-treated mice. The results confirmed that PE showed moderate antiplasmodial activity. In vivo murine malaria model using P. berghei ANKA for experimental cerebral malaria revealed that PE suppressed parasite growth, and modulate the production of interferon-gamma. The findings demonstrate that PE affects malaria progression, targeting parasites and host cells.
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Affiliation(s)
- Temitope Olawale Jeje
- Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki, Miyagi 989-6711, Japan; Department of Biochemistry, Faculty of Science, Federal University Oye-Ekiti, Nigeria; Department of Biochemistry, School of Science, Federal University of Technology, Akure, Nigeria
| | - Hironori Bando
- Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki, Miyagi 989-6711, Japan
| | - Md Thoufic Anam Azad
- Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki, Miyagi 989-6711, Japan; Department of Veterinary and Animal Sciences, Faculty of Veterinary and Animal Sciences, University of Rajshahi, Rajshahi 6205, Bangladesh
| | - Yasuhiro Fukuda
- Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki, Miyagi 989-6711, Japan
| | | | - Kentaro Kato
- Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki, Miyagi 989-6711, Japan.
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Lee SC, Ahn J, Kim J, Lee JY, Kim J, Uddin MS, Lee SW, Kim CY. The Antioxidant and Anti-Inflammatory Properties of Merremia umbellata Extract. Antioxidants (Basel) 2023; 12:2037. [PMID: 38136157 PMCID: PMC10740611 DOI: 10.3390/antiox12122037] [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: 10/10/2023] [Revised: 11/17/2023] [Accepted: 11/21/2023] [Indexed: 12/24/2023] Open
Abstract
Merremia umbellata Hallier f. (MU) has been used as an anti-inflammatory agent to treat burns and scales. However, the potential anti-inflammatory mechanisms of action of this plant have not been elucidated. This study aimed to assess the antioxidant and anti-inflammatory effects of the leaf and shoot of MU grown in Bangladesh. The MU extract exhibited antioxidant activities as demonstrated by DPPH and ABTS free-radical-scavenging activities and the total polyphenol and total flavonoid contents. MU extract significantly reduced the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW264.7 macrophage. Accordingly, the gene levels of inducible NO synthase and cyclooxygenase-2 were suppressed. The MU extract alleviated the LPS-induced expression of TLR4, NF-κB, and inflammatory cytokines (TNF-α, IL-6, and IL-1β). The constituents of a MU extract were tentatively identified using UHPLC-PDA-QTOF/MS techniques. The main compounds were identified as 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, quercitrin, and 4,5-dicaffeoylquinic acid. Molecular docking analysis revealed that these compounds interact with TLR4 protein, with quercitrin showing the highest binding affinity among them. Overall, our findings demonstrate the antioxidant and in vitro anti-inflammatory activities of MU and its potential compounds to target the TLR4-NF-κB signaling pathway. These findings are potentially used to further explore promising natural food ingredients that are effective in regulating inflammation.
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Affiliation(s)
- Sunny Chung Lee
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095-1735, USA;
| | - Jongmin Ahn
- Natural Product Central Bank & Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Chungbuk, Republic of Korea;
| | - Jina Kim
- Department of Food and Nutrition, Yeungnam University, Gyeongsan 38541, Gyeongbuk, Republic of Korea; (J.K.); (J.-Y.L.)
| | - Joo-Yeon Lee
- Department of Food and Nutrition, Yeungnam University, Gyeongsan 38541, Gyeongbuk, Republic of Korea; (J.K.); (J.-Y.L.)
| | - Juhae Kim
- Research Institute of Human Ecology, Yeungnam University, Gyeongsan 38541, Gyeongbuk, Republic of Korea;
| | - Md. Salah Uddin
- Ethnobotanical Database of Bangladesh, Tejgaon, Dhaka 1208, Bangladesh;
| | - Sang Woo Lee
- International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea;
| | - Choon Young Kim
- Department of Food and Nutrition, Yeungnam University, Gyeongsan 38541, Gyeongbuk, Republic of Korea; (J.K.); (J.-Y.L.)
- Research Institute of Human Ecology, Yeungnam University, Gyeongsan 38541, Gyeongbuk, Republic of Korea;
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da Silva BAF, Pessoa RT, da Costa RHS, de Oliveira MRC, Ramos AGB, de Lima Silva MG, da Silva LYS, Medeiros CR, Florencio SGL, Ribeiro-Filho J, Coutinho HDM, Raposo A, Yoo S, Han H, de Menezes IRA, Quintans Júnior LJ. Evaluation of the antiedematogenic and anti-inflammatory properties of Ximenia americana L. (Olacaceae) bark extract in experimental models of inflammation. Biomed Pharmacother 2023; 166:115249. [PMID: 37597323 DOI: 10.1016/j.biopha.2023.115249] [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: 06/02/2023] [Revised: 07/18/2023] [Accepted: 07/27/2023] [Indexed: 08/21/2023] Open
Abstract
Edema is one of the obvious indicators of inflammation and a crucial factor to take into account when assessing a substance's capacity to reduce inflammation. We aimed to evaluate the antiedematogenic and anti-inflammatory profile of the hydroethanolic barks extract of Ximenia americana (HEXA). The possible antiedematogenic and anti-inflammatory effect of EHXA (50, 100 mg/kg and 250 mg/kg v.o) was evaluated using the paw edema induced by carrageenan, zymosan, dextran, CFA and by different agents inflammatory (serotonin, histamine, arachidonic acid and PGE2), and pleurisy model induced by carrageenan and its action on IL-1β and TNF-α levels was also evaluated. HEXA demonstrated a significant antiedematogenic effect at concentrations of 50, 100 and 250 mg/kg on paw edema induced by carrageenan, zymosan and dextran. However, the concentration of 50 mg/kg as standard, demonstrating the effect in the subchronic model, induced CFA with inhibition of 59.06 %. In models of histamine-induced paw edema, HEXA showed inhibition of - 30 min: 40.49 %, 60 min: 44.70 % and 90 min: 48.98 %; serotonin inhibition - 30 min: 57.09 %, 60 min: 66.04 % and 90 min: 61.79 %; arachidonic acid inhibition - 15 min: 36.54 %, 30 min: 51.10 %, 45 min: 50.32 % and 60 min: 76.17 %; and PGE2 inhibition - 15 min: 67.78 %, 30 min: 62.30 %, 45 min: 54.25 % and 60 min: 47.92 %. HEXA significantly reduced (p < 0.01) leukocyte migration in the pleurisy model and reduced TNF-α and IL-1β levels in pleural lavage (p < 0.0001). The results showed that HEXA has the potential to have an antiedematogenic impact in both acute and chronic inflammation processes, with a putative mode of action including the suppression or regulation of inflammatory mediators.
