Phytomedicine最新文献

{"title":"Anti-tumor effects of Guggulsterone in osteosarcoma: Role of SIRT3-mediated PINK1-Parkin mitophagy activation","authors":"Lingyuan Zeng ,&nbsp;Shuwei Li ,&nbsp;Kaidong Wu ,&nbsp;Xiaoyu Bai ,&nbsp;Long Zhang","doi":"10.1016/j.phymed.2026.157860","DOIUrl":"10.1016/j.phymed.2026.157860","url":null,"abstract":"<div><div>Osteosarcoma (OS) is an aggressive primary bone malignancy characterized by limited therapeutic options and poor prognosis in advanced stages. Guggulsterone (GS), a naturally occurring plant-derived sterol, has recently been reported to suppress OS progression by inhibiting glycolysis via the MAPK signaling pathway. Although these findings underscore the therapeutic potential of GS in OS, the contribution of mitochondrial quality control to its antitumor activity remains unclear. Here, we report that GS disrupts mitochondrial integrity, elevates oxidative stress, and drives enhanced mitophagy in OS cells. RNA sequencing combined with functional assays revealed significant enrichment of mitophagy-related pathways, while rescue experiments confirmed that blocking mitophagy or SIRT3 activity markedly alleviated GS-induced mitochondrial damage, apoptosis, and growth inhibition. Mechanistically, GS activated the SIRT3-dependent PINK1/Parkin axis in a time-dependent manner, providing compelling evidence for its involvement in mitophagy regulation. Importantly, GS markedly inhibited OS tumor growth <em>in vivo</em> without causing detectable systemic toxicity. Collectively, our findings identify a mechanism distinct from the previously reported glycolysis/MAPK pathway, thereby broadening the mechanistic understanding of GS and underscoring its potential as a mitochondria-targeted therapeutic strategy for OS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157860"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132961","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":"Berberine reverses impaired adipose angiogenesis to promote beige adipogenesis by HIF-1α/PRDM16 signaling","authors":"Chien-shan Cheng ,&nbsp;Jingxian Chen ,&nbsp;Yuan Wu ,&nbsp;Yijie Song ,&nbsp;Jiayue Xu ,&nbsp;Yu Xu ,&nbsp;Lan Zheng","doi":"10.1016/j.phymed.2026.157902","DOIUrl":"10.1016/j.phymed.2026.157902","url":null,"abstract":"<div><h3>Background</h3><div>Obesity-induced adipose tissue expansion is characterized by capillary rarefaction and hypoxia, which disrupts angiogenesis and impairs beige adipogenesis. While angiogenesis is known to be crucial for beiging, the functional link between impaired vascularization and defective browning remains poorly understood. How natural compounds like berberine (BBR) links angiogenesis with beige adipogenesis remains unexplored.</div></div><div><h3>Methods</h3><div>Using both diet-induced obese (DIO) C57BL/6 J and leptin-deficient (ob/ob) murine models, we administered intraperitoneal BBR for 4 weeks. Adipose tissue remodeling was evaluated through histomorphometry, immunofluorescence, and flow cytometry. RNA sequencing of adipose tissue was performed to identify the potential targets. Chemical hypoxia was induced using CoCl₂ in preadipocytes to examine its effects on browning.</div></div><div><h3>Results</h3><div>BBR improved adipose tissue dysfunction in both the DIO model and the ob/ob model. It increased CD34⁺CD31⁺ endothelial progenitor cells and enhanced protein levels of VEGF/VEGFR2, PRDM16, PPAR-γ, and UCP-1, indicating simultaneous promotion of angiogenesis and adipose browning. Transcriptomic analysis revealed glutathione peroxidase 3 (GPx3) as a novel target through which BBR alleviates adipose dysfunction. GPX3 knockdown <em>in vivo</em> impaired angiogenesis and suppressed browning markers. BBR reversed chemical hypoxia-induced impairment of beige adipocyte differentiation independently of UCP-1 upregulation by inhibiting HIF-1α activation.