Phytomedicine最新文献

{"title":"Loganin epigenetically rescues mitochondrial complex III dysfunction via DNMT1-UQCRC1 demethylation to halt cardiac remodeling after myocardial infarction","authors":"Yunjing Wang ,&nbsp;Renshan Chen ,&nbsp;Huaqian Dou ,&nbsp;Junjun Huang ,&nbsp;Liyou Guo ,&nbsp;Liangyan Lu ,&nbsp;Anran Zheng ,&nbsp;Junhua Qi ,&nbsp;Peihua Li ,&nbsp;Jing Ling ,&nbsp;Xiaoling Zhang ,&nbsp;Xiuhui Chen ,&nbsp;Qing Xiao","doi":"10.1016/j.phymed.2025.157001","DOIUrl":"10.1016/j.phymed.2025.157001","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Loganin, an iridoid glycoside from Cornus officinalis, exhibits cardioprotective potential. While previous studies focused on its antioxidant and anti-inflammatory properties, its role in myocardial infarction (MI) remodeling remains unexplored. This study identifies the DNMT1-UQCRC1 methylation axis as a novel therapeutic target of Loganin, providing the first evidence of mitochondrial complex III regulation through DNA methylation in cardiac injury.</div></div><div><h3>Approach and results</h3><div>In a mouse model of MI, 7-day pretreatment with Loganin (15/30 mg/kg) markedly reduced infarct area, attenuated cardiac fibrosis, and improved functional recovery. RNA sequencing and functional analyses revealed Loganin restores mitochondrial complex III function by reversing MI-induced suppression of UQCRC1—a core subunit regulated through DNA hypermethylation. Loganin’s rescue of UQCRC1 expression and mitochondrial respiration depended on DNMT1, evidenced by reduced promoter methylation and restored complex III activity. Molecular docking and surface plasmon resonance confirmed Loganin directly binds DNMT1’s catalytic domain (KD = 13.5 μM), with in vitro assays showing DNMT1 enzymatic inhibition. Collectively, these results suggest Loganin addresses the epigenetic origin of mitochondrial failure to prevent post-MI remodeling.</div></div><div><h3>Conclusions</h3><div>Our study identifies Loganin as an epigenetic modulator that mitigates post-MI cardiac remodeling through DNMT1 inhibition, reversing methylation-dependent UQCRC1 repression to restore mitochondrial respiration. These findings define the DNMT1-UQCRC1 axis as an actionable therapeutic target for cardiac repair.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157001"},"PeriodicalIF":6.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587491","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":"Cistanoside F acts as a Monoacylglycerol Lipase inhibitor that synergizes the anti-tumor effect of 2-Arachidonoyl Glycerol on Bladder cancer","authors":"Yu-jun Tan ,&nbsp;Yu-shan Ren ,&nbsp;Jun-lin Lv ,&nbsp;Peng Zhao ,&nbsp;Qi He ,&nbsp;Xue-feng Lei ,&nbsp;Qing-yue Liang ,&nbsp;He-meng Zhang ,&nbsp;Shu-fang Na ,&nbsp;Jing-chun Yao ,&nbsp;Jie Li ,&nbsp;Yu-heng Ma ,&nbsp;Gui-cheng Dong","doi":"10.1016/j.phymed.2025.157046","DOIUrl":"10.1016/j.phymed.2025.157046","url":null,"abstract":"<div><h3>Background</h3><div>Bladder cancer (BCa) remains clinically challenging due to high recurrence rates. As an endocannabinoid, 2-arachidonoylglycerol (2-AG) plays a pivotal role in regulating numerous physiological and pathological processes, including tumorigenesis. The maintenance of its levels in the biological system is essential for 2-AG to exert its biological functions. Therefore, inhibitors targeting the 2-AG metabolic enzyme, such as monoacylglycerol lipase (MGLL), are considered promising for clinical application.</div></div><div><h3>Methods</h3><div>The cell viability assay, colony formation, cell migration, and invasion assay were used to demonstrate 2-AG's anti-proliferative and anti-metastatic effects in BCa cells, inversely correlated with MGLL expression. MGLL overexpression or knockdown confirmed its regulatory role in 2-AG efficacy. Transcriptomics identified LKB1 as a potential 2-AG target. From a medicinal-food compound library, the MGLL activity assay was used to discover Cistanoside F (CF) as a potent MGLL inhibitor.