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Affiliation(s)
- Bruno Anderson Fernandes da Silva
- Laboratory of Neurosciences and Pharmacological Assays, Department of Physiology, Federal University of Sergipe, São Cristóvão, SE, Brazil; Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, SE, Brazil
| | - Renata Torres Pessoa
- Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemical, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, CEP 63105- 000, Crato, CE, Brazil
| | - Roger Henrique Sousa da Costa
- Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemical, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, CEP 63105- 000, Crato, CE, Brazil
| | - Maria Rayane Correia de Oliveira
- Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemical, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, CEP 63105- 000, Crato, CE, Brazil
| | - Andreza Guedes Barbosa Ramos
- Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemical, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, CEP 63105- 000, Crato, CE, Brazil
| | - Maria Gabriely de Lima Silva
- Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemical, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, CEP 63105- 000, Crato, CE, Brazil
| | - Lucas Yure Santos da Silva
- Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemical, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, CEP 63105- 000, Crato, CE, Brazil
| | - Cassio Rocha Medeiros
- CECAPE College, Av. Padre Cícero, 3917 - São José, Juazeiro do Norte, CE 63024-015, Brazil
| | | | | | | | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
| | - Sunghoon Yoo
- Audit Team, Hanmoo Convention (Oakwood Premier), 49, Teheran-ro 87-gil, Gangnam-gu, Seoul 06164, South Korea.
| | - Heesup Han
- College of Hospitality and Tourism Management, Sejong University, 98 Gunja-Dong, Gwanjin-Gu, Seoul 143-747, South Korea.
| | - Irwin Rose Alencar de Menezes
- Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemical, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, CEP 63105- 000, Crato, CE, Brazil
| | - Lucindo José Quintans Júnior
- Laboratory of Neurosciences and Pharmacological Assays, Department of Physiology, Federal University of Sergipe, São Cristóvão, SE, Brazil; Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, SE, Brazil
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Jing S, Chen H, Liu E, Zhang M, Zeng F, Shen H, Fang Y, Muhitdinov B, Huang Y. Oral pectin/oligochitosan microspheres for colon-specific controlled release of quercetin to treat inflammatory bowel disease. Carbohydr Polym 2023; 316:121025. [PMID: 37321723 DOI: 10.1016/j.carbpol.2023.121025] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 03/29/2023] [Accepted: 05/11/2023] [Indexed: 06/17/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic, life quality-reducing disease with no cures available yet. To develop an effective medication suitable for long-term use is an urgent but unmet need. Quercetin (QT) is a natural dietary flavonoid with good safety and multifaceted pharmacological activities against inflammation. However, orally administrated quercetin yields unproductive outcomes for IBD treatment because of its poor solubility and extensive metabolism in the gastrointestinal tract. In this work, a colon-targeted QT delivery system (termed COS-CaP-QT) was developed, of which the pectin (PEC)/Ca2+ microspheres were prepared and then crosslinked by oligochitosan (COS). The drug release profile of COS-CaP-QT was pH-dependent and colon microenvironment-responsive, and COS-CaP-QT showed preferential distribution in the colon. The mechanism study showed that QT triggered the Notch pathway to regulate the proliferation of T helper 2 (Th2) cells and group 3 innate lymphoid cells (ILC3s) and the inflammatory microenvironment was remodeled. The in vivo therapeutic results revealed that COS-CaP-QT could relieve the colitis symptoms and maintain the colon length and intestinal barrier integrity.
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Affiliation(s)
- Shisuo Jing
- School of Pharmacy, Zunyi Medical University, Zunyi 563006, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China
| | - Huayuan Chen
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Ergang Liu
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
| | - Meng Zhang
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Feng Zeng
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510450, China
| | - Huan Shen
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; Shanghai Institute of Materia Medica, CAS, Shanghai 201203, China
| | - Yuefei Fang
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China
| | - Bahtiyor Muhitdinov
- Shanghai Institute of Materia Medica, CAS, Shanghai 201203, China; Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Tashkent 100125, Uzbekistan
| | - Yongzhuo Huang
- School of Pharmacy, Zunyi Medical University, Zunyi 563006, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; Shanghai Institute of Materia Medica, CAS, Shanghai 201203, China.
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Wilson SMG, Peach JT, Fausset H, Miller ZT, Walk ST, Yeoman CJ, Bothner B, Miles MP. Metabolic impact of polyphenol-rich aronia fruit juice mediated by inflammation status of gut microbiome donors in humanized mouse model. Front Nutr 2023; 10:1244692. [PMID: 37727634 PMCID: PMC10505616 DOI: 10.3389/fnut.2023.1244692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/16/2023] [Indexed: 09/21/2023] Open
Abstract
Background The Aronia melanocarpa fruit is emerging as a health food owing to its high polyphenolic content and associated antioxidant activity. Antioxidant-rich foods, such as Aronia fruit, may counter inflammatory stimuli and positively modulate the gut microbiome. However, a comprehensive study characterizing the impact of Aronia fruit supplementation has not been completed. Therefore, we completed analyses measuring the metabolic, microbial, and inflammatory effects of a diet supplemented with Aronia fruit juice. Method Humanized mice were generated by colonizing gnotobiotic mice with microbiomes from human donors presenting disparate inflammation levels. Blood and fecal samples were collected throughout the course of an 8-week dietary intervention with either Aronia juice or a carbohydrate-matched beverage alone (2 weeks) or in combination with a high-fat diet to induce inflammation (6 weeks). Samples were analyzed using 16S rRNA gene sequencing (stool) and liquid chromatography-mass spectrometry (serum). Results We demonstrated transfer of microbiome composition and diversity and metabolic characteristics from humans with low and high inflammation levels to second-generation humanized mice. Aronia supplementation provided robust protection against high-fat diet induced metabolic and microbiome changes that were dependent in part on microbiome donor. Aronia induced increases in bacteria of the Eggerthellaceae genus (7-fold) which aligns with its known ability to metabolize (poly)phenols and in phosphatidylcholine metabolites which are consistent with improved gut barrier function. The gut microbiome from a low inflammation phenotype donor provided protection against high-fat diet induced loss of microbiome β-diversity and global metabolomic shifts compared to that from the high inflammation donor. Conclusion These metabolic changes elucidate pathway-specific drivers of reduced inflammation stemming from both Aronia and the gut microbiota.
