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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. 补充藏红花对代谢综合征及相关疾病患者糖脂代谢和血压的影响:随机对照试验的系统回顾和荟萃分析
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-02-11 DOI: 10.1002/ptr.8421
Xiaolei Zhang, Jinxin Miao, Yagang Song, Mingsan Miao
{"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 <sup>2</sup> = 50.0%), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.25%; 95% CI: -0.35, -0.14; p < 0.001; I <sup>2</sup> = 0.0%), total cholesterol (TC) (WMD: -4.77 mg/dL; 95% CI: -8.83, -0.71; p = 0.021; I <sup>2</sup> = 31.8%), systolic blood pressure (SBP) (WMD: -1.15 mmHg; 95% CI: -1.66, -0.64; p < 0.001; I <sup>2</sup> = 41.8%), and diastolic blood pressure (DBP) (WMD: -1.61 mmHg; 95% CI: -1.88, -1.34; p < 0.001; I <sup>2</sup> = 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}
引用次数: 0
Unraveling the Molecular Mechanisms of Osteoarthritis: The Potential of Polyphenols as Therapeutic Agents. 揭示骨关节炎的分子机制:多酚作为治疗剂的潜力。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-03-05 DOI: 10.1002/ptr.8455
Syed Nasar Rahaman, Murugesan Lishadevi, Suresh Kumar Anandasadagopan
{"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}
引用次数: 0
Effects of Curcumin on Postmenopausal Women's Health: A Systematic Review and Meta-Analysis. 姜黄素对绝经后妇女健康的影响:系统综述和荟萃分析。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-03-19 DOI: 10.1002/ptr.8467
Dachuan Jin, Shunqin Jin, Guoping Sheng, Zhongfeng Cui, Peng Gao, Guangming Li
{"title":"Effects of Curcumin on Postmenopausal Women's Health: A Systematic Review and Meta-Analysis.","authors":"Dachuan Jin, Shunqin Jin, Guoping Sheng, Zhongfeng Cui, Peng Gao, Guangming Li","doi":"10.1002/ptr.8467","DOIUrl":"10.1002/ptr.8467","url":null,"abstract":"<p><p>To evaluate curcumin's impact on postmenopausal women's health through a meta-analysis. The databases searched included PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2024. The Cochrane risk of Bias assessment tool was used to assess the quality of the included studies. This meta-analysis reviewed 14 randomized controlled trials involving 982 participants (466 in the intervention group and 516 in the control group) and evaluated curcumin's effects across 30 indicators grouped into cardiovascular health, oxidative stress and antioxidant markers, bone health, metabolic health, and quality of life. We found that curcumin reduced systolic (SMD -0.51, 95% CI -0.83 to 0.19, p = 0.002) and diastolic blood pressure (SMD -0.63, 95% CI -0.96 to -0.30, p = 0.005), increased total antioxidant capacity (SMD 0.93, 95% CI 0.15 to 1.72, p = 0.020) and superoxide dismutase levels (SMD 0.30, 95% CI 0.04 to 0.56, p = 0.026), decreased aspartate aminotransferase (AST) (SMD -0.36, 95% CI -0.66 to -0.06, p = 0.020), and improved vasomotor (SMD -0.39, 95% CI -0.65 to -0.13, p = 0.003) symptoms. Curcumin positively impacts several indicators in postmenopausal women, highlighting its potential therapeutic role in managing cardiovascular risk factors, oxidative stress, hepatoprotective effects, and vasomotor symptoms. Due to variations in the purity and dosages across different studies and the lack of combinable data for certain indicators, the conclusions are still limited. These issues can be addressed through more comprehensive large-scale trials later. A more in-depth investigation into the mechanisms is also crucial.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2202-2216"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658156","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}
引用次数: 0
Angelica dahurica Polysaccharides Ameliorate Colitis by Reducing the Restriction of Gut Microbiota-Derived Imidazole Propionate on PPAR-γ Signaling Activation. 白芷多糖通过降低肠道微生物源咪唑丙酸对PPAR-γ信号激活的限制改善结肠炎。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-03-05 DOI: 10.1002/ptr.8466
