Phytotherapy Research最新文献

{"title":"Portulaca oleracea L. Extract and Its Alkaloid Oleracein E Alleviates Cardiac Remodeling and Heart Failure in Mice by Targeting STAT2 Through the MAPK Signaling Inflammatory Pathway.","authors":"Risheng Zhao, Min Zhang, Gege Yang, Wei Liu, Hui Yu, Shuang Yan, Ting Ren, Linxin Zhang, Mengyang Wang, Haiming Sun","doi":"10.1002/ptr.8501","DOIUrl":"https://doi.org/10.1002/ptr.8501","url":null,"abstract":"<p><p>Hypertensive heart failure pathogenesis involves angiotensin II (Ang II)-mediated mechanisms through both hemodynamic overload and direct cellular signaling pathways. This study investigates the therapeutic potential of Portulaca oleracea L. (POL) extract and its active constituent Oleracein E (OE) in attenuating Ang II-induced pathological cardiac remodeling and subsequent heart failure progression. An experimental model of hypertensive heart failure was established in C57BL/6 mice through continuous subcutaneous infusion of Ang II for 4 weeks, with Oleracein E (OE) intervention administered during the final 2 weeks of the protocol. To elucidate the molecular mechanisms underlying OE's cardioprotective effects, we employed an integrated approach combining RNA sequencing analysis, molecular docking simulations, and target validation through drug affinity response target stability (DARTS) and cellular thermal shift assay (CETSA) techniques. The experimental results demonstrated that both POL extract and its active component OE exerted significant cardioprotective effects against Ang II-induced cardiac dysfunction in murine models, primarily through attenuation of pathological cardiac hypertrophy and suppression of inflammatory responses. Transcriptomic profiling via RNA sequencing identified the MAPK signaling pathway as a critical mediator of these protective effects. Subsequent transcription factor analysis revealed STAT2 as a key regulatory component in this pathway. Importantly, OE treatment effectively mitigated inflammatory responses in both in vivo cardiac tissues and in vitro cultured cardiomyocytes by specifically inhibiting the Ang II-activated MAPKs/STAT2 signaling cascade. Genetic ablation experiments further confirmed the essential role of this pathway, as the anti-inflammatory efficacy of OE was completely abolished in cardiomyocytes with MAPKs or STAT2 deficiency. Molecular interaction studies employing in silico docking simulations combined with experimental validation through DARTS and CETSA techniques provided direct evidence of physical binding between OE and the STAT2 protein. Our findings demonstrate that Oleracein E (OE) confers cardioprotection against Ang II-induced myocardial injury through a novel mechanism involving STAT2 targeting and subsequent suppression of MAPK signaling-mediated inflammatory cascades. These results not only elucidate a previously unrecognized pharmacological pathway but also suggest that OE and its derivatives hold significant therapeutic promise for the clinical management of hypertensive heart failure, potentially offering a targeted approach to modulate pathological cardiac remodeling.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042436","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":"Higher Intake of Resveratrol Is Associated With a Lower Risk of Colorectal Cancer: A Large-Scale Case-Control Study.","authors":"Ke-Xin Tu, Qing-Jian Ou, Fang-Ting Lin, Yu-Tong Zhao, Ru-Hua Zhou, Ruo-Lin Zhou, Yu-Jing Fang, Cai-Xia Zhang","doi":"10.1002/ptr.8510","DOIUrl":"https://doi.org/10.1002/ptr.8510","url":null,"abstract":"<p><p>Resveratrol, a natural bioactive compound derived from plants, has shown potential anti-colorectal cancer effects in preclinical studies, though population-based epidemiologic evidence is limited. This study aimed to investigate the association between resveratrol intake and colorectal cancer risk in a population from Guangdong, China. Conducted between July 2010 and January 2024, this case-control study included 3030 newly diagnosed colorectal cancer patients and 3044 frequency-matched controls by sex and age (± 5 years). Dietary data were collected using a validated food frequency questionnaire with 81 items, and resveratrol intake was estimated from resveratrol and piceid content based on the China Food Composition Table Standard Edition. Multivariable unconditional logistic regression models were applied to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the