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Affiliation(s)
- Stephanie M. G. Wilson
- Department of Food Systems, Nutrition, and Kinesiology, Montana State University, Bozeman, MT, United States
| | - Jesse T. Peach
- Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, United States
| | - Hunter Fausset
- Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, United States
| | - Zachary T. Miller
- Department of Research Centers, Montana State University, Bozeman, MT, United States
| | - Seth T. Walk
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States
| | - Carl J. Yeoman
- Department of Animal and Range Sciences, Montana State University, Bozeman, MT, United States
| | - Brian Bothner
- Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, United States
| | - Mary P. Miles
- Department of Food Systems, Nutrition, and Kinesiology, Montana State University, Bozeman, MT, United States
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Ghorani V, Saadat S, Khazdair MR, Gholamnezhad Z, El-Seedi H, Boskabady MH. Phytochemical Characteristics and Anti-Inflammatory, Immunoregulatory, and Antioxidant Effects of Portulaca oleracea L.: A Comprehensive Review. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2023; 2023:2075444. [PMID: 37693918 PMCID: PMC10484659 DOI: 10.1155/2023/2075444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 07/30/2023] [Accepted: 08/14/2023] [Indexed: 09/12/2023]
Abstract
Portulaca oleracea L. (P. oleracea) or purslane is a plant from the Portulacaceae family, which is used as food and traditional medicine for various diseases. This review article provides comprehensive information on the antioxidant, immunomodulatory, and anti-inflammatory properties of P. oleracea and its constituents. The literature survey of the different databases until the end of June 2023 was explored based on the keywords including the "P. oleracea, purslane, anti-inflammatory, immunomodulatory, and antioxidant properties." The plant contains flavonoids, alkaloids, terpenoids, fatty acids, vitamins, minerals, and some other compounds. The results indicated that P. oleracea and its constituents showed anti-inflammatory and immunomodulatory properties through reduction of inflammatory mediators including interferon gama (IFN-γ), interleukin (IL)-10, IL-4, tumor necrosis factor-alpha (TNF-α), and nitric oxide. Improvement in cytokines' serum levels (IFN-γ, IL-10, and IL-4) and increased IgG and IgM serum levels, as well as reduction of IgE, phospholipase A2, and total protein were demonstrated for P. oleracea. The plant and its constituents also improved oxidative stress by reduction of oxidant and increase of antioxidant markers. P. oleracea could be considered as an effective remedy for various inflammatory and immune diseases.
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Affiliation(s)
- Vahideh Ghorani
- Clinical Research Development Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saeideh Saadat
- Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohammad Reza Khazdair
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Zahra Gholamnezhad
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hesham El-Seedi
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
- International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 210024, China
- Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 31100107, Egypt
| | - Mohammad Hossein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Li G, Yu Q, Li M, Zhang D, Yu J, Yu X, Xia C, Lin J, Han L, Huang H. Phyllanthus emblica fruits: a polyphenol-rich fruit with potential benefits for oral management. Food Funct 2023; 14:7738-7759. [PMID: 37529983 DOI: 10.1039/d3fo01671d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/03/2023]
Abstract
The fruit of Phyllanthus emblica Linn., which mainly grows in tropical and subtropical regions, is well-known for its medicine and food homology properties. It has a distinctive flavor, great nutritional content, and potent antioxidant, anti-inflammatory, anti-cancer and immunoregulatory effects. According to an increasing amount of scientific and clinical evidence, this fruit shows significant potential for application and development in the field of oral health management. Through the supplementation of vitamins, superoxide dismutase (SOD) and other nutrients reduce virulence expression of various oral pathogens, prevent tissue and mucosal damage caused by oxidative stress, etc. Phyllanthus emblica fruit can promote saliva secretion, regulate the balance of the oral microecology, prevent and treat oral cancer early, promote alveolar bone remodeling and aid mucosal wound healing. Thus, it plays a specific role in the prevention and treatment of common oral disorders, producing surprising results. For instance, enhancing the effectiveness of scaling and root planing in the treatment of periodontitis, relieving mucosal inflammation caused by radiotherapy for oral cancer, and regulating the blood glucose metabolism to alleviate oral discomfort. Herein, we systematically review the latest research on the use of Phyllanthus emblica fruit in the management of oral health and examine the challenges and future research directions based on its chemical composition and characteristics.
