Phytomedicine最新文献

{"title":"Yanghe Pingchuan granules induce ferroptosis in airway smooth muscle cells to improve bronchial asthma via the METTL3/P53/SLC7A11 signaling pathway","authors":"Lingyu Pan ,&nbsp;Bangfu He ,&nbsp;Yanquan Han ,&nbsp;Dezhi Yuan ,&nbsp;Xianchun Duan ,&nbsp;Yongzhong Wang","doi":"10.1016/j.phymed.2025.156480","DOIUrl":"10.1016/j.phymed.2025.156480","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies have found that ferroptosis is strongly associated with the development of bronchial asthma (BA). However, the mechanism underlying the role of ferroptosis in asthma remains unclear. Yanghe Pingchuan granules (YPG) have significant curative effect in the clinical treatment of BA. In our previous study, we found that YPG inhibit pyroptosis in the airway smooth muscle cells (ASMCs) of and reducing airway inflammation. Whether ferroptosis participated in the YPG treated BA activity is an interesting project.</div></div><div><h3>Purpose</h3><div>The aim of this study was to investigate the protective effects and the related mechanisms of YPG against BA.</div></div><div><h3>Methods</h3><div>We used ultra high-performance liquid chromatograph (UPLC) to analyze the composition of YPG. Ovalbumin (OVA)-induced BA models were developed <em>in vivo</em>. YPG was administered to rats by gavage and ASMCs were isolated and cultured using α-SMA and CCK8 was used to assess cell viability. Gene editing, m⁶A RNA immunoprecipitation (MeRIP), western blotting, RT-qPCR, and transmission electron microscopy (TEM) was used to assess ferroptosis protein and mRNA expression in ASMCs. Further, the mechanism of YPG-induced regulation of ferroptosis in ASMCs via the METTL3/P53/SLC7A11 signaling axis was interrogated. BA rats were used to verify the therapeutic effects and mechanism of YPG. Moreover, hematoxylin and eosin staining was used to evaluate pathological changes using animal samples, while immunofluorescence, western blotting, RT-qPCR, and TEM were used to verify the mechanism by which YPG improved BA through the METTL3/P53/SLC7A11 signaling axis.</div></div><div><h3>Results</h3><div>Qualitative analysis revealed seven major components in YPG. Our <em>in vivo</em> and <em>in vitro</em> data confirm that YPG significantly induced ferroptosis in ASMCs. YPG treatment effectively increased the expression of Fe²⁺, P53, and PTGS2, while decreasing SLC7A11, GPX4, and FTH1 expression. Moreover, TEM data revealed that YPG-induced mitochondrial membrane rupture and ridge disappearance. Additionally, YPG significantly increased METTL3 expression levels and upregulated the levels of P53 m⁶A, thus promoting its degradation. Notably, overexpression of METTL3 and P53 induces ferroptosis of ASMCs BA rats.</div></div><div><h3>Conclusion</h3><div>We show that YPG may induce ferroptosis of ASMCs in BA rats by activating the METTL3/P53/SLC7A11 signaling pathway, thus alleviating disease symptoms.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156480"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436488","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":"Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates DSS-induced colitis by inhibiting ERK/NF-κB activation in macrophages","authors":"Jiao Liu ,&nbsp;Danye Niu ,&nbsp;Yu Tang ,&nbsp;Ruoheng Zheng ,&nbsp;Yinyin Qin ,&nbsp;Xiuqin Cheng ,&nbsp;Shubo Pan ,&nbsp;Jinfei Yuan ,&nbsp;Xiaohua Shi ,&nbsp;Jiao Yang","doi":"10.1016/j.phymed.2025.156492","DOIUrl":"10.1016/j.phymed.2025.156492","url":null,"abstract":"<div><h3>Background</h3><div>β-Hydroxy β-Methylbutyrate (HMB), derived from leucine, is known for its role in anti-oxidation and anti-inflammation. But, the application of HMB in IBD treatment is not fully understood, highlighting the requirement for further research.</div></div><div><h3>Purpose</h3><div>We aimed to examine the effects of HMB treatment on DSS-induced chronic colitis in mice and explore its underlying mechanisms.</div></div><div><h3>Methods</h3><div>To simulate colonic inflammation, a murine colitis model was generated by using DSS induction. Critical indicators such as body weight, colon length, disease activity index (DAI), and gross pathology were thoroughly monitored. Immunohistochemistry assay was conducted to assess the expression of Occludin and F4/80. Flow cytometry was employed to evaluate the expression levels of CD80 and CD86. qPCR was performed to measure cytokine expression (IL-6, IL-1β, TNF-α, IL-22, CXCL2, iNOS). RNA sequencing was carried out using bone-marrow derived dendritic macrophage cells (BMDMs).