association between resveratrol intake and colorectal cancer risk. The results indicated that higher dietary resveratrol intake was associated with a reduced risk of colorectal cancer. The highest quintile of total resveratrol intake was associated with a 44% lower risk of colorectal cancer compared to the lowest quintile (OR: 0.56, 95% CI: 0.44-0.72, p_trend < 0.001). This association was consistent for resveratrol derived from vegetables, fruits, edible fungi, and nuts. Sex-stratified analysis revealed a stronger protective effect in men (p_interaction = 0.033). Overall, these findings suggest that achievable dietary levels of resveratrol may be associated with a lower risk of colorectal cancer. Further prospective cohort studies and randomized controlled trials are needed to confirm these results.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015697","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":"Fisetin Clears Senescent Cells Through the Pi3k-Akt-Bcl-2/Bcl-xl Pathway to Alleviate Diabetic Aortic Aging.","authors":"Xiao-Man Ji, Xin-Xin Dong, Jia-Peng Li, Guang-Jie Tai, Shu Qiu, Wei Wei, Ceaser Wankumbu Silumbwe, Davaadagva Damdinjav, Joseph Nicolao Otieno, Xiao-Xue Li, Ming Xu","doi":"10.1002/ptr.8507","DOIUrl":"https://doi.org/10.1002/ptr.8507","url":null,"abstract":"<p><p>Vascular aging is a major contributor to age-related cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) induced early arterial aging and excessive senescent cells (SCs) burden in vessels. Inhibiting cellular senescence or eliminating SCs could effectively improve aging-related CVDs. Fisetin, a flavonoid extracted from cotinus coggygria scop, has shown potential in alleviating aging by clearing SCs. This study investigated the unexplored mechanisms and efficacy of fisetin in alleviating T2DM-related aortic aging. The T2DM mouse model was induced using a high-fat diet and low-dose streptozotocin injection. Chronic fisetin treatment's protective effects against aortic aging were assessed via senescence-associated beta-galactosidase (SA-β-Gal) staining, histopathology, and vasomotor function. RNA-sequencing and western blotting identified relevant signaling pathways and protein expression. Fisetin's effects on SCs and senescence-associated secretory phenotype (SASP) factors were evaluated through cell viability, apoptosis, and co-culture assays. Docking simulations suggested fisetin as a potential Phosphoinositide 3-kinase (Pi3k) inhibitor. In vivo, chronic fisetin treatment reduced aortic SCs burden, alleviating T2DM-related and natural aortic aging. In vitro, fisetin selectively induced apoptosis of senescent endothelial cells via regulating the Pi3k-Protein Kinase B (Akt)-B-cell lymphoma (Bcl)-2/Bcl-xl pathway and suppressed SASP and its detrimental effects. Furthermore, fisetin combined with metformin therapy showed superior anti-aging effects on T2DM-related aortic aging compared to metformin monotherapy. In conclusion, chronic fisetin treatment alleviates T2DM-related aortic aging via clearing the SCs burden and abrogating the SASP factors. Fisetin combined with metformin therapy might be a potential therapeutic strategy for T2DM-related CVDs.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042434","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":"Treatment of Insomnia With Traditional Chinese Medicine Presents a Promising Prospect.","authors":"Boyi Zhang, Qianqian Wang, Yuhang Zhang, Hanyu Wang, Jingyu Kang, Yandi Zhu, Baiyan Wang, Shuying Feng","doi":"10.1002/ptr.8495","DOIUrl":"https://doi.org/10.1002/ptr.8495","url":null,"abstract":"<p><p>Insomnia, a prevalent sleep disorder, significantly impacts global health. While Western medications provide temporary relief, their risks of dependency and cognitive impairment have spurred the search for safer alternatives. Traditional Chinese Medicine (TCM) offers a promising approach to treating insomnia by focusing on harmonizing the balance of Yin and Yang and the functions of internal organs. This review explores recent research advances in TCM for insomnia treatment, integrating classical theories with modern scientific understanding of key pathological mechanisms, including neurotransmitter regulation (GABA, monoamines), immune-inflammatory responses, the HPA axis, and interactions with the gut microbiota. Growing clinical evidence supports the effectiveness of classical TCM prescriptions and treatments like acupuncture in improving sleep quality, particularly when combined with Western medications to enhance efficacy and reduce dependency. However, TCM also has its limitations. Future research directions should focus on modernizing TCM applications, addressing comorbidities associated with insomnia, exploring the role of gut microbiota, and optimizing medicinal and edible homologous products. By integrating traditional knowledge with cutting-edge technologies, TCM holds great potential for advancing personalized and effective insomnia treatments globally.