Phytomedicine最新文献

{"title":"Suppressing ferroptosis via modulating FTH1 by silybin for treatment of renal fibrosis","authors":"Jia-Qin Hu ,&nbsp;Cang-Qiong Ning ,&nbsp;Fang-Cao Pi ,&nbsp;Xue-Ni Cai ,&nbsp;Jian Zhou ,&nbsp;Nan Wang ,&nbsp;Li-Li Yu ,&nbsp;Hua Zhou ,&nbsp;Ying Xie","doi":"10.1016/j.phymed.2025.156937","DOIUrl":"10.1016/j.phymed.2025.156937","url":null,"abstract":"<div><h3>Background</h3><div>Renal fibrosis, a hallmark pathological manifestation of chronic kidney disease, arises from diverse etiological factors. While ferroptosis has emerged as a pivotal contributor to renal fibrogenesis, the regulatory mechanisms governing this process—particularly those involving iron metabolism—remain poorly characterized.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the molecular mechanism through which silybin modulates FTH1 to regulate iron homeostasis, thereby suppressing ferroptosis and attenuating fibrotic progression in renal pathology.</div></div><div><h3>Study Design</h3><div>The therapeutic efficacy of ferrostatin-1 (Fer-1) and silybin was systematically evaluated in complementary in vivo and in vitro renal fibrosis models. Mechanistic investigations employed FTH1 knockout and overexpression systems to validate its role as a therapeutic target.</div></div><div><h3>Methods</h3><div>Fibrotic inhibition was assessed histologically and via quantification of fibrotic markers. Iron ion concentrations and reactive oxygen species (ROS) levels were measured using standardized commercial assay kits. The silybin-FTH1 interaction was investigated through surface plasmon resonance (SPR) analysis.</div></div><div><h3>Results</h3><div>Silybin administration demonstrated potent ferroptosis inhibition, significantly ameliorating pathological alterations and fibrotic marker expression across experimental models. FTH1 ablation exacerbated ferroptotic cell death and fibrotic progression, whereas FTH1 overexpression conferred robust protection against renal fibrosis. Mechanistically, silybin directly bound FTH1 protein, stabilizing its expression to counteract iron overload-induced ferroptosis.</div></div><div><h3>Conclusions</h3><div>Our study unveils FTH1 stabilization as a mechanistically novel strategy to disrupt the vicious cycle of iron overload and ferroptosis in renal fibrosis, offering a superior alternative to conventional ferroptosis inhibitors targeting downstream effectors.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156937"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313057","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":"The HIF-1α signaling pathway: A key approach to revealing the effects of Scutellaria baicalensis Georgi against lipopolysaccharide-induced spontaneous abortion","authors":"Jing-xin Gao ,&nbsp;Mei-ying Yue ,&nbsp;Jin-zhu Huang ,&nbsp;Ze-yi Guo ,&nbsp;Huan Wang ,&nbsp;Lin-wen Deng ,&nbsp;Wei-jun Ding ,&nbsp;Hang Zhou","doi":"10.1016/j.phymed.2025.157013","DOIUrl":"10.1016/j.phymed.2025.157013","url":null,"abstract":"<div><h3>Background</h3><div><em>Scutellaria baicalensis</em> Georgi (SBG) is traditionally used to prevent miscarriage through its anti-inflammatory, antioxidant, and antiapoptotic effects. However, its mechanisms in early-stage abortion (ESA) remain unclear.</div></div><div><h3>Materials and methods</h3><div>A novel network pharmacology workflow was developed to identify bioactive compounds in SBG, including the nontargeted detection of SBG components, extraction of compounds from the HERB database, manual screening and filtering. These compounds were confirmed via high-performance liquid chromatography (HPLC). Targets associated with bioactive compounds were enriched via the SWISS database, and disease-related targets were identified via GeneCards. Overlapping targets were analyzed to construct a protein - protein interaction (PPI) network, with interactions predicted via STRING and visualized via Cytoscape. Molecular docking, dynamic simulations, and transcriptomics were used to prioritize key bioactive compounds. Two ESA models were used to evaluate therapeutic effects: one induced by <em>lipopolysaccharide</em> (LPS) and the other by mifepristone (Ru486). Decidual histopathology was observed via transmission electron microscopy (TEM) and hematoxylin - eosin (HE) staining. Key targets and pathways were validated through network pharmacology, immunohistochemistry (IHC), immunofluorescence (IF), Western blotting (WB), and ELISA. Finally, the effects of SBG on pregnancy maintenance were investigated by modulating the HIF-1α pathway, with a focus on its impact on critical biomarkers identified through the screening process.