Phytomedicine最新文献

{"title":"Ethanol extract of Periploca forrestii Schltr. and chlorogenic acid alleviate ischemic stroke by inhibiting TLR4-mediated neuroinflammation","authors":"Wenze Wu ,&nbsp;Libin Xu ,&nbsp;Lu Sun ,&nbsp;Juan Xue ,&nbsp;Feng Wang ,&nbsp;Hua Guo ,&nbsp;Ning Lei ,&nbsp;Dongyao Liu ,&nbsp;Yueyang Liu ,&nbsp;Dong Liang ,&nbsp;Yan Wang ,&nbsp;Yan Mi ,&nbsp;Huifang Chai ,&nbsp;Yue Hou","doi":"10.1016/j.phymed.2025.157026","DOIUrl":"10.1016/j.phymed.2025.157026","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation is a major factor in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). <em>Periploca forrestii</em> Schltr., commonly known as <em>Heiguteng</em> (HGT) in China, is a traditional anti-inflammatory herb that has been found effective in treating cardiovascular and cerebrovascular diseases. However, its potential protective effects against CIRI remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the pharmacological actions and underlying mechanisms of ethanol extract of HGT (EEHGT) on CIRI.</div></div><div><h3>Methods</h3><div>The middle cerebral artery occlusion-reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were used to evaluate the protective effects of EEHGT on CIRI. Additionally, comprehensive metabolomics and systems pharmacology analyses were performed to elucidate the mechanisms of EEHGT.</div></div><div><h3>Results</h3><div>The results demonstrated that EEHGT effectively alleviated CIRI in MCAO/R rats and reduced neuronal damage in OGD/R-treated SH-SY5Y cells. Notably, EEHGT mitigated the secretion of pro-inflammatory cytokines and restored the levels of key inflammation-related metabolites, including arginine, lactate, and L-tyrosine. Network pharmacology analysis indicated that the PI3K-Akt and NF-κB signaling pathways are involved in mediating the neuroprotective and anti-inflammatory activities of EEHGT. Consistent with this result, EEHGT activated PI3K-Akt pathway and inhibited NF-κB signaling in both MCAO/R rats and OGD/R-treated BV2 cells. The results indicated that TLR4 serves as a key mediator of EEHGT on CIRI, and TLR4 knockdown abolished its anti-neuroinflammatory effects. In addition, chlorogenic acid (CGA), an active compound of EEHGT, exhibited strong binding affinity to TLR4, and its anti-inflammatory activity was abolished upon TLR4 knockdown.</div></div><div><h3>Conclusions</h3><div>Collectively, this study provides the first evidence that EEHGT protects against CIRI by attenuating TLR4-mediated neuroinflammation. Mechanistically, EEHGT exerts its anti-inflammatory effects by activating the PI3K-Akt pathway and inhibiting NF-κB signaling. Notably, TLR4 was identified as a shared therapeutic target of both EEHGT and its active component, CGA, highlighting a novel mechanism underlying their neuroprotective effects.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157026"},"PeriodicalIF":6.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel triterpenoid saponin from Pimpinella candolleana alleviates postmenopausal osteoporosis via P38/JNK MAPK-mediated osteogenesis","authors":"Jiajia Wu ,&nbsp;Zhen Cao ,&nbsp;Chuyin Ou ,&nbsp;Lina Wang ,&nbsp;Yan Ji ,&nbsp;Mingyu Ma ,&nbsp;Syed Shams ul Hassan ,&nbsp;Xue Xiao ,&nbsp;Shikai Yan ,&nbsp;Huizi Jin","doi":"10.1016/j.phymed.2025.157004","DOIUrl":"10.1016/j.phymed.2025.157004","url":null,"abstract":"<div><h3>Bacground</h3><div>Postmenopausal osteoporosis (PMOP) involves reduced bone mass and disrupted microarchitecture. Promoting osteoblast differentiation is a key therapeutic strategy. <em>Pimpinella candolleana</em> is a traditional Chinese herb used for bone-related disorders.</div></div><div><h3>Purpose</h3><div>To reveal novel osteogenic constituents and underlying mechanisms of <em>P. candolleana</em> in preventing PMOP.</div></div><div><h3>Methods</h3><div>Triterpenoid saponins from <em>P. candolleana</em> (PCTS) were evaluated for anti-PMOP effects in ovariectomized (OVX) mice. Active constituents were isolated and evaluated for osteogenic activity in MC3T3-E1 cells. Bone effects were examined by micro-computed tomography and histology. Mechanisms were explored by transcriptomic and proteomic analyses, with target validation through Western blot, immunostaining, and cellular thermal shift assays.