</div></div><div><h3>Conclusions</h3><div>This study unveils that BBR counteracts obesity-associated adipose tissue dysfunction: it upregulates GPx3 to reduce oxidative stress, which in turn normalizes HIF-1α levels and activates the PRDM16 signaling, thereby concurrently restoring adipose angiogenesis and promoting beige adipogenesis. This breaks the vicious cycle of hypoxia-impaired angiogenesis and suppressed thermogenesis, positioning BBR as a promising multi-target therapy for obesity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157902"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137866","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":"Renqingchangjue ameliorates MNNG-induced chronic atrophic gastritis by inhibiting the TNF/NF-κB/Caspase-3 axis","authors":"Yuan Chen ,&nbsp;Guang Yue ,&nbsp;Yanjun Liu ,&nbsp;Wei Wang ,&nbsp;Ge Jiang ,&nbsp;Jinhua Zhang ,&nbsp;Zhuo Ga ,&nbsp;Yanfei Zhang ,&nbsp;Xiaoya Liu ,&nbsp;Qingjia Ren ,&nbsp;Caolong Li","doi":"10.1016/j.phymed.2026.157920","DOIUrl":"10.1016/j.phymed.2026.157920","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chronic atrophic gastritis (CAG) is a pivotal premalignant stage in the Correa cascade, characterized by progressive and largely irreversible loss of gastric glands and an elevated risk of gastric cancer. Renqingchangjue (RQCJ), a classical Tibetan multi-herb formula, has demonstrated clinical and pharmacological benefits in gastritis, yet its mechanisms of action in CAG remain inadequately defined.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to clarify the therapeutic efficacy and mechanistic basis of RQCJ in CAG.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We established a network pharmacology–bioinformatics workflow to predict potential RQCJ targets in CAG, integrating targets obtained from TCMSP/SwissTargetPrediction with CAG-related genes to construct a STRING protein–protein interaction (PPI) network and perform GO/KEGG enrichment analyses. Constituents were characterized by UHPLC–HRMS/MS. An MNNG-induced CAG mouse model (control group, model group, Weifuchun positive control group, RQCJ low-dose group and RQCJ high-dose group) was validated by histopathology (H&amp;E), immunohistochemistry (IHC), immunofluorescence (IF), TUNEL, ELISA, and Western blot (WB). In vitro, MNNG-injured GES-1 cells were evaluated using CCK-8, scratch wound-healing, and Annexin V–FITC/PI flow cytometry. Mechanistically, RT-qPCR, WB, and reference-based transcriptome sequencing of gastric tissue were employed, and compound druggability was assessed by AutoDock Vina docking.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;RQCJ markedly ameliorated MNNG-induced chronic atrophic gastritis in vivo and in vitro. UHPLC–HRMS/MS profiling identified 43 constituents, of which 31 were detected as circulating prototypes. Network pharmacology first predicted 154 putative RQCJ–CAG targets enriched in TNF/NF-κB signaling; integrating serum-absorbed component targets with CAG-related genes refined this to 140 high-confidence targets with consistent TNF/NF-κB enrichment. Functionally, RQCJ (20–40 μg/mL) improved GES-1 cell viability and migration while suppressing apoptosis, and in mice dose-dependently repaired gastric mucosal architecture, lowered TNF-α, IL-1β and IL-6, and normalized gastrin and pepsinogen. RQCJ also reduced IL-8, CCL2 and CXCL1 mRNA and increased IL-10 in both models. Mechanistically, it inhibited phosphorylation of IKKβ, IκBα and NF-κB p65 in a dose- and time-dependent manner, decreased cleaved caspase-8/3, restored the Bax/Bcl-2 ratio. Transcriptomics confirmed enrichment of NF-κB and apoptosis pathways, and intersecting differentially expressed genes with the 140 serum-based targets yielded 99 core genes converging on TNF/NF-κB-mediated apoptosis. Molecular docking further supported target engagement, with a chromen-7-ol derivative showing strong predicted affinity for MMP9.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Together, these multi-level data indicate that RQCJ exerts clinically relevant protection against CAG via multi-component su","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157920"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143285","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":"Multi-omics reveals hepatotoxic mechanisms and key toxic components of Polygoni Multiflori Radix and its processed products","authors":"Qi Wu ,&nbsp;Ziyi Chen ,&nbsp;Zong Hou ,&nbsp;Zhiqiang Liu ,&nbsp;Rong Sun ,&nbsp;Shu Liu","doi":"10.1016/j.phymed.2026.157908","DOIUrl":"10.1016/j.phymed.2026.157908","url":null,"abstract":"<div><h3>Background</h3><div><em>Polygoni Multiflori Radix</em> (PMR) and its processed form, <em>Polygoni Multiflori Radix Praeparata</em> (PMRP), are two widely used traditional Chinese medicines (TCM). However, in recent years, frequent reports have emerged regarding their hepatotoxicity. Despite numerous studies, the underlying mechanisms of hepatotoxicity and key toxic components remain poorly understood.