Phytotherapy Research最新文献

{"title":"The Effects of Curcuminoids Supplementation on Serum Adipokines: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials.","authors":"Leila Sadat Bahrami, Iman Rahnama, Mahla Chambari, Abdolreza Norouzy, Sercan Karav, Seyyed Mostafa Arabi, Amirhossein Sahebkar","doi":"10.1002/ptr.8471","DOIUrl":"10.1002/ptr.8471","url":null,"abstract":"<p><p>This umbrella review of randomized clinical trials aims to provide a unique and detailed understanding of curcumin's effects on adipokines, adding a novel perspective to the existing body of research. We carried out a thorough search of international databases up to April 2024, including MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science. A random-effects model was utilized to evaluate the impact of curcuminoid on adipokines. The umbrella review incorporated meta-analyses that examined the effects of curcuminoid supplementation on adipokines, presenting associated effect sizes (ES) and confidence intervals (CI). We applied the GRADE and AMSTAR (A Tool for Assessing the Risk of Bias in Systematic Reviews system) to assess the certainty of the evidence and the quality of the systematic reviews. Our analysis of one meta-analysis, including 14 RCTs plus 1 RCT not included in meta-analyses, revealed significant and impactful findings. We found a substantial increase in serum adiponectin levels with curcuminoid supplementation, indicating a positive effect (SMD: 0.9; 95% CI, 0.4 to 1.3, p < 0.001; I² = 92.2%). However, we did not observe a significant impact on serum leptin. The GRADE assessment supports the effect of curcuminoids on adiponectin with moderate evidence, while the impact on leptin was supported by low evidence. Curcuminoid supplementation significantly increases serum adiponectin levels with moderate-quality evidence and has no significant impact on serum leptin. This provides evidence as to the safety and effectiveness of curcuminoids in enhancing adiponectin without adverse effects, reassuring the audience about their potential in adipokine research.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2250-2261"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin Alleviates Chronic Urticaria by Negatively Regulating IgE-Mediated Mast Cell Activation Through CD300f.","authors":"Chenrui Zhao, Na Wang, Chao Wang, Yujuan Yuan, Hongfen Du, Yuanyuan Ding, Hongli An","doi":"10.1002/ptr.8516","DOIUrl":"https://doi.org/10.1002/ptr.8516","url":null,"abstract":"<p><p>Chronic urticaria (CU) is a skin allergy caused by the excessive activation of mast cells. The main etiology of CU is a type I allergic reaction mediated by immunoglobulin (Ig)E. This study mainly explored the therapeutic effect of quercetin in ovalbumin (OVA)-induced CU mice and investigated its target and mechanism in vitro. The CU symptom-alleviating effect of quercetin was assessed by the CU model. The possible molecular mechanisms of quercetin were initially inferred through bioinformatic and multi-database analyses. Quercetin targets were examined using mast cell activation experiments with CD300f knockdown. RT-PCR and western blot experiments were performed to verify the molecular mechanisms of quercetin. Quercetin relieved wheal and scratching times on the back skin of mice as well as reduced eosinophilic infiltration and mast cell degranulation in the skin lesions and inhibited the release of IgE, histamine, TNF-α, MCP-1, and IL-13 in the serum of mice. In addition, it exhibited potential therapeutic effects on CU through the PI3K-Akt signaling pathway. Meanwhile, quercetin upregulated CD300f in the skin of CU, activated CD300f, and induced downstream SHP-1 phosphorylation. Of note, quercetin bound to CD300f to prevent IgE-mediated LAD2 cell β-hexosaminidase release, histamine release, Ca²⁺ influx, mast cell degranulation, and F-actin cytoskeleton remodeling by inhibiting the AKT/IKK/NF-κB inflammatory pathway. The study results suggest that quercetin alleviates CU by activating the CD300f/SHP-1 signaling pathway. In addition, it activates CD300f to inhibit IgE-mediated mast cell degranulation and F-actin cytoskeleton remodeling by inhibiting the AKT/IKK/NF-κB inflammatory pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Review and Network Meta-Analysis of the Effects of Plant Extracts on Cognitive Function and Quality of Life in Stroke