Phytomedicine最新文献

{"title":"Xing-nao-sheng-jiang powder alleviates ischemic stroke in rats by inhibiting pyroptosis-related microglial ETosis: An emerging perspective on microglial ETosis","authors":"Chang ZHOU ,&nbsp;Ye TANG ,&nbsp;Fuchang LU ,&nbsp;Cheng-hao DU ,&nbsp;Wei-liang ZHU ,&nbsp;Gui-xian CHEN ,&nbsp;Hui XIA ,&nbsp;Min ZHAO ,&nbsp;Ze-quan ZHENG ,&nbsp;Yuan-qi ZHAO","doi":"10.1016/j.phymed.2026.157887","DOIUrl":"10.1016/j.phymed.2026.157887","url":null,"abstract":"<div><h3>Background</h3><div>Stroke imposes a substantial global health burden. Microglial pyroptosis promotes acute cerebral ischemia. Gasdermin D (GSDMD), the principal executor of pyroptosis, has been implicated in a newly characterized form of proinflammatory cell death known as extracellular trap death (ETosis). Thus, targeting GSDMD may represent a promising therapeutic strategy to mitigate ischemic stroke. Xing-nao-sheng-jiang powder (XNSJP) was demonstrated to inhibit GSDMD-mediated pyroptosis in cerebral ischemia-reperfusion injury (CIRI). Based on these findings, we hypothesize that XNSJP may inhibit pyroptosis-related ETosis by targeting the GSDMD, thereby alleviating neuroinflammation in CIRI.</div></div><div><h3>Methods</h3><div>We prepared the MCAO model in SD rats and evaluated the effects of XNSJP on anti-CIRI. The effects of XNSJP on microglia and neutrophil pyroptosis and ETosis were detected. The composition of XNSJP was identified using UPLC and MS/MS methods.</div></div><div><h3>Results</h3><div>UPLC identified the characteristic peaks of XNSJP’s active ingredients. MS/MS and network pharmacology suggested that XNSJP has regulatory effects on atherosclerosis, coagulation, and inflammation. The XNSJP reduced the area of infarction. XNSJP could inhibit the caspase-1/11/GSDMD-mediated pyroptosis. Furthermore, XNSJP impeded microglial pyroptosis-related ETosis by GSDMD, as evidenced by the suppression of MPO, PAD4, and CitH3. We also confirmed that 24 h after CIRI, the ETosis marker CitH3 mainly co-localized with microglia.</div></div><div><h3>Conclusions</h3><div>We confirmed that microglia are crucial contributors to ETosis in CIRI. Furthermore, we demonstrated that XNSJP inhibited microglial pyroptosis and ETosis against CIRI, which is closely related to the inhibition of GSDMD. Mechanistically, XNSJP inhibits caspase-1/11/GSDMD-mediated microglial pyroptosis and MPO/PAD4/CitH3-mediated microglial ETosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157887"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158144","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":"Bupleurum chinense ameliorates metabolic-associated fatty liver disease by modulating Sirtuin 6","authors":"Siqi Liu ,&nbsp;Penglong Chen ,&nbsp;Yayi Li ,&nbsp;Zhisen Pan ,&nbsp;Can Zhang ,&nbsp;Anquan Li ,&nbsp;Chongyan Huang ,&nbsp;Hongxuan Zheng ,&nbsp;Like Chen ,&nbsp;Chuangpeng Shen","doi":"10.1016/j.phymed.2026.157905","DOIUrl":"10.1016/j.phymed.2026.157905","url":null,"abstract":"<div><h3>Background</h3><div><em>Bupleurum chinense</em> (Bc) is a traditional Chinese medicine commonly used to treat metabolic-associated fatty liver disease (MAFLD), demonstrating hepatoprotective, anti-inflammatory, and antioxidant effects. Sirtuin 6 (SIRT6) regulates fatty acid metabolism and oxidative stress, playing a crucial role in MAFLD treatment.</div></div><div><h3>Purpose</h3><div>To investigate Bc’s mechanisms in ameliorating MAFLD and analyze the primary active components contributing to its therapeutic effects.</div></div><div><h3>Methods</h3><div>C57BL/6J mice developed MAFLD through 12-week high-fat diet (HFD) feeding, followed by 4-week interventions with Bc decoction (1.3, 0.65, 0.325 g/kg/d) or pioglitazone (0.1 g/kg/d). Lipid metabolism, oxidative stress, inflammation, and insulin resistance were measured. RNA-seq identified the key Bc targets, which were validated in liver-specific knockout mice. Bioactive constituents were initially screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, followed by molecular docking, dynamics simulations, and microscale thermophoresis (MST) to validate target affinity and binding stability. An in vitro MAFLD model was established using primary mouse hepatocytes (MPHs) challenged with oleic and palmitic acid (OAPA).