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Jiang Q, Xue S, Pan X, Yu T, Wei X, Li L, Qi C, Shi W, Ren Z, Hu D, Fu H. Differential changes in the microglial transcriptome between neonatal and adult mice after spinal cord injury. Sci Rep 2025; 15:13708. [PMID: 40258965 PMCID: PMC12012053 DOI: 10.1038/s41598-025-98429-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 04/11/2025] [Indexed: 04/23/2025] Open
Abstract
Spinal cord injury (SCI) remains a significant therapeutic challenge, lacking effective treatment options. Related studies have found that neonatal microglia are more effective than adult microglia in promoting the recovery of SCI, but the reason why neonatal, not adult, microglia are more conducive to SCI recovery is not clear, the differences of gene expression and pathways between them are still worth exploring. Therefore, we examined changes in the microglial transcriptome after SCI in neonatal and adult mice. We identified hub genes or pathways that exhibited significant differential expression between the two groups. Four Gene sets were established for further analysis, named Gene set 1, Gene set 2, Gene set 3, Gene set 4, respectively. GO analysis revealed enrichment in categories critical for injury repair, including DNA metabolism, replication, recombination, meiotic cell cycle progression, regulation of cell-cell adhesion, megakaryocyte and endothelial development, modulation of the neuroinflammatory response, endocytosis, and regulation of cytokine production and cell migration. KEGG analysis revealed enrichment in pathways critical for various cellular processes, including the p53, TNF, PI3K-AKT, PPAR and B cell receptor signaling pathway, axon guidance, cytokine-cytokine receptor interaction. PPI and TF-hub gene-microRNA networks were constructed to elucidate the underlying gene regulatory mechanisms. Additionally, drug prediction was performed to identify potential therapeutic candidates. Finally, 11 hub genes (Chek1, RRM2, Lyve1, Mboat1, Clec4a3, Ccnd1, Cdk6, Zeb1, Igf1, Pparg, and Cd163) were selected from four Gene sets for further validation using qRT-PCR. We identified candidate genes and pathways involved in microglial transcriptome heterogeneity after SCI in neonatal and adult mice. These findings provide valuable insights into potential therapeutic targets for neonatal microglia in the treatment of SCI.
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Affiliation(s)
- Qi Jiang
- Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- Qingdao Medical College of Qingdao University, Qingdao University, Qingdao, 266071, China
| | - Shiyuan Xue
- Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- Qingdao Medical College of Qingdao University, Qingdao University, Qingdao, 266071, China
| | - Xiaojing Pan
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Tengbo Yu
- Department of Orthopedic Surgery, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266071, China
| | - Xinyi Wei
- Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- Qingdao Medical College of Qingdao University, Qingdao University, Qingdao, 266071, China
| | - Liping Li
- Department of Bone Surgery, Qingdao Central Hospital, Qingdao, 266000, China
| | - Chao Qi
- Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Weipeng Shi
- Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- Qingdao Medical College of Qingdao University, Qingdao University, Qingdao, 266071, China
| | - Zhongkai Ren
- Department of Orthopedic Surgery, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266071, China
| | - Die Hu
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China.
| | - Haitao Fu
- Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
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Goleij P, Tabari MAK, Khandan M, Poudineh M, Rezaee A, Sadreddini S, Sanaye PM, Khan H, Larsen DS, Daglia M. Genistein in focus: pharmacological effects and immune pathway modulation in cancer. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3557-3571. [PMID: 39601821 DOI: 10.1007/s00210-024-03647-x] [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: 10/20/2024] [Accepted: 11/18/2024] [Indexed: 11/29/2024]
Abstract
Cancer is a significant global health concern, responsible for mortality and morbidity of individuals. It is characterized by uncontrolled cellular growth, tumor formation, and potential metastasis. The immune system is pivotal in recognizing and eliminating cancerous cells, with immune cells such as T cells, B cells, natural killer cells (NK), and dendritic cells playing critical roles. Dysregulation of immune responses can contribute to cancer progression. Phytochemicals, bioactive compounds derived from plants, have gained attention for their potential roles in cancer prevention and therapy due to their antioxidant, anti-inflammatory, and immunomodulatory properties. Genistein, an isoflavone found in soy products, is of particular interest. In this study, genistein's mechanisms of action at the molecular and cellular levels in cancer were demonstrated, highlighting its impact on T and B lymphocytes, NK cells and dendritic cells. Genistein's ability to influence cytokine production, reducing levels of inflammatory cytokines such as TNF-α, IL-6, and IL-1β, is emphasized. Genistein modulates inflammatory response pathways like Toll-like receptors (TLRs), NF-κB, chemokines, and MAPK, inhibiting tumor growth, promoting apoptosis, and reducing metastasis. It shows promise in overcoming chemoresistance, particularly in ovarian and neuroblastoma cancers, by inhibiting autophagy. Genistein also affects T-cell execution markers, including granzyme B, TNF-α, and FAS ligand in cancer by influencing key proteins involved in immune response and apoptosis. Clinical trials have investigated genistein's therapeutic potential, revealing its promise in enhancing the efficacy of traditional cancer treatments while mitigating associated toxicities. Genistein helps overcome chemoresistance in various cancers by inhibiting autophagy and promoting apoptosis. It also enhances immunotherapy by boosting immune responses and modifying antigens, but careful dosing is needed when combined with anti-PD-1 treatments to avoid reducing effectiveness.
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Affiliation(s)
- Pouya Goleij
- USERN Office, Kermanshah University of Medical Sciences, Kermanshah, 6715847141, Iran.
- Department of Genetics, Faculty of Biology, Sana Institute of Higher Education, Sari, 4816118761, Iran.
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research, Network (USERN), Tehran, Iran.
| | - Mohammad Amin Khazeei Tabari
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Mazandaran, 4815733971, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohanna Khandan
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Mazandaran, 4815733971, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohadeseh Poudineh
- Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, 4513956184, Iran
| | - Aryan Rezaee
- Medical Doctor, School of Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
| | - Sarvin Sadreddini
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, 51656-87386, Iran
| | - Pantea Majma Sanaye
- School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, 4513956184, Iran
| | - Haroon Khan
- Department of Pharmacy, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan.
- Department of Pharmacy, Korea University, Sejong, 20019, South Korea.
| | - Danaé S Larsen
- School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland, 1010, New Zealand
| | - Maria Daglia
- Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, Naples, 80131, Italy
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, 212013, China
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Zeng FF, Chen ZH, Luo FH, Liu CJ, Yang X, Zhang FX, Shi W. Sophorae tonkinensis radix et rhizoma: A comprehensive review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, toxicology and detoxification strategy. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118784. [PMID: 39244176 DOI: 10.1016/j.jep.2024.118784] [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: 06/20/2024] [Revised: 08/08/2024] [Accepted: 09/02/2024] [Indexed: 09/09/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Sophorae tonkinensis Radix et Rhizoma (STR), the dried root and rhizome of Sophora tonkinensis Gagnep., is commonly used in the treatment of tonsillitis and pharyngitis, throat soreness and throat obstruction, swelling and aching of gum, etc. in China or other Asian countries. STR is usually used as the core herb in traditional Chinese medicine preparations, such as "Biyanling Tablets", "Fufang Muji Granules" and "Ganyanling Injections", etc. AIM OF THE REVIEW: This review aimed to provide a comprehensive analysis of STR in terms of botany, traditional use, phytochemistry, ethnopharmacology, pharmacology, pharmacokinetics, toxicology and detoxification strategy, to provide a rational application in future research. MATERIALS AND METHODS The information involved in the study was gathered from a variety of electronic resources, including China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations. RESULTS Till now, a total of 333 chemical components have been identified in STR, including 85 alkaloids, 124 flavonoids, 24 triterpenes, 27 triterpene saponins, 34 organic acids, 8 polysaccharides, etc. STR and its main active constituents have cardiovascular protection, anti-tumor activity, anti-inflammatory activity, antipyretic activity, analgesic activity, antibacterial activity, antifungal activity, antiviral activity, and hepatoprotective activity, etc. However, toxic effects of STR on the liver, nerves, heart, and gastrointestinal tract have also been observed. To mitigate these risks, STR needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. The pharmacokinetics of STR in vivo and traditional and clinical prescriptions containing STR have been sorted out. Despite the potential therapeutic benefits of STR, further research is warranted to elucidate its hepatotoxicity, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and mechanisms. CONCLUSION This review serves to emphasize the therapeutic potential of STR and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the toxicological properties of STR, with particular emphasis on its hepatotoxicity and neurotoxicity. Such research endeavors have the potential to standardize the rational application of STR for optimal therapeutic outcomes.
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Affiliation(s)
- Fen-Fen Zeng
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China
| | - Zi-Hao Chen
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China
| | - Fu-Hui Luo
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China
| | - Cheng-Jun Liu
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China
| | - Xia Yang
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China
| | - Feng-Xiang Zhang
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China.
| | - Wei Shi
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China.
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Chervet A, Nehme R, Defois-Fraysse C, Decombat C, Blavignac C, Auxenfans C, Evrard B, Michel S, Filaire E, Berthon JY, Dreux-Zigha A, Delort L, Caldefie-Chézet F. Development and characterization of a chicory extract fermented by Akkermansia muciniphila: An in vitro study on its potential to modulate obesity-related inflammation. Curr Res Food Sci 2025; 10:100974. [PMID: 39906505 PMCID: PMC11791162 DOI: 10.1016/j.crfs.2025.100974] [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: 11/12/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 02/06/2025] Open
Abstract
Obesity, the fifth leading cause of death globally and linked to chronic low-grade inflammation and development of numerous severe pathologies, is a major public health problem. Fermented foods, probiotics, and postbiotics emerge as promising avenues for combating obesity and inflammation. The aim of our study was to develop and characterize phyto-postbiotics corresponding to prebiotic compounds fermented by gut bacteria, which could act on obesity and related-inflammation. Chicory extract fermented by Akkermansia muciniphila (C-Akm) was selected as the most antioxidant of 20 fermented extracts. The identification of metabolites derived from C-Akm extract has enabled us to detect mostly amino acids, acids, and some polyphenols (daidzein and genistein). The anti-inflammatory and anti-obesity activities of C-Akm extract were studied by testing the extract (50 μg/mL) on the polarization of THP-1 into macrophages, the secretion of pro-inflammatory cytokines in LPS-stimulated PBMCs, and the secretion of leptin and adiponectin in adipospheroids derived from human adipose stem cells. Finally, the extract was examined in 3D co-culture model mimicking inflamed obese adipose tissue. We found that C-Akm extract decreased ROS generation, TNF-α and Il-6 gene expression in polarized macrophages, INFγ and IL-17A secretion in LPS-stimulated PBMCs stimulated with LPS. It also decreased leptin expression while increasing adiponectin and HSL expression levels in both adipocytes and co-cultures. In addition, C-Akm extract stimulated adiponectin secretion in the co-culture model. Finally, our in vitro investigations demonstrated the potential benefits of C-Akm extract in the prevention and treatment of obesity-related inflammation.
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Affiliation(s)
- A. Chervet
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - R. Nehme
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | | | - C. Decombat
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - C. Blavignac
- Université Clermont-Auvergne, Centre d’Imagerie Cellulaire Santé (CCIS), Clermont-Ferrand, France
| | - C. Auxenfans
- Banque de Tissus et de Cellules, Hôpital Edouard-Herriot, 69000, Lyon, France
| | - B. Evrard
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - S. Michel
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - E. Filaire
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - J.-Y. Berthon
- Greentech, Biopôle Clermont-Limagne, 63360, Saint-Beauzire, France
| | - A. Dreux-Zigha
- Greencell, Biopôle Clermont-Limagne, 63360, Saint-Beauzire, France
| | - L. Delort
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
| | - F. Caldefie-Chézet
- Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000, Clermont-Ferrand, France
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Liu X, Zheng T, Bao Y, Li P, Zhao T, Liu Y, Wang H, Sun C. Genistein Implications in Radiotherapy: Kill Two Birds with One Stone. Molecules 2025; 30:188. [PMID: 39795243 PMCID: PMC11723059 DOI: 10.3390/molecules30010188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/27/2024] [Accepted: 01/03/2025] [Indexed: 01/13/2025] Open
Abstract
More than 70% of cancer patients receive radiotherapy during their treatment, with consequent various side effects on normal cells due to high ionizing radiation doses despite tumor shrinkage. To date, many radioprotectors and radiosensitizers have been investigated in preclinical studies, but their use has been hampered by the high toxicity to normal cells or poor tumor radiosensitization effects. Genistein is a naturally occurring isoflavone found in soy products. It selectively sensitizes tumor cells to radiation while protecting normal cells from radiation-induced damage, thus improving the efficacy of radiotherapy and consequent therapeutic outcomes while reducing adverse effects. Genistein protects normal cells by its potent antioxidant effect that reduces oxidative stress and mitigates radiation-induced apoptosis and inflammation. Conversely, genistein increases the radiosensitivity of tumor cells through specific mechanisms such as the inhibition of DNA repair, the arrest of the cell cycle in the G2/M phase, the generation of reactive oxygen species (ROS), and the modulation of apoptosis. These effects increase the cytotoxicity of radiation. Preclinical studies demonstrated genistein efficacy in various cancer models, such as breast, prostate, and lung cancer. Despite limited clinical studies, the existing evidence supports the potential of genistein in improving the therapeutic effect of radiotherapy. Future research should focus on dosage optimization and administration, the exploration of combination therapies, and long-term clinical trials to establish genistein benefits in clinical settings. Hence, the unique ability of genistein to improve the radiosensitivity of tumor cells while protecting normal cells could be a promising strategy to improve the efficacy and safety of radiotherapy.