Patients.","authors":"Ji Li, Jingfen Jin, Yifeng Cheng, Yuping Zhang, Xuyang Wang, Yali Chen, Chunfen Wang, Wenxue Tang, Ning Zhang","doi":"10.1002/ptr.8472","DOIUrl":"10.1002/ptr.8472","url":null,"abstract":"&lt;p&gt;&lt;p&gt;In recent years, numerous researchers have focused on plant extracts derived from traditional medicines to treat stroke, as these extracts may improve patients' cognitive function and quality of life. This study aims to evaluate the effects of nine distinct plant extracts ( Ginkgo biloba extract, Ginsenosides, Berberine, St. John's Wort extract, Resveratrol, Gastrodin, Crocus sativus L., Moringa oleifera Seed extract, and Panax Notoginseng Saponins) on cognitive function and quality of life in stroke patients. This study seeks to conduct a network meta-analysis to assess the impact of these plant extracts on cognitive function and quality of life in stroke patients. Researchers systematically searched the Embase, PubMed, Cochrane Library, and Web of Science databases from database inception through October 2024 searched for randomized controlled trials (RCTs) exclusively(no language restrictions). The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The primary outcome measures included the following assessment scales: National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Activities of Daily Living Scale (ADLs), Barthel Index (BI), Montreal Cognitive Assessment (MOCA), and Mini-Mental State Examination (MMSE). Treatment effects were ranked based on probability values derived from the surface under the cumulative ranking curve (SUCRA). Moreover, cluster analysis was applied to evaluate the effects of plant extracts on six scales that reflect cognitive function and quality of life in patients. After screening, 48 eligible randomized controlled trials were included, covering 6599 stroke patients and evaluating nine different plant extract treatments. Specifically, results from 33 trials were included in the NIHSS score, 10 in the mRS score, 11 in the ADL score, 11 in the BI score, nine in the MMSE score, and eight in the MOCA score. Findings indicate that St. John's Wort extract (SUCRA 71.2%) was the most effective in reducing NIHSS scores, Berberine (SUCRA 84.1%) was most effective in reducing mRS scores, and St. John's Wort extract (SUCRA 99.1%) showed the highest efficacy in enhancing ADL scores. Ginsenosides were the most effective in improving Barthel Index (SUCRA 74.7%), MMSE (SUCRA 93%), and MOCA (SUCRA 79.7%) scores. The NMA indicates that, compared to placebo, St. John's Wort extract, Berberine, and Ginsenosides can enhance cognitive function and improve quality of life in stroke patients. This study provides valuable insights into using plant extracts for stroke treatment, potentially guiding clinical practice, but there are some unavoidable limitations to our study, including heterogeneity, differences in extraction methods of plant extracts, and lack of consideration of social support systems and dose effects. Future longer follow-up, larger samples, and more methodologically rigorous ","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2110-2130"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing NK Cell Antitumor Activity With Natural Compounds: Research Advances and Molecular Mechanisms.","authors":"Yu Wu, Mingxiao Yin, Wenjiao Xia, Baokai Dou, Xiaoyu Liu, Ru Sun","doi":"10.1002/ptr.8456","DOIUrl":"10.1002/ptr.8456","url":null,"abstract":"<p><p>In recent years, immunotherapy has become a novel antitumor strategy in addition to traditional surgery, radiotherapy, and chemotherapy and has exhibited promising results in clinical applications. Despite significant breakthroughs in immunotherapy, such as immune checkpoint blockade and CAR-T cell therapy, it remains necessary to develop more efficacious, safer, and cheaper immunotherapeutic drugs due to factors including small reaction populations, acquired resistance, adverse side effects, and high costs. Natural killer (NK) cells are preeminent cytotoxic lymphocytes of the innate immune system that act as the first line of defense against tumors and synergistically enhance the adaptive immune response of T lymphocytes. Therefore, boosting the antitumor function of NK cells is an important direction in the development of immunotherapy. For decades, various immunotherapies such as adoptive cell therapy, antibody drugs, cytokines