Jingyi Hu, Feng Xu, Lei Zhu, Yuan Cui, Ryan Au, Yanan Li, Yiheng Tong, Hong Shen
{"title":"Angelica dahurica Polysaccharides Ameliorate Colitis by Reducing the Restriction of Gut Microbiota-Derived Imidazole Propionate on PPAR-γ Signaling Activation.","authors":"Jingyi Hu, Feng Xu, Lei Zhu, Yuan Cui, Ryan Au, Yanan Li, Yiheng Tong, Hong Shen","doi":"10.1002/ptr.8466","DOIUrl":"10.1002/ptr.8466","url":null,"abstract":"<p><p>Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica, species Angelica dahurica (Hoffm.)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2072-2090"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567936","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}
引用次数: 0
Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication. Ouratein D是一种来自Ouratea spectabilis的双黄酮,通过减轻炎症、肺损伤和病毒复制来减轻betacoravirus感染。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-03-18 DOI: 10.1002/ptr.8462
Adelson Héric A Monteiro, Kátia M Freitas, Ana Clara M Montuori-Andrade, Erick Bryan Sousa de Lima, Antônio Felipe S Carvalho, Camila Cardoso, Edvaldo S Lara, Leonardo Camilo Oliveira, Isabella Zaidan, Felipe Rocha Silva da Santos, Filipe Resende, Luiz Pedro Souza-Costa, Celso M Queiroz-Junior, Ian de Meira Chaves, Natália R C Nóbrega, Maria Beatriz O Rabelo, Marina P Rocha, Priscilla R V Campana, Rodrigo M Pádua, Rafaela S Ferreira, Luiza V Barreto, Thales Kronenberger, Vinícius G Maltarollo, Mariana O de Godoy, Glaucius Oliva, Rafael V C Guido, Mauro M Teixeira, Vivian V Costa, Lirlândia P Sousa, Fernão C Braga
{"title":"Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication.","authors":"Adelson Héric A Monteiro, Kátia M Freitas, Ana Clara M Montuori-Andrade, Erick Bryan Sousa de Lima, Antônio Felipe S Carvalho, Camila Cardoso, Edvaldo S Lara, Leonardo Camilo Oliveira, Isabella Zaidan, Felipe Rocha Silva da Santos, Filipe Resende, Luiz Pedro Souza-Costa, Celso M Queiroz-Junior, Ian de Meira Chaves, Natália R C Nóbrega, Maria Beatriz O Rabelo, Marina P Rocha, Priscilla R V Campana, Rodrigo M Pádua, Rafaela S Ferreira, Luiza V Barreto, Thales Kronenberger, Vinícius G Maltarollo, Mariana O de Godoy, Glaucius Oliva, Rafael V C Guido, Mauro M Teixeira, Vivian V Costa, Lirlândia P Sousa, Fernão C Braga","doi":"10.1002/ptr.8462","DOIUrl":"10.1002/ptr.8462","url":null,"abstract":"<p><p>Severe coronavirus outbreaks, including SARS, MERS, and COVID-19, have underscored the urgent need for effective antiviral therapies. This study evaluated the antiviral activity of biflavanones isolated from Ouratea spectabilis-specifically ouratein (Our-) A, B, C, and D-against murine hepatitis virus (MHV-3) and human SARS-CoV-2. Cells infected with MHV-3 or SARS-CoV-2 were treated with ourateins, and viral replication was assessed using plaque assays. Mice infected with MHV-3 were treated with Our-D either orally or intraperitoneally. Key assessments included leukocyte counts, cytokine and chemokine levels, histological analysis, and survival rates. The mechanism of action was explored through in silico and in vitro studies focused on the binding and inhibition of the main protease (M<sup>pro</sup>). Our-D significantly inhibited the replication of both viruses, with a selective index of 2.5 for MHV-3 and 14.9 for SARS-CoV-2. In vivo, Our-D reduced leukocyte infiltration in the lungs, decreased CCL2 levels, increased IL-10, and lowered plasma IL-6 and CXCL1 levels. Additionally, Our-D mitigated lung damage, partially restored betacoronavirus-induced lymphopenia, and reduced viral loads in the lungs, heart, and spleen, ultimately improving survival in mice. In silico studies revealed that Our-A and Our-C had strong binding affinity for M<sup>pro</sup>, and both significantly inhibited M<sup>pro</sup> activity in vitro, unlike Our-D. Our-D protected mice from coronavirus infection by modulating the inflammatory response and reducing viral loads, with minimal effect on M<sup>pro</sup> inhibition, suggesting alternative mechanisms for its antiviral activity.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2180-2196"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658182","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}