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Affiliation(s)
- Xiongxiong Liu
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; (X.L.); (T.Z.); (Y.B.); (P.L.); (T.Z.)
- Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou 730000, China
- Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Tong Zheng
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; (X.L.); (T.Z.); (Y.B.); (P.L.); (T.Z.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yanyu Bao
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; (X.L.); (T.Z.); (Y.B.); (P.L.); (T.Z.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ping Li
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; (X.L.); (T.Z.); (Y.B.); (P.L.); (T.Z.)
- Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou 730000, China
- Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ting Zhao
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; (X.L.); (T.Z.); (Y.B.); (P.L.); (T.Z.)
- Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou 730000, China
- Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yan Liu
- School of Medical Imaging, Binzhou Medical University, Yantai 264003, China;
| | - Hui Wang
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; (X.L.); (T.Z.); (Y.B.); (P.L.); (T.Z.)
- Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou 730000, China
- Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chao Sun
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; (X.L.); (T.Z.); (Y.B.); (P.L.); (T.Z.)
- Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou 730000, China
- Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, China
- University of Chinese Academy of Sciences, Beijing 100049, China
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Miceli G, Basso MG, Pennacchio AR, Cocciola E, Pintus C, Cuffaro M, Profita M, Rizzo G, Sferruzza M, Tuttolomondo A. The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1796. [PMID: 39596981 PMCID: PMC11596194 DOI: 10.3390/medicina60111796] [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: 09/16/2024] [Revised: 10/24/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024]
Abstract
The impact of diabetic foot (DF) on the healthcare system represents a major public health problem, leading to a considerable clinical and economic burden. The factors contributing to DF's development and progression are strongly interconnected, including metabolic causes, neuropathy, arteriopathy, and inflammatory changes. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), novel oral hypoglycemic drugs used as an adjunct to standard treatment, have recently changed the pharmacological management of diabetes. Nevertheless, data about the risk of limb amputation, discordant and limited to canagliflozin, which is currently avoided in the case of peripheral artery disease, have potentially discouraged the design of specific studies targeting DF. There is good evidence for the single immunomodulatory, neuroprotective, and beneficial vascular effects of SGLT2-i. Still, there is no clinical evidence about the early use of SGLT2-i in diabetic foot due to the lack of longitudinal and prospective studies proving the effect of these drugs without confounders. This narrative review aims to discuss the main evidence about the impact of SGLT2-i on the three complications of diabetes implicated in the development of DF, the state of the art, and the potential future implications.
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Affiliation(s)
- Giuseppe Miceli
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Maria Grazia Basso
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Andrea Roberta Pennacchio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Elena Cocciola
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Chiara Pintus
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Mariagiovanna Cuffaro
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Martina Profita
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Giuliana Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Mariachiara Sferruzza
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
| | - Antonino Tuttolomondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (M.G.B.); (A.R.P.); (E.C.); (C.P.); (M.C.); (M.P.); (G.R.); (M.S.); (A.T.)
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90127 Palermo, Italy
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Sae-Foo W, Yusakul G, Nualkaew N, Putalun W. Estrogenic Activity of Derris scandens Stem Extract and its Major Compounds Using MCF-7 Cell Proliferation Assay and Estrogen-Related Gene Expression. PLANTA MEDICA 2024; 90:766-773. [PMID: 38749481 DOI: 10.1055/a-2328-2750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/30/2024]
Abstract
Derris scandens, which contains isoflavones and prenylated derivatives, has analgesic and anti-inflammatory properties and is an ingredient in traditional Thai medicine for perimenopause and menopause. However, the estrogenic activity of D. scandens has not yet been explored. Therefore, this study aimed to examine the estrogenic activity of the stem extract of D. scandens and its isoflavone derivatives. In this study, we conducted a proliferation assay in MCF-7 cells, and used quantitative reverse transcription polymerase chain reaction to assess gene expression. We found that the relative cell proliferation of the compounds (1 µM) was ranked in the following order as compared to 0.1 nM 17β-estradiol (100%): genistein (97.84%) > derrisisoflavone A (83.17%) > genistein-7-O-[α-rhamnopyranosyl-(1 → 6)-glucopyranoside] (69.55%) > 6,8-diprenylgenistein (51.91%) > lupalbigenin (18.72%). Furthermore, cotreatment with 1 µM lupalbigenin and 0.1 nM 17β-estradiol was performed, which decreased cell proliferation to 80.38%. In vitro results suggest that lupalbigenin has an estrogen-antagonistic effect. At a dose of 1 µM, genistein had the strongest efficacy in increasing the expression of human estrogen receptor β by 4.0-fold compared to the control. Furthermore, genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside augmented the gene expression of human estrogen receptor α and human estrogen receptor β by 1.5- and 3.4-fold, respectively. Prenylated derivatives of genistein (derrisisoflavone A, 6,8-diprenylgenistein, and lupalbigenin) significantly suppressed the gene expression of the human androgen receptor. The administration of the crude extract at 10 µg/mL significantly suppressed human androgen receptor (0.6-fold) and transmembrane protease serine 2 (0.1-fold) expression but did not significantly affect human estrogen receptor α and human estrogen receptor β gene expression. This herbal medicine may be safe for estrogen-exposed breast cancer patients.
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Affiliation(s)
- Worapol Sae-Foo
- Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
| | - Gorawit Yusakul
- School of Pharmacy, Walailak University, Nakhon Si Thammarat, Thailand
| | - Natsajee Nualkaew
- Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
| | - Waraporn Putalun
- Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
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8
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Gonçalves AC, Rodrigues S, Fonseca R, Silva LR. Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports. Pharmaceuticals (Basel) 2024; 17:590. [PMID: 38794160 PMCID: PMC11124183 DOI: 10.3390/ph17050590] [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: 04/08/2024] [Revised: 04/30/2024] [Accepted: 05/01/2024] [Indexed: 05/26/2024] Open
Abstract
Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental components. Globally, in 2019, 18 million people had RA. RA is characterized by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are the most prevalent secondary metabolites in plants, with a diverse spectrum of biological actions that benefit functional meals and nutraceuticals. These compounds have received a lot of attention recently because they have antioxidant, anti-inflammatory, immunomodulatory, and anti-rheumatoid activity by modulating tumor necrosis factor, mitogen-activated protein kinase, nuclear factor kappa-light-chain-enhancer of activated B cells, and c-Jun N-terminal kinases, as well as other preventative properties. This article discusses dietary polyphenols, their pharmacological properties, and innovative delivery technologies for the treatment of RA, with a focus on their possible biological activities. Nonetheless, commercialization of polyphenols may be achievable only after confirming their safety profile and completing successful clinical trials.
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Affiliation(s)
- Ana C. Gonçalves
- CICS-UBI—Health Sciences Research Center, University of Beira Interior, 6201-001 Covilhã, Portugal;
- CIBIT—Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, 3000-548 Coimbra, Portugal
- SPRINT Sport Physical Activity and Health Research & Innovation Center, Instituto Politécnico da Guarda, 6300-559 Guarda, Portugal
| | - Sofia Rodrigues
- Health Superior School, Polytechnic Institute of Viseu, 3500-843 Viseu, Portugal;
| | - Rafael Fonseca
- Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal;
| | - Luís R. Silva
- CICS-UBI—Health Sciences Research Center, University of Beira Interior, 6201-001 Covilhã, Portugal;
- SPRINT Sport Physical Activity and Health Research & Innovation Center, Instituto Politécnico da Guarda, 6300-559 Guarda, Portugal
- CERES, Department of Chemical Engineering, University of Coimbra, 3030-790 Coimbra, Portugal
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9
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Sae-Foo W, Yusakul G, Nualkaew N, Putalun W. Identification of Major Bioactive Anti-inflammatory Compounds of Derris scandens Stem Using RAW 264.7 Cells and HPLC-UV Analysis. PLANTA MEDICA 2024; 90:126-137. [PMID: 37846500 DOI: 10.1055/a-2192-2281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2023]
Abstract
Derris scandens (DS) is widely recognized for its therapeutic properties, specifically its analgesic effects, which significantly alleviate muscle pain. The chemical constituents of DS stem include various isoflavone derivatives. However, there is currently a lack of specified anti-inflammatory chemical markers and analytical methods for quality control. The present study aimed to evaluate the anti-inflammatory activity of DS and its constituents using the RAW 264.7 cell model. The expression of inflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and 5-lipoxygenase (5-LOX) was examined using quantitative RT-PCR. An high-performance liquid chromatography with a UV detection method was developed to quantitatively analyze genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside, genistein, derrisisoflavone A, lupalbigenin, and 6,8-diprenylgenistein in DS stem. The developed HPLC-UV method demonstrated high sensitivity with limits of detection and quantification ranging from 0.01 to 0.06 µg/mL and 0.03 to 0.18 µg/mL, respectively. The accuracy of the method ranged from 93.3 to 109.6%. Furthermore, the repeatability and reproducibility of the method were suitable, as indicated by the relative standard deviations of ≤ 3.02% and ≤ 6.22%, respectively. The DS extract notably inhibited NO production, exhibiting effects comparable to those of 500 µM diclofenac, and substantially suppressed the expression of iNOS, COX-2, IL-6, and 5-LOX of lipopolysaccharide (LPS)-induced genes. As to the pure isoflavone derivatives, the order of NO production inhibition was found to be genistein > lupalbigenin > derrisisoflavone A > 6,8-diprenylgenistein > genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside. Genistein, derrisisoflavone A, and 6,8-diprenylgenistein significantly suppressed the upregulation of all LPS-induced genes. Consequently, these compounds are recommended as anti-inflammatory markers for the quantitative chemical analysis of DS.
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Affiliation(s)
- Worapol Sae-Foo
- Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
| | - Gorawit Yusakul
- School of Pharmacy, Walailak University, Nakhon Si Thammarat, Thailand
| | - Natsajee Nualkaew
- Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
| | - Waraporn Putalun
- Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
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10
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Ali SI, Salama A. Natural Immunomodulatory Agents as a Complementary Therapy for Poxviruses. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1451:337-354. [PMID: 38801589 DOI: 10.1007/978-3-031-57165-7_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
Abstract
Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4+ T cells, CD4+ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.
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Affiliation(s)
- Sami I Ali
- Plant Biochemistry Department, National Research Centre (NRC), 33 El Buhouth St. (Former El-Tahrir St.), Dokki, Cairo, 12622, Egypt.
| | - Abeer Salama
- Pharmacology Department, National Research Centre (NRC), 33 El Buhouth St. (Former El-Tahrir St.), Dokki, Cairo, 12622, Egypt
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11
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Yuan Y, Wang F, Liu X, Shuai B, Fan H. The Role of AMPK Signaling in Ulcerative Colitis. Drug Des Devel Ther 2023; 17:3855-3875. [PMID: 38170149 PMCID: PMC10759424 DOI: 10.2147/dddt.s442154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/22/2023] [Indexed: 01/05/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients' quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.
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Affiliation(s)
- Yuyi Yuan
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Fang Wang
- Department of Rehabilitation Medicine, Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Jingshan, Hubei, 431800, People’s Republic of China
| | - Xingxing Liu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Bo Shuai
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Heng Fan
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
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12
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Sezer A, Mahmutović L, Akçeşme B. In silico study of polyphenols as potential inhibitors of MALT1 protein in non-Hodgkin lymphoma. Med Oncol 2023; 41:37. [PMID: 38155268 DOI: 10.1007/s12032-023-02261-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 11/16/2023] [Indexed: 12/30/2023]
Abstract
Non-Hodgkin lymphoma (NHL) is one of the most common cancer types. Deregulated signaling pathways can trigger certain NHL subtypes, including Diffuse Large B-cell lymphoma. NF-ĸB signaling pathway, which is responsible for the proliferation, growth, and survival of cells, has an essential role in lymphoma development. Although different signals control NF-ĸB activation in various lymphoid malignancies, the characteristic one is the CARD11-BCL10-MALT1 (CBM) complex. The CBM complex is responsible for the initiation of adaptive immune response. Our study is focused on the molecular docking of ten polyphenols as potential CARD11-BCL10-MALT1 complex inhibitors, essentially through MALT1 inhibition. Molecular docking was performed by Auto Dock Tools and AutoDock Vina tool, while SwissADME was used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of the ligands. Out of 66 ligands that were used in this study, we selected and visualized five. Selection criteria were based on the binding energy score and position of the ligands on the used protein. 2D and 3D visualizations showed interactions of ligands with the protein. Five ligands are considered potential inhibitors of MALT1, thus affecting NF-ĸB signaling pathway. However, additional in vivo and in vitro studies are required to confirm their mechanism of inhibition.