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Affiliation(s)
- Gefei Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Qiang Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Mengqi Li
- Pharmacy department, Sichuan Nursing Vocational College, Chengdu 610100, China
| | - Dingkun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Ji Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Xiaohan Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Chenxi Xia
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, PR China.
| | - Li Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Haozhou Huang
- State key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
- Meishan Hospital of Chengdu University of Traditional Chinese Medicine, Meishan, 620010, China
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Hong GH, Lee SY, Yoo JI, Chung JH, Park KY. Catechin with Lactic Acid Bacteria Starters Enhances the Antiobesity Effect of Kimchi. J Med Food 2023; 26:560-569. [PMID: 37405755 DOI: 10.1089/jmf.2023.k.0067] [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] [Indexed: 07/06/2023] Open
Abstract
The antiobesity effects of kimchi with catechin and lactic acid bacteria as starters were studied in C57BL/6 mice with high-fat diet (HFD)-induced obesity. We prepared four types of kimchi: commercial kimchi, standard kimchi, green tea functional kimchi, and catechin functional kimchi (CFK). Body weight and weight of adipose tissue were significantly lower in the kimchi-treated groups than in the HFD and Salt (HFD +1.5% NaCl) groups. In addition, in the CFK group, the serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol were significantly lower and those of high-density lipoprotein cholesterol were markedly higher than the corresponding levels in the HFD and Salt groups. Moreover, CFK reduced fat cells and crown-like structures in the liver and epididymal fat tissues. The protein expression of adipo/lipogenesis-related genes in the liver and epididymal fat tissues was significantly lower (1.90-7.48-fold) in the CFK group than in the HFD and Salt groups, concurrent with upregulation of lipolysis-related genes (1.71-3.38-fold) and downregulation of inflammation-related genes (3.17-5.06-fold) in epididymal fat tissues. In addition, CFK modulated the gut microbiomes of obese mice by increasing the abundance of Bacteroidetes (7.61%), while in contrast, Firmicutes (82.21%) decreased. In addition, the presence of the Erysipelotrichaceae (8.37%) family in the CFK group decreased, while the number of beneficial bacteria of the families, Akkermansiaceae (6.74%), Lachnospiraceae (14.95%), and Lactobacillaceae (38.41%), increased. Thus, CFK exhibited an antiobesity effect through its modulation of lipid metabolism and the microbiome.
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Affiliation(s)
- Geun-Hye Hong
- Department of Food Science and Biotechnology, CHA University, Seongnam, Gyeonggi-do, South Korea
- Immunobiotech Corp., Seoul, South Korea
| | - So-Young Lee
- Department of Food Science and Biotechnology, CHA University, Seongnam, Gyeonggi-do, South Korea
- Immunobiotech Corp., Seoul, South Korea
| | - Jung-Im Yoo
- Pungmi Food Agricultural Co. Ltd., Suwon, South Korea
| | - Ji Hyung Chung
- Department of Applied Bioscience, CHA University, Seongnam, Gyeonggi-do, South Korea
| | - Kun-Young Park
- Department of Food Science and Biotechnology, CHA University, Seongnam, Gyeonggi-do, South Korea
- Immunobiotech Corp., Seoul, South Korea
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Gupta A, Kumar Mehta S, Qayoom I, Gupta S, Singh S, Kumar A. Biofunctionalization with Cissus quadrangularis Phytobioactives Accentuates Nano-Hydroxyapatite Based Ceramic Nano-Cement for Neo-Bone Formation in Critical Sized Bone Defect. Int J Pharm 2023:123110. [PMID: 37302672 DOI: 10.1016/j.ijpharm.2023.123110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 06/02/2023] [Accepted: 06/05/2023] [Indexed: 06/13/2023]
Abstract
Developing biofunctionalized ceramic bone substitutes with phytobioactives for their sustained delivery is highly desired to enhance the osteo-active potential of ceramic bone substitutes, reduce the systemic toxicity of synthetic drugs, and increase the bioavailability of phytobioactives. The present work highlights the local delivery of phytobioactives of Cissus quadrangularis (CQ) through nano-hydroxyapatite (nHAP) based ceramic nano-cement. The phytoconstituent profiling represented the optimized CQ fraction to be rich in osteogenic polyphenols and flavonoids like quercetin, resveratrol, and their glucosides. Further, CQ phytobioactives-based formulation was biocompatible, increased bone formation, calcium deposition, proliferation, and migration of cells with simultaneous alleviation of cellular oxidative stress. In the in vivo critical-sized bone defect model, enhanced formation of highly mineralized tissue (BV mm3) in CQ phytobioactives functionalized nano-cement (10.5 ± 2 mm3) were observed compared to the control group (6.5 ± 1.2 mm3). Moreover, the addition of CQ phytobioactives to the bone nano-cement increased the fractional bone volume (BV/TV%) to 21 ± 4.2% compared to 13.1 ± 2.5% in non-functionalized nano-cement. The results demonstrated nHAP-based nano-cement as a carrier for phytobioactives which could be a promising approach for neo-bone formation in different bone defect conditions.
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Affiliation(s)
- Archita Gupta
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India
| | - Sanjay Kumar Mehta
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India
| | - Irfan Qayoom
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur- 208016, Uttar Pradesh, India
| | - Sneha Gupta
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur- 208016, Uttar Pradesh, India
| | - Sneha Singh
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India.
| | - Ashok Kumar
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur- 208016, Uttar Pradesh, India; Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur- 208016, Uttar Pradesh, India; The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur- 208016, Uttar Pradesh, India; Centre for Nanosciences, Indian Institute of Technology Kanpur, Kanpur- 208016, Uttar Pradesh, India.
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Zarenezhad E, Abdulabbas HT, Kareem AS, Kouhpayeh SA, Barbaresi S, Najafipour S, Mazarzaei A, Sotoudeh M, Ghasemian A. Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review. Arch Microbiol 2023; 205:252. [PMID: 37249707 DOI: 10.1007/s00203-023-03590-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/14/2023] [Accepted: 05/18/2023] [Indexed: 05/31/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.