引用次数: 0
Coffee peel polyphenols ameliorate nonalcoholic fatty liver disease by modulating cannabinoid receptor type-1-ceramide axis. 咖啡皮多酚通过调节大麻素受体1型神经酰胺轴改善非酒精性脂肪性肝病。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1002/ptr.8078
Ze-Kai Fan, Yan-Fang Chen, Wei-Wei Han, Xiao-Fei Guo, Duo Li
{"title":"Coffee peel polyphenols ameliorate nonalcoholic fatty liver disease by modulating cannabinoid receptor type-1-ceramide axis.","authors":"Ze-Kai Fan, Yan-Fang Chen, Wei-Wei Han, Xiao-Fei Guo, Duo Li","doi":"10.1002/ptr.8078","DOIUrl":"10.1002/ptr.8078","url":null,"abstract":"<p><p>Cannabinoid receptor type-1 (CB1) signaling plays an important part in maintenance of energy homeostasis, and CB1 blockers have shown promise in the treatment of obesity-related metabolic dysfunction. Coffee peel contains abundant phytochemicals and possesses hypolipidemic and anti-inflammatory activities. The present study aimed to elucidate the preventive effect of coffee peel polyphenols (CPPs) on nonalcoholic fatty liver disease (NAFLD) from the perspective of CB1 signaling. Male C57BL/6J mice were fed a high-fat and high-cholesterol diet and CPPs (200/400 mg/kg/day) for 8 weeks. Serum biochemical indexes and liver pathological analysis were used to evaluate the effect of CPPs on NAFLD. Untargeted/targeted lipidomics analyses were used to evaluate the levels of endocannabinoid ligands and ceramides in serum and liver. The expression levels of proteins were detected by using Western blotting analysis. Administration of CPPs significantly improved hepatic steatosis, insulin resistance and biomarkers of liver function. Meanwhile, CPPs administration indicated reductions in endocannabinoid ligands, including anandamide and 2-arachidonoylglycerol levels, associated with blockade of CB1 overexpression. Blockage of CB1 signaling depleted hepatic C16:0- and C18:0-ceramide concentrations by enhancing ceramide metabolism. The reductions in hepatic ceramide concentrations contributed to down-regulating sterol regulatory element-binding protein-1c and up-regulating proliferator activated receptor alpha, leading to decrease de novo lipogenesis and increase fatty acid β-oxidation in the liver, respectively. This study demonstrated a novel mechanism that CPPs could ameliorate NAFLD through modulating CB1-ceramide axis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2312-2323"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710946","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}
引用次数: 0
Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease. 人参皂苷Re抗非酒精性脂肪肝机制中的肠道菌群和胆汁酸代谢
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1002/ptr.8474
Yanfang Zheng, Jiaying Chen, Ying Zhang, Huaying Guan, Shan Deng, Dennis Chang, Yitao Wang, JinJian Lu, Xian Zhou, Qin Xie, Jianyuan Song, Mingqing Huang
{"title":"Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease.","authors":"Yanfang Zheng, Jiaying Chen, Ying Zhang, Huaying Guan, Shan Deng, Dennis Chang, Yitao Wang, JinJian Lu, Xian Zhou, Qin Xie, Jianyuan Song, Mingqing Huang","doi":"10.1002/ptr.8474","DOIUrl":"10.1002/ptr.8474","url":null,"abstract":"<p><p>Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens , and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2339-2356"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764597","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}
引用次数: 0
Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK-ULK1-FUNDC1 Signaling Pathway. 黄腐醇通过AMPK-ULK1-FUNDC1信号通路调控骨肉瘤细胞的有丝分裂