</div></div><div><h3>Results</h3><div>The <em>in vitro</em> experiments confirmed 2-AG's selective anti-proliferative and anti-metastatic effects in BCa cells, while MGLL attenuates the anti-tumor effect of 2-AG in BCa cells via metabolizing 2-AG into AA. In mechanism, 2-AG activated the LKB1-AMPKα-mTOR axis to suppress BCa progression. At non-cytotoxic concentrations (4–8 nM), CF enhanced 2-AG's effects in BCa cells by sustaining endogenous 2-AG levels through MGLL suppression. <em>In vivo</em>, CF synergized with 2-AG to significantly inhibit tumor growth and lung metastasis compared to 2-AG monotherapy.</div></div><div><h3>Conclusion</h3><div>These findings establish CF as a novel MGLL-targeting adjuvant that amplifies 2-AG's anti-BCa efficacy via LKB1 pathway activation, providing dual therapeutic strategies: MGLL inhibition for 2-AG potentiation and LKB1 modulation for pathway-directed therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157046"},"PeriodicalIF":6.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587478","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":"Maiwei Yangfei decoction protects against pulmonary fibrosis by suppressing NLRP3 inflammasome-mediated pyroptosis of alveolar macrophage","authors":"Dongwei Zhu ,&nbsp;Qi Zhao ,&nbsp;Tingyu Pan ,&nbsp;Le Bai ,&nbsp;Yisheng Zhao ,&nbsp;Jing Wang ,&nbsp;Zhichao Wang ,&nbsp;Yong Xu ,&nbsp;Xianmei Zhou","doi":"10.1016/j.phymed.2025.157041","DOIUrl":"10.1016/j.phymed.2025.157041","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary fibrosis (PF) is a progressive and irreversible pathological manifestation of fibrotic interstitial lung diseases, characterized by chronic inflammation, excessive extracellular matrix (ECM) deposition, and architectural distortion of lung parenchyma, ultimately leading to respiratory failure. Maiwei Yangfei Decoction (MWYF) has been clinically applied in PF treatment, and can effectively improve the lung function and life quality of PF patients. Nevertheless, the precise regulatory mechanisms underlying its anti-fibrotic effects require further investigation.</div></div><div><h3>Purpose</h3><div>To investigate MWYF's pharmacological action and potential mechanism against PF.</div></div><div><h3>Methods</h3><div>Firstly, a PF mouse model was established by intratracheal nebulization of bleomycin (BLM). The effect of MWYF on PF was evaluated through micro-CT imaging and histopathological analysis. Subsequently, transcriptomics and proteomics were employed to investigate the crucial mechanism underlying the anti-fibrotic effects of MWYF. Immunofluorescence (IF), ELISA, TEM, SEM, Western blot (WB), and qPCR were then conducted to validate the inhibitory effects of MWYF on alveolar macrophages (AM) pyroptosis both in vivo and in vitro. Finally, the NLRP3 inhibitor (MCC950) was applied in MH-S cells to investigate the impact of MWYF on NLRP3 inflammasome.</div></div><div><h3>Results</h3><div>MWYF exhibited significant efficacy against BLM-induced PF. Integrated transcriptomic and proteomic analyses suggested that NLRP3 inflammasome-mediated pyroptosis intrinsically participated in the anti-fibrotic effects of MWYF. Further in-vivo experiments confirmed that MWYF alleviated AM pyroptosis in lung tissues via modulating the assembly of the NLRP3 inflammasome. In vitro, MWYF inhibited LPS plus Nigericin-induced pyroptosis in MH-S cells, as well as primary mouse lung fibroblast (PMLF) proliferation, activation, and ECM secretion, by suppressing NLRP3 inflammasome activation.</div></div><div><h3>Conclusion</h3><div>This study illustrated that MWYF alleviated PF by inhibiting NLRP3 inflammasome-mediated AM pyroptosis by integrating multi-omics approaches, indicating that MWYF had promising clinical translational potential in PF therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157041"},"PeriodicalIF":6.