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Affiliation(s)
- Elham Zarenezhad
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Hussein T Abdulabbas
- Department of Medical Microbiology, Medical College, Al Muthanna University, Al Muthanna, Iraq
| | - Ahmed Shayaa Kareem
- Department of Medical Laboratories Techniques, Imam Ja'afar Al-Sadiq University, Al-Muthanna, 66002, Iraq
| | - Seyed Amin Kouhpayeh
- Department of Pharmacology, Faculty of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Silvia Barbaresi
- Department of Movement and Sports Sciences, Ghent University, Ghent, Belgium
| | - Sohrab Najafipour
- Department of Microbiology, Faculty of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Abdulbaset Mazarzaei
- Department of Immunology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Mitra Sotoudeh
- Department of Nutrition, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Abdolmajid Ghasemian
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
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Eo HJ, Lee SY, Park GH. UHPLC/TOFHRMS analysis and anti-inflammatory effect of leaf extracts from Zizyphus jujuba in LPS-stimulated RAW264.7 cells. JOURNAL OF PLANT BIOTECHNOLOGY 2023; 50:27-33. [DOI: 10.5010/jpb.2023.50.004.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 01/05/2025]
Affiliation(s)
- Hyun Ji Eo
- Special Forest Resources Division, Department of Forest Bio-Resources, National Institute of Forest Science, Suwon 16631, Korea
| | - Sun-Young Lee
- Forest Medicinal Resources Research Center, National Institute of Forest Science, Yeongju 36040, Korea
| | - Gwang Hun Park
- Forest Medicinal Resources Research Center, National Institute of Forest Science, Yeongju 36040, Korea
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Tsenguun T, Altanchime A, Soyolmaa G, Otgonsugar P, Byambajav T, Batkhuu J, Davaapurev BO. Extract of Scabiosa comosa Exhibits an Anti-Inflammatory Effect on Carrageenan and Lipopolysaccharide-Induced Acute Inflammation in Rats. INT J PHARMACOL 2023. [DOI: 10.3923/ijp.2023.157.165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2023]
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40
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Lu P, Zhang C, Zheng J, Li C, Zhang Q, Huang B. A comparison review of Hehuan flowers and Hehuan bark on the traditional applications, phytochemistry and pharmacological effects. JOURNAL OF ETHNOPHARMACOLOGY 2023; 303:116002. [PMID: 36509253 DOI: 10.1016/j.jep.2022.116002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/22/2022] [Accepted: 11/25/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Albizia julibrissin Durazz is a well-known medicinal plant with the Chinese name Hehuan []. Hehuan bark and Hehuan flowers have long been recognized as traditional Chinese herbal medicine for treating anxiety, melancholy, insomnia, bruises, pulmonary abscess, fractures, carbuncle, amnesia, acute conjunctivitis, blurred vision, neonatal tetanus and stroke for thousands of years. They are recorded in Chinese Pharmacopoeia separately with different properties. Until now, new chemical constituents and pharmacological activities of Hehuan have been continuously studied and revealed. THE AIM OF THE REVIEW This review aims to provide a comprehensive summary of traditional applications, phytochemistry, pharmacology effects, and toxicology of Hehuan bark and Hehuan flowers, and give critical assessment and point out the promising direction for further research on Hehuan. MATERIAL AND METHODS A literature search was undertaken on Hehuan bark and Hehuan flowers by analyzing the information from scientific databases (SciFinder, Pubmed, Elsevier, Google Scholar, Web of Science, and Baidu Scholar). We also gathered the information of Hehuan from classic herbal literatures and conference papers on ethnopharmacology. RESULTS According to Chinese and English documents, the medicinal history of Hehuan in China can be traced back to ad 25. Meanwhile, its medicinal history as a kind of herbal medicine can also be found in other Asian countries. So far about 140 compounds have been isolated from Hehuan bark and Hehuan flowers, including triterpenoids, flavonoids, lignans, phenolic acids, alkaloids, etc. Among them, flavonoids mainly exist in Hehuan flowers, while Hehuan bark contains lignans and saponins. The composition differences between the barks and flowers of Hehuan account for the different effects and applications. Modern pharmacological studies have indicated that crude extracts and pure compounds of Hehuan flowers and Hehuan bark have multiple pharmacological activities, such as antineoplastic, immunomodulatory, anti-inflammatory, anxiolytic, antidepressant, metabolic regulation, anti-insomnia, neuroprotective, hepatoprotective, sedative, and anti-osteolytic activities. CONCLUSIONS Hehuan (Albizia julibrissin Durazz) is traditionally used to relieve depression, calm nerves, promote blood circulation and reduce swelling. Modern pharmacological studies have revealed that natural products from Hehuan bark and Hehuan flowers possess extensive pharmacological activities in treating cancer, enhancing immunity, regulating metabolism, improving mental state, etc. These properties make it great clinical application potential. Further research on natural pharmaceutical chemistry, pharmacology, toxicology, pharmacokinetics, and quality standards of Hehuan are still required to verify the efficacy and safety for future clinical applications.
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Affiliation(s)
- Pengfei Lu
- School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China
| | - Chengzhong Zhang
- School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China
| | - Jiadong Zheng
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350000, China
| | - Chunyan Li
- School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China
| | - Qijin Zhang
- School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China
| | - Baokang Huang
- School of Pharmacy, Naval Medical University, 325 Guohe Road, Shanghai, 200433, China.
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Culhuac EB, Maggiolino A, Elghandour MMMY, De Palo P, Salem AZM. Antioxidant and Anti-Inflammatory Properties of Phytochemicals Found in the Yucca Genus. Antioxidants (Basel) 2023; 12:574. [PMID: 36978823 PMCID: PMC10044844 DOI: 10.3390/antiox12030574] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/19/2023] [Accepted: 02/22/2023] [Indexed: 03/02/2023] Open
Abstract
The Yucca genus encompasses about 50 species native to North America. Species within the Yucca genus have been used in traditional medicine to treat pathologies related to inflammation. Despite its historical use and the popular notion of its antioxidant and anti-inflammatory properties, there is a limited amount of research on this genus. To better understand these properties, this work aimed to analyze phytochemical composition through documentary research. This will provide a better understanding of the molecules and the mechanisms of action that confer such antioxidant and anti-inflammatory properties. About 92 phytochemicals present within the genus have reported antioxidant or anti-inflammatory effects. It has been suggested that the antioxidant and anti-inflammatory properties are mainly generated through its free radical scavenging activity, the inhibition of arachidonic acid metabolism, the decrease in TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), iNOS (Inducible nitric oxide synthase), and IL-1β (Interleukin 1β) concentration, the increase of GPx (Glutathione peroxidase), CAT (Catalase), and SOD (Superoxide dismutase) concentration, and the inhibition of the MAPK (Mitogen-Activated Protein Kinase), and NF-κB (Nuclear factor kappa B), and the activation of the Nrf2 (Nuclear factor erythroid 2-related factor) signaling pathway. These studies provide evidence of its use in traditional medicine against pathologies related to inflammation. However, more models and studies are needed to properly understand the activity of most plants within the genus, its potency, and the feasibility of its use to help manage or treat chronic inflammation.