</div></div><div><h3>Results</h3><div>Our study indicates that HMB treatment substantially mitigated colonic damage in murine models of DSS-induced colitis, highlighting its anti-inflammatory potential. Notably, HMB significantly enhanced the expression of Occludin in these mice. Furthermore, HMB downregulated proinflammatory markers such as IL-6, IL-1β, and TNF-α as well as CXCL2 in the colon tissue. In vitro experiments also revealed that HMB reduced production of proinflammatory cytokines induced by DSS and suppressed the expression levels of CD80 and CD86 in macrophage cells. On a mechanistic level, we demonstrated the anti-inflammatory effects of HMB by reducing the phosphorylation of p-ERK and p-p65, thereby limiting cytokine production in both in vivo and in vitro settings.</div></div><div><h3>Conclusion</h3><div>These findings indicate that HMB possesses anti-inflammation against intestinal inflammation and may hold promise as a potential therapeutic candidate for IBD treatment. There's growing interest in combining traditional anti-inflammatory agents with supplements like HMB to improve outcomes in complex IBD cases. HMB's role in established muscle preservation and reduction of systemic inflammation as described in this study could make it a valuable adjunct in IBD therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156492"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintained homeostasis: LGYD facilitated the restoration of ISCs following radiation exposure by activating Hes1","authors":"Ziqiao Yan ,&nbsp;Yangshuo Li ,&nbsp;Mingyang Chang ,&nbsp;Tiantian Xia ,&nbsp;Yuguo Wang ,&nbsp;Hongyang Yu ,&nbsp;Liangliang Zhang ,&nbsp;Pan Shen ,&nbsp;Zhijie Bai ,&nbsp;Ningning Wang ,&nbsp;Wei Zhou ,&nbsp;Zhexin Ni ,&nbsp;Yongqi Dou ,&nbsp;Yue Gao","doi":"10.1016/j.phymed.2025.156506","DOIUrl":"10.1016/j.phymed.2025.156506","url":null,"abstract":"<div><div>Background: Radiation-induced Intestinal Injury (RIII) affects quality of life in radiotherapy patients; Liangxue Guyuan Yishen Decoction (LGYD) offers protection but requires further study on its mechanism. Purpose: The aim of this study was to investigate the heterogeneity of cellular responses in the intestine at a single-cell level following radiation and LGYD treatment. Study design: This study's design includes <em>in vivo</em> and <em>in vitro</em> assessments to evaluate LGYD's effects on intestinal cells post-radiation, targeting survival, recovery, and molecular pathways. Methods: Mice were categorized into four groups: LGYD group, NC group, IR group, and Am group. Each group received daily drug administrations. All groups, except for the NC group, were subjected to a single whole-body irradiation at a dose rate of 70 R/min with a source-to-skin distance of 250 cm. Subsequent experiments were conducted following the irradiation, which led to severe survival impairments in the mice. Results: Our findings demonstrate that LGYD intervention substantially improves survival rates following lethal doses (8.5 Gy, 70R/min) of whole-body irradiation. Moreover, LGYD expedites the recovery period for intestinal injury on the fifth day after radiation by promoting repair mechanisms within intestinal tissue, with particular focus on mitigating intestinal stem cells (ISCs) damage and immune disorders. Through both <em>in vivo</em> and <em>in vitro</em> experiments, we have discovered that LGYD effectively treats RIII by activating Hes1 transcription factor activity through its key active ingredients in drug-containing serum. This activation further upregulates the downstream Stat3 and Akt gene, thereby facilitating repair processes within intestinal stem cells. Conclusion: In this study, we discovered that LGYD can enhance the downstream expression and phosphorylation pathways of Stat3 and Akt by upregulating the expression of Hes1 gene following high-dose radiation exposure.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156506"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422726","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":"Novel application of cycloastragenol target microglia for the treatment of Alzheimer's disease: Evidence from single-cell analysis, network pharmacology and experimental assessment","authors":"Weipin Weng ,&nbsp;Baoping Lin ,&nbsp;Jiahao Zheng ,&nbsp;Yixin Sun ,&nbsp;Zijing Li ,&nbsp;Xiaochun Chen ,&nbsp;Yanping Wang ,&nbsp;Xiaodong Pan","doi":"10.1016/j.phymed.2025.156502","DOIUrl":"10.1016/j.phymed.2025.156502","url":null,"abstract":"<div><h3>Background</h3><div>Cycloastragenol (CAG), a compound extracted from Astragalus, is known for its telomerase activation and anti-inflammatory, antioxidant properties. However, its potential pharmacological effects on Alzheimer's disease (AD) remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to explore potential targets and molecular mechanisms for the role of CAG in alzheimer’s disease (AD) treatment.