</div></div><div><h3>Purpose</h3><div>This study aimed to comprehensively elucidate the hepatotoxic processes of PMR and PMRP and identify the principal toxic components.</div></div><div><h3>Methods</h3><div><em>In vivo</em> toxicity tests were carried out to assess the toxicity levels and characteristics of PMR and PMRP. The integration of untargeted serum metabolomics, liver spatial transcriptomics, and liver spatial metabolomics was first employed to elucidate the toxicity mechanisms, which were further validated through metabolite and sensitive index levels and by evaluating protein expression. Mass spectrometry and cytotoxicity tests were utilised to determine the primary toxic components.</div></div><div><h3>Results</h3><div>The findings revealed that PMR and PMRP primarily regulate tryptophan metabolism, the tricarboxylic acid (TCA) cycle, purine metabolism, and glutathione metabolism. Furthermore, PMR and PMRP can inhibit the expression of bile acid transporters, causing obstruction of bile acid secretion. These modulations trigger oxidative stress, which subsequently leads to cholestasis. The accumulation of bile acids further intensifies oxidative stress, creating a vicious cycle. Furthermore, emodin was identified as the primary toxic component.</div></div><div><h3>Conclusion</h3><div>PMR and PMRP can induce cholestatic liver injury. They exert hepatotoxic effects by establishing a vicious cycle between cholestasis and oxidative stress, with emodin being the key component responsible for this toxicity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157908"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Effusol ameliorates ischemic stroke by targeting NLRP3 protein to regulate NLRP3 inflammasome-mediated pyroptosis\" [Phytomedicine, 136 (2025) 156253/PMID: 39615210].","authors":"Libin Xu, Siyu Li, Jiaxin Qi, Yan Mi, Ying Zhang, Yuxin Yang, Yingjie Wang, Di Zhou, Ning Li, Yue Hou","doi":"10.1016/j.phymed.2026.157968","DOIUrl":"10.1016/j.phymed.2026.157968","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"157968"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284342","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":"Cordyceps cicadae polysaccharides ameliorate ulcerative colitis by modulating the gut microbiota and regulating the bile acid/FXR/NF-κB signaling pathway.","authors":"Siyu Zhou, Fayu Su, Qinhan Gao, Majie Wang, Jialin Duan, Jiankang Li","doi":"10.1016/j.phymed.2026.158007","DOIUrl":"10.1016/j.phymed.2026.158007","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease, closely linked to dysbiosis of the intestinal microbiota and abnormal bile acid homeostasis. Polysaccharides derived from Paecilomyces cicadae (CCP) exhibit immunomodulatory and anti-inflammatory effects. However, their therapeutic potential and underlying mechanisms in UC remain poorly elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This research seeks to evaluate the therapeutic efficacy of CCP in the treatment of UC and utilizing the \"microbiota-bile acid metabolism-immunity\" axis, elucidates the mechanisms by which CCP enhances intestinal barrier integrity and ameliorates inflammation via modulation of the gut microbiota-mediated farnesoid X receptor (FXR)/NF-κB signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The physicochemical properties of CCP were characterized by FTIR spectroscopy, HPLC, and SEM analyses. A dextran sulfate sodium (DSS)-induced colitis mouse model was used to evaluate the ameliorative effects of CCP. Gut microbial alterations were profiled by 16S rDNA sequencing, while targeted metabolomics enabled comprehensive quantification of bile acid profiles in serum and fecal samples. Fecal microbiota transplantation (FMT) was conducted to validate the microbiota-mediated actions of CCP. Downstream molecular mechanisms were examined using Western blotting and immunofluorescence assays to assess modulation along the microbiota-bile acid axis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CCP is primarily composed of glucose, mannose, and galactose, exhibiting a characteristic polysaccharide structure with a uniform molecular weight distribution. Treatment with CCP significantly ameliorated DSS-induced colitis in mice, as evidenced by reduced weight loss, preserved colon length, and decreased histopathological damage. 