</div></div><div><h3>Results</h3><div>Bc significantly ameliorated lipid accumulation and HFD-induced oxidative stress. Pioglitazone and Bc (1.3 g/kg/d) administration demonstrated marked reductions in circulating TG, ALT, and AST concentrations in a dose-responsive manner. Furthermore, Bc ameliorated hepatic oxidative stress, as evidenced by elevated GSH and SOD levels alongside reduced H₂O₂ content. Transcriptomic profiling and mechanistic validation identified SIRT6 as the central mediator. Bc upregulated SIRT6 expression and enhanced its deacetylase activity, resulting in reduced acetylation of histone H3K9 and H3K56 compared to HFD controls. This promoted PPARα/NRF2 nuclear translocation, upregulating fatty acid β-oxidation genes (such as <em>Cpt1a</em>) and antioxidant genes (such as <em>Ho-1</em>). Crucially, hepatocyte-specific Sirt6 knockout abolished Bc's therapeutic effects. Moreover, molecular docking, molecular dynamics, and MST results indicated that Saikosaponin C (SSc), the major component of Bc, has a strong affinity for SIRT6. Cell experiments confirmed that SSc (25 μM) significantly improved lipid deposition and redox imbalance in MAFLD models, exhibiting SIRT6-dependent efficacy.</div></div><div><h3>Conclusion</h3><div>Bc alleviates MAFLD by activating SIRT6 through its core component SSc. This activation, via SIRT6-mediated histone deacetylation, enhances PPARα/NRF2-driven metabolic-redox homeostasis, establishing the Bc-SSc-SIRT6 axis as a therapeutic target.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157905"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158089","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":"Pedunculoside ameliorates metabolic dysfunction-associated steatotic liver disease by targeting HNRNPA1 and modulating PPARα signaling pathway to enhance Mitochondrial Fatty Acid β-Oxidation","authors":"Yang Zhou ,&nbsp;Jingyun Chi ,&nbsp;Xining Xu ,&nbsp;Rongrong Zhu ,&nbsp;Tianhao Wang ,&nbsp;Tao Zhang ,&nbsp;Dandan Hong ,&nbsp;Huazhou Fu ,&nbsp;Xizhen Zhou ,&nbsp;Kun Zhao","doi":"10.1016/j.phymed.2026.157910","DOIUrl":"10.1016/j.phymed.2026.157910","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a significant global health challenge, underscoring an urgent need for novel therapeutic agents that offer enhanced efficacy and improved safety. Pedunculoside (PE), a naturally occurring triterpenoid saponin, has demonstrated promising lipid-modulating properties. Nevertheless, its precise mechanisms of action in the context of MASLD remain unclear.</div></div><div><h3>Purpose</h3><div>To investigate the anti-MASLD effect of PE and uncover its novel mechanism via targeting heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and regulating downstream PPARα pathway.</div></div><div><h3>Method</h3><div>The therapeutic potential of PE was evaluated both in primary mouse hepatocytes and in vivo using high-fat, high-cholesterol (HFHC) and high-fat diet (HFD) induced MASLD mouse models. A multi-omics and multi-technique approach was applied, including biochemical assays, histopathology, transcriptomic and lipidomic profiling, alongside target-engagement validation via drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), surface plasmon resonance (SPR), molecular docking, molecular dynamics simulations, and HNRNPA1 knockout models.</div></div><div><h3>Results</h3><div>PE significantly improved key metabolic and histological features in MASLD models. Mechanistically, PE was found to directly bind HNRNPA1 (a previously unreported target in MASLD therapeutics). This interaction enhanced the mRNA stability of PPARα, leading to activation of fatty acid β-oxidation. Crucially, HNRNPA1 knockout abolished the beneficial effects of PE, confirming the functional necessity of the PE–HNRNPA1–PPARα axis in vivo.