</div></div><div><h3>Methods</h3><div>CAG was administered to 5 × FAD mice. The senescent cell count was verified by senescence-associated β-galactosidase (SA-β-gal) staining. The impact of CAG on microglial phagocytosis was assessed by <em>in vitro</em> and <em>in vivo</em> assays. The potential targets of CAG were identified by network pharmacology and single-nucleus RNA sequencing (snRNA-seq). The underlying mechanism was validated by molecular docking, surface plasmon resonance (SPR) and western blotting.</div></div><div><h3>Results</h3><div>CAG effectively ameliorated cognitive impairments and microglial senescence in 5 × FAD mice. <em>In vivo</em> and <em>in vitro</em> experiments revealed that CAG modulated microglial phagocytic activity and reduced hippocampal Aβ deposition The analysis of single-nucleus RNA sequencing data of AD patients reported 13 microglial targets for AD intervention. Phosphodiesterase 4B (PDE4B) was identified as the target through which CAG regulated microglial activity by utilizing network pharmacology, molecular docking and SPR. Western blotting revealed that the PDE4B/CREB/BDNF pathway may mediate the regulatory effect of CAG.</div></div><div><h3>Conclusion</h3><div>CAG can enhance microglial phagocytosis and alleviate memory dysfunction and amyloid plaque pathology. Our findings suggest that CAG may regulate microglial function through its interaction with PDE4B, providing a novel therapeutic strategy for AD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156502"},"PeriodicalIF":6.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436571","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":"Therapeutic potential of p-coumaric acid in alleviating renal fibrosis through inhibition of M2 macrophage infiltration and cellular communication","authors":"Qinfan Yao ,&nbsp;Xinyi Zhang ,&nbsp;Lefeng Wang ,&nbsp;Jingyi Li ,&nbsp;Junhao Lv ,&nbsp;Jianghua Chen ,&nbsp;Dajin Chen","doi":"10.1016/j.phymed.2025.156507","DOIUrl":"10.1016/j.phymed.2025.156507","url":null,"abstract":"<div><h3>Background</h3><div>p-coumaric acid (p-CA), a hydroxycinnamic acid derivative, is recognized for its antioxidant and anti-inflammatory properties; however, its pharmacological effects on renal fibrosis remain insufficiently explored.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the therapeutic potential of p-CA in renal fibrosis and elucidate its underlying mechanisms through extensive molecular and cellular analyses.</div></div><div><h3>Methods</h3><div>Liquid chromatography-tandem mass spectrometry (LC-MS) was employed to analyze metabolic alterations associated with renal fibrosis induced by unilateral ureteral obstruction (UUO). Immune cell dynamics were assessed using cytometry by time of flight (CyTOF) and single-cell RNA sequencing (scRNA-seq). Further validation was performed using flow cytometry, Western blot (WB), quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), and immunofluorescence (IF) to evaluate the renoprotective effects of p-CA at the cellular and molecular levels.</div></div><div><h3>Results</h3><div>p-CA levels were significantly reduced in fibrotic renal tissues. Administration of exogenous p-CA restored renal function, alleviated tissue damage, and inhibited G2/M cell cycle arrest and epithelial-mesenchymal transition (EMT) in tubular epithelial cells (TECs). CyTOF and scRNA-seq analyses revealed that p-CA treatment decreased M2 macrophage proliferation, intercellular communication, and differentiation in fibrotic kidney tissues, resulting in reduced renal fibrosis. Additional experimental validations confirmed that p-CA specifically targeted M2 macrophages, suppressing their contribution to fibrotic progression.</div></div><div><h3>Conclusions</h3><div>p-CA exerts renoprotective effects by targeting M2 macrophages, disrupting their interaction with TECs, and attenuating fibrotic progression. These findings underscore the potential of p-CA as a novel therapeutic approach for renal fibrosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156507"},"PeriodicalIF":6.