16S rDNA analysis demonstrated CCP-driven restoration of intestinal microbial diversity and a marked increase in Clostridium Kas107-2 (cluster XIVa). Metabolomics revealed normalization of bile acid metabolism, with elevated synthesis of secondary bile acids (deoxycholic acid, lithocholic acid, 12-keto LCA) and reduced levels of primary bile acids (α/β-MCA). Mechanistically, CCP activated FXR signaling, suppressed IκBα phosphorylation, downregulated NF-κB signaling, and reduced production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Enhanced expression of tight junction proteins (ZO-1, Occludin, Claudin-1) indicated improved epithelial barrier function. Notably, FMT from CCP-treated donors replicated these protective effects, confirming colitis attenuation, bile acid restoration, and inhibition of FXR/NF-κB signaling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;CCP ameliorate experimental UC by promoting the proliferation of Clostridium cluster XIVa, modulating bile acid metabolism to facilitate secondary bile acid biosynthesis, activating FXR pathways, and suppressing NF-κB-driven inflammatory responses, thereby reinforcing int","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"158007"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322173","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":"Semen Sojae Praeparatum ameliorates triptolide-induced liver injury by regulating bile acid homeostasis and the Keap1/Nrf2/p62 axis","authors":"Lin Zhou ,&nbsp;Qi Qian ,&nbsp;Yaqin Zhen ,&nbsp;Hanyu Ma ,&nbsp;Liying Niu ,&nbsp;Xinguo Wang","doi":"10.1016/j.phymed.2026.157878","DOIUrl":"10.1016/j.phymed.2026.157878","url":null,"abstract":"<div><h3>Background</h3><div>Semen Sojae Praeparatum (SSP) exhibits both preventive and therapeutic effects against drug-induced liver injury (DILI). Traditionally, SSP is used in combination with <em>Gardeniae fructus</em> to prevent its hepatotoxicity. Isoflavones, the primary components of SSP, can mitigate DILI induced by chemotherapeutic agents such as acetaminophen and cisplatin. However, the potential of SSP to alleviate the hepatotoxicity of triptolide (TP, a prototypical compound in DILI research) remains unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the protective effects and potential mechanisms of SSP on TP-induced liver injury.</div></div><div><h3>Methods</h3><div>The phytochemical profile of the SSP extracts was characterized using UPLC-Q-TOF-MS. Hepatoprotective effects of SSP were assessed using a TP-induced liver injury mouse model. The mechanisms were predicted by metabolomic and proteomic analyses, and further elucidated by RT-qPCR, western blotting and transmission electron microscopy.</div></div><div><h3>Results</h3><div>Isoflavones were identified as the main components of the SSP extracts. SSP treatment alleviated TP-induced abnormalities in serum biochemical markers, liver index and pathological damage. Multi-omics analysis revealed SSP modulated bile acid (BA) metabolism and autophagy, with Keap1 serving as a core protein. Furthermore, SSP reduced intrahepatic BA accumulation by enhancing hepatic BA transport rather than inhibiting BA synthesis. Additionally, SSP reversed TP-induced abnormalities in Keap1 and p62 expression and nuclear translon cation of the Nrf2 transcription factor, and mitigated oxidative imbalance and autophagic cell death.