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Affiliation(s)
- Erick Bahena Culhuac
- Facultad de Ciencias, Universidad Autónoma del Estado de México, Toluca 50000, Estado de México, Mexico
| | - Aristide Maggiolino
- Department of Veterinary Medicine, University of Bari A. Moro, 70010 Valenzano, Italy
| | - Mona M. M. Y. Elghandour
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma del Estado de México, Toluca 50000, Estado de México, Mexico
| | - Pasquale De Palo
- Department of Veterinary Medicine, University of Bari A. Moro, 70010 Valenzano, Italy
| | - Abdelfattah Z. M. Salem
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma del Estado de México, Toluca 50000, Estado de México, Mexico
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Bee Pollen as Functional Food: Insights into Its Composition and Therapeutic Properties. Antioxidants (Basel) 2023; 12:antiox12030557. [PMID: 36978805 PMCID: PMC10045447 DOI: 10.3390/antiox12030557] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 02/15/2023] [Accepted: 02/17/2023] [Indexed: 02/25/2023] Open
Abstract
Bee pollen is a hive product made up of flower pollen grains, nectar, and bee salivary secretions that beekeepers can collect without damaging the hive. Bee pollen, also called bee-collected pollen, contains a wide range of nutritious elements, including proteins, carbs, lipids, and dietary fibers, as well as bioactive micronutrients including vitamins, minerals, phenolic, and volatile compounds. Because of this composition of high quality, this product has been gaining prominence as a functional food, and studies have been conducted to show and establish its therapeutic potential for medical and food applications. In this context, this work aimed to provide a meticulous summary of the most relevant data about bee pollen, its composition—especially the phenolic compounds—and its biological and/or therapeutic properties as well as the involved molecular pathways.
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Usmani J, Kausar H, Akbar S, Sartaj A, Mir SR, Hassan MJ, Sharma M, Ahmad R, Rashid S, Ansari MN. Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies. MOLECULES (BASEL, SWITZERLAND) 2023; 28:molecules28020574. [PMID: 36677632 PMCID: PMC9862608 DOI: 10.3390/molecules28020574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 12/31/2022] [Accepted: 01/02/2023] [Indexed: 01/09/2023]
Abstract
Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.
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Affiliation(s)
- Juveria Usmani
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India
| | - Hina Kausar
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India
| | - Saleem Akbar
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India
| | - Ali Sartaj
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India
| | - Showkat R. Mir
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India
| | - Mohammed Jaseem Hassan
- Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh 202002, India
| | - Manju Sharma
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India
| | - Razi Ahmad
- Department of Pharmacology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard University, New Delhi 110062, India
- Correspondence: (R.A.); (M.N.A.)
| | - Summaya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Mohd Nazam Ansari
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
- Correspondence: (R.A.); (M.N.A.)
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Peng F, Ren X, Du B, Yang Y. Pyrus ussuriensis Maxim 70% ethanol eluted fraction ameliorates inflammation and oxidative stress in LPS-induced inflammation in vitro and in vivo. Food Sci Nutr 2023; 11:458-469. [PMID: 36655082 PMCID: PMC9834841 DOI: 10.1002/fsn3.3077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 09/04/2022] [Accepted: 09/10/2022] [Indexed: 01/21/2023] Open
Abstract
Pyrus ussuriensis Maxim (PUM) is a popular fruit among consumers, and also used as medical diet for dissolving phlegm and arresting cough. The present study aims to investigate the potential protective effect of P. ussuriensis Maxim 70% ethanol eluted fraction (PUM70) on lipopolysaccharide (LPS)-induced alveolar macrophages and acute lung injury (ALI) in mice. A total of 18 polyphenol compounds were tentatively identified in PUM70 by mass spectrometry (MS) analysis. The results in vivo suggested that PUM70 treatment could effectively alleviate the histological changes, and significantly inhibit the activity of myeloperoxidase (MPO) and the expression of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)). The cell test results show that PUM70 exerted its protective effect by suppressing the messenger RNA (mRNA) expression levels (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreasing nitric oxide (NO) and prostaglandin 2 (PGE2) contents. In addition, it also inhibited the overproduction of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Furthermore, PUM70 induced the production of heme oxygenase 1 (HO-1) protein and nuclear translocation of Nrf2 (nuclear factor erythroid 2-related factor 2), indicating that PUM70 could mitigate oxidative injury via the Nrf2/HO-1 pathway. Moreover, PUM70 inhibited LPS-induced inflammation by blocking the phosphorylation of mitogen-activated protein kinases (MAPKs). The above results indicate that PUM70 has protective effects on LPS-induced ALI, possibly be related to the inhibition of MAPK and Nrf2/HO-1 signaling pathways.
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Affiliation(s)
- Fei Peng
- Hebei Key Laboratory of Active Components and Functions in Natural ProductsHebei Normal University of Science and TechnologyQinhuangdaoChina
- Collaborative Innovation Centre of Hebei Chestnut IndustryHebei Normal University of Science and TechnologyQinhuangdaoChina
| | - Xin Ren
- Hebei Key Laboratory of Active Components and Functions in Natural ProductsHebei Normal University of Science and TechnologyQinhuangdaoChina
| | - Bin Du
- Hebei Key Laboratory of Active Components and Functions in Natural ProductsHebei Normal University of Science and TechnologyQinhuangdaoChina
- Collaborative Innovation Centre of Hebei Chestnut IndustryHebei Normal University of Science and TechnologyQinhuangdaoChina
| | - Yuedong Yang
- Hebei Key Laboratory of Active Components and Functions in Natural ProductsHebei Normal University of Science and TechnologyQinhuangdaoChina
- Collaborative Innovation Centre of Hebei Chestnut IndustryHebei Normal University of Science and TechnologyQinhuangdaoChina
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45
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Santos AL, Sinha S. Ageing, Metabolic Dysfunction, and the Therapeutic Role of Antioxidants. Subcell Biochem 2023; 103:341-435. [PMID: 37120475 DOI: 10.1007/978-3-031-26576-1_15] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2023]
Abstract
The gradual ageing of the world population has been accompanied by a dramatic increase in the prevalence of obesity and metabolic diseases, especially type 2 diabetes. The adipose tissue dysfunction associated with ageing and obesity shares many common physiological features, including increased oxidative stress and inflammation. Understanding the mechanisms responsible for adipose tissue dysfunction in obesity may help elucidate the processes that contribute to the metabolic disturbances that occur with ageing. This, in turn, may help identify therapeutic targets for the treatment of obesity and age-related metabolic disorders. Because oxidative stress plays a critical role in these pathological processes, antioxidant dietary interventions could be of therapeutic value for the prevention and/or treatment of age-related diseases and obesity and their complications. In this chapter, we review the molecular and cellular mechanisms by which obesity predisposes individuals to accelerated ageing. Additionally, we critically review the potential of antioxidant dietary interventions to counteract obesity and ageing.