</div></div><div><h3>Results</h3><div>PCTS ameliorated bone loss in OVX mice and obtained eight novel triterpenoid saponins. And CP-1 exhibited the strongest osteogenic activity, promoting osteoblast differentiation in MC3T3-E1 and improving trabecular bone structure <em>in vivo</em> with efficacy comparable to alendronate. Mechanistically, CP-1 activated the P38/JNK MAPK pathway and upregulated the OPG/RANKL axis, thereby regulating bone metabolism and promoting osteogenesis.</div></div><div><h3>Conclusion</h3><div>CP-1 is a promising natural candidate for PMOP therapy by enhancing osteogenesis <em>via</em> MAPK activation and bone metabolism regulation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157004"},"PeriodicalIF":6.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydrotanshinone I inhibits ovarian tumor growth by suppressing ITGB1/FAK-mediated extracellular matrix signaling","authors":"Bing Han ,&nbsp;Chengtao Sun ,&nbsp;Ruiwen Yang ,&nbsp;Xuan Li ,&nbsp;Jie Kang ,&nbsp;Jinyong Cai ,&nbsp;Shuiping Zhou ,&nbsp;Genbei Wang ,&nbsp;Jing Wang ,&nbsp;Jizhou Zhang ,&nbsp;Yun Sun ,&nbsp;Guoyin Kai","doi":"10.1016/j.phymed.2025.157023","DOIUrl":"10.1016/j.phymed.2025.157023","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer is a major lethal malignancy of the female reproductive system. Dihydrotanshinone I (DHT) is a tanshinone compound derived from <em>Salvia miltiorrhiza</em> and possesses significant anti-ovarian cancer activity. However, the mechanism underlying its antitumor effect remains unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the antitumor effect of DHT on ovarian cancer and elucidate the mechanisms through proteomics analysis.</div></div><div><h3>Methods</h3><div>ES2 ovarian cancer nude mice were established and 4D label-free quantitative proteomics was performed. Bioinformatics analysis, RT-PCR, and western blot were conducted for validation. Further confirmation was achieved by shRNA knockdown, CCK-8 assay, wound healing, transwell, and western blot analysis.</div></div><div><h3>Results</h3><div>DHT significantly inhibited tumor growth in ES2 xenograft nude mice. Mechanistically, proteomics and GSEA analysis showed that DHT strikingly inhibited pathways related to extracellular matrix (ECM) receptor interaction, cell adhesion molecules, and focal adhesion. RT-PCR and western blot indicated integrin β1 (ITGB1) as a potential target of DHT. DHT downregulated ITGB1 and its downstream effector, focal adhesion kinase (FAK), both in vitro and in vivo. Bioinformatics analysis revealed that high ITGB1 expression correlated with poor prognosis in ovarian cancer patients. Knockdown of ITGB1 markedly inhibited cell viability, wound healing, and migration ability in ES2 cells, and reduced the expression of anti-apoptosis protein Bcl2, ECM proteins FAK, FN1, and cell adhesion protein Claudin1. Additionally, DHT attenuated ECM activator pyrintegrin-induced migration in ES2 cells.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that DHT inhibits ovarian tumor growth by suppressing ECM pathway <em>via</em> the ITGB1/FAK axis, highlighting its potential as a therapeutic candidate for ovarian cancer treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157023"},"PeriodicalIF":6.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taraxerol induces ferroptosis in breast cancer by targeting Nrf2 transcriptional activity to promote MIB2-mediated GPX4 ubiquitination","authors":"Pan Du ,&nbsp;Anna Han ,&nbsp;Jiajing Liu ,&nbsp;Wenxuan Li ,&nbsp;Xinyue Feng ,&nbsp;Liyan Chen","doi":"10.1016/j.phymed.2025.157024","DOIUrl":"10.1016/j.phymed.2025.157024","url":null,"abstract":"<div><h3>Background</h3><div>Eradicating tumors through targeted ferroptosis represents a novel approach to BC treatment. Taraxerol, a natural triterpenoid derived from dandelions, has shown anti-tumor effects. However, the ferroptosis dependency of Taraxerol’s anticancer effects remains to be elucidated.