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For: Ji G, Zhang Y, Yang Q, Cheng S, Hao J, Zhao X, Jiang Z. Genistein suppresses LPS-induced inflammatory response through inhibiting NF-κB following AMP kinase activation in RAW 264.7 macrophages. PLoS One 2012;7:e53101. [PMID: 23300870 PMCID: PMC3534028 DOI: 10.1371/journal.pone.0053101] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2012] [Accepted: 11/23/2012] [Indexed: 01/11/2023] Open

For:	Ji G, Zhang Y, Yang Q, Cheng S, Hao J, Zhao X, Jiang Z. Genistein suppresses LPS-induced inflammatory response through inhibiting NF-κB following AMP kinase activation in RAW 264.7 macrophages. PLoS One 2012;7:e53101. [PMID: 23300870 PMCID: PMC3534028 DOI: 10.1371/journal.pone.0053101] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2012] [Accepted: 11/23/2012] [Indexed: 01/11/2023] Open

Number

Cited by Other Article(s)

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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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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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

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: 3] [Impact Index Per Article: 3.0] [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]

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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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

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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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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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: 10] [Impact Index Per Article: 5.0] [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

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]

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: 33] [Impact Index Per Article: 16.5] [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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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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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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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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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

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]

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]

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: 9] [Impact Index Per Article: 3.0] [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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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]

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]

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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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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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]

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

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: 5] [Impact Index Per Article: 1.7] [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]

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]

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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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: 110] [Impact Index Per Article: 36.7] [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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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

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]

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

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]

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

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

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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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

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: 29] [Impact Index Per Article: 7.3] [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]

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

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: 38] [Impact Index Per Article: 9.5] [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]

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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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

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

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

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]

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: 18] [Impact Index Per Article: 3.6] [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]

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: 29] [Impact Index Per Article: 5.8] [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

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]