supplement, and chemical immunomodulators have been developing rapidly to improve the function of NK cells. Compared to biological immunotherapy, immunomodulators derived from natural products have outstanding advantages of low immunogenicity, multi-targeting, and cost-effectiveness. Currently, increasing attention is being focused on discovering NK cell-stimulating agents from natural products, such as polysaccharides, alkaloids, terpenoids, saponins, phenolics, and quinones. This review aims to categorize and summarize the comprehensive research progress on these natural products, discuss their potential molecular mechanisms in regulating NK cells, and explore their clinical applications as standalone treatments or in combination with conventional chemotherapy regimens.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1905-1929"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forsythiaside A Alleviates Ulcerative Colitis and Inhibits Neutrophil Extracellular Traps Formation in the Mice.","authors":"Zhuyun Wang, Weiyan Yan, Xiaojing Lin, Guangcheng Qin, Kemeng Li, Lincheng Jiang, Xingwang Li, Xiaoqiu Xiao, Ting Luo, Yi Hou","doi":"10.1002/ptr.8440","DOIUrl":"10.1002/ptr.8440","url":null,"abstract":"<p><p>Forsythiaside A (FA), the primary compound found in Forsythia suspensa (Thunb.) Vahl, has demonstrated various pharmacological effects, but its impact on ulcerative colitis (UC) is underexplored. Our study examined the distribution of FA in different parts of the gastrointestinal tracts and its therapeutic effects on UC, along with the underlying mechanisms. The levels of FA in gastrointestinal tracts and plasma were analyzed by high-performance liquid chromatography; mice were given dextran sulfate sodium in drinking water to develop the UC model. The UC mice were treated with FA (15, 30, and 60 mg/kg) for 10 days. FA showed relatively high concentration retention in the colon within 4 h. The treatment of FA improved body weight loss, diarrhea, rectal bleeding, colon shortening, and histological damage in UC mice. It also increased the expression of the tight junction protein and decreased inflammatory cytokines in the colon. The microbiota analysis using 16S rRNA sequencing revealed that FA could alleviate gut dysbiosis in colitis mice. Of importance, we found FA resulted in a reduction of neutrophil extracellular traps formation (NETosis) and inhibited peptidyl arginine deiminase 4 (PAD4) in colon tissue of colitis mice. In cultured neutrophils, FA pretreatment led to a suppression of PAD4 expression and NETosis induced by PMA. These findings suggest that FA can be retained in the colon and may alleviate UC by inhibiting NETs formation, indicating its potential for preventing or treating UC.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2165-2179"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Therapeutic Potential of Autophagy Modulation by Natural Products in Tackling Non-Alcoholic Fatty Liver Disease.","authors":"Farshad Niazpour, Reza Meshkani","doi":"10.1002/ptr.8463","DOIUrl":"10.1002/ptr.8463","url":null,"abstract":"<p><p>It is widely recognized that there is currently no established treatment for individuals with Non-alcoholic Fatty Liver Disease (NAFLD). In recent years, there has been a surge of interest in natural products derived from plants, driven by their minimal toxicity and notable efficacy. It was reported that natural products could ameliorate NAFLD via various mechanisms. On the other hand, autophagy has been suggested to be involved in the pathogenesis of NAFLD. The aim of this review is to understand whether the beneficial effects of natural products on NAFLD are mediated by affecting autophagy pathways. In this review, we have compiled data elucidating how these natural products exhibit the potential to improve NAFLD by modulating core autophagic pathways. Specifically, we demonstrate that these natural products, including resveratrol, berberine, curcumin, quercetin, punicalagin, epigallocatechin-3-gallate, apigenin, and many others, regulate autophagy through key signaling pathways, such as AMPK/SIRT1/mTOR. Interestingly, these compounds might activate or inhibit autophagy, depending on the context. We explore how autophagy activation promotes the degradation of lipid droplets and alleviates liver injury, while autophagy inhibition contributes to reducing