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Affiliation(s)
- Abas Sezer
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička Cesta 15, 71000, Sarajevo, Bosnia and Herzegovina
| | - Lejla Mahmutović
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička Cesta 15, 71000, Sarajevo, Bosnia and Herzegovina
| | - Betül Akçeşme
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička Cesta 15, 71000, Sarajevo, Bosnia and Herzegovina.
- Department of Basic Medical Sciences, Division of Medical Biology, University of Health Sciences, 34000, Istanbul, Turkey.
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13
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Schönberger E, Mihaljević V, Steiner K, Šarić S, Kurevija T, Majnarić LT, Bilić Ćurčić I, Canecki-Varžić S. Immunomodulatory Effects of SGLT2 Inhibitors-Targeting Inflammation and Oxidative Stress in Aging. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:6671. [PMID: 37681811 PMCID: PMC10487537 DOI: 10.3390/ijerph20176671] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 08/26/2023] [Accepted: 08/28/2023] [Indexed: 09/09/2023]
Abstract
Given that the increase in the aging population has grown into one of the largest public health issues, inflammation and oxidative stress, which are closely associated with the aging process, became a focus of recent research. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a group of drugs initially developed as oral antidiabetics, have shown many beneficial effects over time, including improvement in renal function and cardioprotective effects. It has been shown that SGLT2 inhibitors, as a drug class, have an immunomodulatory and antioxidative effect, affecting endothelial function as well as metabolic parameters. Therefore, it is not surprising that various studies have investigated the potential mechanisms of action of SGLT2 inhibitors in age-related diseases. The proposed mechanisms by which SGLT2 inhibitors can achieve their anti-inflammatory effects include influence on AMPK/SIRT1/PGC-1α signaling, various cytokines, and the NLRP3 inflammasome. The antioxidative effect is related to their action on mitochondria and their influence on the signaling pathways of transforming growth factor β and nuclear erythroid 2-related factor 2/antioxidant response element. Also, SGLT2 inhibitors achieve their anti-inflammatory and antioxidative effects by affecting metabolic parameters, such as uric acid reduction, stimulation of ketogenesis, reduction of body weight, lipolysis, and epicardial fat tissue. Finally, SGLT2 inhibitors display anti-atherosclerotic effects that modulate inflammatory reactions, potentially resulting in improvement in endothelial function. This narrative review offers a complete and comprehensive overview of the possible pathophysiologic mechanisms of the SGLT2 inhibitors involved in the aging process and development of age-related disease. However, in order to use SGLT2 inhibitor drugs as an anti-aging therapy, further basic and clinical research is needed to elucidate the potential effects and complex mechanisms they have on inflammation processes.
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Affiliation(s)
- Ema Schönberger
- Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia; (E.S.); (K.S.); (S.C.-V.)
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Vjera Mihaljević
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia;
| | - Kristina Steiner
- Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia; (E.S.); (K.S.); (S.C.-V.)
| | - Sandra Šarić
- Department for Cardiovascular Disease, University Hospital Osijek, 31000 Osijek, Croatia;
- Department of Internal Medicine and History of Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
| | - Tomislav Kurevija
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia; (T.K.); (L.T.M.)
- Health Center Osjecko-Baranjska County, 31000 Osijek, Croatia
| | - Ljiljana Trtica Majnarić
- Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia; (T.K.); (L.T.M.)
| | - Ines Bilić Ćurčić
- Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia; (E.S.); (K.S.); (S.C.-V.)
- Department of Pharmacology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
| | - Silvija Canecki-Varžić
- Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia; (E.S.); (K.S.); (S.C.-V.)
- Department of Pathophysiology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
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14
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Tirani SA, Lotfi K, Mirzaei S, Asadi A, Akhlaghi M, Saneei P. The relation between dietary phytochemical index and metabolic health status in overweight and obese adolescents. Sci Rep 2023; 13:12059. [PMID: 37491451 PMCID: PMC10368731 DOI: 10.1038/s41598-023-39314-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 07/23/2023] [Indexed: 07/27/2023] Open
Abstract
Previous studies have rarely investigated dietary phytochemicals consumption in relation to metabolic health of adolescents. The current study was performed to investigate dietary phytochemical index (DPI) in relation to metabolic health status in overweight and obese adolescents. This cross-sectional study was conducted among 203 adolescents with overweight or obesity. Dietary intakes of participants were obtained through a validated 147-item food frequency questionnaire. DPI was calculated [(dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)) ⨯100]. Glycemic and lipid profiles, blood pressure, and anthropometric indices were also measured. A metabolically unhealthy overweight/obesity (MUO) profile was determined based on the International Diabetes Federation (IDF) and IDF/Homeostasis Model Assessment Insulin Resistance (HOMA-IR) definitions. Study subjects had a mean age of 13.98 years and 50.2% of them were girls. According to IDF and IDF/HOMA-IR criteria, 38.9% (37 boys, and 42 girls) and 33% (35 boys, and 32 girls) of the study participants were respectively MUO. According to IDF and IDF/HOMA-IR definitions, adolescents in the third DPI tertile had respectively 61% (maximally-adjusted OR = 0.39, 95%CI 0.16-0.91) and 67% (maximally-adjusted OR = 0.33, 95%CI 0.13-0.83) lower odds of being MUO, compared to the first tertile. Stratified analysis by sex indicated that DPI was inversely related to MUO phenotype based on IDF criteria in girls (maximally-adjusted OR = 0.25, 95%CI 0.06-0.98), but not in boys. The current study found that adolescents with a higher dietary intake of phytochemicals have lower odds of being MUO, particularly among girls. However, further large-scale prospective cohort studies are required to confirm this finding.
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Affiliation(s)
- Shahnaz Amani Tirani
- Department of Community Nutrition, School of Nutrition and Food Science, Nutrition and Food Security Research Center, Students' Research Committee, Isfahan University of Medical Sciences, PO Box 81745-151, Isfahan, Iran
| | - Keyhan Lotfi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeideh Mirzaei
- Department of Community Nutrition, School of Nutrition and Food Science, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Asadi
- Department of Exercise Physiology, School of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran
| | - Masoumeh Akhlaghi
- Department of Community Nutrition, School of Nutrition and Food Science, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Parvane Saneei
- Department of Community Nutrition, School of Nutrition and Food Science, Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, PO Box 81745-151, Isfahan, Iran.
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15
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Li MY, Wu YZ, Qiu JG, Lei JX, Li MX, Xu N, Liu YH, Jin Z, Su ZR, Lee SMY, Zheng XB, Xiao-Qi H. Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 311:116430. [PMID: 36997133 DOI: 10.1016/j.jep.2023.116430] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/15/2023] [Accepted: 03/22/2023] [Indexed: 06/19/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC). AIM OF THE STUDY To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. MATERIALS AND METHODS Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model. RESULTS The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. CONCLUSIONS The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.
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Affiliation(s)
- Min-Yao Li
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, China
| | - Yu-Zhu Wu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, China
| | - Jian-Guo Qiu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, China
| | - Jun-Xuan Lei
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, China
| | - Mu-Xia Li
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Nan Xu
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Yu-Hong Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhen Jin
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zi-Ren Su
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Simon Ming-Yuen Lee
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China; Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao
| | - Xue-Bao Zheng
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, China.
| | - Huang Xiao-Qi
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, China.
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16
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Shoaib S, Ansari MA, Kandasamy G, Vasudevan R, Hani U, Chauhan W, Alhumaidi MS, Altammar KA, Azmi S, Ahmad W, Wahab S, Islam N. An Attention towards the Prophylactic and Therapeutic Options of Phytochemicals for SARS-CoV-2: A Molecular Insight. Molecules 2023; 28:795. [PMID: 36677853 PMCID: PMC9864057 DOI: 10.3390/molecules28020795] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/05/2023] [Accepted: 01/07/2023] [Indexed: 01/15/2023] Open
Abstract
The novel pathogenic virus was discovered in Wuhan, China (December 2019), and quickly spread throughout the world. Further analysis revealed that the pathogenic strain of virus was corona but it was distinct from other coronavirus strains, and thus it was renamed 2019-nCoV or SARS-CoV-2. This coronavirus shares many characteristics with other coronaviruses, including SARS-CoV and MERS-CoV. The clinical manifestations raised in the form of a cytokine storm trigger a complicated spectrum of pathophysiological changes that include cardiovascular, kidney, and liver problems. The lack of an effective treatment strategy has imposed a health and socio-economic burden. Even though the mortality rate of patients with this disease is lower, since it is judged to be the most contagious, it is considered more lethal. Globally, the researchers are continuously engaged to develop and identify possible preventive and therapeutic regimens for the management of disease. Notably, to combat SARS-CoV-2, various vaccine types have been developed and are currently being tested in clinical trials; these have also been used as a health emergency during a pandemic. Despite this, many old antiviral and other drugs (such as chloroquine/hydroxychloroquine, corticosteroids, and so on) are still used in various countries as emergency medicine. Plant-based products have been reported to be safe as alternative options for several infectious and non-infectious diseases, as many of them showed chemopreventive and chemotherapeutic effects in the case of tuberculosis, cancer, malaria, diabetes, cardiac problems, and others. Therefore, plant-derived products may play crucial roles in improving health for a variety of ailments by providing a variety of effective cures. Due to current therapeutic repurposing efforts against this newly discovered virus, we attempted to outline many plant-based compounds in this review to aid in the fight against SARS-CoV-2.
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Affiliation(s)
- Shoaib Shoaib
- Department Biochemistry, Faculty of Medicine, J. N. Medical College, Aligarh Muslim University, Aligarh 202002, India
| | - Mohammad Azam Ansari
- Department of Epidemic Disease Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Geetha Kandasamy
- Department of Clinical Pharmacy, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia
| | - Rajalakshimi Vasudevan
- Department of Pharmacology, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia
| | - Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia
| | - Waseem Chauhan
- Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India
| | - Maryam S. Alhumaidi
- Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi Arabia
| | - Khadijah A. Altammar
- Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi Arabia
| | - Sarfuddin Azmi
- Molecular Microbiology Biology Division, Scientific Research Centre (SRC), Prince Sultan Military Medical City (PSMMC), Riyadh 11159, Saudi Arabia
| | - Wasim Ahmad
- Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Dammam 34222, Saudi Arabia
| | - Shadma Wahab
- Deparment of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
| | - Najmul Islam
- Department Biochemistry, Faculty of Medicine, J. N. Medical College, Aligarh Muslim University, Aligarh 202002, India
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17
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Shao X, Li J, Zhang H, Zhang X, Sun C, Ouyang X, Wang Y, Wu X, Chen C. Anti-inflammatory effects and molecular mechanisms of bioactive small molecule garlic polysaccharide. Front Nutr 2023; 9:1092873. [PMID: 36698476 PMCID: PMC9868249 DOI: 10.3389/fnut.2022.1092873] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 12/12/2022] [Indexed: 01/11/2023] Open
Abstract
Although garlic polysaccharides have been found to possess anti-inflammatory activities, anti-inflammatory study on small molecule water-soluble garlic polysaccharide (WSGP) is few. In this study, a novel WSGP with a molecular weight of 1853 Da was isolated by DEAE-52 and Sephadex G-100 column and the chemical composition was identified by monosaccharide composition and methylation analysis. Furthermore, the antioxidant effects of WSGP and the potential molecular mechanisms on LPS-induced inflammatory responses in RAW264.7 macrophage cells were investigated. The results showed that WSGP has strong antioxidant activity, such as DPPH, hydroxyl, superoxide anion, ABTS radical scavenging capacity, Fe2+ chelating ability and reducing power. Meanwhile, WSGP could considerably suppress the manufacturing of NO and the mRNA and protein expression degrees of IL-6, TNF-α, and IL-1β in LPS inspired RAW264.7 macrophages WSGP could significantly suppress the production of NO and the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α in LPS stimulated RAW264.7 macrophage cells (p < 0.05). In addition, the phosphorylated IκB-α, p65, and STAT3 proteins were significantly increased in LPS-induced macrophages, while this trend was significantly reversed by WSGP treatment in a concentration-dependent manner (p < 0.05). Consequently, WSGP supplementation might reduce LPS-induced inflammatory responses by suppressing proinflammatory cytokines and NF-κB and STAT3 pathway activation. The finding of this research would give scientific guidelines for the judicious use of small molecular garlic polysaccharide in anti-inflammatory treatments.