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Affiliation(s)
- Ana L Santos
- IdISBA - Fundación de Investigación Sanitaria de las Islas Baleares, Palma, Spain.
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Kottakis G, Kambouri K, Giatromanolaki A, Valsami G, Kostomitsopoulos N, Tsaroucha A, Pitiakoudis M. Effects of the Antioxidant Quercetin in an Experimental Model of Ulcerative Colitis in Mice. MEDICINA (KAUNAS, LITHUANIA) 2022; 59:87. [PMID: 36676712 PMCID: PMC9861512 DOI: 10.3390/medicina59010087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/27/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023]
Abstract
Background and Objectives: Quercetin, a member of the flavanol family found in many fruits, vegetables, leaves and grains has been found to have a wide range of biological effects on human physiology. The aim of this study was to investigate the effects of quercetin, when administered orally in the form of the water-soluble inclusion complex with hydroxypropyl-b-cyclodextrin (Que-HP-β-CD), in an experimental model of ulcerative colitis in mice. Materials and Methods: Animals received either Dextran Sodium Sulphate (DSS), to induce colitis, + Que-HP-β-CD (Group A), DSS alone (Group B) or no intervention (control, Group C) for 7 days. All animals were weighed daily, and evaluation of colitis was performed using the Disease Activity Index (DAI). On day 7 a blood sample was taken from all animals, they were then euthanised, the large intestine was measured, and histological and immunochemical analyses were performed. Results: The DAI demonstrated an increase over time for the groups receiving DSS (Groups A and B) compared with the control group (Group C), with a significant degree of protection being observed in the group that also received quercetin (Group A): The DAI over time slope for Group B was higher than that for Group A by 0.26 points/day (95% Cl 0.20−0.33, p < 0.01). Weight calculations and immunohistochemistry results validated the DAI findings. Conclusions: In conclusion, the administration of quercetin in an ulcerative colitis model in mice presents a therapeutic/prophylactic potential that warrants further investigation.
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Affiliation(s)
- George Kottakis
- Department of Experimental Surgery, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Katerina Kambouri
- Department of Pediatric Surgery, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | | | - Georgia Valsami
- Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece
| | - Nikolaos Kostomitsopoulos
- Biomedical Research Foundation (BRFAA) of the Academy of Athens, Experimental Surgery and Translational Research, 11527 Athens, Greece
| | - Alexandra Tsaroucha
- Department of Experimental Surgery, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Michael Pitiakoudis
- 2nd Department of General Surgery, University of Thrace, 68100 Alexandroupolis, Greece
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Quercetin Ameliorates Testicular Damage in Zucker Diabetic Fatty Rats through Its Antioxidant, Anti-Inflammatory and Anti-Apoptotic Properties. Int J Mol Sci 2022; 23:ijms232416056. [PMID: 36555696 PMCID: PMC9781092 DOI: 10.3390/ijms232416056] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 12/09/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
The aim of this study was to investigate the effects of quercetin (QUE) on the testicular architecture as well as markers of oxidative, inflammatory, and apoptotic profile of male gonads in Zucker diabetic fatty (ZDF) rats suffering from Type 2 diabetes mellitus in the absence or presence of obesity. QUE was administered orally at a dose of 20 mg/kg/day for 6 weeks. Morphometric analysis revealed that QUE treatment led to an improvement in testicular appearance, particularly in the case of Obese ZDF rats. Furthermore, a significant stabilization of the antioxidant capacity (p < 0.05), superoxide dismutase and catalase activity (p < 0.01), with a concomitant decrease in lipid peroxidation (p < 0.05) were observed in Obese ZDF animals exposed to QUE. Our data also indicate a significant decline in the levels of interleukin (IL)-1 (p < 0.05), IL-6 (p < 0.01) and tumor necrosis factor alpha (p < 0.001) following QUE supplementation to Obese ZDF rats in comparison with their respective control. Finally, a significant down-regulation of the pro-apoptotic BAX protein (p < 0.0001) was observed in Obese ZDF rats administered with QUE, while a significant Bcl-2 protein overexpression (p < 0.0001) was recorded in Lean ZDF animals when compared to their untreated control. As such, our results suggest that QUE is a potentially beneficial agent to reduce testicular damage in ZDF rats with Type 2 diabetes mellitus by decreasing oxidative stress, chronic inflammation, and excessive cell loss through apoptosis.