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the effects and molecular mechanism of action of taraxerol on ferroptosis in BC.</div></div><div><h3>Methods</h3><div>The effects of Taraxerol on the proliferation, lipid peroxidation, iron accumulation, and glutathione (GSH) and malondialdehyde (MDA) levels in BC cells were investigated. Western blotting, qRT-PCR, Co-IP, and dual-luciferase reporter assays were used to detect Taraxerol-induced protein expression and regulation. Network pharmacology and molecular docking were employed to explore the regulation of ferroptosis-related signaling pathways and specific proteins by Taraxerol. The in vivo anti-tumor effect mediated by Taraxerol was explored using a xenograft tumor model.</div></div><div><h3>Results</h3><div>Taraxerol markedly inhibited BC cell proliferation both in vitro and in vivo, increasing lipid peroxidation and Fe²⁺ levels, and reducing GSH levels. Moreover, Taraxerol triggered ferroptosis in BC cells by targeting Nrf2, which is involved in the PI3K/AKT/mTOR signaling pathway. It also promoted the ubiquitin-mediated degradation of GPX4 by regulating the interaction between Nrf2 and the E3 ubiquitin ligase MIB2.</div></div><div><h3>Conclusion</h3><div>Our findings are the first to demonstrate that Taraxerol mediates ferroptosis in BC via the Nrf2/MIB2/GPX4 axis, representing a potential therapeutic candidate for BC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157024"},"PeriodicalIF":6.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoliquiritigenin alleviates abnormal sarcomere contraction and inflammation in myofascial trigger points via the IL‐17RA/Act1/p38 pathway in rats","authors":"Xuan Li ,&nbsp;Tian Qi ,&nbsp;Lingwei Zhou ,&nbsp;Pengyu Lin ,&nbsp;Qinghe Chen ,&nbsp;Xiaoyue Li ,&nbsp;Ren He ,&nbsp;Shaozhong Yang ,&nbsp;Yu Liu ,&nbsp;Feng Qi","doi":"10.1016/j.phymed.2025.156993","DOIUrl":"10.1016/j.phymed.2025.156993","url":null,"abstract":"<div><h3>Background</h3><div>Myofascial trigger points (MTrPs) are a primary cause of myofascial pain syndrome. Current studies suggest that MTrPs consist of persistent sarcomere contraction and an inflammatory microenvironment. IL-17 has been implicated in the progression of inflammation. However, its expression of IL-17 in MTrPs and the underlying mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to characterise IL-17 signalling and elucidate the associated molecular mechanisms in the context of MTrPs, and evaluate the therapeutic effects of isoliquiritigenin (ISL) on MTrPs.</div></div><div><h3>Methods</h3><div>We examined IL-17A signalling expression using immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis in MTrPs rat. Haematoxylin and eosin staining and transmission electron microscopy were used to assess muscle fibre and sarcomere morphology. The Randall-Selitto test was employed to evaluate pain-like behaviours in rats. Dihydroethidium staining, JC-1 assay, and ATP quantification were used to assess inflammation-associated mitochondrial function in vitro and in vivo. Additionally, molecular docking, cellular thermal shift, and drug affinity responsive target stability assays were conducted to examine the interaction between ISL and the IL-17 receptor subunit A (IL‐17RA) protein.</div></div><div><h3>Results</h3><div>IL-17A and IL-17RA were significantly expressed in rats with MTrPs. These rats exhibited elevated oxidative stress level and reduced ATP production. Studies on IL-17A stimulated myotubes and gastrocnemius muscle indicated that IL-17RA signalling contributes to inflammation, abnormal sarcomere contraction and mitochondrial dysfunction in MTrPs. Lentivirus-mediated IL-17RA knockdown in the rats further confirmed these findings. Inhibition of the mitogen-activated protein kinase p38 and subsequent rescue experiments highlighted the critical role of IL-17RA/Act1/p38 signalling. Notably, molecular docking and validation experiments revealed that ISL binds to and inhibits IL-17RA, thereby disrupting IL-17RA/Act1/p38 signalling, and ultimately suppressing the maintenance of MTrPs.