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Affiliation(s)
- Xin Shao
- Department of Critical Care Medicine, Maoming People's Hospital, Maoming, China,Department of Food Science and Engineering, Jinan University, Guangzhou, China
| | - Jialong Li
- Department of Food Science and Engineering, Jinan University, Guangzhou, China
| | - Huidan Zhang
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xuhui Zhang
- Department of Food Science and Engineering, Jinan University, Guangzhou, China
| | - Chongzhen Sun
- Department of Food Science and Engineering, Jinan University, Guangzhou, China
| | - Xin Ouyang
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yong Wang
- Department of Food Science and Engineering, Jinan University, Guangzhou, China
| | - Xiyang Wu
- Department of Food Science and Engineering, Jinan University, Guangzhou, China,Xiyang Wu ✉
| | - Chunbo Chen
- Department of Critical Care Medicine, Maoming People's Hospital, Maoming, China,Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China,Department of Critical Care Medicine, Shenzhen People's Hospital, Shenzhen, China,*Correspondence: Chunbo Chen ✉
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18
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Lee D, Hong S, Jung K, Choi S, Kang KS. Suppressive Effects of Flavonoids on Macrophage-Associated Adipocyte Inflammation in a Differentiated Murine Preadipocyte 3T3-L1 Cells Co-Cultured with a Murine Macrophage RAW264.7 Cells. PLANTS (BASEL, SWITZERLAND) 2022; 11:3552. [PMID: 36559664 PMCID: PMC9783032 DOI: 10.3390/plants11243552] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/11/2022] [Accepted: 12/13/2022] [Indexed: 06/17/2023]
Abstract
The suppressive effects of flavonoids on macrophage-associated adipocyte inflammation in a differentiated murine preadipocyte cell line (3T3-L1) co-cultured with a murine macrophage cell line (RAW264.7) were evaluated. Extracellular lipid accumulation was investigated via Oil Red O staining. The expression levels of adipogenesis- and inflammation-associated proteins, including CCAAT/enhancer-binding protein (C/EBP)-α, inducible nitric oxide synthase (iNOS), C/EBPβ, peroxisome proliferator-activated receptor γ (PPARγ), and cyclooxygenase-2 (COX-2), were determined via Western blotting. Proinflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1) and interleukin-6 (IL-6), were assessed using enzyme-linked immunosorbent assay kits. We found that silybin, formononetin, and diosmetin inhibited lipid accumulation and production of proinflammatory cytokines in the co-cultures of 3T3-L1 and RAW264.7 cells. Moreover, they inhibited the protein expression of PPARγ, C/EBPα, COX-2, C/EBPβ, and iNOS in the co-cultures of 3T3-L1 and RAW264.7 cells. These data support that silybin, formononetin, and diosmetin inhibit macrophage-associated adipocyte inflammation and lipid accumulation.
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Affiliation(s)
- Dahae Lee
- Department of Preventive Medicine, College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
| | - Sukyong Hong
- College of Pharmacy, CHA University, Sungnam 13844, Republic of Korea
| | - Kiwon Jung
- College of Pharmacy, CHA University, Sungnam 13844, Republic of Korea
- Oncobix Co., Ltd., Yongin-si 16950, Republic of Korea
| | - Sungyoul Choi
- Department of Neuropsychiatry, College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
| | - Ki Sung Kang
- Department of Preventive Medicine, College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
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Kusumah J, Gonzalez de Mejia E. Impact of soybean bioactive compounds as response to diet-induced chronic inflammation: A systematic review. Food Res Int 2022; 162:111928. [DOI: 10.1016/j.foodres.2022.111928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 09/07/2022] [Accepted: 09/08/2022] [Indexed: 11/04/2022]
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20
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Siriviriyakul P, Sriko J, Somanawat K, Chayanupatkul M, Klaikeaw N, Werawatganon D. Genistein attenuated oxidative stress, inflammation, and apoptosis in L-arginine induced acute pancreatitis in mice. BMC Complement Med Ther 2022; 22:208. [PMID: 35927726 PMCID: PMC9351145 DOI: 10.1186/s12906-022-03689-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 07/28/2022] [Indexed: 11/10/2022] Open
Abstract
Aim Acute pancreatitis is a common and potentially serious condition. However, a specific treatment for this condition is still lacking. Genistein, with its anti-oxidant and anti-inflammatory effects, could possibly be used to tackle the underlying pathophysiology of acute pancreatitis. Therefore, the aim of this study was to investigate the effects of genistein on oxidative stress, inflammation, and apoptosis in acute pancreatitis induced by L-arginine in mice. Methods Twenty-four male ICR mice were equally divided into 4 groups: Control (Con); Acute pancreatitis (AP) group: Two doses of i.p. 350 mg/100 g body weight (BW) of L-arginine were administered 1 h apart; AP and low-dose genistein (LG) group: mice were given i.p. injection of 10 mg/kg genistein 2 h prior to L-arginine injection followed by once-daily dosing for 3 days; and AP and high-dose genistein (HG) group: mice were given 100 mg/kg genistein with the similar protocol as the LG group. Pancreatic tissue was evaluated for histopathological changes and acinar cell apoptosis, malondialdehyde (MDA) levels, immunohistochemical staining for myeloperoxidase (MPO), nuclear factor-kappa beta (NF-kB), and 4-hydroxynonenal (4-HNE). Serum levels of amylase (AMY), c-reactive protein (CRP), and interleukin (IL)-6 were measured. Results Significant increases in the degree of acinar cell apoptosis, pancreatic MDA, serum IL-6 and amylase, MPO, NF-kB and 4-HNE positivity were observed in the AP group. All these parameters declined after low- and high-dose genistein treatment. Severe pancreatic inflammation, edema, and acinar cell necrosis were observed in the AP group. Significant improvement of histopathological changes was seen in both low- and high-dose genistein groups. There were no significant differences in any parameters between low and high doses of genistein. Conclusion Genistein could attenuate the severity of histopathological changes in acute pancreatitis through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Supplementary Information The online version contains supplementary material available at 10.1186/s12906-022-03689-9.
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21
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Abdul Khaliq H, Alhouayek M, Quetin-Leclercq J, Muccioli GG. 5'AMP-activated protein kinase: an emerging target of phytochemicals to treat chronic inflammatory diseases. Crit Rev Food Sci Nutr 2022; 64:4763-4788. [PMID: 36450301 DOI: 10.1080/10408398.2022.2145264] [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: 12/05/2022]
Abstract
Inflammation is a defensive response of the organism to traumatic, infectious, toxic, ischemic, and autoimmune injury. Inflammatory mediators are released to effectively eliminate the inflammatory trigger and restore homeostasis. However, failure of these processes can lead to chronic inflammatory conditions and diseases such as inflammatory bowel diseases, rheumatoid arthritis, inflammatory lung diseases, atherosclerosis, and neurodegenerative diseases. The cure of chronic inflammatory diseases remains challenging as current therapies have various limitations, such as pronounced side effects, progressive loss of efficacy, and high cost especially for biologics. In this context, phytochemicals (such as alkaloids, flavonoids, lignans, phenolic acids, saponins, terpenoids, and other classes) are considered as an interesting alternative approach. Among the numerous targets of phytochemicals, AMP-activated protein kinase (AMPK) can be considered as an interesting target in the context of inflammation. AMPK regulates inflammatory response by inhibiting inflammatory pathways (NF-κB, JAK/STAT, and MAPK) and regulating several other processes of the inflammatory response (oxidative stress, autophagy, and apoptosis). In this review, we summarize and discuss the studies focusing on phytochemicals that showed beneficial effects by blocking different inflammatory pathways implicating AMPK activation in chronic inflammatory disease models. We also highlight elements to consider when investigating AMPK in the context of phytochemicals.
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Affiliation(s)
- Hafiz Abdul Khaliq
- Pharmacognosy Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
- Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
- Department of Pharmacognosy, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Mireille Alhouayek
- Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
| | - Joëlle Quetin-Leclercq
- Pharmacognosy Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
| | - Giulio G Muccioli
- Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
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22
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Gou ZC, Lu MJ, Cui XY, Wang XQ, Jiang MY, Wang YS, Wang ZQ, Yu XX, Tang SS, Chen G, Su YJ. Enhanced laccase production by mutagenized Myrothecium verrucaria using corn stover as a carbon source and its potential in the degradation of 2-chlorophen. Bioprocess Biosyst Eng 2022; 45:1581-1593. [PMID: 35932338 DOI: 10.1007/s00449-022-02767-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 07/30/2022] [Indexed: 12/18/2022]
Abstract
Chlorophenols are widely used in industry and are known environmental pollutants. The degradation of chlorophenols is important for environmental remediation. In this study, we evaluated the biodegradation of 2-chlorophenol using crude laccase produced by Myrothecium verrucaria. Atmospheric and room temperature plasma technology was used to increase laccase production. The culture conditions of the M-6 mutant were optimized. Our results showed that corn stover could replace glucose as a carbon source and promote laccase production. The maximum laccase activity of 30.08 U/mL was achieved after optimization, which was a 19.04-fold increase. The biodegradation rate of 2-chlorophenol using crude laccase was 97.13%, a positive correlation was determined between laccase activity and degradation rate. The toxicity of 2-CP was substantially reduced after degradation by laccase solution. Our findings show the feasibility of the use of corn stover in laccase production by M. verrucaria mutant and the subsequent biodegradation of 2-chlorophenol using crude laccase.
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Affiliation(s)
- Ze-Chang Gou
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Min-Jie Lu
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Xiao-Yu Cui
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Xi-Qing Wang
- College of Food Science Technology and Chemical Engineering, Hubei University of Arts and Science, Xiangyang, 441000, Hubei, China
| | - Mei-Yi Jiang
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Ya-Shuo Wang
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Zi-Qi Wang
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Xiao-Xiao Yu
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Shan-Shan Tang
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Guang Chen
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China.,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China
| | - Ying-Jie Su
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, Jilin, China. .,Key Laboratory of Straw Comprehensive Utilization and Black Soil Conservation, Ministry of Education, Changchun, 130118, Jilin, China.
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23
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Fu J, Xu H, Wu F, Tu Q, Dong X, Xie H, Cao Z. Empagliflozin inhibits macrophage inflammation through AMPK signaling pathway and plays an anti-atherosclerosis role. Int J Cardiol 2022; 367:56-62. [PMID: 35931206 DOI: 10.1016/j.ijcard.2022.07.048] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/06/2022] [Accepted: 07/29/2022] [Indexed: 11/05/2022]
Abstract
OBJECTIVE In recent years, some authoritative clinical studies have found that SGLT2 inhibitor can reduce cardiovascular risk in patients with diabetes, which may imply that SGLT2 inhibitor can play a role beyond lowering blood glucose. In this study, we explored the effect of empagliflozin on vascular atherosclerosis after removing the effect of diabetes. METHODS The interaction between SGLT2 inhibitor and the AMPK(Adenosine 5'-monophosphate-activated protein kinase) signal pathway to attenuate atherosclerosis was studied in both spontaneously atherosclerotic mice in vivo and oxidized low-density lipoprotein(ox-LDL) induced macrophage inflammation model in vitro. In vivo experiment the aorta tree and aortic valve area were stained with oil red, and the level of inflammatory factors in the diseased tissue was evaluated by immunohistochemistry. Meanwhile, serum was collected to detect the levels of inflammatory factors. In vitro experiment, the RAW264.7 cell line was selected and ox-LDL was used to induce the release of proinflammatory factors, and different doses of empagliflozin were added. The phagocytosis of macrophages to ox-LDL density lipoprotein, and the expression of inflammatory factors at the protein and RNA levels were measured. RESULTS Empagliflozin reduced the area of atherosclerotic plaque and macrophage infiltration in atherosclerotic plaques, decreased the expression of inflammatory factors in local plaque tissues and serum of APOE-/- mice fed with high-fat diet. Empagliflozin can improve the protein expression level of p-AMPK affected by ox-LDL in cell and reduce the gene expression level of inflammatory factors and protein expression level of NF-κB, thus playing an anti-atherosclerosis role. CONCLUSIONS Empagliflozin improves energy metabolism and reduces the expression of inflammatory factors by activating AMPK. As empagliflozin inhibits atherosclerosis progression, it may be of use in prevention of cardiovascular diseases.