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1002/ptr.8468
Qiaofeng Ge, Zhiliang Yan, Qian Tian, Jiyan Zhang, Jia Li, Fang Cai, Long Zhang, Yonggang Zhu
{"title":"Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK-ULK1-FUNDC1 Signaling Pathway.","authors":"Qiaofeng Ge, Zhiliang Yan, Qian Tian, Jiyan Zhang, Jia Li, Fang Cai, Long Zhang, Yonggang Zhu","doi":"10.1002/ptr.8468","DOIUrl":"10.1002/ptr.8468","url":null,"abstract":"<p><p>Osteosarcoma (OS) is the most common primary bone malignancy. The therapeutic efficacy for OS patients has remained stagnant in recent decades. Xanthohumol (XN), a flavonoid naturally found in hops, has demonstrated significant anticancer properties in lung and breast cancer. However, its effect on OS and the underlying molecular mechanisms remains uncertain. Therefore, the purpose of this study is to explore the relationship between XN and OS. Firstly, we assessed the impact of XN on OS cell proliferation and migration using CCK-8, wound-healing, transwell, and clonogenicity assays. Subsequently, we examined the effect of XN on mitophagy in OS cells through flow cytometry, immunofluorescence, transmission electron microscopy, and western blot analysis. Finally, we constructed siRNA targeting AMPK to validate the pathway. In vitro, we demonstrated that XN inhibited the proliferation and migration of OS cells in a concentration- and time-dependent manner. Furthermore, XN induced mitochondrial damage in OS cells and increased reactive oxygen species (ROS) levels. RNA-seq analysis suggested a potential mitophagy pathway, which we confirmed experimentally by showing that XN reduced ATP levels, altered mitochondrial membrane potential, and increased the expression of Atg5, Beclin-1, and LC3 proteins. Interestingly, the mitophagy inhibitor Mdivi-1 reversed the damage caused by XN to OS cells. Furthermore, we found that XN induced mitophagy and exerted anti-OS effects through the activation of the AMPK-ULK1-FUNDC1 signaling pathway, which was effectively reversed after AMPK knockdown. In vivo, we demonstrated the therapeutic potential of XN using a subcutaneous OS nude mouse model without any organ toxicity. XN emerges as a promising pharmaceutical agent for targeting OS.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2393-2406"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796140","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}
引用次数: 0
Emodin Promotes Peripheral Nerve Repair by Modulating Inflammasome Activation Through Autophagy via the EGFR/PI3K/AKT/mTOR Pathway. 大黄素通过EGFR/PI3K/AKT/mTOR通路自噬调节炎性体激活,促进周围神经修复。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1002/ptr.8469
Zhengyang Long, Yixun Huang, Tao Lin, Shanying Xiao, Kaiye Chen, Jiahao Ying, Ke Wang, Zhe Zhang, Long Wu
{"title":"Emodin Promotes Peripheral Nerve Repair by Modulating Inflammasome Activation Through Autophagy via the EGFR/PI3K/AKT/mTOR Pathway.","authors":"Zhengyang Long, Yixun Huang, Tao Lin, Shanying Xiao, Kaiye Chen, Jiahao Ying, Ke Wang, Zhe Zhang, Long Wu","doi":"10.1002/ptr.8469","DOIUrl":"10.1002/ptr.8469","url":null,"abstract":"<p><p>To investigate the potential of emodin in promoting nerve regeneration following PNI by targeting macrophage polarization, NLRP3 inflammasome activation, autophagy, and the EGFR/PI3K/Akt/mTOR pathway. A cohort of 78 male Sprague-Dawley rats was used to develop models of sciatic nerve damage, with an additional 18 rats in the sham surgery group. The rats were randomly assigned to eight groups: Sham, Control, PNI + Emodin (20 mg/kg), PNI + Emodin (80 mg/kg), PNI + MCC950 (10 mg/kg), PNI + Rapamycin (2 mg/kg), PNI + Emodin (80 mg/kg) + 3-MA (15 mg/kg), and PNI + Emodin (80 mg/kg) + NSC 228155 (5 mg/kg). Emodin was administered intragastrical daily, while the inhibitors or