inflammation, apoptosis, and pyroptosis, and also resulting in improved NAFLD outcomes. Taken together, these findings suggest that targeting autophagy with natural products presents a promising mechanism for preventing and treating NAFLD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2357-2373"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytosomes as a New Frontier and Emerging Nanotechnology Platform for Phytopharmaceuticals: Therapeutic and Clinical Applications.","authors":"Suresh Koppula, Bajee Shaik, Srinivas Maddi","doi":"10.1002/ptr.8465","DOIUrl":"10.1002/ptr.8465","url":null,"abstract":"<p><p>A complete investigation into phytosome-based formulations and innovative nanotechnology is presented in this review. This investigation aims to improve the bioavailability and therapeutic effectiveness of herbal components. Phytosomes can significantly increase solubility, absorption, and stability compared to standard herbal formulations by encapsulating active phytoconstituents into phospholipid complexes. This unique ability of phytosomes to overcome the limits of traditional herbal formulations is a potential game changer in medicine. This study highlights the different uses of phytosomes across various health disorders, such as neurodegenerative illnesses, inflammatory conditions, diabetes, cardiovascular diseases, and wound healing. The review also discusses the potential of phytosomes in treating infectious diseases by improving the delivery of bioactive compounds that have improved anticancer efficacy and antibacterial properties. Despite the emergence of numerous groundbreaking discoveries, substantial barriers remain that hinder their widespread application. Challenges that must be addressed include stability, large-scale manufacture, regulatory hurdles, and limited clinical translation. This review also examines the limitations present in clinical practice, mainly focusing on the variability in bioavailability. The review highlights the crucial need for future research in phytosomes, engaging the researchers and emphasizing the continuous evolution of this promising area of medicine.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2217-2249"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review of Biologically Active Natural Products on Human Papillomavirus (HPV) at a Glance.","authors":"Mahsa Sadat Hosseini, Amirreza Sadeqi, Zinat Heidari, Motahareh Boozari","doi":"10.1002/ptr.8444","DOIUrl":"10.1002/ptr.8444","url":null,"abstract":"<p><p>Human papillomavirus (HPV) is widespread known as the sexually transmitted infection, which is responsible, for genital warts and certain types of cancer. Low-risks HPV types are responsible for genital warts. Genital warts can be treated through various medical and surgical methods. High-risks HPV types may cause dangerous cancers such as cervical cancer. The clinical approach in treatment of HPV-related cancers were different depending on the diseases stage ranging from surveillance and minor procedures for dysplasia to chemotherapy for more advanced cases. It is crucial to vaccinate adolescents against HPV to prevent infections from high risk strains. Researchers have explored natural products as potential solutions against viral infections with eight biologically active compounds. Including EGCG, curcumin, podophyllotoxin, resveratrol, pterostilbene, tanshinone IIA, indole-3-carbinol, and carrageenan. They are showing promising therapeutic effects in treating different stages of HPV-related diseases. Clinical trials have demonstrated the effectiveness of EGCG and podophyllotoxin in treating warts while other compounds, like curcumin, resveratrol, pterostilbene, indole-3-carbinol, and tanshinone IIA offer benefits in combating cervical cancer. In addition, carrageenan shows promising effects in HPV transmission prevention. It appears that compounds from nature may have an impact, on different phases of the HPV infection like genital warts treatment, disease transmission prevention, and healing-related cancers. These findings highlight the potential of natural products as valuable sources to combat HPV infection and related cancers. Further more extensive studies are necessary to discover the effective mechanism of these natural compounds as anti-HPV agents.