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614115","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":"Lycopene ameliorates Di-(2-ethylhexyl) phthalate-induced neurotoxicity in mice via the gut-brain axis","authors":"Li-Jian Chen ,&nbsp;Yi Liu ,&nbsp;Jia-Li Liu ,&nbsp;Zhi-Jiang Chen ,&nbsp;Wei Zhao ,&nbsp;Ji-Hui Li ,&nbsp;Clare Hsu ,&nbsp;Long Chen ,&nbsp;Jia-Hao Zeng ,&nbsp;Xiu-Wen Li ,&nbsp;Jian-Zheng Yang ,&nbsp;Jia-Hao Li ,&nbsp;Xiao-Li Xie ,&nbsp;Shao-Hua Tao ,&nbsp;Qi Wang","doi":"10.1016/j.phymed.2025.157057","DOIUrl":"10.1016/j.phymed.2025.157057","url":null,"abstract":"<div><h3>Background</h3><div>Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer present in numerous consumer products, poses a substantial neurotoxic risk through environmental and dietary exposure. Growing evidence highlights a critical association between DEHP-induced neurotoxicity and gut microbiota dysbiosis. Renowned for its potent antioxidant and anti-inflammatory capabilities, the natural carotenoid lycopene (Lyc) demonstrates therapeutic promise in treating various neurological disorders.</div></div><div><h3>Purpose</h3><div>The potential neuroprotective mechanisms of Lyc against DEHP-induced neurotoxicity in mice were investigated in this study, with a specific focus on its interaction with the gut-brain axis.</div></div><div><h3>Methods</h3><div>For 35 consecutive days, mice received daily intragastric administrations of DEHP or Lyc. A comprehensive approach involving integrated transcriptome, microbiome, and molecular biology analyses, in conjunction with bacteriotherapy, was utilized to thoroughly investigate the underlying mechanisms.</div></div><div><h3>Results</h3><div>Our findings demonstrated that Lyc administration or fecal microbiota transplantation (FMT) from Lyc-treated mice effectively ameliorated DEHP-induced anxiety- and depression-like behaviors. At the molecular level, Lyc mitigated neuroinflammation in the hippocampus, potentially through modulation of the NOD-like receptor signaling pathway. Furthermore, Lyc treatment improved gut microbiota composition by promoting the growth of beneficial bacteria, such as <em>Akkermansiaceae</em>, and enhanced intestinal barrier integrity via increased expression of tight junction proteins. Lyc also regulated the LPS-TLR4/MyD88 signaling pathway in the colon, thereby reducing local inflammation.</div></div><div><h3>Conclusion</h3><div>These results provide compelling evidence that Lyc confers protection against DEHP-induced neurotoxicity through a multifaceted strategy involving modulation of gut-brain axis, suppression of neuroinflammation, and restoration of gut homeostasis. We propose a novel therapeutic strategy to alleviate the risks posed by DEHP to both neurological and intestinal health. This approach involves either supplementation with Lyc or the application of bacteriotherapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157057"},"PeriodicalIF":6.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597331","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":"Plant-based strategies against aging: Focus on bioactive compounds from medicine-food homology plants","authors":"Yun-Fei Zhu ,&nbsp;An-Guo Wu ,&nbsp;Meng-Yi Chen ,&nbsp;Xing-Yue Zhou ,&nbsp;Fei-Hong Huang ,&nbsp;Long Wang ,&nbsp;Lu Yu ,&nbsp;Yong-Ping Wen ,&nbsp;Da-Lian Qin ,&nbsp;Jian-Ming Wu ,&nbsp;Xiao-Gang Zhou","doi":"10.1016/j.phymed.2025.157052","DOIUrl":"10.1016/j.phymed.2025.157052","url":null,"abstract":"<div><h3>Background</h3><div>As a biologically intricate process, aging entails functional impairment and predisposes individuals to chronic conditions. Medicine-food homology (MFH) plants, deeply rooted in traditional Chinese medicine, are increasingly recognized for their potential to delay aging through natural bioactive compounds.</div></div><div><h3>Study Design</h3><div>We conducted a comprehensive review of 56 MFH plants with documented anti-aging effects, focusing on 83 identified bioactive compounds grouped into 14 chemical categories, including phenols, polysaccharides, glycosides, and proteins.