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987423","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":"Maslinic Acid Ameliorates DSS-Induced Experimental Colitis by Suppressing Th Cell-Mediated Inflammation via AICD Induction.","authors":"Dan Li, Zhan-Dong Ye, Mu-Xia Li, Ying-Yi Luo, Can-Kun Zhou, Qing-Hua Mei, Cheng-Lai Xia, Song Huang, Ji-Yan Su","doi":"10.1002/ptr.8479","DOIUrl":"10.1002/ptr.8479","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a nonspecific chronic inflammatory disease that occurs in the gastrointestinal tract and is characterized by the breakdown of mucosal immunity. T helper (Th) cells paradigm disequilibrium is a critical for pathogenesis. Maslinic acid (MA), a naturally occurring pentacyclic triterpene isolated from olive pomace and Fructus crataegi, has a variety of applications in both medicine and food. This study investigated the molecular mechanism of the anti-inflammatory potential of MA in a colitis model and activated Th cells. A dextran sulfate sodium-induced experimental colitis model was established. Clinical symptoms were evaluated, and biological samples were collected to examine intestinal mucosal function, inflammation levels, and Th cell-mediated immune responses. The mechanism of the activation-induced cell death (AICD) effect regulated by MA was investigated in the anti-CD3ε/CD28-stimulated Th cell activation model using molecular biotechnology and transcriptome analysis. Key results:MA treatment protected intestinal mucosa, which manifested as reduced inflammatory cytokines, Th cell infiltration, and subset differentiation. Additionally, it was found to suppress Th cell proliferation and differentiation of subsets, regulate cell cycle distribution, and promote AICD by regulating the mitochondria-mediated intrinsic pathway in vitro. JAK-STAT and FcεRI pathways were probable essential pathways, and MAF might be a crucial potential targeting molecule in activated Th cells with MA treatment. This finding demonstrated that MA induced remission of the colitis-related inflammation, which may depend on the resolution of acute inflammation by reducing Th cell-mediated inflammation via AICD induction, emphasizing its promising potential in the treatment of UC.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037855","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":"Green Tea Ameliorates Depression-Like Behavior and Cognitive Impairment Induced by High-Fat Diet and Chronic Mild Stress.","authors":"Minghao Fan, Yudi Jiang, Chao Cai, Zhe Wang, Lu Chen, Shumin Hu, Xin Zhang, Hua Yin, Zhonghua Qian, Shuli Huang, Jiachen Yang","doi":"10.1002/ptr.8499","DOIUrl":"https://doi.org/10.1002/ptr.8499","url":null,"abstract":"<p><p>Depression often develops in young individuals and is linked to complications like cognitive impairment. Conventional antidepressants show limited efficacy in restoring cognitive function and may cause adverse effects. Green tea, a safe and health-promoting beverage, offers various health benefits. This study investigated the effects of long-term green tea consumption on stress-induced depression-like behavior and mild cognitive impairment in animal models. We established a rodent model of mild depression and studied the effects of green tea on depression-like behavior and cognitive impairment through comprehensive evaluation, including behavioral assessments, neurotransmitter quantification, gene and protein expression analysis, blood metabolite profiling, and gut microbiota characterization. Results demonstrated significant improvements in mood, long-term memory, and sterol and glycerophospholipid metabolism. Green tea repaired the intestinal barrier and upregulated genes vital for tight junctions and mucin production. It also enhanced gut microbiota composition, reducing the Firmicutes-to-Bacteroidetes ratio and promoting beneficial bacteria such as NK4A136, Muribaculum, and Gordonibacter. These microbiota changes improved liver lipid metabolism and alleviated depressive symptoms. Green tea effectively mitigates depression-like behavior and cognitive deficits by modulating the gut-liver-brain axis.