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Affiliation(s)
- Jie Fu
- Hubei University of Medicine, Shiyan 442000, Hubei, China
| | - Hualin Xu
- Hubei University of Medicine, Shiyan 442000, Hubei, China
| | - Fuyun Wu
- Hubei University of Medicine, Shiyan 442000, Hubei, China
| | - Qiang Tu
- Taihe Hospital, Shiyan 442000, Hubei, China
| | - Xiao Dong
- Taihe Hospital, Shiyan 442000, Hubei, China
| | | | - Zheng Cao
- Hubei University of Medicine, Shiyan 442000, Hubei, China; Taihe Hospital, Shiyan 442000, Hubei, China.
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24
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Jafari A, Esmaeilzadeh Z, Khezri MR, Ghasemnejad-Berenji H, Pashapour S, Sadeghpour S, Ghasemnejad-Berenji M. An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS-CoV-2 infection: A hypothesis. J Food Biochem 2022; 46:e14345. [PMID: 35866873 PMCID: PMC9350103 DOI: 10.1111/jfbc.14345] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/02/2022] [Accepted: 07/05/2022] [Indexed: 11/28/2022]
Abstract
The Coronavirus Disease 2019 (COVID‐19) pandemic has been caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It is a global problem that humanity has not yet found a definitive solution for it. In this regard, a global effort has been done to find effective or potential adjuvant therapies in order to fight this infection. Genistein is a small, biologically active phytoestrogen flavonoid that is found in high amounts in soy and plants of the Fabaceae family. This important compound is known due to its anti‐cancer, anti‐inflammatory, and antioxidant effects. Additionally, protective effects of genistein have been reported in different pathological conditions through modulating intracellular pathways such as PI3K, Akt, mTOR, NF‐κB, PPARγ, AMPK, and Nrf2. Scientific evidence suggests that genistein could have a potential role to treat COVID‐19 through its anti‐inflammatory and anti‐oxidant effects. Furthermore, it appears to interfere with intracellular pathways involved in viral entry into the cell. This review provides a basis for further research and development of clinical applications of genistein as a potential alternative therapy to decrease inflammation and oxidative stress in COVID‐19 patients.
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Affiliation(s)
- Abbas Jafari
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Zeinab Esmaeilzadeh
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | | | | | - Sarvin Pashapour
- Department of Pediatrics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Sonia Sadeghpour
- Department of Obstetrics & Gynecology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Morteza Ghasemnejad-Berenji
- Experimental and Applied Pharmaceutical Research Center, Urmia University of Medical Sciences, Urmia, Iran.,Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
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25
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Alginate Oligosaccharides Ameliorate DSS-Induced Colitis through Modulation of AMPK/NF-κB Pathway and Intestinal Microbiota. Nutrients 2022; 14:nu14142864. [PMID: 35889822 PMCID: PMC9321948 DOI: 10.3390/nu14142864] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 07/07/2022] [Accepted: 07/11/2022] [Indexed: 02/04/2023] Open
Abstract
Alginate oligosaccharides (AOS) are shown to have various biological activities of great value to medicine, food, and agriculture. However, little information is available about their beneficial effects and mechanisms on ulcerative colitis. In this study, AOS with a polymerization degree between 2 and 4 were found to possess anti-inflammatory effects in vitro and in vivo. AOS could decrease the levels of nitric oxide (NO), IL-1β, IL-6, and TNFα, and upregulate the levels of IL-10 in both RAW 264.7 and bone-marrow-derived macrophage (BMDM) cells under lipopolysaccharide (LPS) stimulation. Additionally, oral AOS administration could significantly prevent bodyweight loss, colonic shortening, and rectal bleeding in dextran sodium sulfate (DSS)-induced colitis mice. AOS pretreatment could also reduce disease activity index scores and histopathologic scores and downregulate proinflammatory cytokine levels. Importantly, AOS administration could reverse DSS-induced AMPK deactivation and NF-κB activation in colonic tissues, as evidenced by enhanced AMPK phosphorylation and p65 phosphorylation inhibition. AOS could also upregulate AMPK phosphorylation and inhibit NF-κB activation in vitro. Moreover, 16S rRNA gene sequencing of gut microbiota indicated that supplemental doses of AOS could affect overall gut microbiota structure to a varying extent and specifically change the abundance of some bacteria. Medium-dose AOS could be superior to low- or high-dose AOS in maintaining remission in DSS-induced colitis mice. In conclusion, AOS can play a protective role in colitis through modulation of gut microbiota and the AMPK/NF-kB pathway.
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A Randomized Controlled Trial of Thai Medicinal Plant-4 Cream versus Diclofenac Gel in the Management of Symptomatic Osteoarthritis of the Knee. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8657000. [PMID: 35733624 PMCID: PMC9208949 DOI: 10.1155/2022/8657000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 05/24/2022] [Indexed: 11/18/2022]
Abstract
Background Osteoarthritis of the knee is a common degenerative musculoskeletal condition. Thai Medicinal Plant-4 (TMP-4) cream is made up of Garcinia mangostana peel, Sesamum indicum seeds, Glycine max (L.) Merr. seeds, and Centella asiatica leaves, all of which have anti-inflammatory and analgesic properties. The present study aimed at determining the efficacy and safety of TMP-4 cream versus diclofenac gel in the treatment of symptomatic osteoarthritis of the knee. Methods A randomized-controlled trial was conducted to assess knee pain on a scale of 100 mm Visual Analog Scale (VAS) and other key metrics, including VAS knee stiffness, a modified 10-step stair climb test, a timed up and go test, the Knee Injury and Osteoarthritis Outcome Score, and safety outcomes, following administration of either TMP-4 cream or diclofenac gel for 4 weeks. Results A total of 199 patients with moderate knee pain intensity were randomly assigned to either TMP-4 cream or diclofenac gel (allocation ratio 1 : 1). The mean changes of VAS knee pain in the TMP-4 cream and diclofenac gel groups were −31.68 ± 14.18 mm and −31.09 ± 12.41 mm, respectively, (mean difference = −0.58, 95% confidence interval = −4.37–3.20, P=0.761). The upper limit of 95% confidence interval for the comparison between TMP-4 cream and diclofenac gel was within the predefined margin of 7 mm for noninferiority. The safety was comparable between the two interventions. Conclusions TMP-4 cream was noninferior to diclofenac gel in relieving osteoarthritic knee pain and may be considered as an alternative therapeutic option in the treatment of symptomatic osteoarthritis of the knee.
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Mas-Bargues C, Borrás C, Viña J. The multimodal action of genistein in Alzheimer's and other age-related diseases. Free Radic Biol Med 2022; 183:127-137. [PMID: 35346775 DOI: 10.1016/j.freeradbiomed.2022.03.021] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 02/07/2023]
Abstract
Genistein is a phytoestrogen that, due to its structural similarity with estrogen, can both mimic and antagonize estrogen effects. Early analysis proved that at high concentrations, genistein inhibits breast cancer cell proliferation, thereby suggesting an anticancer activity. Since then, many discoveries have identified the genistein mechanism of action, including cell cycle arrest, apoptosis induction, as well as angiogenesis, and metastasis inhibition. In this review, we aim to discuss the multimodal action of genistein as an antioxidant, anti-inflammatory, anti-amyloid β, and autophagy promoter, which could be responsible for the genistein beneficial effect on Alzheimer's. Furthermore, we pinpoint the main signal transduction pathways that are known to be modulated by genistein. Genistein has thus several beneficial effects in several diseases, many of them associated with age, such as the above mentioned Alzheimer disease. Indeed, the beneficial effects of genistein for health promotion depend on each multimodality. In the context of geroscience, genistein has promising beneficial effects due to its multimodal action to treat age associated-diseases.
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Affiliation(s)
- Cristina Mas-Bargues
- Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia, 46010, Spain.
| | - Consuelo Borrás
- Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia, 46010, Spain.
| | - José Viña
- Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia, 46010, Spain
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Park JE, Kang E, Han JS. HM-chromanone attenuates TNF-α-mediated inflammation and insulin resistance by controlling JNK activation and NF-κB pathway in 3T3-L1 adipocytes. Eur J Pharmacol 2022; 921:174884. [PMID: 35288193 DOI: 10.1016/j.ejphar.2022.174884] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/14/2022] [Accepted: 03/09/2022] [Indexed: 11/03/2022]
Abstract
Obesity is a major public health problem worldwide and causes inflammation and insulin resistance in adipose tissue. We investigated the ability of (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (HM-chromanone) isolated from Portulaca oleracea to attenuate the activation of inflammatory cytokines and signaling pathways associated with tumor necrosis factor (TNF)-α-mediated inflammation and insulin resistance in 3T3-L1 adipocytes. TNF-α triggers the release of inflammatory cytokines and activation of the mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathways. In this study, HM-chromanone inhibited the production of inflammatory cytokines and chemokines [TNF-α, interleukin (IL)-6, IL-1β, and monocyte chemoattractant protein 1] involved in inflammation and insulin resistance. Furthermore, TNF-α treatment increased c-Jun-NH2 terminal kinase (JNK) phosphorylation, whereas HM-chromanone significantly decreased JNK phosphorylation in a dose-dependent manner. TNF-α treatment increased the activation of inhibitor kappa B (IκB) kinase (IKK), IκBα, and NF-κBp65 compared with that of the control. However, HM-chromanone significantly blocked IKK, IκBα, and NF-κBp65 activation. Upon adipocyte stimulation with TNF-α, phosphorylated insulin receptor substrate (pIRS)-1 serine 307 levels increased and pIRS-1 tyrosine 612 levels decreased compared with those of the control. Upon treatment with HM-chromanone, serine 307 phosphorylation of IRS-1 was inhibited and tyrosine 612 phosphorylation of IRS-1 was increased. Thus, HM-chromanone improved TNF-α-mediated inflammation and insulin resistance by regulating JNK activation and the NF-κB pathway, thereby reducing inflammatory cytokine secretion and inhibiting serine phosphorylation of IRS-1 in the insulin signaling pathway. These results suggest the potential of HM-chromanone to improve inflammatory conditions and insulin resistance in adipocytes.
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Affiliation(s)
- Jea Eun Park
- Department of Food Science and Nutrition, Pusan National University, Busan, 46241, South Korea.
| | - Eunji Kang
- Department of Food Science and Nutrition, Pusan National University, Busan, 46241, South Korea.
| | - Ji Sook Han
- Department of Food Science and Nutrition, Pusan National University, Busan, 46241, South Korea.
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Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM. Genistein: A Review on its Anti-Inflammatory Properties. Front Pharmacol 2022; 13:820969. [PMID: 35140617 PMCID: PMC8818956 DOI: 10.3389/fphar.2022.820969] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/04/2022] [Indexed: 11/29/2022] Open
Abstract
Nowadays, non-resolving inflammation is becoming a major trigger in various diseases as it plays a significant role in the pathogenesis of atherosclerosis, asthma, cancer, obesity, inflammatory bowel disease, chronic obstructive pulmonary disease, neurodegenerative disease, multiple sclerosis, and rheumatoid arthritis. However, prolonged use of anti-inflammatory drugs is usually accompanied with undesirable effects and hence more patients tend to seek for natural compounds as alternative medicine. Considering the fact above, there is an urgency to discover and develop potential novel, safe and efficacious natural compounds as drug candidates for future anti-inflammatory therapy. Genistein belongs to the flavonoid family, in the subgroup of isoflavones. It is a phytoestrogen that is mainly derived from legumes. It is a naturally occurring chemical constituent with a similar chemical structure to mammalian estrogens. It is claimed to exert many beneficial effects on health, such as protection against osteoporosis, reduction in the risk of cardiovascular disease, alleviation of postmenopausal symptoms and anticancer properties. In the past, numerous in vitro and in vivo studies have been conducted to investigate the anti-inflammatory potential of genistein. Henceforth, this review aims to summarize the anti-inflammatory properties of genistein linking with the signaling pathways and mediators that are involved in the inflammatory response as well as its toxicity profile. The current outcomes are analysed to highlight the prospect as a lead compound for drug discovery. Data was collected using PubMed, ScienceDirect, SpringerLink and Scopus databases. Results showed that genistein possessed strong anti-inflammatory activities through inhibition of various signaling pathways such as nuclear factor kappa-B (NF-κB), prostaglandins (PGs), inducible nitric oxide synthase (iNOS), proinflammatory cytokines and reactive oxygen species (ROS). A comprehensive assessment of the mechanism of action in anti-inflammatory effects of genistein is included. However, evidence for the pharmacological effects is still lacking. Further studies using various animal models to assess pharmacological effects such as toxicity, pharmacokinetics, pharmacodynamics, and bioavailability studies are required before clinical studies can be conducted. This review will highlight the potential use of genistein as a lead compound for future drug development as an anti-inflammatory agent.