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that ISL ameliorates sarcomere contraction and inflammatory responses by inhibiting the IL-17RA/Act1/p38 signalling pathway in rats with MTrPs, highlighting its potential as a novel therapeutic strategy for myofascial pain syndrome (MPS).</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156993"},"PeriodicalIF":6.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traditional Chinese medicine protects against doxorubicin cardiotoxicity via epigenetic modification and beyond","authors":"Jingquan Zhou ,&nbsp;Huan Liu ,&nbsp;Feng Jiang ,&nbsp;Xiyong Yu ,&nbsp;Panxia Wang ,&nbsp;Xiaoqian Wu","doi":"10.1016/j.phymed.2025.157020","DOIUrl":"10.1016/j.phymed.2025.157020","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (DOX), a cornerstone chemotherapeutic agent, is plagued by dose-dependent cardiotoxicity that compromises its clinical utility. Despite advances in understanding DOX-induced cardiotoxicity (DIC), effective interventions remain limited. Emerging evidence highlights Traditional Chinese Medicine (TCM) – with its multi-target epigenetic modulatory potential – as a promising therapeutic strategy.</div></div><div><h3>Purpose</h3><div>This review systematically evaluates the epigenetic landscape of DIC pathogenesis and critically summarizes the cardioprotective effects of TCM through epigenetic reprogramming, aiming to bridge mechanistic insights with translational opportunities.</div></div><div><h3>Study-design/methods</h3><div>Data for this review were sourced from various scientific databases up to March 2025. Search terms include “Doxorubicin”, “Adriamycin”, “Cardiotoxicity”, “DOX-induced cardiotoxicity”, “Doxorubicin induced cardiomyopathy”, “epigenetic modifications”, “Histone Modification”, “DNA Methylation”, “Noncoding RNAs”, “long noncoding RNA”, “microRNA”, circular RNAs, “inflammation”, “ferroptosis”, “autophagy”, “apoptosis” and “Traditional Chinese Medicine” as well as several combinations thereof. Exclusions comprised non-TCM interventions, studies lacking mechanistic clarity, non-cardiotoxicity endpoints, case reports, or inaccessible data.</div></div><div><h3>Results</h3><div>By regulating various signaling pathways including oxidative stress, inflammation, autophagy and epigenetic modification, TCM has been positioned as a promising therapeutic strategy in alleviating DIC. We thoroughly review the pathological mechanism of DIC especially the epigenetic modification and further summarize the potential role of TCM. While preclinical data are compelling, clinical trials validating TCM's epigenetic effects (e.g., circulating miRNA biomarkers) are urgently needed.</div></div><div><h3>Conclusion</h3><div>This review synthesizes current evidence on TCM's cardioprotective effects via epigenetic modulation, providing a foundation for clinical translation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157020"},"PeriodicalIF":6.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Efficacy and safety of standardized lime peel supplement in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study\" [Phytomedicine 139 (2025) 156510].","authors":"Seonghui Kim, Min Young Um, Jin-Kyu Han, Duhyeon Kim, Yunjin Choi, Gibeom Choi, Chaeyoung Bang, Youngtaek Oh, Jang H Youn, Suengmok Cho","doi":"10.1016/j.phymed.2025.156978","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156978","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156978"},"PeriodicalIF":6.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huotan Jiedu Tongluo Decoction targets Nrf2-mediated macrophage autophagy to inhibit ferroptosis and reduce atherosclerotic lesions","authors":"Di Gao ,&nbsp;Tenghui Tian ,&nbsp;Keying Yu ,&nbsp;Xiao Shao ,&nbsp;Rui Shi ,&nbsp;Wen Xue ,&nbsp;Huiyan Feng ,&nbsp;Zhixuan Zhao ,&nbsp;Yue Deng","doi":"10.1016/j.phymed.2025.157012","DOIUrl":"10.1016/j.phymed.2025.157012","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) serves as a fundamental pathological basis for cardiovascular diseases (CVDs), with its progression intimately linked to ferroptosis-mediated disruptions in intracellular iron homeostasis and lipid peroxidation. Huotan Jiedu Tongluo Decoction (HTJDTLD), an effective compound formulafor treating AS based on traditional Chinese medicine (TCM) theory, has exhibited remarkable efficacy in stabilizing plaques and delaying disease progression. However, its underlying mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>This study sought to clarify the therapeutic function and molecular pathways of HTJDTLD in addressing AS, with particular emphasis on its ability to inhibit ferroptosis by influencing macrophage autophagy.