</div></div><div><h3>Results</h3><div>Compared with RU486, SBG demonstrated greater efficacy in treating LPS-induced ESAs, as evidenced by lower embryo absorption rates, fewer miscarriages, and milder decidual pathological changes. Through multilevel screening, we identified 10 compounds in SBG with the highest drug potential, which were confirmed in the original plant. These compounds are predicted to specifically modulate LPS-ESA through 38 targets, influencing 525 biological processes and 126 signaling pathways. Integrated pharmacological analysis highlighted the HIF-1α signaling pathway as the key mechanism underlying the therapeutic effects of SBG on ESAs. Experiments involving HIF-1α pathway activation and inhibition confirmed that SBG inhibits decidual and embryonic cell apoptosis and hypoxia by blocking HIF-1α signal transmission.</div></div><div><h3>Conclusions</h3><div>This study established a rigorous framework for screening and analyzing the therapeutic components of SBG and revealed that SBG is specifically effective against ESAs and maternal–fetal interface inflammation through the HIF-1α signaling pathway. These findings highlight SBG as a therapeutic agent for ESA and provide a foundation for future mechanistic studies.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157013"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489546","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":"Shoutai pill exhibits anti-miscarriage efficacy through tripartite modulation of gut microbiota, systemic metabolism, and maternal-fetal immunity: A multi-omics analysis","authors":"Wanfeng Xu ,&nbsp;Bo Li ,&nbsp;Zhihao Ge ,&nbsp;Lu Li ,&nbsp;Xinglishang He ,&nbsp;Xuannan Chen ,&nbsp;Chu Chu ,&nbsp;Guiyuan Lv ,&nbsp;Suhong Chen","doi":"10.1016/j.phymed.2025.156991","DOIUrl":"10.1016/j.phymed.2025.156991","url":null,"abstract":"<div><h3>Background</h3><div>Shoutai pill (STP)—a classical Chinese herbal formula—is clinically used to manage miscarriage, albeit its bioactive constituents and pharmacological mechanisms are not incompletely characterized.</div></div><div><h3>Purpose</h3><div>To elucidate the bioactive components and molecular mechanisms underpinning the efficacy against miscarriage of STP, we integrated spectral analysis with multi-omics profiling (encompassing 16S rRNA sequencing, transcriptomics, and metabolomics) to establish a novel system-to-molecule framework for deciphering the conventional herbal formulations.</div></div><div><h3>Methods</h3><div>Active components were identified using LC-MS. A miscarriage mouse model was established to evaluate the embryo loss rate, serum estradiol (E₂), and progesterone (P) levels. Spectrum-effect relationship analysis correlated chemical constituents with their efficacy. Mechanistic insights were explored via uterine transcriptomics, 16S rRNA gut microbiota sequencing, serum metabolomics, and molecular validation (qPCR, western blotting, immunohistochemistry).</div></div><div><h3>Results</h3><div>STP was found to significantly reduce embryo loss and elevate the serum E₂/P levels, with the STP extract (STE) displaying maximal efficacy. Histopathological analysis revealed improved endometrial decidualization in STE-treated mice. Transcriptomics identified 1,476 differentially expressed uterine genes (434 upregulated and 1,042 downregulated), notably suppressing the IL-17-signaling pathway genes. STE upregulated Foxp3 mRNA while downregulating IL-17, RORγt, and NFκB. Western bloting confirmed STE-mediated suppression of IL-17/JAK2/p-STAT3/NFκB/IL-6 axis and induction of Foxp3/IL-10 proteins. Gut microbiota analysis demonstrated that STE improved the composition and abundance of gut microbiota at the phylum and genus levels. Immunohistochemistry validated intestinal Foxp3⁺/IL-10⁺ cell increase and IL-6/RORγt reduction. Metabolomics identified 237 differentially regulated serum metabolites (134 upregulated and 103 downregulated), which were closely associated with gene expressions and microbial abundance.