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Affiliation(s)
- Yu Xian Goh
- Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Juriyati Jalil
- Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Kok Wai Lam
- Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Khairana Husain
- Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Chandini Menon Premakumar
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Maharjan CK, Mo J, Wang L, Kim MC, Wang S, Borcherding N, Vikas P, Zhang W. Natural and Synthetic Estrogens in Chronic Inflammation and Breast Cancer. Cancers (Basel) 2021; 14:cancers14010206. [PMID: 35008370 PMCID: PMC8744660 DOI: 10.3390/cancers14010206] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/17/2021] [Accepted: 12/19/2021] [Indexed: 12/17/2022] Open
Abstract
The oncogenic role of estrogen receptor (ER) signaling in breast cancer has long been established. Interaction of estrogen with estrogen receptor (ER) in the nucleus activates genomic pathways of estrogen signaling. In contrast, estrogen interaction with the cell membrane-bound G-protein-coupled estrogen receptor (GPER) activates the rapid receptor-mediated signaling transduction cascades. Aberrant estrogen signaling enhances mammary epithelial cell proliferation, survival, and angiogenesis, hence is an important step towards breast cancer initiation and progression. Meanwhile, a growing number of studies also provide evidence for estrogen's pro- or anti-inflammatory roles. As other articles in this issue cover classic ER and GPER signaling mediated by estrogen, this review will discuss the crucial mechanisms by which estrogen signaling influences chronic inflammation and how that is involved in breast cancer. Xenoestrogens acquired from plant diet or exposure to industrial products constantly interact with and alter innate estrogen signaling at various levels. As such, they can modulate chronic inflammation and breast cancer development. Natural xenoestrogens generally have anti-inflammatory properties, which is consistent with their chemoprotective role in breast cancer. In contrast, synthetic xenoestrogens are proinflammatory and carcinogenic compounds that can increase the risk of breast cancer. This article also highlights important xenoestrogens with a particular focus on their role in inflammation and breast cancer. Improved understanding of the complex relationship between estrogens, inflammation, and breast cancer will guide clinical research on agents that could advance breast cancer prevention and therapy.
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Affiliation(s)
- Chandra K. Maharjan
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Jiao Mo
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Lei Wang
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Myung-Chul Kim
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
| | - Sameul Wang
- Canyonoak Consulting LLC, San Diego, CA 92127, USA;
| | - Nicholas Borcherding
- Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110, USA;
| | - Praveen Vikas
- Department of Internal Medicine, Carver College of Medicine, Iowa City, IA 52242, USA;
| | - Weizhou Zhang
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA; (C.K.M.); (J.M.); (L.W.); (M.-C.K.)
- Mechanism of Oncogenesis Program, University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610, USA
- Correspondence: to: ; Tel.: +1-352-273-6748
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Zamani-Garmsiri F, Emamgholipour S, Rahmani Fard S, Ghasempour G, Jahangard Ahvazi R, Meshkani R. Polyphenols: Potential anti-inflammatory agents for treatment of metabolic disorders. Phytother Res 2021; 36:415-432. [PMID: 34825416 DOI: 10.1002/ptr.7329] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 10/17/2021] [Accepted: 10/23/2021] [Indexed: 12/31/2022]
Abstract
Ample evidence highlights the potential benefits of polyphenols in health status especially in obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, and cardiovascular diseases. Mechanistically, due to the key role of "Metainflammation" in the pathomechanism of metabolic disorders, recently much focus has been placed on the properties of polyphenols in obesity-related morbidities. This narrative review summarizes the current knowledge on the role of polyphenols, including genistein, chlorogenic acid, ellagic acid, caffeic acid, and silymarin in inflammatory responses pertinent to metabolic disorders and discusses the implications of this evidence for future directions. This review provides evidence that the aforementioned polyphenols benefit health status in metabolic disorders via direct and indirect regulation of a variety of target proteins involved in inflammatory signaling pathways. However, due to limitations of the in vitro and in vivo studies and also the lack of long-term human clinical trials studies, further high-quality investigations are required to firmly establish the clinical efficacy of the polyphenols for the prevention and management of metabolic disorders.
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Affiliation(s)
- Fahimeh Zamani-Garmsiri
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Solaleh Emamgholipour
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Soheil Rahmani Fard
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Antimicrobial Resistance Research Center, Institute of immunology and infectious Disease, Iran University of Medical Sciences, Tehran, Iran
| | - Ghasem Ghasempour
- Department of Clinical Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Roya Jahangard Ahvazi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Meshkani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Moderate Beer Intake Downregulates Inflammasome Pathway Gene Expression in Human Macrophages. BIOLOGY 2021; 10:biology10111159. [PMID: 34827151 PMCID: PMC8614923 DOI: 10.3390/biology10111159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 10/29/2021] [Accepted: 11/06/2021] [Indexed: 12/28/2022]
Abstract
Simple Summary Moderate consumption of fermented beverages is associated with prevention against diseases involving inflammation and immunity. Conversely, for high drinking levels, an increase of inflammatory mediators and the susceptibility to infections occur, which tend to offset the benefits in terms of health. Unfortunately, this area remains poorly understood. Inflammation is now recognized as an overwhelming burden for public health. Thus, subcellular molecular complexes such as the “inflammasomes” have been identified as key players in cellular stress and tissue damage, and as regulators of immune and inflammatory responses. Here, we investigated the impact of moderate intake of alcohol-free and traditional beer in humans on the inflammasome pathway of activated pro-inflammatory human macrophages. The results of this study showed that macrophages submitted to a pro-inflammatory stimulus to activate the inflammosome had a mitigated inflammatory response in the presence of blood serum obtained from healthy volunteers after consuming alcohol-free or traditional beer for four weeks (women one can and men two cans per day) compared to the response found in the presence of blood serum obtained before beer intake. This was shown by a decrease in end components of the inflammasome cascade (IL-1β and TNF) at gene expression and protein level as found with alcohol-free and traditional beer, respectively. Abstract Inflammasomes are key components of the innate immunity system that trigger the inflammatory response. Inappropriate activity of the inflammasome system has been linked to onset and perpetuation of inflammation in atherosclerotic plaques and cardiovascular disease. Low-to-moderate beer consumption is inversely associated with cardiovascular event presentation, while high levels of alcohol intake are associated with increased cardiovascular risk. Although fermented beverages have been suggested to exert their beneficial effects through their anti-oxidant and anti-inflammatory properties, little is known regarding the capacity of beer to modulate innate immunity cell responses. To this aim, primed or activated THP-1 macrophages were conditioned with human serum obtained from a prospective two-arms longitudinal crossover study to investigate the effect of a moderate and regular daily intake of beer, either alcohol-free or traditional, in the regulation of TLR-mediated inflammatory responses in healthy but overweight individuals. Conditioned macrophages with serum obtained after four-week intervention with alcohol-free beer significantly reduced the transcription of pro-inflammatory interleukins such as IL-1β and TNF. The serum of traditional beer consumers did not exhibit the same capacity as the serum of alcohol-free beer consumers to reduce gene expression of pro-inflammatory interleukins; however, serum from traditional beer consumers showed a regulatory effect at the protein level by significantly decreasing the intracellular protein levels of pro-IL-1β in primed macrophages and preventing cleaved-IL-1β protein release.
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Abdelhameed RFA, Ibrahim AK, Elfaky MA, Habib ES, Mahamed MI, Mehanna ET, Darwish KM, Khodeer DM, Ahmed SA, Elhady SS. Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-κB Pathway/miR-146a Expression Modulation. Antioxidants (Basel) 2021; 10:antiox10111713. [PMID: 34829584 PMCID: PMC8615122 DOI: 10.3390/antiox10111713] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 10/21/2021] [Accepted: 10/21/2021] [Indexed: 12/11/2022] Open
Abstract
Cynanchum acutum L. is a climbing vine that belongs to the family Apocynaceae. Using different chromatographic techniques, seven compounds were isolated from the methanolic extract of the plant. The isolated compounds include six flavonoid compounds identified as rutin (1), quercetin-3-O-neohesperidoside (2), quercetin-3-O-β-galactoside (3), isoquercitrin (4), quercetin (5), and kaempferol 3-O-β-glucoside (6), in addition to a coumarin, scopoletin (7). The structures of the compounds were elucidated based on 1D NMR spectroscopy and high-resolution mass spectrometry (HR-MS), and by comparison with data reported in the literature. The first five compounds were selected for in vivo investigation of their anti-inflammatory and antioxidant properties in a rat model of type 2 diabetes. All tested compounds significantly reduced oxidative stress and increased erythrocyte lysate levels of antioxidant enzymes, along with the amelioration of the serum levels of inflammatory markers. Upregulation of miR-146a expression and downregulation of nuclear factor kappa B (NF-κB) expression were detected in the liver and adipose tissue of rats treated with the isolated flavonoids. Results from the biological investigation and those from the validated molecular modeling approach on two biological targets of the NF-κB pathway managed to highlight the superior anti-inflammatory activity of quercetin-3-O-galactoside (3) and quercetin (5), as compared to other bioactive metabolites.
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Affiliation(s)
- Reda F. A. Abdelhameed
- Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; (R.F.A.A.); (E.S.H.); (M.I.M.); (S.A.A.)
- Department of Pharmacognosy, Faculty of Pharmacy, Galala University, New Galala 43713, Egypt
| | - Amany K. Ibrahim
- Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; (R.F.A.A.); (E.S.H.); (M.I.M.); (S.A.A.)
- Correspondence: (A.K.I.); (E.T.M.)
| | - Mahmoud A. Elfaky
- Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.A.E.); (S.S.E.)
- Centre for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Eman S. Habib
- Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; (R.F.A.A.); (E.S.H.); (M.I.M.); (S.A.A.)
| | - Mayada I. Mahamed
- Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; (R.F.A.A.); (E.S.H.); (M.I.M.); (S.A.A.)
| | - Eman T. Mehanna
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
- Correspondence: (A.K.I.); (E.T.M.)
| | - Khaled M. Darwish
- Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt;
| | - Dina M. Khodeer
- Department of Pharmacology, and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt;
| | - Safwat A. Ahmed
- Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; (R.F.A.A.); (E.S.H.); (M.I.M.); (S.A.A.)
| | - Sameh S. Elhady
- Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.A.E.); (S.S.E.)
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Khazdair MR, Saadat S, Aslani MR, Shakeri F, Boskabady MH. Experimental and clinical studies on the effects of Portulaca oleracea L. and its constituents on respiratory, allergic, and immunologic disorders, a review. Phytother Res 2021; 35:6813-6842. [PMID: 34462981 DOI: 10.1002/ptr.7268] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/04/2021] [Accepted: 08/05/2021] [Indexed: 12/13/2022]
Abstract
Various pharmacological effects for Portulaca oleracea were shown in previous studies. Therefore, the effects of P. oleracea and its derivatives on respiratory, allergic, and immunologic diseases according to update experimental and clinical studies are provided in this review article. PubMed/Medline, Scopus, and Google Scholar were searched using appropriate keywords until the end of December 2020. The effects of P. oleracea and its constituents such as quercetin and kaempferol on an animal model of asthma were shown. Portulaca oleracea and its constituents also showed therapeutic effects on chronic obstructive pulmonary disease and chronic bronchitis in both experimental and clinical studies. The possible bronchodilatory effect of P. oleracea and its ingredients was also reported. Portulaca oleracea and its constituents showed the preventive effect on lung cancer and a clinical study showed the effect of P. oleracea on patients with lung adenocarcinoma. In addition, a various constituents of P. oleracea including, quercetin and kaempferol showed therapeutic effects on lung infections. This review indicates the therapeutic effect of P. oleracea and its constituents on various lung and allergic disorders but more clinical studies are required to establish the clinical efficacy of this plant and its constituents on lung and allergic disorders.