</div></div><div><h3>Conclusion</h3><div>Our study uncovers a novel therapeutic axis in MASLD, in which PE enhances the stability of PPARα mRNA by directly binding to HNRNPA1, and consequently upregulates fatty acid β-oxidation. These findings not only position PE as a promising therapeutic candidate for MASLD but also identify the HNRNPA1–PPARα regulatory pathway as a potential mechanistic target for treating metabolic liver diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157910"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166394","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":"Lycorine improves inflammatory imbalance in diabetic cardiomyopathy by targeting ILF3.","authors":"Qian Zhou, Xuejin Jin, Miao Yuan, Huanyan Tao, Shenjie Bao, Jingnan Zhang, Zheng Xu, Nipon Chattipakorn, Yi Wang, Hong Zhu, Guang Liang","doi":"10.1016/j.phymed.2026.157976","DOIUrl":"10.1016/j.phymed.2026.157976","url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiomyopathy (DCM) is characterized by chronic low-grade inflammation and metabolic disturbances, leading to progressive cardiac dysfunction. Lycorine (LY), a complex tetracyclic pyrrolo[de]phenanthridine alkaloid from the Amaryllidaceae family, has shown potential anti-inflammatory effects, but its role in DCM pathogenesis remains unexplored.</p><p><strong>Purpose: </strong>This study investigated the cardioprotective effect of LY in DCM and its underlying molecular mechanisms.</p><p><strong>Methods: </strong>We employed both in vitro (high glucose/palmitic acid-treated cardiomyocytes) and in vivo (streptozotocin-induced diabetic mice) models to investigate LY's cardioprotective effects. Liquid chromatography-tandem mass spectrometry, molecular docking, surface plasmon resonance binding assay, cellular thermal shift assay, and RNA interference approaches were utilized to identify the key target and mechanistic pathways.</p><p><strong>Results: </strong>In vitro and in vivo models of DCM revealed that LY significantly attenuated cardiac inflammation. Mechanistically, liquid chromatography-tandem mass spectrometry analysis revealed that LY targeted interleukin enhancer-binding factor 3 (ILF3), a critical regulator of inflammatory responses. Notably, surface plasmon resonance and cellular thermal shift assay data validated a direct interaction between LY and ILF3. By interacting with ILF3, LY enhanced nuclear factor erythroid 2-related factor 2-mediated anti-inflammatory responses while suppressing NF-κB-driven pro-inflammatory signaling, thereby restoring inflammatory homeostasis and reducing myocardial injury. Furthermore, ILF3 knockdown mimicked the protective effects of LY, and ILF3 activity was essential for LY's cardioprotective effects.</p><p><strong>Conclusion: </strong>These findings suggest that LY ameliorates DCM by modulating ILF3-dependent nuclear factor erythroid 2-related factor 2 and NF-κB crosstalk to restore inflammatory balance, suggesting its potential as a novel therapeutic agent for diabetic cardiovascular complications.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"157976"},"PeriodicalIF":11.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259097","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":"Ginsenoside Rg5 targets the KAT8-CISD2 axis to maintain mitochondrial homeostasis and antagonize senescence","authors":"Jinmeng Chu,&nbsp;Qingzhi Zhao,&nbsp;Yizhen Wang,&nbsp;Chengyu Cai,&nbsp;Xueli Cui,&nbsp;Na Zhang,&nbsp;Tiantian Xu,&nbsp;Haoqing Dou,&nbsp;Fei Wang,&nbsp;Feiran Yu,&nbsp;Yong Cai,&nbsp;Jingji Jin","doi":"10.1016/j.phymed.2026.157923","DOIUrl":"10.1016/j.phymed.2026.157923","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Mitochondria are central regulators of cellular energy metabolism and its dysfunction drives cellular senescence. CISD2, a mitochondrial outer membrane protein and longevity gene, declines with age, highlighting its role in cellular senescence; however, how its post-translational modifications (PTMs) regulate cellular senescence remains poorly understood.