</div></div><div><h3>Conclusions</h3><div>SSP ameliorated TP-induced liver injury by modulating bile acid homeostasis and the Keap1/Nrf2/p62 pathway, thereby alleviating oxidative stress and excessive autophagy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157878"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192028","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":"Curcumol targets the ATG4B–PKM2–lactate signaling axis to reverse EMT and inhibit colorectal cancer liver metastasis","authors":"Gang Wang ,&nbsp;Zengyaran Yue ,&nbsp;Wen Zhou ,&nbsp;Cong Peng ,&nbsp;Tingting Bi ,&nbsp;Xiying Tan ,&nbsp;Weiwei He ,&nbsp;Yuwei Zhang ,&nbsp;Zhuo Deng ,&nbsp;Danning Zhang ,&nbsp;Wenhao Yuan ,&nbsp;Yong Bian ,&nbsp;Gang Yin ,&nbsp;Lifeng Zhu ,&nbsp;Decai Tang","doi":"10.1016/j.phymed.2026.157933","DOIUrl":"10.1016/j.phymed.2026.157933","url":null,"abstract":"<div><h3>Background</h3><div>Distant metastasis of colorectal cancer (CRC) is strongly driven by metabolic reprogramming and epithelial–mesenchymal transition (EMT). Increasing evidence suggests that these two processes form a reinforcing positive feedback loop; however, the integrated regulatory mechanism and its potential for pharmacological intervention remain insufficiently understood.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the mechanistic coupling between autophagy, metabolic reprogramming, and EMT, and to develop a targeted pharmacological strategy capable of disrupting this positive feedback loop.</div></div><div><h3>Study Design</h3><div>We systematically constructed and validated an autophagy–metabolism–phenotypic transformation regulatory axis centered on ATG4B and PKM2, and evaluated the therapeutic efficacy of Curcumol as a pathway-specific natural compound intervention.</div></div><div><h3>Methods</h3><div>Biochemical assays, protein–protein interaction analyses, and functional experiments were performed to determine how ATG4B regulates PKM2 Tyr105 phosphorylation, nuclear translocation, and glycolytic activity. Curcumol was applied to assess its ability to activate ATG4B-dependent autophagy and inhibit PKM2 activation. Anti-tumor efficacy was validated using colorectal cancer organoids, orthotopic implantation, and liver metastasis mouse models.</div></div><div><h3>Results</h3><div>ATG4B was identified as a core autophagy enzyme that directly binds to and shields the PKM2 Tyr105 site, preventing FGFR1-mediated phosphorylation and nuclear translocation. This blockade suppressed the Warburg effect, reduced lactate production, and synergistically inhibited EMT progression. Curcumol activated ATG4B-dependent autophagy, inhibited PKM2 activation, and effectively disrupted the metabolism–EMT positive feedback loop. In multiple CRC models, Curcumol markedly suppressed tumor growth and metastasis, supporting its therapeutic potential.</div></div><div><h3>Conclusion</h3><div>This study reveals the ATG4B–PKM2 axis as a critical regulatory node linking autophagy, metabolic reprogramming, and EMT. Targeting this axis with Curcumol provides a precise strategy to interrupt metabolism–phenotype coupling, offering a mechanistically grounded and translationally promising approach for inhibiting CRC progression and metastasis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157933"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192292","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":"Dehydrocavidine alleviates lipopolysaccharide-induced acute liver injury by activating Nrf2 signaling pathway to inhibit hepatocyte ferroptosis","authors":"Hongbiao Liang ,&nbsp;Guizimeng Hu ,&nbsp;Dongmin Yang ,&nbsp;Yuwei Song ,&nbsp;Peng Zhang ,&nbsp;Tianqi Chen ,&nbsp;Xiangrui Zhu ,&nbsp;Peiyi Li ,&nbsp;Yuan Wang ,&nbsp;Xinmei Huo ,&nbsp;Xiaoyi Wang ,&nbsp;Yi Zhang ,&nbsp;Yujie Zhang ,&nbsp;Jian Liu ,&nbsp;Juan Feng","doi":"10.1016/j.phymed.2026.157845","DOIUrl":"10.1016/j.phymed.2026.157845","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced acute liver injury (SALI) remains a major challenge with limited effective treatments. Although Corydalis saxicola Bunting (CSB) exhibits anti-inflammatory and hepatoprotective properties, its role in SALI remains poorly understood.</div></div><div><h3>Purpose</h3><div>To identify the active components and molecular mechanisms of CSB in protecting against SALI.