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436585","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":"Cortex Dictamni-induced hepatotoxicity by enhanced oxidative phosphorylation: Insights from integrative transcriptomics, proteomics, and metabolomics analyses","authors":"Huijuan Sun ,&nbsp;Yu Wang ,&nbsp;Geyu Deng ,&nbsp;Rui Gao ,&nbsp;Mengmeng Zhang ,&nbsp;Lin Huang ,&nbsp;Wenjie He ,&nbsp;Zhendong Zhang ,&nbsp;Donghua Yu ,&nbsp;Pingping Chen ,&nbsp;Fang Lu ,&nbsp;Shumin Liu","doi":"10.1016/j.phymed.2025.156511","DOIUrl":"10.1016/j.phymed.2025.156511","url":null,"abstract":"<div><h3>Background</h3><div>Cortex Dictamni (CD) is a traditional Chinese medicine that is commonly used to treat various skin diseases. Recently, clinical reports have highlighted its potential to induce severe hepatotoxicity. However, the underlying mechanisms of toxicity remain inadequately explored.</div></div><div><h3>Purpose</h3><div>The aim of this study was to elucidate the intrinsic mechanisms of CD-induced hepatotoxicity.</div></div><div><h3>Study design</h3><div>Hepatotoxicity was assessed in SD rats, and human primary hepatocytes (HPHs) and differentiated HepaRG (dHepaRG) cells were used for in vitro testing.</div></div><div><h3>Methods</h3><div>The major components of CD were determined using ultra-performance liquid chromatography (UPLC). Rats were randomly divided into control, CD-high (CD-H), CD-middle (CD-M), CD-low (CD-L), and isoniazid (INH) groups and administered oral gavage for four weeks. Serum biochemical indices, histopathological changes, apoptotic markers, and liver function were evaluated to assess hepatotoxicity. A comprehensive analysis of rat liver samples was performed using transcriptomic, proteomic, and metabolomic approaches to identify key pathways involved in CD-induced hepatotoxicity. In vitro toxicity validation of CD was performed using HPHs and dHepaRG cells. The key pathway was validated in vivo and in vitro.</div></div><div><h3>Results</h3><div>CD primarily contained obacunone, fraxinellone, and dictamine. Administration of CD-H (9 times the maximum daily clinical dose in adults) and CD-M (3 times the maximum daily clinical dose in adults) for 4 weeks induced varying degrees of hepatotoxicity in rats. The CD-H group presented increased absolute and relative liver weights, reduced alanine aminotransferase (ALT) and bile acid transporter levels, and increased albumin (ALB) and cytochrome P450 (CYP) 3A4 levels, indicating significant hepatotoxicity in rats. Integrated multiomics analysis revealed that NADH dehydrogenase (ubiquinone) Fe-S protein 2 (Ndufs2) is a critical regulator of CD-induced hepatotoxicity involving oxidative phosphorylation (OXPHOS). CD inhibited the viability of HPHs and dHepaRG cells, demonstrating its significant cytotoxicity. Mechanistic validation revealed that CD upregulated Ndufs2, reactive oxygen species (ROS) and mitochondrial respiratory chain complex (MRCC) I, leading to nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation, apoptosis, mitochondrial dysfunction, and hepatotoxicity.</div></div><div><h3>Conclusion</h3><div>In summary, our study presents a comprehensive picture of the toxicity of CD in terms of dose and sex and reveals, for the first time, the central role of Ndufs2-regulated OXPHOS in CD-induced hepatotoxicity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156511"},"PeriodicalIF":6.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422721","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":"Brusatol inhibits malignant phenotypes and lipid metabolism of osteosarcoma cells by regulating PI3K/AKT and MAPK pathways","authors":"Xuhui Yuan ,&nbsp;Shaolin Yu ,&nbsp;Lan Lin ,&nbsp;Yang Chen ,&nbsp;Zhaoyang Wu ,&nbsp;Xinyu Fang ,&nbsp;Wenming Zhang","doi":"10.1016/j.phymed.2025.156464","DOIUrl":"10.1016/j.phymed.2025.156464","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS), the most frequent type of primary bone cancer, has a poor prognosis in metastatic cases, with overall 5-year survival rates stagnating at 20 %–30 %. This highlights the critical need for innovative therapies to address the significant survival gap between metastatic and non-metastatic cases. Brusatol (BRU), a compound extracted from Brucea javanica, has shown promising anti-tumor properties in various cancers; however, its effects on OS have yet to be investigated.</div></div><div><h3>Purpose</h3><div>To investigate the anti-tumor mechanisms of BRU in OS and evaluate its potential therapeutic efficacy, with a particular focus on its impact on lipid metabolism and related signaling pathways.