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to elucidate the molecular mechanisms by which ginsenoside Rg5, as a regulator of histone acetyltransferase KAT8 activity, modulates CISD2 PTMs and thereby exerts anti-aging effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Using SILAC-based acetyl-proteomics, CISD2 was identified as a substrate of the KAT8/MSL acetyltransferase complex. The interaction between KAT8 and CISD2 was examined by Co-immunoprecipitation, GST pull-down, cycloheximide chase, and protein stability assays. KAT8-mediated acetylation of CISD2 was evaluated using in vitro lysine acetyltransferase assays, modification-specific antibodies, and site-directed mutagenesis. The functional impact of CISD2 acetylation on mitochondrial homeostasis was assessed by comparing CISD2 wild-type and K74 mutant cell lines using a series of assays, including ROS production, JC-1 staining, ATP measurement, SA-β-Gal staining, and analyses of mitochondrial morphology. The interaction between Rg5 and KAT8 was investigated using cellular thermal shift assays (CETSA), Rg5-PEGA pull-down, competitive binding assays, and UV-absorption spectroscopy. Evolutionary conservation was evaluated in C. elegans through genetic depletion of mys-2 (the KAT8 homolog) and cisd-1 (the CISD2 homolog). Mitochondrial function (JC-1, DCFH-DA, mtDNA content, and ATP levels) and cellular senescence (SA-β-Gal staining, EdU incorporation, and CCK-8 assays) were assessed in senescent cells and in C. elegans following CISD-1 and/or MYS-2 RNAi.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We demonstrate for the first time that the KAT8/MSL complex acetylates CISD2 at K74, thereby preventing STUB1-mediated ubiquitination and degradation at K105. Importantly, acetylation of CISD2 at K74 preserves mitochondrial homeostasis and enhances cellular resistance to oxidative stress and aging. In &lt;em&gt;C. elegans&lt;/em&gt;, simultaneous knockdown of MYS-2 and CISD-1 exacerbates mitochondrial dysfunction and shortens lifespan. Moreover, ginsenoside Rg5 directly binds to KAT8, promotes CISD2 acetylation at the K74 site, maintaining mitochondrial homeostasis, and alleviates aging-associated phenotypes in both cells and nematodes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study reveals that KAT8-mediated acetylation of CISD2 at K74 preserves mitochondrial homeostasis by inhibiting ubiquitin-mediated degradation, representing a critical mechanism for counteracting cellular senescence. Ginsenoside Rg5 acts as a KAT8 agonist to target and activate this pathway, thereby providing a novel strategy for anti-aging intervention.&lt;/di","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157923"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192106","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":"Gut microbiota-derived deoxycholic acid mediates the exercise performance-potentiating efficacy of gypenosides","authors":"Xiangchang Yin ,&nbsp;Xiaojuan Chen ,&nbsp;Guang Yang ,&nbsp;Gang Li ,&nbsp;Haizhen Liang ,&nbsp;Juan Song ,&nbsp;Jie Zhang ,&nbsp;Lan Yao ,&nbsp;Rui Xue ,&nbsp;Yaling Xing ,&nbsp;Youzhi Zhang ,&nbsp;Baiping Ma","doi":"10.1016/j.phymed.2026.157950","DOIUrl":"10.1016/j.phymed.2026.157950","url":null,"abstract":"<div><h3>Background</h3><div>Pharmacological interventions of exercise adaptation offer a viable strategy to enhance athletic performance and improve the quality of life in both the elderly and manual workers. Gypenosides (Gyp), a group of bioactive dammarane-type triterpenoid saponins from genus <em>Gynostemma</em>, can increase exercise performance and muscle function in rodents and healthy males, whose mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>We explored the role of the gut microbiota (GM) in exercise performance-potentiation by Gyp administration.</div></div><div><h3>Methods</h3><div>Multiple behavioral tests, immunofluorescence staining, 16 s rRNA gene sequencing, and targeted metabolomics were assessed to demonstrate the altered endurance phenotype induced by Gyp. GM depletion and bile acid pool depletion models were introduced to evaluate the effects of these two factors on the performance-enhancing efficacy of Gyp. UPLC-Q/TOF-MS analysis and luciferase assays were performed to identify FXR antagonists in Gyp. In vitro and in vivo experiments were validated whether deoxycholic acid (DCA) can mimic the benefits of Gyp.