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045064","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":"Pterostilbene Exhibits Broad-Spectrum Antiviral Activity by Targeting the Enterovirus Capsid, Inactivating Viral Particles, Blocking Viral Binding, and Protecting Mice From Lethal EV-A71 Challenge.","authors":"Kuan-Ting Chuang, Siao-Cian Pan, Bor-Luen Chiang, Shih-Hsun Chen, Min-Hsiung Pan, Yu-Li Chen, Cheng-Sheng Lin, Chun-Kai Pan, Jing-Yi Lin, Yu-Li Lin","doi":"10.1002/ptr.8496","DOIUrl":"10.1002/ptr.8496","url":null,"abstract":"<p><p>Human enteroviruses (EVs) are a major public health issue worldwide owing to their potential to cause respiratory illnesses, hand-foot-and-mouth disease, and severe neurological complications. Currently, no effective drugs or multivalent vaccines are available. Pterostilbene (Pte), a naturally occurring compound found in blueberries and other plants, is a type of stilbene with a similar structure to resveratrol. Pterostilbene exerts antioxidant, anti-inflammatory, and anticancer properties. However, few studies have explored its antiviral activity. This study aimed to investigate the anti-enteroviral effect and mechanisms of Pte against EV-A71 and EV-D68. Cytotoxicity and antiviral assays were performed to assess the safety of Pte to cells and its antiviral effects against enteroviruses. Viral attachment, inactivation assays, cellular receptor binding, western blotting, time-of-addition and time-of-removal assays, particle stability thermal release assay, and molecular docking were performed to elucidate the antiviral mechanisms of Pte. Additionally, we validated the antiviral effects of Pte using in vivo experiments. Among the stilbenes examined, Pte exerted a broad-spectrum inhibitory effect on various enteroviruses, including EV-A71, EV-D68, and coxsackieviruses at 40 μM, without cytotoxicity. Mechanistically, Pte significantly inhibited enteroviral attachment, inactivated viral particles, blocked viral binding to its receptors, and increased virion stability. Molecular docking analysis revealed that Pte occupied a hydrophobic pocket in viral protein 1, indicating a strong binding affinity and acting as an efficient inhibitor. Notably, sequence alignment of multiple enteroviruses indicated that the Pte-interacting residues in VP1 were highly conserved. In vivo studies demonstrated that oral administration of Pte significantly alleviated infection symptoms and reduced mortality in hSCARB2 transgenic mice. Pte possesses potential application as a broad-efficacy antiviral drug against enteroviral infections.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038347","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":"Advances in Therapeutic Targets and Traditional Chinese Medicine for Cardiomyopathy.","authors":"Si-Hui Yang, Shuai-Nan Zhang, Xu-Zhao Li","doi":"10.1002/ptr.8494","DOIUrl":"https://doi.org/10.1002/ptr.8494","url":null,"abstract":"<p><p>Cardiomyopathy is a kind of heart disease caused by multiple factors of myocardial structure and function disorders. In this paper, we summarized and found the targets and mechanisms with therapeutic potential by querying the relevant literature on cardiomyopathy in the past 10 years from databases. Numerous pieces of literature have proven the significant efficacy of traditional Chinese medicine (TCM) in the treatment of cardiomyopathy. Through effective screening methods, we quickly identified a variety of commonly used Chinese herbs such as Astragalus, Danggui, Danshen, Pueraria Root, and ginseng, and further analyzed the active ingredients that play key roles in the treatment of cardiomyopathy. Specifically, our study revealed significant interaction activity at the molecular level of active ingredients such as calycosin, formononetin, and beta-sitosterol, which were strongly validated by sophisticated molecular docking experiments. These active ingredients can be precisely combined with 14 core targets (such as AKT1, TP53, IL6, and other key proteins), which not only reveals their potential therapeutic mechanisms but also provides direct and solid scientific support for the application of TCM in the treatment of cardiomyopathy. It is helpful to develop new TCM preparations further and provide more treatment options for patients with cardiomyopathy.