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Affiliation(s)
- Mohammad Reza Khazdair
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Saeideh Saadat
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohammad Reza Aslani
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Lung Inflammatory Diseases Research Center, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farzaneh Shakeri
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran.,Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, 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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Rao A, Douglas SC, Hall JM. Endocrine Disrupting Chemicals, Hormone Receptors, and Acne Vulgaris: A Connecting Hypothesis. Cells 2021; 10:cells10061439. [PMID: 34207527 PMCID: PMC8228950 DOI: 10.3390/cells10061439] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/31/2021] [Accepted: 06/01/2021] [Indexed: 12/11/2022] Open
Abstract
The relationship between endocrine disrupting chemicals (EDCs) and the pathogenesis of acne vulgaris has yet to be explored in the literature. Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit. The pathogenesis of acne involves several hormonal pathways, including androgens, insulin-like growth factor 1(IGF-1), estrogens, and corticosteroids. EDCs influence these pathways primarily through two mechanisms: altering endogenous hormone levels and interfering with hormone receptor function. This review article describes the mechanistic links between EDCs and the development of acne lesions. Highlighted is the contributory role of androgen receptor ligands, such as bisphenol A (BPA) and mono-2-ethylhexyl Phthalate (MEHP), via upregulation of lipogenic genes and resultant exacerbation of cholesterol synthesis. Additionally discussed is the protective role of phytoestrogen EDCs in counteracting androgen-induced sebocyte maturation through attenuation of PPARy transcriptional activity (i.e., resveratrol) and restoration of estrogen-regulated TGF-B expression in skin cells (i.e., genistein). Examination of the relationship between EDCs and acne vulgaris may inform adjunctive avenues of treatment such as limiting environmental exposures, and increasing low-glycemic, plant-rich foods in the diet. With a better understanding of the cumulative role that EDCs play in acne, clinicians can be better equipped to treat and ultimately improve the lives of their patients.
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Čoma M, Lachová V, Mitrengová P, Gál P. Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review. Curr Issues Mol Biol 2021; 43:127-141. [PMID: 34067763 PMCID: PMC8929053 DOI: 10.3390/cimb43010011] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/12/2021] [Accepted: 05/16/2021] [Indexed: 02/07/2023] Open
Abstract
Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM.
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Affiliation(s)
- Matúš Čoma
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 11 Košice, Slovakia;
- Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., 040 11 Košice, Slovakia
| | - Veronika Lachová
- Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia; (V.L.); (P.M.)
| | - Petra Mitrengová
- Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia; (V.L.); (P.M.)
| | - Peter Gál
- Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., 040 11 Košice, Slovakia
- Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia; (V.L.); (P.M.)
- Laboratory of Cell Interactions, Faculty of Medicine, Pavol Jozef Šafárik University, 040 11 Košice, Slovakia
- Prague Burn Center, Third Faculty of Medicine, Charles University, 100 34 Prague, Czech Republic
- Correspondence: ; Fax: +421-55-789-1613
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Behl T, Mehta K, Sehgal A, Singh S, Sharma N, Ahmadi A, Arora S, Bungau S. Exploring the role of polyphenols in rheumatoid arthritis. Crit Rev Food Sci Nutr 2021; 62:5372-5393. [PMID: 33998910 DOI: 10.1080/10408398.2021.1924613] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disorder which is mainly characterized by inflammation in joints, bone erosions and cartilaginous destruction that leads to joint dysfunction, deformation, and/or permanent functional impairment. The prevalence of RA is increasing, incurring a considerable burden on healthcare systems globally. The exact etiology of RA is unknown, with various pathways implicated in its pathophysiology. Non-steroidal anti-inflammatory drugs (NSAIDs) including celecoxib, diclofenac and ibuprofen, disease-modifying anti-rheumatic drugs (DMARD) including azathioprine, methotrexate and cyclosporine, biological agents including anakinra, infliximab, and rituximab and immunosuppressants are used for symptomatic relief in patients with RA, but these medications have severe adverse effects such as gastric ulcers, hypertension, hepatotoxicity and renal abnormalities which restrict their use in the treatment of RA; new RA treatments with minimal side-effects are urgently required. There is accumulating evidence that dietary polyphenols may show therapeutic efficacy in RA through their antioxidant, anti-inflammatory, apoptotic, and immunosuppressant activities and modulation of the tumor necrosis factor-α (TNF-α), interleukin (IL)-6, mitogen-activated protein kinase (MAPK), IL-1β, c-Jun N-terminal kinase (JNK), and nuclear factor κ light-chain-enhancer of activated B cell (NF-κB) pathways. While resveratrol, genistein, carnosol, epigallocatechin gallate, curcumin, kaempferol, and hydroxytyrosol have also been studied for the treatment of RA, the majority of data are derived from animal models. Here, we review the various pathways involved in the development of RA and the preclinical and clinical data supporting polyphenols as potential therapeutic agents in RA patients. Our review highlights that high-quality clinical studies are required to decisively establish the anti-rheumatic efficacy of polyphenolic compounds.
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Affiliation(s)
- Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Keshav Mehta
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Aayush Sehgal
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Sukhbir Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Neelam Sharma
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Amirhossein Ahmadi
- Faculty of Pharmacy, Mazandaran University of Medial Sciences, Sari, Iran
| | - Sandeep Arora
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
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Subedi L, Gaire BP, Kim SY, Parveen A. Nitric Oxide as a Target for Phytochemicals in Anti-Neuroinflammatory Prevention Therapy. Int J Mol Sci 2021; 22:ijms22094771. [PMID: 33946349 PMCID: PMC8124914 DOI: 10.3390/ijms22094771] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/27/2021] [Accepted: 04/27/2021] [Indexed: 12/23/2022] Open
Abstract
Nitric oxide (NO) is a neurotransmitter that mediates the activation and inhibition of inflammatory cascades. Even though physiological NO is required for defense against various pathogens, excessive NO can trigger inflammatory signaling and cell death through reactive nitrogen species-induced oxidative stress. Excessive NO production by activated microglial cells is specifically associated with neuroinflammatory and neurodegenerative conditions, such as Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, ischemia, hypoxia, multiple sclerosis, and other afflictions of the central nervous system (CNS). Therefore, controlling excessive NO production is a desirable therapeutic strategy for managing various neuroinflammatory disorders. Recently, phytochemicals have attracted considerable attention because of their potential to counteract excessive NO production in CNS disorders. Moreover, phytochemicals and nutraceuticals are typically safe and effective. In this review, we discuss the mechanisms of NO production and its involvement in various neurological disorders, and we revisit a number of recently identified phytochemicals which may act as NO inhibitors. This review may help identify novel potent anti-inflammatory agents that can downregulate NO, specifically during neuroinflammation and neurodegeneration.
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Bagherniya M, Khedmatgozar H, Fakheran O, Xu S, Johnston TP, Sahebkar A. Medicinal plants and bioactive natural products as inhibitors of NLRP3 inflammasome. Phytother Res 2021; 35:4804-4833. [PMID: 33856730 DOI: 10.1002/ptr.7118] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 02/02/2021] [Accepted: 03/26/2021] [Indexed: 12/11/2022]
Abstract
The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that induces caspase-1 activation and the downstream substrates involved with the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and tumor necrosis factor-α (TNF- α). The NLRP3 inflammasome is activated by a wide range of danger signals that derive from metabolic dysregulation. Activation of this complex often involves the adaptor ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. It has been shown that nutraceuticals and medicinal plants have antiinflammatory properties and could be used as complementary therapy in the treatment of several chronic diseases that are related to inflammation, for example, cardiovascular diseases and diabetes mellitus. Herb-based medicine has demonstrated protective effects against NLRP3 inflammasome activation. Therefore, this review focuses on the effects of nutraceuticals and bioactive compounds derived from medicinal plants on NLRP3 inflammasome activation and the possible mechanisms of action of these natural products. Thus, herb-based, natural products/compounds can be considered novel, practical, and accessible agents in chronic inflammatory diseases by inhibiting NLRP3 inflammasome activation.
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Affiliation(s)
- Mohammad Bagherniya
- Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.,Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamed Khedmatgozar
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Omid Fakheran
- Dental Research Center, Department of Periodontics, Dental Research Institute, Isfahan University of Medical sciences, Isfahan, Iran
| | - Suowen Xu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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40
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Saleh HA, Yousef MH, Abdelnaser A. The Anti-Inflammatory Properties of Phytochemicals and Their Effects on Epigenetic Mechanisms Involved in TLR4/NF-κB-Mediated Inflammation. Front Immunol 2021; 12:606069. [PMID: 33868227 PMCID: PMC8044831 DOI: 10.3389/fimmu.2021.606069] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 03/08/2021] [Indexed: 12/11/2022] Open
Abstract
Innate immune response induces positive inflammatory transducers and regulators in order to attack pathogens, while simultaneously negative signaling regulators are transcribed to maintain innate immune homeostasis and to avoid persistent inflammatory immune responses. The gene expression of many of these regulators is controlled by different epigenetic modifications. The remarkable impact of epigenetic changes in inducing or suppressing inflammatory signaling is being increasingly recognized. Several studies have highlighted the interplay of histone modification, DNA methylation, and post-transcriptional miRNA-mediated modifications in inflammatory diseases, and inflammation-mediated tumorigenesis. Targeting these epigenetic alterations affords the opportunity of attenuating different inflammatory dysregulations. In this regard, many studies have identified the significant anti-inflammatory properties of distinct naturally-derived phytochemicals, and revealed their regulatory capacity. In the current review, we demonstrate the signaling cascade during the immune response and the epigenetic modifications that take place during inflammation. Moreover, we also provide an updated overview of phytochemicals that target these mechanisms in macrophages and other experimental models, and go on to illustrate the effects of these phytochemicals in regulating epigenetic mechanisms and attenuating aberrant inflammation.
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Affiliation(s)
- Haidy A. Saleh
- Department of Chemistry, School of Sciences and Engineering, The American University in Cairo, Cairo, Egypt
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
| | - Mohamed H. Yousef
- Biotechnology Graduate Program, School of Sciences and Engineering, The American University in Cairo, Cairo, Egypt
| | - Anwar Abdelnaser
- Institute of Global Public Health, School of Sciences and Engineering, The American University in Cairo, Cairo, Egypt
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Negrescu AM, Necula MG, Gebaur A, Golgovici F, Nica C, Curti F, Iovu H, Costache M, Cimpean A. In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy. Int J Mol Sci 2021; 22:ijms22020909. [PMID: 33477539 PMCID: PMC7831122 DOI: 10.3390/ijms22020909] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/14/2021] [Accepted: 01/14/2021] [Indexed: 12/12/2022] Open
Abstract
Due to its excellent bone-like mechanical properties and non-toxicity, magnesium (Mg) and its alloys have attracted great interest as biomaterials for orthopaedic applications. However, their fast degradation rate in physiological environments leads to an acute inflammatory response, restricting their use as biodegradable metallic implants. Endowing Mg-based biomaterials with immunomodulatory properties can help trigger a desired immune response capable of supporting a favorable healing process. In this study, electrospun poly(ε-caprolactone) (PCL) fibers loaded with coumarin (CM) and/or zinc oxide nanoparticles (ZnO) were used to coat the commercial AZ31 Mg alloy as single and combined formulas, and their effects on the macrophage inflammatory response and osteoclastogenic process were investigated by indirect contact studies. Likewise, the capacity of the analyzed samples to generate reactive oxygen species (ROS) has been investigated. The data obtained by attenuated total reflection Fourier-transform infrared (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS) analyses indicate that AZ31 alloy was perfectly coated with the PCL fibers loaded with CM and ZnO, which had an important influence on tuning the release of the active ingredient. Furthermore, in terms of degradation in phosphate-buffered saline (PBS) solution, the PCL-ZnO- and secondary PCL-CM-ZnO-coated samples exhibited the best corrosion behaviour. The in vitro results showed the PCL-CM-ZnO and, to a lower extent, PCL-ZnO coated sample exhibited the best behaviour in terms of inflammatory response and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated differentiation of RAW 264.7 macrophages into osteoclasts. Altogether, the results obtained suggest that the coating of Mg alloys with fibrous PCL containing CM and/or ZnO can constitute a feasible strategy for biomedical applications.
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Affiliation(s)
- Andreea-Mariana Negrescu
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (A.-M.N.); (M.-G.N.); (C.N.); (M.C.)
| | - Madalina-Georgiana Necula
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (A.-M.N.); (M.-G.N.); (C.N.); (M.C.)
| | - Adi Gebaur
- Advance Polymer Materials Group, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu 17, 011061 Bucharest, Romania; (A.G.); (F.C.); (H.I.)
| | - Florentina Golgovici
- Department of General Chemistry, Faculty of Applied Chemistry and Material Science, University Politehnica of Bucharest, Gh. Polizu 1-7, 011061 Bucharest, Romania;
| | - Cristina Nica
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (A.-M.N.); (M.-G.N.); (C.N.); (M.C.)
| | - Filis Curti
- Advance Polymer Materials Group, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu 17, 011061 Bucharest, Romania; (A.G.); (F.C.); (H.I.)
| | - Horia Iovu
- Advance Polymer Materials Group, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu 17, 011061 Bucharest, Romania; (A.G.); (F.C.); (H.I.)
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (A.-M.N.); (M.-G.N.); (C.N.); (M.C.)
| | - Anisoara Cimpean
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (A.-M.N.); (M.-G.N.); (C.N.); (M.C.)