</div></div><div><h3>Methods</h3><div>Relevant studies were retrieved from PubMed, Scopus, Web of Science, and Google Scholar up to December 2024. Keywords included “aging,” “anti-aging,” “cellular senescence,” and the Latin names of MFH plants (<em>e.g., Astragalus membranaceus, Curcuma longa</em>). Inclusion criteria required experimental evidence of anti-aging activity using markers such as ROS, MDA, SA-β-gal, SOD, p16^INK4a, and p21^Waf1/Cip1 across organisms ranging from yeast to mammals and <em>in vitro</em> systems were considered. Key signaling pathways involved were also analyzed.</div></div><div><h3>Results</h3><div>Of the 156 MFH plants screened, 78 showed anti-aging potential, with 56 containing partially characterized active compounds. Phenols were the most prevalent, followed by polysaccharides and glycosides. These compounds primarily exerted effects by modulating oxidative stress and activating signaling pathways such as MAPK and DAF-16/FOXO. Less common constituents, such as carrier oils and naphthalene derivatives, also demonstrated notable efficacy. Clinical evidence supports the beneficial effects of certain MFH-derived compounds—such as curcumin and piperine—on skin aging, cognitive decline, and cardiovascular health.</div></div><div><h3>Conclusions</h3><div>MFH plants offer a promising source of natural anti-aging agents. Their bioactive compounds target multiple aging-related pathways and show potential for development into functional foods or phytotherapeutics. To support their potential in aging-related therapies, it is imperative to conduct more in-depth mechanistic investigations alongside well-designed clinical trials that can substantiate their effectiveness and facilitate their translational application.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157052"},"PeriodicalIF":6.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604471","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":"Mai Guan Fu Kang tablet (MGFK) accelerates diabetic foot ulcer healing via antioxidant defense and inflammation suppression","authors":"Xiaowen Jiang ,&nbsp;Ziyang Han ,&nbsp;Yue Jin ,&nbsp;Jie Liu ,&nbsp;Yijia Zhao ,&nbsp;Yujia Gu ,&nbsp;Dapeng Zhou ,&nbsp;Keqiang Li ,&nbsp;Huiyuan Gao","doi":"10.1016/j.phymed.2025.157038","DOIUrl":"10.1016/j.phymed.2025.157038","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic foot ulcer (DFU), a severe complication of diabetes characterized by impaired healing and high morbidity, demand novel therapeutic strategies. Mai Guan Fu Kang tablets (MGFK) and combined therapy have been used in the clinical treatment of DFU, showing potential in DFU management, but their mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the molecular mechanisms of MGFK in DFU, focusing on oxidative stress, inflammation, and vascular-neural repair.</div></div><div><h3>Methods</h3><div>Firstly, we performed a comprehensive pathological analysis of tissue samples obtained from patients with chronic diabetic wounds. Subsequently, we conducted in-depth investigations using DFU mouse model and diabetic lower limb ischemia rat model, as well as network pharmacology approaches. The efficacy and underlying mechanisms of MGFK were further elucidated through advanced analytical techniques, including liquid chromatography-mass spectrometry (LC-MS), molecular docking, qPCR, Western blotting, and immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>Clinical pathological analysis of tissue samples demonstrated significantly elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines in patients with DFU. MGFK-treated DFU mice could significantly increase the wound healing rate, reduce inflammation and inhibit oxidative stress. In diabetic limb ischemia rat model, MGFK improved blood flow, reduced coagulation markers (FIB, PT), and restored sciatic nerve function, correlating with increased VEGF and NO levels. Network pharmacology and molecular docking highlighted key components suggesting that MGFK is related to inflammation-related pathways and targets. Finally, through the construction of LPS-induced Raw264.7 cell models and tert‑butyl hydroperoxide (TBHP)-induced L929 cell models, it was found that MGFK has significant anti-inflammatory and antioxidant stress effects in vitro. Finally, we formulated a compound prescription, whose anti-inflammatory effect in vitro is superior to that of MGFK.