agonist were administered via intraperitoneal injection, as per the respective dosages and schedules. The treatment period included assessments of nerve regeneration and functional recovery, such as histological staining, immunofluorescence for cellular markers, TEM for ultrastructural changes, SFI for functional recovery, and western blot analysis for autophagy and inflammatory proteins. IF and TEM images showed that emodin enhanced axonal and myelin regeneration. Histological analysis revealed emodin reduced muscular atrophy and collagen deposition. Emodin decreased pro-inflammatory macrophage markers (CD68) while increasing M2 markers (CD206), inhibited the NLRP3 inflammasome, and reduced IL-1β and caspase-1. It activated autophagy in Schwann cells, with increased LC3-II levels. Network pharmacology and molecular docking identified EGFR in the PI3K/AKT/mTOR pathway as a key target, with emodin inhibiting EGFR activation. This study reveals that emodin promotes early nerve recovery by enhancing functional outcomes, axonal remyelination, and reducing muscle atrophy. It boosts autophagy in Schwann cells, inhibits NLRP3 inflammasome activation, and promotes M2 macrophage polarization. These effects are closely related to the EGFR/PI3K/AKT/mTOR pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2324-2338"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710947","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}
引用次数: 0
Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39-dominant purinergic braking and downstream NLRP3 inflammasome. 麻天碱通过调节cd39显性嘌呤能制动和下游NLRP3炎性体减轻细胞因子风暴继发性肺损伤。
IF 6.1 2区 医学
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1002/ptr.8062
Yuejia Lan, Huan Wang, Lijia Jing, Rui Li, Jiayi Sun, Xianli Meng, Jiasi Wu
{"title":"Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39-dominant purinergic braking and downstream NLRP3 inflammasome.","authors":"Yuejia Lan, Huan Wang, Lijia Jing, Rui Li, Jiayi Sun, Xianli Meng, Jiasi Wu","doi":"10.1002/ptr.8062","DOIUrl":"10.1002/ptr.8062","url":null,"abstract":"<p><p>Cytokine storm secondary lung injury (CSSLI) is a form of acute lung injury (ALI) comparable to that caused by sepsis for which there are no effective therapeutic strategies. Coptis chinensis Franch. and Scutellaria baicalensis Georgi. are two botanical medicines that exhibit anti-inflammatory properties. This study aimed to investigate the underlying therapeutic mechanism of the combination (CCSB) treatment in mice with ALI. A high dosage of lipopolysaccharide (LPS) was administered intraperitoneally to C57BL/6 mice to establish an ALI model. The AMP-Glo™ assay was applied to screen for the component with the most potent CD39-promoting enzyme activity from CCSB constituents migrating to the bloodstream. The PMA-differentiated THP-1 and RAW264.7 macrophage cell lines were stimulated with LPS and adenosine triphosphate, followed by treatment with Jatrorrhizine (JH). The administration of CCSB demonstrated a notable improvement in lung injury through the modulation of the CD39-P2X7 purinergic pathway and subsequent regulation of the NLRP3 inflammasome. The restrained CD39 and A2b were reversed by JH, leading to the suppression of the P2X7-NLRP3 signaling pathway. In addition, the utilization of a CD39 inhibitor (POM-1) attenuated the inhibitory effect of JH on the NLRP3 signaling pathway. CCSB successfully rescued CSSLI, along with its small-molecule component JH, which demonstrated the ability to inhibit the NLRP3 signaling pathway and pyroptosis, at least partially through regulating the CD39 enzyme.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"2374-2392"},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796065","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}
引用次数: 0
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