</div></div><div><h3>Materials</h3><div>We employed UPLC-HRMS to analyze HTJDTLD constituents, identified key ingredients. An atherosclerotic model was established using ApoE^-/- mice, alongside an in vitro foam cell model derived from RAW264.7 macrophages. A combination of histopathological staining, biochemical assays, dihydroethidium (DHE) staining, transmission electron microscopy (TEM), immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB) analysis, and assessments of lipid peroxidation and mitochondrial membrane potential using BODIPY 581/591 C11 and JC-1 fluorescent probes was employed to systematically investigate the molecular mechanisms of HTJDTLD against AS by activating autophagy and inhibiting ferroptosis. The Nrf2 inhibitor ML385 was employed to validate the core mechanism.</div></div><div><h3>Results</h3><div>UPLC-HRMS analysis revealed that HTJDTLD contains 537 chemical components, among which 24 prototype components were detected in the blood, indicating its potential to exert pharmacological effects via bloodstream absorption. In vivo studies demonstrated that HTJDTLD activated the Nrf2 signaling pathway, thereby upregulating autophagy- and ferroptosis-related proteins, significantly improving lipid metabolism, suppressing inflammatory cytokine release, reducing iron ion accumulation, and decreasing reactive oxygen species (ROS) production in ApoE^-/- mice, ultimately enhancing plaque stability. In vitro findings corroborated that HTJDTLD exerted anti-ferroptotic effects by mitigating lipid peroxidation, restoring mitochondrial function, and engaging multiple antioxidant pathways. Mechanism studies further confirmed that inhibition of Nrf2 eliminated the protective effect of HTJDTLD on autophagy and the inhibition of ferroptosis.</div></div><div><h3>Conclusion</h3><div>This study represents the initial exploration of a new mechanism through which HTJDTLD reduces macrophage ferroptosis and improves AS by stimulating the Nrf2/autophagy axis. These findings establish an essential theoretical basis for utilizing TCM in the prevention and management of AS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157012"},"PeriodicalIF":6.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-affinity driven repurposing of natural compounds and herbal prescriptions for ulcerative colitis and psoriasis","authors":"Rui Tian ,&nbsp;Ting Hu ,&nbsp;Jinyuan Chang ,&nbsp;Xue Chen ,&nbsp;Zhenglong Jiang ,&nbsp;Xuanyi Wang ,&nbsp;Li Feng ,&nbsp;Shaosheng Bei","doi":"10.1016/j.phymed.2025.156999","DOIUrl":"10.1016/j.phymed.2025.156999","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis and ulcerative colitis (UC) are immune-mediated chronic inflammatory diseases that affect barrier organs and share significant overlap in both pathogenesis and treatment strategies. Although the advent of biologics has transformed therapeutic options, their high cost often limits long-term accessibility, underscoring the need for alternative approaches.</div></div><div><h3>Purpose</h3><div>Natural compounds and traditional medicine represent valuable sources for novel drug discovery and repurposing, but systematic strategies for repurposing traditional medicines remain underdeveloped.</div></div><div><h3>Methods</h3><div>Here, we present a computational framework for drug repurposing based on drug-target affinity and structural rationality, focused on the traditional herbs and prescriptions of JAK family and chemokine receptors.