</div></div><div><h3>Results</h3><div>Preventive Gyp treatment led to an improved endurance exercise phenotype and shifted oxidative metabolic pattern of myofibers from Type II to I in sedentary mice. Gyp reshaped the GM and enriched a group of secondary bile acids (BAs), which were the key signature of global metabolic remodeling. Mechanistically, Gypenosides including gypenoside V specifically inhibited the intestinal farnesoid X receptor (FXR) signaling and increased secondary BA levels such as DCA. DCA enhanced myogenic differentiation and myoblast fusion in C2C12 myotubes, and mimicked performance-enhancing effect of Gyp in vivo by activating TGR5-cAMP-PKA signaling pathway.</div></div><div><h3>Conclusion</h3><div>We identified gypenosides as a promising exercise mimetic and suggested the potential of the GM as a key target for physical performance enhancement. DCA-mediated TGR5 activation provides novel mechanistic insight into the pharmacological targeting of exercise adaptations.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157950"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192105","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":"Homoplantaginin alleviates high glucose-induced vascular endothelial barrier dysfunction by regulating Yes-associated protein 1","authors":"Xulu Li ,&nbsp;Jingwen Wang ,&nbsp;Lei Wang,&nbsp;Xiaotong Sha,&nbsp;Shuci Huang,&nbsp;Mingshi Ren,&nbsp;Lu Cheng,&nbsp;Yifei Zhang,&nbsp;Wuliu Zhou,&nbsp;Yining Lin,&nbsp;Feihua Wu","doi":"10.1016/j.phymed.2026.157953","DOIUrl":"10.1016/j.phymed.2026.157953","url":null,"abstract":"<div><h3>Background</h3><div>The vascular endothelial (VE) barrier dysfunction is critical for the onset and progression of diabetic macrovascular complications. Homoplantaginin (HPG), the flavone glucoside hispidulin 7-O-β-<span>d</span>-glucoside, one of the main components of <em>Salvia plebeia</em> R.Br., possesses endothelium protective properties. However, the molecular mechanisms of HPG against diabetic VE barrier dysfunction remain unclear.</div></div><div><h3>Objective</h3><div>To investigate the protective effects and potential mechanisms of HPG on VE barrier function using high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs) and type 1 diabetic (T1D) mice.</div></div><div><h3>Methods</h3><div>In vitro, the protective effect of HPG on endothelial barrier function was assessed by western blotting, RT-qPCR, immunofluorescence, trans endothelial electric resistance, and transwell cell permeability assay. Additionally, T1D mice induced by streptozotocin were gavaged with HPG or combined with EX-527 for 28 days to evaluate the therapeutic effect of HPG.</div></div><div><h3>Results</h3><div>HPG upregulated the protein and mRNA expression of VE-cadherin, Zonula occludens-1 (ZO-1), occludin, and claudin-1, inhibiting the permeability and the cytoplasmic translocation of high mobility group box 1 (HMGB1) in HG-treated HUVECs. Additionally, HPG significantly inhibited YAP1 phosphorylation, promoted YAP1 nuclear translocation, and enhanced YAP1-SIRT1 interaction. Moreover, molecular docking and cell thermal shift assay revealed that HPG interacted with YAP1. Knockdown of YAP1 gene attenuated the beneficial effect of HPG in vitro. HPG also alleviated glucose and lipid metabolism disorders, oxidative stress, and inflammation; increased the expression of VE-cadherin, ZO-1, SIRT1 and YAP1 in aortic endothelium; improved aortic endothelial barrier function; and attenuated aortic injury in T1D mice. The SIRT1 inhibitor EX-527 significantly reversed the protective effect of HPG on endothelial barrier function in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>HPG protects against HG-mediated VE barrier dysfunction via the YAP1/SIRT1/HMGB1 pathway. This study provides valuable insights into HPG as a potential candidate compound for the treatment of diabetic macrovascular complications.