</div></div><div><h3>Conclusions</h3><div>These findings highlight the multi-target mechanism of MGFK, which integrates antioxidant, anti-inflammatory, and vascular repair properties. Specifically, MGFK promotes wound healing by restoring antioxidant capacity, inhibiting NF-κB-mediated inflammatory responses, and enhancing vascular function.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157038"},"PeriodicalIF":6.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613987","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":"Coptisine activates aryl hydrocarbon receptor to regulate colonic epithelial homeostasis in DSS induced ulcerative colitis and TNF-α challenged intestinal organoids","authors":"Bingyan Tan ,&nbsp;Jingyan Zhang ,&nbsp;An Kang ,&nbsp;Li Zhang ,&nbsp;Dan Fang ,&nbsp;Hong Wu ,&nbsp;Tai Han ,&nbsp;Rongli Qiu ,&nbsp;Hui Li ,&nbsp;Dongdong Sun","doi":"10.1016/j.phymed.2025.157054","DOIUrl":"10.1016/j.phymed.2025.157054","url":null,"abstract":"<div><h3>Background</h3><div>Coptisine is a bioactive isoquinoline alkaloid derived from <em>Coptis Chinensis</em>, exhibiting significant pharmacological potential. Emerging evidence suggests its therapeutic efficacy in gastrointestinal disorders through modulating inflammation and maintaining gut homeostasis.</div></div><div><h3>Purpose</h3><div>The study aimed to elucidate the molecular mechanisms underlying coptisine mediated restoration of intestinal barrier integrity in ulcerative colitis (UC) and TNF-α challenged intestinal organoids.</div></div><div><h3>Methods</h3><div>A murine UC model was established by dextran sulfate sodium (DSS) induction to evaluate coptisine's therapeutic effects on colonic inflammation and mucosal barrier dysfunction. Complementary <em>in vitro</em> investigations were conducted using TNF-α-challenged HT-29 cells and intestinal organoids derived from wild-type mice to assess epithelial barrier repair capabilities. Additionally, we utilized an integrated experimental approach incorporating cellular thermal shift assay, luciferase reporter assays to explore the influence of coptisine on AhR activation. Lastly, specific AhR dependency of coptisine on barrier protective effects were further validated through three independent model systems: shAhR-transfected HT-29 cells, AhR KO murine intestinal organoids, and AhR KO mice subjected to DSS challenge.</div></div><div><h3>Results</h3><div>Coptisine administration significantly attenuated colitis severity in DSS-treated mice, evidenced by reduced histopathological scores, decreased colonic inflammation, and enhanced gut barrier integrity through upregulation of tight junction proteins (TJ proteins). In a barrier dysfunction model of TNF-α stimulation in HT-29 cells and intestinal organoids, coptisine treatment effectively normalized the expression levels of TJ proteins. Mechanistically, coptisine exhibited potent AhR activation through increased nuclear translocation and transcriptional regulation of CYP1A1. Coptisine dose-dependently inhibited reactive oxygen species (ROS) production and NF-κB activation in TNF-α treated HT-29 cells. Crucially, AhR knockdown or knockout completely abolished coptisine's inhibitory effects on NF-κB activation and the protective efficacy in barrier function, confirming pathway dependency.</div></div><div><h3>Conclusion</h3><div>Coptisine ameliorates intestinal barrier dysfunction and improves UC related symptom in an AhR-dependent manner. This mechanistic insight positions coptisine as a promising phytochemical candidate for UC therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157054"},"PeriodicalIF":6.