</div></div><div><h3>Conclusion</h3><div>The anti-miscarriage efficacy of STP was mediated by chlorogenic acid, isochlorogenic acid A, asperosaponin VI, and others. STP administration could restore the gut microbial ecosystem and reprogram the host metabolism. In addition, STP administration normalized the Th17/Treg cell ratio at the maternal-fetal interface through JAK2/STAT3-signaling inhibition, thereby stabilizing immune tolerance during early gestation. The results offer novel insights into the anti-miscarriage mechanism and bioactive components of STP.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156991"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501915","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":"Xinmailong injection ameliorates Doxorubicin‑induced cardiotoxicity via the MDH2/OAA pathway","authors":"Sa Liu ,&nbsp;Suifen Xie ,&nbsp;Taoli Sun ,&nbsp;Yikun Wang ,&nbsp;Wenhu Zhou ,&nbsp;Yuanying Yang ,&nbsp;Bikui Zhang ,&nbsp;Wenqun Li","doi":"10.1016/j.phymed.2025.157010","DOIUrl":"10.1016/j.phymed.2025.157010","url":null,"abstract":"<div><h3>Background</h3><div>As a broad-spectrum anticancer drug, the clinical utility of Doxorubicin (Dox) is hampered by its side effects, known as Dox-induced cardiotoxicity (DIC). Xinmailong Injection (XML), a bioactive compound formulation extracted from the American cockroach, has been approved by China’s National Medical Products Administration for the treatment of heart failure. However, whether XML could alleviate DIC still remains unclear.</div></div><div><h3>Purpose</h3><div>This study aims to explore the protective role of XML against DIC and unveil the molecular mechanisms underlying its cardioprotective effects.</div></div><div><h3>Methods</h3><div>The DIC models of H9c2 cells and C57BL/6 mice were established. HPLC-MS, network pharmacology, metabolomics and experimental verification were combined to identify the core target and mechanism of XML against DIC.</div></div><div><h3>Results</h3><div>XML alleviated Dox-induced apoptosis in vitro and in vivo. HPLC/MS in conjunction with swissADME identified 30 effective components within XML. Network pharmacology screened 179 “co-targeted genes” related to XML and DIC. Metabolomics identified 24 differential metabolites, mainly enriched in oxaloacetate (OAA) metabolism and the TCA cycle. Four intersecting genes, including MDH2, EHMT2, CAD and MIF, were determined through Metascape and MetaboAnalyst analysis. MDH2 was chose as the core target as it regulated OAA regeneration within the TCA cycle. The levels of MDH2 and OAA were downregulated by Dox, whereas they were upregulated following XML intervention. When MDH2 was inhibited using LW6, the protective effects of XML on cell apoptosis, cardiac dysfunction, and ATP depletion were all reversed, indicating that XML alleviated DIC by upregulating MDH2.</div></div><div><h3>Conclusion</h3><div>XML effectively mitigated DIC by upregulating MDH2 to promote the generation of ATP and inhibit cell apoptosis, providing new theoretical insights and strategies for the prevention and treatment of DIC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157010"},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366722","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, a main compound of Salvia miltiorrhiza, alleviates autoimmune and inflammatory diseases by directly targeting IRF3","authors":"Wei Shi ,&nbsp;Jincai Wen ,&nbsp;Yuan Gao ,&nbsp;Tingting Liu ,&nbsp;Hui Li ,&nbsp;Huijie Yang ,&nbsp;Jia Zhao ,&nbsp;Ziying Wei ,&nbsp;Chengwei Li ,&nbsp;Qing Yao ,&nbsp;Xiaohe Xiao ,&nbsp;Zhaofang Bai","doi":"10.1016/j.phymed.2025.157005","DOIUrl":"10.1016/j.phymed.2025.157005","url":null,"abstract":"<div><h3>Background</h3><div>Interferon regulatory factor 3 (IRF3) is an essential component of the immune system to protect the host from aggression, but excessive IRF3 activation leads to the release of type I interferon, interferon-stimulated genes (ISGs) and pro-inflammatory factors, which closely linked to multiple inflammatory diseases. Therefore, suppression of aberrant activation of IRF3 can be applied to the therapy of inflammatory diseases and have promising applications.