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157953"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192190","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":"Gualou Huoxue Jiedu Decoction inhibits VSMC phenotypic switching to alleviate atherosclerosis via promoting Mfap4 DNA methylation","authors":"Yiming Li ,&nbsp;Wenxin Zou ,&nbsp;Yan Zhang ,&nbsp;Zhongwen Qi ,&nbsp;Qing Wang ,&nbsp;Zijun Jia ,&nbsp;Qingbing Zhou ,&nbsp;Fengqin Xu","doi":"10.1016/j.phymed.2026.157881","DOIUrl":"10.1016/j.phymed.2026.157881","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) is a chronic disease characterized by lipid deposition in the vascular intima. As the pathological basis of cardiovascular diseases, AS represents a major contributor to global morbidity and mortality. While Gualou Huoxue Jiedu Decoction (GHJD) has been widely used in clinical practice for the treatment of AS, the molecular mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>To investigate the anti-atherosclerotic effects and underlying mechanisms of GHJD.</div></div><div><h3>Methods</h3><div>Apoe^-/- mice were treated with GHJD to evaluate its effects on plaque formation, lipid profiles, and inflammatory responses. The main compounds in GHJD were identified using UHPLC-Q-Orbitrap HRMS. Integrated analyses of network pharmacology, methyl-capture sequencing (MC-seq), and RNA-seq were performed to elucidate the molecular mechanisms of GHJD. In vitro experiments were conducted to validate its mechanism of action.</div></div><div><h3>Results</h3><div>GHJD alleviated plaque formation, improved lipid metabolism, and suppressed inflammation in vivo. Multi-omics analysis revealed that DNA methylation of Mfap4 could be a pivotal target of GHJD efficacy. In vitro assays confirmed that GHJD suppressed <em>Mfap4</em> transcription and translation, leading to downregulation of integrin receptor family expression and inhibition of VSMC phenotypic switching.</div></div><div><h3>Conclusion</h3><div>GHJD exerts anti-atherosclerotic effects through epigenetic modulation of <em>Mfap4</em> and downstream integrin/FAK signaling pathway, thereby inhibiting VSMC phenotypic switching. These findings provide pharmacological evidence supporting GHJD as a potential therapy for AS and, for the first time, validate MFAP4 as a pharmacological target, offering new insights into AS prevention and treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157881"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192189","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":"Oligopeptides from Gynura divaricata improve glycemic control via inhibition of gluconeogenesis and gut-brain axis regulation","authors":"Fang Zhang ,&nbsp;Haonan Xu ,&nbsp;Yan Zuo ,&nbsp;Ke Che ,&nbsp;Yu Cui ,&nbsp;Zhenhua Niu ,&nbsp;Weiliang Cao ,&nbsp;Tingting Sun ,&nbsp;Yan Che ,&nbsp;Hao Yu ,&nbsp;Hao Chen","doi":"10.1016/j.phymed.2026.157876","DOIUrl":"10.1016/j.phymed.2026.157876","url":null,"abstract":"<div><h3>Background</h3><div>Oligopeptides derived from dietary sources are regarded as ideal functional ingredients for nutritional interventions in diabetes due to their favorable bioavailability, target specificity, and safety profiles. Gynura divaricata (GD), a medicinal food plant, has shown hypoglycemic properties; however, the potential of GD-derived oligopeptides in glycemic control and their mechanistic underpinnings remain largely unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-diabetic efficacy of GD oligopeptides and elucidate their mechanisms of action, particularly via the gut-microbiota-brain axis, in a streptozotocin (STZ)/high-fat diet-induced diabetic mouse model.</div></div><div><h3>Methods</h3><div>The therapeutic effects of GD oligopeptides were assessed through longitudinal blood glucose monitoring and systemic biochemical profiling. Organ-specific protection was evaluated via histopathological examination of the liver, pancreas, intestine, and brain. The influence on gluconeogenesis was analyzed by quantifying key glycogen metabolic proteins. Gut microbiota composition was assessed by sequencing, short-chain fatty acids (SCFAs) were measured, and appetite/energy metabolism regulators in the brain were detected. And a subset of diabetic mice was subjected to broad-spectrum antibiotic treatment to validate the effcst of gut microbes. Bioactive peptides were identified using LC-ESI-MS/MS, and molecular docking was performed to evaluate binding affinity to AKT.