</div></div><div><h3>Methods</h3><div><em>In vitro</em> experiments to assess the anti-tumor effects of BRU involved colony formation, CCK-8, Transwell analysis, as well as flow cytometry. RNA sequencing was conducted to identify transcriptional changes in BRU-treated cells. The mechanism of action was investigated through analysis of lipid metabolism and key signaling pathways. Therapeutic efficacy and safety were evaluated <em>in vivo</em> using xenograft models.</div></div><div><h3>Results</h3><div>BRU significantly inhibited OS cell proliferation, migration, and invasion, while also inducing G2/M phase cell cycle arrest as well as promoting apoptosis. Transcriptome analysis revealed that BRU affected lipid metabolism-related genes and suppressed the PI3K/AKT and MAPK pathways. BRU treatment reduced fatty acid synthase expression and free fatty acid content in OS cells. <em>In vivo</em> experiments demonstrated that BRU effectively restricted xenograft growth.</div></div><div><h3>Conclusion</h3><div>This study revealed that BRU exhibits potent anti-tumor effects in OS by modulating lipid metabolism through the PI3K/AKT and MAPK pathways.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156464"},"PeriodicalIF":6.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436572","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":"Baicalin alleviates lipid metabolism disorders in diabetic kidney disease via targeting FKBP51","authors":"Mi Li ,&nbsp;Hong-Yan Zhu ,&nbsp;Shu-Yan Zhao,&nbsp;Xian-Deng Li,&nbsp;Shuang-Mei Tong,&nbsp;Jing Ma,&nbsp;A-Jing Xu,&nbsp;Jian Zhang","doi":"10.1016/j.phymed.2025.156473","DOIUrl":"10.1016/j.phymed.2025.156473","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic kidney disease (DKD) represents the primary aetiological factor in end-stage renal disease, wherein lipid metabolism disorders contribute to the progression of DKD. Baicalin, a composition from Scutellaria baicalensis, has exhibited the potential to mitigate lipid metabolism disorders of DKD, but the precise mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>High-fat-diet (HFD)/streptozotocin (STZ)-induced DKD mouse model was established to appraise the effects of baicalin on renal function, dyslipidemia, and renal ectopic lipid deposition. The effects of baicalin on lipid accumulation in vitro were assessed in tubular epithelial cells derived from mice (TCMK-1) treated with palmitic acid (PA). The potential targets of baicalin were identified by drug affinity responsive target stability (DARTS) -LC/MS. The impact of the identified target on lipid metabolism was elucidated in TCMK-1 cells through both knockdown and overexpression experiments.</div></div><div><h3>Results</h3><div>The findings indicated that baicalin effectively mitigated dyslipidemia and renal ectopic lipid deposition in the HFD/STZ-induced DKD mouse model. FK506-binding protein 51(FKBP51) was identified as an endogenous target of baicalin, with the Tyr113 residue playing a crucial role in the binding interaction. Additionally, FKBP51 knockdown brought about intracellular lipid accumulation, but FKBP51 overexpression was found to effectively counteract the lipid accumulation induced by PA. Further investigation revealed that FKBP51 regulates lipid accumulation through the Tyr113 residue. Notably, the lipid-lowering effect of baicalin was diminished following FKBP51 knockdown.</div></div><div><h3>Conclusion</h3><div>This study first identifies that FKBP51 is beneficial for lipid metabolism homeostasis in DKD and suggests baicalin as an effective molecule for targeting FKBP51 in the treatment of lipid metabolism disorders associated with DKD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156473"},"PeriodicalIF":6.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453125","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":"JTCD attenuates HF by inhibiting activation of HSCs through PPARα-TFEB axis-mediated lipophagy","authors":"Chang Shao ,&nbsp;Wenfang Lan ,&nbsp;Ying Ding ,&nbsp;Linmao Ye,&nbsp;Jiaxin Huang,&nbsp;Xiaofan Liang,&nbsp;Yi He,&nbsp;Junjie Zhang","doi":"10.1016/j.phymed.2025.156501","DOIUrl":"10.1016/j.phymed.2025.156501","url":null,"abstract":"<div><h3>Background</h3><div>Hepatic fibrosis (HF) is an intermediate stage in the progression of chronic liver disease to cirrhosis and has been shown to be a reversible pathological process. Known evidence suggests that activation of hepatic stellate cells (HSCs) and degradation of their lipid droplets (LDs) play an indispensable role in the process of HF. Jiawei Taohe Chengqi Decoction (JTCD) can inhibit the activation of HSCs in the process of HF, but the exact mechanism remains to be elucidated.