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587476","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":"Calycosin alleviates myocardial fibrosis after myocardial infarction by restoring fatty acid metabolism homeostasis through inhibiting FAP","authors":"Shu-Ning Sun ,&nbsp;Xin Liu ,&nbsp;Xing-Ling Chen ,&nbsp;Shu-Lin Liang ,&nbsp;Jin Li ,&nbsp;Hui-Li Liao ,&nbsp;Hong-Cheng Fang ,&nbsp;Shi-Hao Ni ,&nbsp;Yue Li ,&nbsp;Lu Lu ,&nbsp;Zhong-Qi Yang ,&nbsp;Hui Wu ,&nbsp;Ling-Jun Wang","doi":"10.1016/j.phymed.2025.157045","DOIUrl":"10.1016/j.phymed.2025.157045","url":null,"abstract":"<div><h3>Background</h3><div>Myocardial fibrosis is a pivotal pathological mechanism underlying heart failure (HF) following myocardial infarction (MI). Natural herbal compounds exhibit great potential for anti-fibrotic applications, thereby warranting further in-depth investigation and development.</div></div><div><h3>Objective</h3><div>To find the critical gene characteristic of the early myocardial fibrosis following MI and identify the specifically targeted natural herbal compounds.</div></div><div><h3>Methods</h3><div>Through bioinformatics analysis and molecular phenotypic screening combined with various drug target validation methods, we sought to identify key fibrosis regulatory factors and related targeted natural herbal components. RNA-seq analysis was employed to explore potential downstream mechanisms. Both in vitro and in vivo experiments were conducted to evaluate the effects of FAP and Calycosin (CA) on fibrosis and lipid metabolism phenotypes in fibroblasts and cardiac tissues.</div></div><div><h3>Results</h3><div>RNA-Seq analysis revealed FAP as a core regulator of early post-MI fibrosis. CA, a natural herbal compound, could effectively inhibit FAP, thereby improving post-MI cardiac dysfunction via regulating FAP-mediated myocardial fibrosis. Further investigations demonstrated the pro-fibrotic efficacy of FAP may be closely related to its induction of lipid metabolic disorders. Correcting fatty acid (FA) metabolic disorders could abolish the pro-fibrotic effects of FAP. CA could ameliorate FA metabolic disorders in fibroblasts and cardiac tissues by inhibiting FAP. PPARα may be a downstream target of FAP to induce FA metabolic disorders, and CA could restore cardiac PPARα expression level by inhibiting FAP.</div></div><div><h3>Conclusion</h3><div>CA could alleviate post-MI myocardial fibrosis through inhibiting FAP, with the underlying mechanism involving the restoration of FA metabolism homeostasis by inhibiting FAP.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157045"},"PeriodicalIF":6.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571180","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":"Bupi Yishen formula improves chronic kidney disease by restoring renal energy metabolism and mitochondrial oxidative phosphorylation","authors":"Bingran Liu ,&nbsp;Guowei Chen ,&nbsp;Haoyu Mo ,&nbsp;Xiaolin Liang ,&nbsp;Xiaoyan Su ,&nbsp;Fuhua Lu ,&nbsp;Qizhan Lin ,&nbsp;Xusheng Liu ,&nbsp;Jiankun Deng ,&nbsp;Difei Zhang","doi":"10.1016/j.phymed.2025.157055","DOIUrl":"10.1016/j.phymed.2025.157055","url":null,"abstract":"<div><h3>Background</h3><div>Bupi Yishen formula (BYF) is a traditional Chinese herbal mixture with proven efficacy in attenuating kidney function deterioration among patients with advanced chronic kidney disease (CKD), and improving renal fibrosis of CKD animal models. Previous studies have shown that BYF rehabilitates metabolic dysregulation under CKD condition, but its exact mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the therapeutic effect and its potential mechanism on regulating renal energy metabolism in CKD.</div></div><div><h3>Methods</h3><div>An adenine-induced CKD rat model was treated with two doses of BYF decoction (15 g/kg/day or 30 g/kg/day) and losartan (as the positive control) for 4 weeks. Lipidomic and transcriptomic analyses of kidney samples from CKD rats revealed the BYF-reversed different lipid species and gene expression profiles respectively, thereby identifying potential pharmacological mechanisms. Further <em>in vivo</em> and <em>in vitro</em> experiments, network analyses, and molecular docking was used to confirm the proposed mechanisms affected by BYF.