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994131","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":"Inhibition of Hepatoblastoma by Ganoderma Lucidum Polysaccharide via the Induction of HDAC4-p16-RB Axis-Mediated Cellular Senescence.","authors":"Ting Ye, Yang Ge, Jing Zhang, Hang Gao, Peng-Cheng Zhang, Rui Shen, Can Peng, Bin Liu, Hang Song","doi":"10.1002/ptr.8493","DOIUrl":"https://doi.org/10.1002/ptr.8493","url":null,"abstract":"<p><p>Hepatoblastoma (HB), the most common primary malignant liver tumor in children, is characterized by high metastatic potential and poor prognosis. Ganoderma lucidum polysaccharide (GLP), the main bioactive compound of Ganoderma lucidum, has not been fully investigated for its therapeutic effects on HB. This study aimed to evaluate the anti-tumor effects of GLP on HB cells and explore the underlying biological mechanisms. GLP was chemically characterized using ultraviolet-visible spectroscopy, monosaccharide composition analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy. The effects of GLP on the malignant phenotype of HB cells were assessed using CCK-8, EdU, Transwell assays, and other standard in vitro techniques. Mechanistic investigations included proteomics, western blotting, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. In vivo anti-HB effects of GLP were evaluated through animal models. Crude GLP, exhibiting anti-tumor activity, was prepared through water extraction, alcohol precipitation, and column chromatography. In vitro, GLP inhibited proliferation, invasion, and induced apoptosis in HuH6 and HepG2 cells. In vivo, GLP suppressed tumor growth in a dose-dependent manner. Mechanistically, GLP induced cellular senescence by downregulating histone deacetylase 4 (HDAC4) expression and enhancing p16 histone acetylation, which activated the p16-retinoblastoma (p16-RB) pathway and suppressed the malignant phenotype of HB cells. Furthermore, overexpression of HDAC4 reversed the senescence-inducing effects of GLP. GLP inhibits HB progression by promoting cellular senescence via the HDAC4-p16-RB axis. These findings establish a mechanistic link between GLP's anti-tumor activity and cellular senescence, providing new insights for its potential clinical application.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796064","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":"Chrysophanol Attenuates Cardiac Fibrosis and Arrhythmia by Suppressing the Endoplasmic Reticulum Stress/Pyroptosis Axis and Inflammation.","authors":"Chengyin Liu, Shuang Qiu, Xiaoqiong Liu, Rui Huang, Zhao Fang","doi":"10.1002/ptr.8476","DOIUrl":"https://doi.org/10.1002/ptr.8476","url":null,"abstract":"<p><p>Chrysophanol (CHR), one of the principal bioactive compounds extracted from the rhizome of Rheum palmatum L., is known for its anti-inflammatory, antioxidative, anti-cancer, and cardioprotective effects. However, the effect of CHR on cardiac fibrosis remains elusive. In this study, mice were administered isoproterenol (ISO) to induce cardiac fibrosis in vivo, and cardiac fibroblasts were pretreated with transforming growth factor-β1 (TGF-β1) to induce the transformation of fibroblasts into myofibroblasts in vitro. Western blot and reverse transcription-quantitative polymerase chain reaction analyses were performed to evaluate the endoplasmic reticulum (ER) stress and pyroptosis. Immunohistochemistry staining and ELISA analyses were used to detect the inflammation level. In vivo electrophysiological studies were conducted to assess arrhythmia susceptibility. Our findings revealed that CHR treatment ameliorated cardiac dysfunction and fibrosis in ISO-challenged mice. Moreover, CHR reduced susceptibility to ventricular fibrillation by reducing ventricular electrical remodeling and increasing the expression of gap junction proteins and ion channels. Additionally, CHR inhibited the TGF-β1-stimulated transformation of cardiac fibroblasts into myofibroblasts in vitro. CHR inhibited ER stress, pyroptosis, and inflammation in vivo and in vitro. Furthermore, tunicamycin (TM)-induced activation of ER stress abolished the protective effects of CHR. CHR treatment attenuates cardiac fibrosis and arrhythmia by suppressing the ER stress/pyroptosis axis and inflammation.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788766","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}