</div></div><div><h3>Methods</h3><div>DNA or RNA can induce the release of type I interferon and pro-inflammatory cytokines, and cell models or multiple mice models were used to assess the anti-inflammatory potential of Dihydrotanshinone 1 (DHT), the main active component of Salvia miltiorrhiza, <em>in vivo</em> and <em>in vitro</em>. Mechanistically, IRF3 and P65 nuclear translocation, STING oligomerization and stimulator of interferon genes (STING)- or mitochondrial antiviral signaling protein (MAVS)-TANK-binding kinase 1 (TBK1)-IRF3 complex expression were detected to evaluate the mechanisms of DHT on the inhibition of type I interferon and pro-inflammatory cytokines.</div></div><div><h3>Results</h3><div>DHT, an active ingredient isolated from Salvia miltiorrhiza, was effective in suppressing the aberrant secrection of interferon-β (IFN-β), ISGs and pro-inflammatory cytokines in THP-1 and BMDMs in WT or <em>Trex1^-/-</em> mice. Mechanistically, DHT have no influence on the interaction of STING-TBK1, IRF3-TBK1 and MAVS-TBK1, but directly binds to IRF3 and affects the recruitment of STING to IRF3. Significantly, DHT has promising therapeutic effects on IRF3-mediated inflammatory diseases, including Trex1 deficiency-related systemic inflammatory response, obesity-induced insulin resistance, and NASH.</div></div><div><h3>Conclusion</h3><div>In conclusion, DHT, a novel inhibitor of the production of type I interferon and pro-inflammatory cytokines, is a potential candidate for the therapeutic of IRF3-driven autoimmune and inflammatory diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157005"},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534733","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":"Xiaoer Huanglong pellets remodels the periphery microenvironment to improve attention deficit hyperactivity disorder based on the microbiota–gut–brain axis","authors":"Longtai You ,&nbsp;Hulinyue Peng ,&nbsp;Jing Liu ,&nbsp;Na Sai ,&nbsp;Wenwen Zhao ,&nbsp;Xiao Li ,&nbsp;Chunjing Yang ,&nbsp;Peng Guo ,&nbsp;Jian Ni","doi":"10.1016/j.phymed.2025.157007","DOIUrl":"10.1016/j.phymed.2025.157007","url":null,"abstract":"<div><h3>Background</h3><div>Recently, research interest in attention deficit hyperactivity disorder (ADHD) has grown significantly, driven by its increasing incidence and substantial societal impact. Among the various pathogenic mechanisms under investigation, the microbiota–gut–brain axis has emerged as a crucial area of focus. In the context of ADHD treatment, Xiaoer Huanglong Pellets (XRHLP), a traditional Chinese herbal formulation, have demonstrated therapeutic efficacy, although the underlying mechanisms remain partially understood.</div></div><div><h3>Purpose</h3><div>This study aimed to analyze and compare the therapeutic effects and underlying mechanisms of XRHLP, including gastric release (WR_HL), enteric release (CR_HL), and colon release (JCR_HL) pellets, for ADHD treatment.</div></div><div><h3>Methods</h3><div>This study employed a multi-modal approach to investigate the effects of XRHLP on ADHD. Behavioral assessments combined with Enzyme-linked immunosorbent assay and Western-blot analyses were conducted to evaluate the therapeutic outcomes in model rats with ADHD. Comprehensive profiling of the gut–brain axis was performed using 16S ribosomal RNA sequencing and untargeted and targeted metabolomic analyses. The causal role of the gut microbiota was further validated using fecal microbiota transplantation (FMT).