</div></div><div><h3>Results</h3><div>BYF had a profound impact on alleviating renal impairment and profibrotic phenotypes in CKD rats. Lipid profiling of kidneys from CKD rats showed that the dysmetabolism of glycerophospholipids, sphingolipids, and glycerolipids was primarily influenced by BYF. Transcriptome analysis of CKD rats identified renal energy metabolism (including fatty acid oxidation [FAO], glucose metabolism) and mitochondrial oxidative phosphorylation (OXPHOS) as the key dysregulated pathways, which were reversed by BYF. Further experiments confirmed that BYF partially restored defective FAO, dysregulated glucose metabolism, and impaired mitochondrial OXPHOS in the kidneys of CKD rats and TGFβ1-induced human tubule HK-2 cells. Besides, network analyses combined with molecular docking demonstrated a strong binding effect of BYF’s core compounds on key targets related to energy metabolism.</div></div><div><h3>Conclusions</h3><div>These results suggest that BYF protects against CKD by restoring renal energy homeostasis and mitochondrial OXPHOS, offering potential as an alternative therapy for renal fibrosis inherent to CKD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157055"},"PeriodicalIF":6.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579141","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":"Enhancing Sirt1-mediated deacetylation of p62 with a self-assembling nanopeptide and resveratrol hydrogel to mitigate sepsis-induced inflammation","authors":"Baoquan Wang ,&nbsp;Ying Wang ,&nbsp;Zhansheng Hu ,&nbsp;Shuang Peng ,&nbsp;Na Li ,&nbsp;Zhang Dan ,&nbsp;Haiyan Fu ,&nbsp;Huiping Wu","doi":"10.1016/j.phymed.2025.157047","DOIUrl":"10.1016/j.phymed.2025.157047","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced inflammatory damage remains a significant clinical challenge with limited effective treatments. Elucidating the molecular mechanisms that regulate macrophage function may reveal key therapeutic targets to combat sepsis.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the role of Sirtuin 1 (Sirt1) in regulating mitochondrial autophagy and immunometabolic remodeling in macrophages to alleviate inflammation associated with septic shock.</div></div><div><h3>Study design</h3><div>A controlled laboratory study was conducted using a murine sepsis model to elucidate the contribution of Sirt1 to macrophage function during sepsis-induced inflammation, employing both in vivo and in vitro approaches.</div></div><div><h3>Methods</h3><div>Sepsis was induced in mice via cecal ligation and puncture (CLP). Peritoneal macrophages (PMs) from sham-operated and septic mice were analyzed using single-cell RNA sequencing (scRNA-seq). Differential gene expression, immunostaining, transmission electron microscopy (TEM), and metabolomics were performed to evaluate the roles of Sirt1 and Sqstm1 (p62) in modulating macrophage autophagy and inflammation.</div></div><div><h3>Results</h3><div>Sirt1 expression was markedly reduced in PMs from septic mice. Sirt1-mediated deacetylation of p62 activated mitochondrial autophagy, suppressed lipopolysaccharide (LPS)-induced pro-inflammatory responses, and decreased mitochondrial reactive oxygen species (mtROS) production. Treatment with a self-assembling nanopeptide and resveratrol (Res) composite hydrogel improved survival rates and reduced tissue damage in septic mice. Integrated single-cell transcriptomics and metabolomics analyses demonstrated that Sirt1 modulated macrophage mitophagy and immunometabolic reprogramming, providing new insights into the molecular mechanisms of sepsis.</div></div><div><h3>Conclusion</h3><div>The self-assembling nanopeptide and Res hydrogel enhances Sirt1-mediated deacetylation of p62, promoting mitochondrial autophagy and immunometabolic remodeling, thereby mitigating sepsis-induced inflammation. This strategy represents a promising therapeutic approach for reducing inflammation-related damage in sepsis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157047"},"PeriodicalIF":6.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571179","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}