</div></div><div><h3>Results</h3><div>We identified 204 natural compounds, among which 9-hydroxycamptothecin showed the most promising therapeutic potential for both psoriasis and UC. Notably, WU MEI PILL, a classical prescription in East Asian traditional medicine, also emerged as a promising multi-target therapy for both diseases. In vivo experiments confirmed that 9-hydroxycamptothecin and WU MEI PILL significantly alleviated disease symptoms, improved intestinal mucosal and epidermal pathologies, and upregulated intestinal Claudin-1 and MUC-2 expression. These effects were mediated through suppression of JAK1/STAT3 phosphorylation.</div></div><div><h3>Conclusion</h3><div>This study introduces a tailored approach for traditional medicine-based drug repurposing, offering a scalable and efficient strategy for identifying natural therapeutics and guiding clinical decision-making, modernization, and standardization of traditional medicine.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156999"},"PeriodicalIF":6.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alisol B ameliorated metabolic dysfunction-associated steatotic liver disease via regulating purine metabolism and restoring the gut microbiota disorders","authors":"Lin Yiyou ,&nbsp;Zhang Congcong ,&nbsp;Ren Guilin ,&nbsp;Qiu Jiannan ,&nbsp;Fu Yilong ,&nbsp;Liu Fucai ,&nbsp;Liu Qingsheng ,&nbsp;Yu Zhiling ,&nbsp;Chen Lin ,&nbsp;Dou Xiaobing","doi":"10.1016/j.phymed.2025.156992","DOIUrl":"10.1016/j.phymed.2025.156992","url":null,"abstract":"<div><h3>Background</h3><div>Alisol B (AB) has been demonstrated to be a potential lead compound in improving obesity-related metabolic disorders. Nevertheless, the effects and mechanisms of AB on Metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the improvement of AB on MASLD and explore the intricate mechanism involving gut microbiota and liver metabolism.</div></div><div><h3>Materials and methods</h3><div>The MASLD mice model was established by feeding a high-fat diet and oral treatment with AB. The effects of AB on lipid metabolism in MASLD were initially measured. Subsequently, 16S rRNA gene sequencing, untargeted metabolomics combined with network pharmacology analysis was used to unveil the potential mechanism of AB on MASLD. A series of molecular biology experiments was conducted to confirm the results of the multi-omics analysis and to elucidate the key mechanism.</div></div><div><h3>Results</h3><div>AB attenuated liver steatosis and improved liver injury in MASLD mice. AB treatment improved the diversity of gut microbiota and increased the abundance of <em>Akkermansia, Escherichia-Shigella, and Muribaculu</em> in MASLD mice. Based on correlation analysis between differential intestinal microbiota and metabolites, metabolites involving sodium oleate, helleolate acetate 3-acetate and oxaminate were identified as key metabolites. In addition, integrating metabolomics and network pharmacology showed that AB alleviated MASLD by regulating the purine metabolism pathway and <em>de novo</em> fatty acid biosynthesis. Then, we focused on the role of purine metabolism in the treatment of MASLD by AB. Notably, AB inhibited the urine acid level in serum and liver of MASLD mice and hepatic XO activity and expression. AB markedly reduced the hypoxanthine and allantoin levels, increased the inosine level in the livers of MASLD mice, indicating that AB significantly reversed the dysfunction of hepatic purine metabolism in MASLD. Moreover, Molecular docking and surface plasmon resonance (SPR) results demonstrated that AB directly binds to XO. Overexpressing XO abolished the effect of AB in lipid accumulations in AML-12 cells. AB may alleviate MASLD by directly targeting XO to inhibit purine metabolism disorders in the liver.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that AB treatment attenuates HFD-induced MASLD through dual mechanisms involving gut microbiota modulation and restoration of hepatic metabolic homeostasis. Comprehensive mechanistic analysis revealed that AB ameliorates hepatic steatosis and corrects purine metabolism dysregulation in MASLD pathogenesis through specific inhibition of XO. These findings provide novel mechanistic insights into the hepatoprotective properties of AB and establish its therapeutic potential for MASLD intervention.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156992"},"PeriodicalIF":6.7,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}