</div></div><div><h3>Results</h3><div>WR_HL, CR_HL, and JCR_HL improved ADHD-like behaviors and neurotransmission dysfunction, with JCR_HL exhibiting superior intervention effects compared to WR_HL and CR_HL. These therapeutic effects are mediated through multiple pathways, including the restoration of gut microbial homeostasis, attenuation of inflammatory cascades, and repair of compromised intestinal and blood-brain barrier. The intervention also corrected systemic metabolic imbalances by specifically addressing the abnormalities in amino acid metabolism, neurotransmitter regulation, and short-chain fatty acid production. FMT experiments further confirmed the critical role of microbial modulation in mediating the behavioral and microbial regulatory effects of XRHLP.</div></div><div><h3>Conclusion</h3><div>In summary, XRHLP exerts anti-ADHD effects by improving the microbiota-gut-brain axis and correcting amino acid metabolic disorders, providing new insights into the molecular mechanisms by which traditional Chinese medicine influences ADHD and offers potential avenues for drug development.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157007"},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338558","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":"Dendrobium huoshanense improves atherosclerosis in high-fat-induced ApoE mice by regulating gut microbiota and serum metabolite profiles","authors":"Shao-Jun Zheng ,&nbsp;Xiao-Yan Gao ,&nbsp;Xiao-Han Diao ,&nbsp;Nai-Dong Chen","doi":"10.1016/j.phymed.2025.156964","DOIUrl":"10.1016/j.phymed.2025.156964","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular diseases, particularly atherosclerosis (AS), remain leading causes of mortality, with limited effective treatments available. <em>Dendrobium huoshanense</em>, a traditional medicinal herb, has shown promising anti-inflammatory and antioxidant effects, but its cardiovascular protective potential remains underexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the protective effects of <em>Dendrobium huoshanense</em> polysaccharides (DHP) against AS and elucidate the underlying mechanisms involved.</div></div><div><h3>Methods</h3><div>An ApoE(−/−) mice model of AS was established, and DHP was administered at different concentrations via gavage. After 14 weeks, serum and fecal samples were collected. The effects of DHP on lipid profiles, aortic plaques, matrix metalloproteinases (MMP-2 and MMP-9), and the Nrf2/HO-1 pathway were assessed. Additionally, metagenomic sequencing of fecal samples and untargeted metabolomics of serum were conducted and correlations between these findings were explored.</div></div><div><h3>Results</h3><div>DHP improved lipid profiles, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and enhanced superoxide dismutase (SOD) activity. It stabilized aortic plaques, suppressed MMP-2 and MMP-9 overexpression, and activated the Nrf2/HO-1 pathway. DHP also promoted gut microbiota balance, increasing <em>Mucispirillum, Bifidobacterium</em>, and <em>Faecalibaculum</em> while decreasing <em>Desulfovibrionaceae</em> and <em>Eubacterium</em>. Metabolomics revealed alterations in metabolites, including taurochenodeoxycholic acid and ursocolic acid, influencing amino acid, glycerophospholipid, and bile acid metabolism.</div></div><div><h3>Conclusions</h3><div>DHP effectively lowers lipid levels, stabilizes aortic plaques, restores gut microbiota balance, and corrects metabolic disturbances, thereby inhibiting the progression of atherosclerosis. These findings provide a scientific basis for the clinical use of DHP in AS prevention and treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156964"},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338559","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":"Selective PPARγ modulator alpinetin restores insulin sensitivity and protects from bone loss in type 2 diabetes","authors":"Yaoyu Zhao ,&nbsp;Hantao Yao ,&nbsp;Yilin Liao ,&nbsp;Bulin Jiang ,&nbsp;Ting Li ,&nbsp;Jingqiu Chen ,&nbsp;Yue Sheng ,&nbsp;Mengjie Yin ,&nbsp;Wengwanyue Ye ,&nbsp;Qi Yan ,&nbsp;Yaoting