- Correspondence: ; Tel.: +40-21-318-1575 (ext. 106)
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Zamani-Garmsiri F, Hashemnia SMR, Shabani M, Bagherieh M, Emamgholipour S, Meshkani R. Combination of metformin and genistein alleviates non-alcoholic fatty liver disease in high-fat diet-fed mice. J Nutr Biochem 2021; 87:108505. [DOI: 10.1016/j.jnutbio.2020.108505] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 07/16/2020] [Accepted: 08/26/2020] [Indexed: 12/12/2022]
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Siriviriyakul P, Werawatganon D, Phetnoo N, Somanawat K, Chatsuwan T, Klaikeaw N, Chayanupatkul M. Genistein attenuated gastric inflammation and apoptosis in Helicobacter pylori-induced gastropathy in rats. BMC Gastroenterol 2020; 20:410. [PMID: 33297977 PMCID: PMC7724785 DOI: 10.1186/s12876-020-01555-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 11/23/2020] [Indexed: 02/07/2023] Open
Abstract
Background Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, peptic ulcer diseases and cancer. Genistein (4′,5,7-trihydroxyisoflavone), a tyrosine-specific-protein kinase inhibitor, has been shown to exert an anti-inflammatory property. The aim of this study was to examine the treatment effects of genistein and its mechanisms in rats with H. pylori infection.
Methods Eighteen male Sprague-Dawley rats were divided into three groups (6 rats per group): (1) control group (Con); (2) H. pylori infected group (HP): the rats were inoculated with H. pylori (108− 1010 CFU/mL; 1 mL/rat.) for 3 consecutive days; and (3) HP + genistein group (HP + Gen): the rats were inoculated with H. pylori as above. Then, they were gavaged with genistein (16 mg/kg BW) for 14 days. Gastric tissue was used for the determination of nuclear factor (NF)-κB expression by immunohistochemistry (IHC), degree of apoptosis by the terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) reaction, and histopathology. Serum samples were used to measure the levels of tumor necrosis factor-alpha (TNF-α) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). Results Rats in the HP group had significantly higher levels of pro-inflammatory mediators, NF-κB expression and apoptotic cells when compared with the Con group, and these markers significantly decreased in HP + Gen group when compared with the HP group. The histopathology of HP group showed moderate gastric inflammation and many HP colonization. Gastric pathology in HP + Gen group demonstrated the attenuation of inflammatory cell infiltration and H. pylori colonization. Conclusion Genistein exerted its gastroprotective effects through the reduction of pro-inflammatory mediators, nuclear receptor NF-κB expression and gastric mucosal apoptosis in rats with H. pylori-induced gastropathy.
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Affiliation(s)
- Prasong Siriviriyakul
- Department of Physiology, Faculty of Medicine, Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Duangporn Werawatganon
- Department of Physiology, Faculty of Medicine, Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand.
| | - Nisarat Phetnoo
- Department of Physiology, Faculty of Medicine, Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Kanjana Somanawat
- Department of Physiology, Faculty of Medicine, Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Tanittha Chatsuwan
- Department of Microbiology, Faculty of Medicine, Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Naruemon Klaikeaw
- Department of Pathology, Faculty of Medicine, Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Maneerat Chayanupatkul
- Department of Physiology, Faculty of Medicine, Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand
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44
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Zhang L, Chen J, Liao H, Li C, Chen M. Anti-inflammatory effect of lipophilic grape seed proanthocyanidin in RAW 264.7 cells and a zebrafish model. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104217] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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45
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Zhang F, Pan T, Wu X, Gao X, Li Z, Ren X. Non-cytotoxic doses of shikonin inhibit lipopolysaccharide-induced TNF-α expression via activation of the AMP-activated protein kinase signaling pathway. Exp Ther Med 2020; 20:45. [PMID: 32952636 PMCID: PMC7480124 DOI: 10.3892/etm.2020.9173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 06/24/2020] [Indexed: 12/12/2022] Open
Abstract
Shikonin has been reported to exhibit a wide variety of medical functions. However, the strong non-selective cytotoxicity of shikonin can restrict its clinical application. The aim of the present study was to investigate the effects of shikonin at non-cytotoxic doses on the pro-inflammation functions of monocytes and macrophages. The present results suggested that the non-cytotoxic doses of shikonin effectively inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production, NF-κB activation and TNF-α expression in RAW 264.7 mouse macrophages via AMP-activated protein kinase (AMPK) signaling pathway. In addition, the non-cytotoxic doses of shikonin downregulated LPS-induced TNF-α expression via AMPK signaling activation in primary murine bone marrow-derived macrophages, and also in monocytes cultured ex vivo from patients with chronic obstructive pulmonary disease (COPD). The present in vivo results indicated that the low-toxic dose of shikonin suppressed LPS-induced endotoxin shock and TNF-α expression in mice. Collectively, the present results may provide clinical and translational relevance for treating COPD and other TNF-α-related inflammatory disorders.
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Affiliation(s)
- Fang Zhang
- Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Tao Pan
- Shaanxi Key Laboratory of Brain Disorders, Institute of Basic Medical Sciences and Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China
| | - Xiaohui Wu
- Shaanxi Key Laboratory of Brain Disorders, Institute of Basic Medical Sciences and Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China
| | - Xingchun Gao
- Shaanxi Key Laboratory of Brain Disorders, Institute of Basic Medical Sciences and Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China
| | - Zhikui Li
- Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Xinling Ren
- Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.,Carson International Cancer Center, Shenzhen University, Shenzhen, Guangdong 518055, P.R. China.,Shenzhen University Clinical Medical Academy, Shenzhen, Guangdong 518060, P.R. China
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Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages. Molecules 2020; 25:molecules25184089. [PMID: 32906766 PMCID: PMC7570554 DOI: 10.3390/molecules25184089] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 09/03/2020] [Indexed: 12/30/2022] Open
Abstract
We evaluated the anti-inflammatory effects of SNAH in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by performing nitric oxide (NO) assays, cytokine enzyme-linked immunosorbent assays, Western blotting, and real-time reverse transcription-polymerase chain reaction analysis. SNAH inhibited the production of NO (nitric oxide), reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6. Additionally, 100 μM SNAH significantly inhibited total NO and ROS inhibitory activity by 93% (p < 0.001) and 34% (p < 0.05), respectively. Protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) stimulated by LPS were also decreased by SNAH. Moreover, SNAH significantly (p < 0.001) downregulated the TNF-α, IL-6, and iNOS mRNA expression upon LPS stimulation. In addition, 3–100 µM SNAH was not cytotoxic. Docking simulations and enzyme inhibitory assays with COX-2 revealed binding scores of −6.4 kcal/mol (IC50 = 47.8 μM) with SNAH compared to −11.1 kcal/mol (IC50 = 0.45 μM) with celecoxib, a known selective COX-2 inhibitor. Our results demonstrate that SNAH exerts anti-inflammatory effects via suppression of ROS and NO by COX-2 inhibition. Thus, SNAH may be useful as a pharmacological agent for treating inflammation-related diseases.
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Arya VS, Kanthlal SK, Linda G. The role of dietary polyphenols in inflammatory bowel disease: A possible clue on the molecular mechanisms involved in the prevention of immune and inflammatory reactions. J Food Biochem 2020; 44:e13369. [PMID: 32885438 DOI: 10.1111/jfbc.13369] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/08/2020] [Accepted: 06/16/2020] [Indexed: 12/17/2022]
Abstract
Inflammatory bowel disease (IBD) is one of the major complications of the gastrointestinal tract, characterized by chronic inflammation, which disturbs the quality of life of the affected individuals. Genetic predisposition, immune, inflammatory, and enzyme-mediated signaling cascades are the primary mechanisms involved in the pathogenesis of the disease. Currently, the treatment strategy involves the maintenance of remission and induction of inflammation by anti-inflammatory agents and immune suppressants. Polyphenol-containing diets, including fruits and vegetables of regular use, possess anti-inflammatory, and antioxidant potential through the inhibition of major contributing pathways to IBD. This review discusses the role of these dietary polyphenols in downregulating the major signaling cascades in IBD. Our review encourages the development of nutritional strategies to improve the efficiency of current therapies for IBD and reduce the risks of side effects associated with conventional therapy. PRACTICAL APPLICATIONS: At present, almost every third person in society is under stress and having chronic disorders like diabetes, arthritis, allergy, cardiovascular disease, IBD, etc. This insists on the direct/indirect role of changes in the lifestyle for such deterioration in society. This review would emphasize the medicinal value of polyphenols present in fruits and vegetables for chronic inflammatory disorders. This concept portrays the food components which have the potential to promote health, improve general well-being, and reduce the risk of IBD. We propose to add fruits with bioactive polyphenols in the regular diet to help in preventing the immune-mediated intestinal chronic inflammatory syndrome and reduce the risks of colorectal cancer development.
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Affiliation(s)
- V S Arya
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
| | - S K Kanthlal
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
| | - Geevarghese Linda
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
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Jheng HF, Hayashi K, Matsumura Y, Kawada T, Seno S, Matsuda H, Inoue K, Nomura W, Takahashi H, Goto T. Anti-Inflammatory and Antioxidative Properties of Isoflavones Provide Renal Protective Effects Distinct from Those of Dietary Soy Proteins against Diabetic Nephropathy. Mol Nutr Food Res 2020; 64:e2000015. [PMID: 32281228 DOI: 10.1002/mnfr.202000015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/25/2020] [Indexed: 01/29/2023]
Abstract
SCOPE Dietary soy reportedly protects from diabetic nephropathy (DN), but its active components and mechanism of action remain unknown. METHODS AND RESULTS In this study, KKAy mice are fed three types of diet: Dietary soy isoflavones with soy protein (Soy-IP) diet, reduced isoflavones soy protein (RisoP), and oral administration of isoflavones aglycones (IsoAgc). Albuminuria and glycosuria are decreased only in the soy-IP group. The risoP group show reduced expansion of mesangial matrix and renal fibrosis, the IsoAgc group show renal anti-fibrotic and anti-inflammatory effects; however, these renal pathological changes are repressed in the soy-IP group, suggesting the distinct protective roles of soy protein or isoflavones in DN. The isoflavone genistein has a better inhibitory effect on the inflammatory response and cellular interactions in both mouse tubular cells and macrophages when exposed to high glucose and albumin (HGA). Genistein also represses HGA-induced activator protein 1 activation and reactive oxidases stress generation, accompanied by reduced NADPH oxidase (NOX) gene expression. Finally, diabetic mice show a decrease in lipid peroxidation levels in both plasma and urine, along with lower NOXs gene expression. CONCLUSION The data elucidate the detailed mechanism by which isoflavones inhibit renal inflammation and provide a potential practical adjunct therapy to restrict DN progression.
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Affiliation(s)
- Huei-Fen Jheng
- Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
| | - Kanako Hayashi
- Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
| | - Yasuki Matsumura
- Division of Agronomy and Horticultural Science, Laboratory of Quality Analysis and Assessment, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
| | - Teruo Kawada
- Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
| | - Shigeto Seno
- Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita, 565-0871, Japan
| | - Hideo Matsuda
- Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita, 565-0871, Japan
| | - Kazuo Inoue
- Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
| | - Wataru Nomura
- Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
| | - Haruya Takahashi
- Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
| | - Tsuyoshi Goto
- Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, 611-0011, Japan
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Zhang CH, Xiao Q, Sheng JQ, Liu TT, Cao YQ, Xue YN, Shi M, Cao Z, Zhou LF, Luo XQ, Deng KZ, Chen C. Gegen Qinlian Decoction abates nonalcoholic steatohepatitis associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of toll-like receptor 4 signaling pathways. Biomed Pharmacother 2020; 126:110076. [PMID: 32169759 DOI: 10.1016/j.biopha.2020.110076] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/01/2020] [Accepted: 03/03/2020] [Indexed: 02/07/2023] Open
Abstract
Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.
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Affiliation(s)
- Chang-Hua Zhang
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Qin Xiao
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Jun-Qing Sheng
- College of Life Science, Nanchang University, Nanchang, 330031, PR China.
| | - Tong-Tong Liu
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Ying-Qian Cao
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Ya-Nan Xue
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Min Shi
- College of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Zheng Cao
- College of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Li-Fen Zhou
- Large Precise Instruments Shared Services Center of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Xiao-Quan Luo
- Experimental Animal Science and Technology Center of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, PR China
| | - Ke-Zhong Deng
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, PR China
| | - Chen Chen
- School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
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50
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Hu Z, Du R, Xiu L, Bian Z, Ma C, Sato N, Hattori M, Zhang H, Liang Y, Yu S, Wang X. Protective effect of triterpenes of Ganoderma lucidum on lipopolysaccharide-induced inflammatory responses and acute liver injury. Cytokine 2020; 127:154917. [DOI: 10.1016/j.cyto.2019.154917] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 10/16/2019] [Accepted: 10/31/2019] [Indexed: 02/06/2023]
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