</div></div><div><h3>Purpose</h3><div>The aim of this study is to determine whether JTCD inhibits lipophagy and to explore the possible mechanisms of its HF effect in HSCs by regulating the PPARα/TFEB axis.</div></div><div><h3>Methods</h3><div>Network pharmacology and molecular docking were firstly applied to predict the potential mechanism of JTCD for the treatment of HF. In vivo, a mouse model of HF was constructed using carbon tetrachloride (CCl₄) solution, and the efficacy of JTCD was assessed by staining of pathological sections, oil red O staining, immunofluorescence (IF), immunohistochemistry (IHC) staining, Western blotting and qRT-PCR. The intervention of JTCD was verified in vitro by induction of activated LX-2 cells with TGF-β solution and intervention using agonists and antagonists of PPARα. Finally, transient transfection of cells using TFEB siRNA was performed for validation studies.</div></div><div><h3>Results</h3><div>JTCD effectively alleviated CCl₄-induced HF in mice and reduced the levels of HF markers α-smooth muscle actin (α-SMA) and collagen I (COL1A1), and inhibited PPARα expression and lipophagy process. In vitro, JTCD delayed the degradation of LDs and reduced lipophagy in LX-2 cells, suggesting a mechanism involving PPARα/TFEB axis signaling regulation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156501"},"PeriodicalIF":6.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436587","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":"Yinaoxin granule alleviates cerebral ischemia-reperfusion injury by ferroptosis inhibition through Nrf2 pathway activation","authors":"Jingyu Weng ,&nbsp;Lang Liu ,&nbsp;Shuming Li ,&nbsp;Yuangui Yang ,&nbsp;Rui Zhou ,&nbsp;Zhen Zhang ,&nbsp;Yanru Liu ,&nbsp;Lin Chen ,&nbsp;Zeyu Feng ,&nbsp;Zhishu Tang ,&nbsp;Hongbo Xu","doi":"10.1016/j.phymed.2025.156476","DOIUrl":"10.1016/j.phymed.2025.156476","url":null,"abstract":"<div><h3>Background</h3><div>Lipid peroxide accumulation plays significant roles in cerebral ischemia-reperfusion injury (CIRI) through various mechanisms, including ferroptosis. Preserving the neuronal metabolic equilibrium and averting cell death during cerebral ischemia-reperfusion are pivotal for protecting brain function. Yinaoxin granule (YNX) is a widely used Chinese herbal preparations for treating cerebrovascular diseases, but pharmacological mechanism remains ambiguous..</div></div><div><h3>Purpose</h3><div>The aim in this study was to assess the effectiveness of YNX in treating CIRI and to investigate the underlying mechanisms.</div></div><div><h3>Methods</h3><div>The active ingredients of YNX were quantified using high-performance liquid chromatography. To explore the effects of YNX on CIRI and ferroptosis, both an <em>in vitro</em> oxygen-glucose deprivation and reperfusion model and a middle cerebral artery occlusion and reperfusion rat model were used. To assess the neuroprotective effects of YNX in the latter, neurological scores and cerebral blood flow were evaluated. Neuronal damage was determined through 2,3,5-triphenyltetrazolium chloride, Nissl, and H&amp;E staining. Ferroptosis-related markers, including ferrous ion, glutathione, 4-hydroxynonenal, and malondialdehyde were also investigated. Furthermore, the gene expression and protein levels of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4) and glutamate-cysteine ligase modulator (GCLM) were determined.</div></div><div><h3>Results</h3><div>YNX enhanced neurological scores and cerebral blood flow, reduced infarct volume, and rescued necrotic neurons in rats. Additionally, YNX mitigated lipid peroxidation and upregulated the SLC7A11, GCLM, and GPX4 levels. The absence of Nrf2 rendered neurons more susceptible to ischemia-reperfusion damage and abrogated the anti-ferroptotic neuroprotective effects of YNX.</div></div><div><h3>Conclusion</h3><div>YNX activates the Nrf2 pathway, resulting in the transcription of genes associated with antioxidants, including SLC7A11, GCLM, and GPX4. This suggests that YNX reduces lipid peroxidation and alleviates ferroptosis-induced CIRI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156476"},"PeriodicalIF":6.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422727","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}