</div></div><div><h3>Methods</h3><div><em>In vivo</em> LPS-induced rat liver injury and <em>in vitro</em> cytokine-induced HepG2 injury models were established, treated with CSB extract or dehydrocavidine (DC). A series of advanced techniques including ferroptosis PCR array, super-resolution stimulated emission depletion (STED) microscopy, assay for transposase-accessible chromatin with sequencing (ATAC-seq), cellular thermal shift assay (CETSA), surface plasmon resonance (SPR), molecular dynamics simulation, and site-directed mutation were employed to investigate the underlying mechanisms.</div></div><div><h3>Results</h3><div>DC significantly mitigated LPS-induced liver injury, microcirculatory disorder, and leukocyte adhesion. It also alleviated liver ferroptosis under LPS challenge. <em>In vitro</em> studies revealed that LPS-activated macrophages secreted tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), which triggered hepatocyte ferroptosis. DC countered this process by inhibiting the production of these cytokines and correcting cytokine-induced mitochondrial abnormalities in hepatocytes. Mechanistically, DC bound to Kelch-like ECH-associated protein 1 (Keap1) at arginine 415 (R415), disrupting the formation of the Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) complex. This enabled Nrf2 nuclear translocation and promoted antioxidant gene expression, thereby correcting LPS-induced redox imbalance in hepatocytes.</div></div><div><h3>Conclusions</h3><div>In addition to inhibiting LPS-induced macrophage activation, DC activates the Nrf2 signaling pathway in hepatocytes to alleviate inflammation-enhanced liver ferroptosis. It provides potential therapeutic strategies for sepsis and Gram-negative bacteria-associated liver injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157845"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137871","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":"Rewiring the regulated cell death network in diabetic retinopathy: natural products as system-level modulators","authors":"Qun Huang ,&nbsp;Tingru Chen ,&nbsp;Fang Wang ,&nbsp;Jieying Wang ,&nbsp;Biying Fan ,&nbsp;Ruolan Wu ,&nbsp;Jinlian Wang ,&nbsp;Shunlin Peng ,&nbsp;Yanlin Zheng","doi":"10.1016/j.phymed.2026.157844","DOIUrl":"10.1016/j.phymed.2026.157844","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic retinopathy (DR) pathogenesis is driven by the dysregulation of an interconnected network of regulated cell death (RCD) modalities, including apoptosis, autophagy-dependent cell death, pyroptosis, and ferroptosis. Current therapies often fail to address this upstream cellular damage. Natural products (NPs), with their inherent polypharmacology, offer a promising strategy to modulate this complex network.</div></div><div><h3>Purpose</h3><div>This review advances a framework conceptualizing DR as the collapse of a dynamic RCD network and positions NPs as \"RCD network modulators\". We delineate how these agents can restore homeostasis and overcome the limitations of existing mono-target therapies.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted using Web of Science and PubMed, integrating keywords related to \"natural products\", \"diabetic retinopathy\", and specific \"regulated cell death\" modalities. All animal experiments adhered to ethical guidelines and complied with both international and institutional ethical standards.</div></div><div><h3>Results</h3><div>NPs simultaneously engage the master regulatory nodes—mitochondrial dysfunction, hyperactivation of the inflammasome, and oxidative stress. By modulating the Bcl-2 rheostat, normalizing autophagic flux, suppressing NLRP3 assembly, and activating Nrf2/SIRT1 pathways, NPs orchestrate a \"network rewiring\" to halt DR progression. However, clinical translation is significantly constrained by pharmacokinetic challenges, including low oral bioavailability and poor ocular penetration.</div></div><div><h3>Conclusion</h3><div>DR pathology emerges from network-level RCD dysregulation. NPs, which function as modulators of the RCD network, represent a compelling therapeutic shift toward addressing the root drivers of retinal degeneration.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157844"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143292","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}