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2262-2290"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Saffron Supplementation on Glycolipid Metabolism and Blood Pressure in Patients With Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Xiaolei Zhang, Jinxin Miao, Yagang Song, Mingsan Miao","doi":"10.1002/ptr.8421","DOIUrl":"10.1002/ptr.8421","url":null,"abstract":"<p><p>Saffron is a traditional herbal medicine used to treat conditions associated with metabolic syndrome (MetS). However, the conclusions of relevant clinical studies have been inconsistent. This study aimed to assess the impact of saffron supplementation on the metabolism of glycolipids and blood pressure in individuals with MetS and related disorders. Web of Science, PubMed, Cochrane Library, Scopus, and Embase were comprehensively searched for studies investigating saffron supplementation for MetS and related disorders up to February 2024. Stata 17.0 was used to conduct the Meta-analysis. Twenty-five randomized controlled trials (RCTs) were included in this study, involving 1486 participants with MetS and related conditions. Compared to placebo, saffron supplementation triggered significant reductions in fasting blood glucose (FBG) (WMD: -6.67 mg/dL; 95% CI: -10.55, -2.78; p = 0.001; I ² = 50.0%), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.25%; 95% CI: -0.35, -0.14; p < 0.001; I ² = 0.0%), total cholesterol (TC) (WMD: -4.77 mg/dL; 95% CI: -8.83, -0.71; p = 0.021; I ² = 31.8%), systolic blood pressure (SBP) (WMD: -1.15 mmHg; 95% CI: -1.66, -0.64; p < 0.001; I ² = 41.8%), and diastolic blood pressure (DBP) (WMD: -1.61 mmHg; 95% CI: -1.88, -1.34; p < 0.001; I ² = 7.0%). However, no significant changes were observed for homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), and waist circumference (WC). Saffron supplementation has an improving effect on FBG, HbA1c, TC, DBP, and SBP in patients with MetS and related disorders. Nonetheless, additional high-quality RCTs involving diverse ethnic populations are necessary to validate this effect.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"1883-1904"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Molecular Mechanisms of Osteoarthritis: The Potential of Polyphenols as Therapeutic Agents.","authors":"Syed Nasar Rahaman, Murugesan Lishadevi, Suresh Kumar Anandasadagopan","doi":"10.1002/ptr.8455","DOIUrl":"10.1002/ptr.8455","url":null,"abstract":"<p><p>The complex nature of osteoarthritis (OA), driven by the intricate interplay of genetic, environmental, and lifestyle factors, necessitates the development of a single treatment method, which is highly challenging. The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids often leads to adverse side effects like kidney damage and stomach ulcers. Major health threats like obesity and aging create a milieu of chronic low-grade inflammation and increased mechanical stress on the joints resulting in cartilage deterioration. Additionally, postmenopausal women with lower circulating 17β-estradiol levels experience accelerated joint deterioration due to increased immune activity resulting in the increased production of pro-inflammatory cytokines, with elevated MMP expression and decreased type II collagen synthesis. Polyphenols are nature's gifted magic molecules, which possess diverse biological properties like anti-oxidant, anti-bacterial, anti-inflammatory, estrogenic, and insulin-sensitizing effects, which can manage and treat all the multi-factorial contributing factors of OA effectively. Certain polyphenols can act as phytoestrogens and mimic the effects of natural estrogen by binding to ERα and ERβ and can act as SERMs and prevent degradation of the articular cartilage thereby alleviating osteoarthritic conditions. These molecules downregulate the expression of various pro-inflammatory cytokines, apoptotic genes, and matrix-degrading proteases (MMPs) while upregulating major ECM proteins like type II collagen, aggrecan, and proteoglycans in various osteoarthritic animal models. This review provides a comprehensive overview of the molecular mechanisms involved in OA development and also explores the therapeutic potential of different polyphenols in mitigating joint inflammation and their protective effect in inhibiting the degradation of cartilage extracellular matrix (ECM) and enhancing joint homeostasis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2038-2071"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}