</div></div><div><h3>Results</h3><div>GD oligopeptides significantly ameliorated hyperglycemia, dyslipidemia, and insulin resistance in diabetic mice. They enhanced hepatic glycogen synthesis and suppressed gluconeogenesis through activation of the AKT/FoxO1 pathway, and reduced pancreatic apoptosis via modulation of Bcl-2/Bax expression. A total of 37 bioactive peptides were identified, with molecular docking confirming strong binding between GD oligopeptides and AKT. Importantly, GD oligopeptides restored intestinal barrier integrity, enriched SCFA-producing Lachnospiraceae, and promoted GPR43-dependent GLP-1 secretion, leading to hypothalamic GLP-1R activation, subsequent POMC upregulation, and NPY/AgRP suppression, collectively normalizing energy homeostasis. Crucially, all these therapeutic benefits were substantially reduced following antibiotic-induced microbiota depletion.</div></div><div><h3>Conclusion</h3><div>These findings underscore the potential of GD oligopeptides as a novel functional food ingredient for diabetes management by simultaneously targeting gluconeogenesis, gut microbiota, and central energy regulation, providing a mechanistic foundation for clinical translation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157876"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192188","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":"8-Shogaol from White Ginger induces cell apoptosis and autophagy in human colon cancer HCT116 cells and in vivo","authors":"Rui Zhang ,&nbsp;Jing-Yu Feng ,&nbsp;Kiran Thakur ,&nbsp;Fei Hu ,&nbsp;Jian-Guo Zhang ,&nbsp;Yi-Long Ma ,&nbsp;Zhao-Jun Wei","doi":"10.1016/j.phymed.2026.157954","DOIUrl":"10.1016/j.phymed.2026.157954","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) constitutes a leading global health challenge, with incidence and mortality on an upward trajectory across diverse populations. Ginger (<em>Zingiber officinale</em> Roscoe) is a widely recognized traditional medicinal plant with established therapeutic and culinary applications. 8-Shogaol, a key phenolic component of ginger, exhibits diverse pharmacological activities including antitumor, anti-inflammatory, and analgesic effects. However, its specific mechanisms against colon cancer remain incompletely understood.</div></div><div><h3>Purpose</h3><div>Our study outlines the anti-cancer efficacy of 8-Shogaol against human colon cancer HCT116 cells and its underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>miRNA-omics was employed to delineate the molecular mechanisms through which 8-Shogaol induces apoptosis in HCT116 cells. <em>In vivo</em> and <em>in vitro</em> validations were conducted by flow cytometry, Immunohistochemistry, and Western blotting for cell apoptosis and autophagy.</div></div><div><h3>Results</h3><div>We identified 193 differentially expressed miRNAs (98 up-regulated, 95 down-regulated) among 1289 detected miRNAs, with KEGG pathway analysis revealing significant enrichment in the PI3K/AKT signaling pathway. <em>In vivo</em> experiments revealed that 8-Shogaol (40mg/kg) significantly suppressed tumor growth. In addition, 8-Shogaol induced cell cycle arrest exclusively at the G2/M phase and enhanced apoptotic effects in HCT116 cells by modulating key regulatory proteins (Bcl-2, Caspase 3, AKT, PI3K). 8-Shogaol also induced autophagy by regulating related proteins (LC3II/LC3I, ULK-1, Beclin-1). Mechanistic exploration suggested that 8-shogaol induced autophagy and apoptosis through inhibition of PI3K/AKT signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that 8-Shogaol exerts potent anticancer effects against colon cancer through PI3K/AKT pathway modulation, concurrently inducing apoptosis and autophagy. This study provides comprehensive mechanistic insights into the therapeutic potential of 8-Shogaol for CRC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157954"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192290","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}