Ji","doi":"10.1016/j.phymed.2025.157003","DOIUrl":"10.1016/j.phymed.2025.157003","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) poses a significant global health burden, with its escalating prevalence and related complications. Although peroxisome proliferator–activated receptor gamma (PPARγ) agonists such as thiazolidinediones effectively enhance insulin sensitivity, their use is limited by adverse effects, including bone loss. Recent research has focused on developing selective PPARγ modulators with improved safety profiles. Alpinetin (Apt), a naturally occurring flavonoid, has demonstrated anti-inflammation potential; however, its impact on insulin signaling and bone metabolism under diabetic conditions has yet to be investigated.</div></div><div><h3>Purpose</h3><div>This study aims to investigate whether Apt acts as a selective PPARγ modulator that can restore insulin sensitivity while preventing diabetes-associated bone deterioration.</div></div><div><h3>Methods</h3><div>Molecular docking and dynamics simulations assessed the interaction between Apt and PPARγ. The cellular thermal shift assay (CETSA) evaluated Apt’s binding affinity, and dual-luciferase reporter assays measured its activation of PPARγ. Single-cell RNA sequencing analysis, network pharmacology and RNA sequencing were used to explore Apt’s mechanisms in T2DM treatment. The insulin-sensitizing and bone-protecting effects of Apt were tested both <em>in vitro</em> and in a streptozotocin (STZ)-induced T2DM mouse model.</div></div><div><h3>Results</h3><div>Apt was found to enhance glucose uptake in insulin-resistant adipocytes through the PI3K/AKT signaling pathway and facilitate GLUT4 translocation. Furthermore, Apt was identified as a selective PPARγ agonist, binding directly to Ser342 of PPARγ and inhibiting phosphorylation at Ser273. Besides, Apt inhibited osteoclast differentiation <em>in vitro. In vivo</em>, Apt exhibited comparable glycemic control to rosiglitazone (Rosi) while protecting against bone loss in STZ-induced T2DM mice.</div></div><div><h3>Conclusions</h3><div>These findings suggest that Apt is a promising therapeutic candidate for T2DM treatment, selectively activating PPARγ to improve insulin sensitivity and prevent skeletal complications.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157003"},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481372","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":"The protective mechanism of Hydroxysafflor yellow A for the treatment of stroke - heart - syndrome via activating the ZBP1-NLRP3 signaling pathway","authors":"Chaowen Ge ,&nbsp;Hao Sun ,&nbsp;Ning Wang ,&nbsp;Ping Huang","doi":"10.1016/j.phymed.2025.157011","DOIUrl":"10.1016/j.phymed.2025.157011","url":null,"abstract":"<div><h3>Background</h3><div>Hydroxysafflor yellow A (HSYA), the primary active constituent of Safflower, a traditional Chinese medicine, has demonstrated promising therapeutic potential in the treatment of cardiovascular and cerebrovascular injuries. However, the impact of HSYA on stroke-induced cardiac syndrome and the underlying mechanisms remain to be elucidated.</div></div><div><h3>Methods</h3><div>Laser super-resolution microscopy and transmission electron microscopy were employed to examine cerebral ischemic injury. Echocardiography and immunofluorescence techniques were utilized to assess cardiac function and inflammatory damage. Western blot analysis was conducted to measure the expression levels of apoptosis-related proteins in heart tissue.</div></div><div><h3>Results</h3><div>HE revealed that SHS induced inflammatory infiltration in the myocardium. Echocardiographic findings indicated that SHS impaired cardiac function. ELISA results demonstrated that SHS led to elevated levels of norepinephrine and epinephrine. Transmission electron microscopy (TEM) observations confirmed that SHS resulted in mitochondrial damage within cardiac cells. Immunofluorescence analysis further showed that SHS facilitated the recruitment of cardiac macrophages, upregulated the expression of ZBP1 and NLRP3, and increased the production of inflammatory cytokines and inflammasomes. Co-immunoprecipitation