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Wu Y, Wang H, Liu Y, Zhao L, Pei J. An efficient preparation and biocatalytic synthesis of novel C-glycosylflavonols kaempferol 8-C-glucoside and quercetin 8-C-glucoside through using resting cells and macroporous resins. BIOTECHNOLOGY FOR BIOFUELS AND BIOPRODUCTS 2022; 15:129. [PMID: 36434691 PMCID: PMC9700910 DOI: 10.1186/s13068-022-02228-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/12/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND C-glycosylated flavonoids are a main type of structural modification and can endow flavonoids with greater stability, bioactivity, and bioavailability. Although some C-glycosylated flavonoids have been biosynthesized in vivo or vitro, only a few C-glycosylflavonols have been prepared by these methods. RESULTS In this study, several uridine 5'-diphosphate (UDP)-glucose biosynthesis pathways and Escherichia coli hosts were screened to reconstruct recombinant strains for producing the novel C-glycosylflavonols kaempferol 8-C-glucoside and quercetin 8-C-glucoside. To increase C-glycosylflavonol production, the timing of flavonol addition was adjusted, and glycerol was added to avoid degradation of C-glycosylflavonols. By using resting cell bioconversion, the highest kaempferol 8-C-glucoside and quercetin 8-C-glucoside production reached 16.6 g/L and 12.5 g/L, respectively. Then, ultrasound-assisted adsorption/desorption was used to prepare C-glycosylflavonols by using macroporous resins. Through screening macroporous resins and optimizing the adsorption/desorption conditions, the highest adsorption capacity and desorption capacity for kaempferol 8-C-glucoside on HPD100 reached 28.57 mg/g and 24.15 mg/g, respectively. Finally, kaempferol 8-C-glucoside (15.4 g) with a yield of 93% and quercetin 8-C-glucoside (11.3 g) with a yield of 91% were obtained from 1 L of fermentation broth. CONCLUSIONS Kaempferol 8-C-glucoside and quercetin 8-C-glucoside are novel C-glycosylflavonols, which have not been extracted from plants. This study provides an efficient method for the preparation and biocatalytic synthesis of kaempferol 8-C-glucoside and quercetin 8-C-glucoside by metabolic engineering of Escherichia coli.
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Affiliation(s)
- Yangbao Wu
- Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China
- Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing, 210037, China
| | - Huan Wang
- Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China
- Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing, 210037, China
| | - Yang Liu
- Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China
- Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing, 210037, China
| | - Linguo Zhao
- Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
- Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing, 210037, China.
| | - Jianjun Pei
- Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
- Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, Nanjing, 210037, China.
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Vaghari-Tabari M, Alemi F, Zokaei M, Moein S, Qujeq D, Yousefi B, Farzami P, Hosseininasab SS. Polyphenols and inflammatory bowel disease: Natural products with therapeutic effects? Crit Rev Food Sci Nutr 2022; 64:4155-4178. [PMID: 36345891 DOI: 10.1080/10408398.2022.2139222] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Inflammatory bowel disease (IBD) is a long-life disease with periods of recurrence and relief. Oxidative stress plays an important role in the pathogenesis of this disease. Recent years' studies in the field of IBD treatment mostly have focused on targeting cytokines and immune cell trafficking using antibodies and inhibitors, altering the composition of intestinal bacteria in the line of attenuation of inflammation using probiotics and prebiotics, and attenuating oxidative stress through antioxidant supplementation. Studies in animal models of IBD have shown that some polyphenolic compounds including curcumin, quercetin, resveratrol, naringenin, and epigallocatechin-3-gallate can affect almost all of the above aspects and are useful compounds in the treatment of IBD. Clinical studies performed on IBD patients have also confirmed the findings of animal model studies and have shown that supplementation with some of the above-mentioned polyphenolic compounds has positive effects in reducing disease clinical and endoscopic activity, inducing and maintaining remission, and improving quality of life. In this review article, in addition to a detailed reviewing the effects of the above-mentioned polyphenolic compounds on the events involved in the pathogenesis of IBD, the results of these clinical studies will also be reviewed.
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Affiliation(s)
- Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Forough Alemi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Zokaei
- Department of Food Science and Technology, Faculty of Nutrition Science, Food Science and Technology/National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Soheila Moein
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Bahman Yousefi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Payam Farzami
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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50
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Wang D, Ali F, Liu H, Cheng Y, Wu M, Saleem MZ, Zheng H, Wei L, Chu J, Xie Q, Shen A, Peng J. Quercetin inhibits angiotensin II-induced vascular smooth muscle cell proliferation and activation of JAK2/STAT3 pathway: A target based networking pharmacology approach. Front Pharmacol 2022; 13:1002363. [PMID: 36324691 PMCID: PMC9618806 DOI: 10.3389/fphar.2022.1002363] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 10/05/2022] [Indexed: 11/25/2022] Open
Abstract
The rapid growth of vascular smooth muscle cells (VSMCs) represents crucial pathological changes during the development of hypertensive vascular remodeling. Although quercetin exhibits significantly therapeutic effects on antihypertension, the systematic role of quercetin and its exact mode of action in relation to the VSMCs growth and its hypertension-related networking pharmacology is not well-documented. Therefore, the effect of quercetin was investigated using networking pharmacology followed by in vitro strategies to explore its efficacy against angiotensin II (Ang II)-induced cell proliferation. Putative genes of hypertension and quercetin were collected using database mining, and their correlation was investigated. Subsequently, a network of protein-protein interactions was constructed and gene ontology (GO) analysis was performed to identify the role of important genes (including CCND1) and key signaling pathways [including cell proliferation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway]. We therefore further investigated the effects of quercetin in Ang II-stimulated VSMCs. This current research revealed that quercetin significantly reduced the cell confluency, cell number, and cell viability, as well as expression of proliferating cell nuclear antigen (PCNA) in Ang II-stimulated VSMCs. Mechanistic study by western blotting confirmed that quercetin treatment attenuated the activation of JAK2 and STAT3 by reducing its phosphorylation in Ang II stimulated VSMCs. Collectively, the current study revealed the inhibitory effects of quercetin on proliferation of Ang II stimulated VSMCs, by inhibiting the activation of JAK2/STAT3 signaling might be one of underlying mechanisms.
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Affiliation(s)
- Di Wang
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Farman Ali
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Huixin Liu
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Ying Cheng
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Meizhu Wu
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Muhammad Zubair Saleem
- Fujian Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, Fujian, China
| | - Huifang Zheng
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Lihui Wei
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Jiangfeng Chu
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Qiurong Xie
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
| | - Aling Shen
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
- *Correspondence: Aling Shen, ; Jun Peng,
| | - Jun Peng
- Clinical Research Institute, the Second Affiliated Hospital and Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, China
- *Correspondence: Aling Shen, ; Jun Peng,
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