experiments demonstrated that ZBP1 interacts with NLRP3. Inhibiting sympathetic overactivation exerts a protective effect on the heart. Furthermore, HSYA not only reversed the aforementioned conditions but also exerted protective effects on both cardiac and cerebral tissues. Immunofluorescence analysis revealed that HSYA inhibited the formation of the ZBP1 and NLRP3 complexes, as well as the inflammasome complex. Molecular docking studies indicated that HSYA and ZBP1 share the LYS-166 binding site, and protein docking results demonstrated that ZBP1 and NLRP3 also share this binding site. Mutations at this site diminished the protective efficacy of HSYA against SHS.</div></div><div><h3>Conclusions</h3><div>HSYA mitigates macrophage recruitment through the inhibition of the ZBP1-NLRP3 signaling pathway, thereby improving sympathetic nerve function, suppressing panoptosis, and alleviating SHS injury by competitively binding to the LYS-166 site of ZBP1 with NLRP3.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157011"},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523332","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":"Core-multiplex-micro component profiling for precision discrimination of multi-sources and adulterated arnebiae radix, from herbs to formulations","authors":"Fei Sha ,&nbsp;Jianqing Zhang ,&nbsp;Cuicui Wang ,&nbsp;Huiting Ou ,&nbsp;Yun Li ,&nbsp;Wenlong Wei ,&nbsp;Changliang Yao ,&nbsp;Qirui Bi ,&nbsp;Xiaochi Ma ,&nbsp;De-an Guo","doi":"10.1016/j.phymed.2025.156954","DOIUrl":"10.1016/j.phymed.2025.156954","url":null,"abstract":"<div><h3>Background</h3><div>The “one-to-multiple” phenomenon and counterfeiting are prevalent in herbal medicines. Accurately identifying these issues in both crude herbs and commercial formulated products is crucial for ensuring drug safety and efficacy. However, this task remains inherently challenging due to the complex nature of the matrices involved.</div></div><div><h3>Purpose</h3><div>This study aims to develop methodologies for the precise authentication of multi-sourced herbal medicines and their counterfeits, and to trace constituent species in commercial products.</div></div><div><h3>Methods</h3><div>This paper proposes an integrated strategy termed “Core-Multiplex-Micro (CMM) component profiling for precision discrimination amid multi-sources and adulterants”, using Arnebiae Radix as a case study. The strategy begins with the comparative analysis of primary component, shikonin derivatives, across two genuine species and three adulterants, employing a single standard to determine multi-components (SSDMC) approach. It then expands to include a broader range of mid- to low-abundance metabolites through fingerprinting-based classification. Subsequently, trace-level components are explored using LTQ-Orbitrap MS combined with metabolomics to authenticate the five species. Robust chemical markers are identified, validated, and translated to a cost-effective QDa MS platform for targeted detection. This tiered methodology was applied to authenticate 15 batches of commercially available raw materials and 10 batches of formulations.</div></div><div><h3>Results</h3><div>The study successfully distinguished between two authentic Arnebiae Radix species and three adulterants simultaneously for the first time. Through cross-validation, nine diagnostic chemical markers were identified and effectively transferred from the expensive LTQ-Orbitrap MS platform to a more cost-effective QDa MS system for practical use in commercial product traceability. The research revealed that 60% of raw Arnebiae Radix materials were authentic, while 30% of the formulations matched their labeled species composition.</div></div><div><h3>Conclusion</h3><div>This study sets a precedent for precise traceability for “one-to-multiple” and counterfeit products: tracing them from raw herbs to final formulations.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156954"},"PeriodicalIF":6.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579142","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}