Phytomedicine最新文献

{"title":"Baohuoside I induces GSDME-dependent pyroptosis and synergistically inhibits lung adenocarcinoma with cisplatin","authors":"Ying Yang ,&nbsp;Luchanghao Zheng ,&nbsp;Tao Zhao ,&nbsp;Yi Zhang ,&nbsp;Ruiguang Luo ,&nbsp;Shiyan Xie ,&nbsp;Guilan Wen ,&nbsp;Zhujun Cheng ,&nbsp;Tianyu Han","doi":"10.1016/j.phymed.2026.157899","DOIUrl":"10.1016/j.phymed.2026.157899","url":null,"abstract":"<div><h3>Background</h3><div>Pyroptosis is a form of inflammatory programmed cell death and has been proven to be a promising therapeutic strategy for cancer. To date, little is known about the natural product inducers of pyroptosis. Baohuoside I is a flavonoid compound extracted from plants of the <em>Epimedium genus</em> and has been reported to have antitumor effects. However, the mechanisms underlying Baohuoside I-induced cell death in lung adenocarcinoma (LUAD) remain unclear.</div></div><div><h3>Purpose</h3><div>To explore the effects and mechanisms of Baohuoside I-induced cell death in LUAD.</div></div><div><h3>Methods</h3><div>A cell counting kit-8 (CCK-8) was used to examine the inhibitory effects of Baohuoside I on LUAD cells. Cell death was detected by LDH release and PI staining. Cell membrane separation followed by western blotting and fluorescence microscopy were used to detect the cleavage and membrane translocation of GSDME. RNA sequencing was used to evaluate changes in overall gene expression.</div></div><div><h3>Results</h3><div>Baohuoside I induced significant cell death in LUAD cells, and this effect could be blocked by pyroptosis inhibitors rather than other cell death inhibitors or ROS scavengers. Further studies demonstrated that Baohuoside I treatment induced the cleavage and membrane translocation of GSDME, leading to pyroptosis. Through RNA sequencing analysis, we found that Baohuoside I inhibited the DNA damage repair process and that combined treatment with and cisplatin had a synergistic effect on LUAD.</div></div><div><h3>Conclusion</h3><div>Baohuoside I is a new pyroptosis inducer in LUAD, and combined treatment with Baohuoside I and cisplatin has a synergistic inhibitory effect on LUAD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157899"},"PeriodicalIF":8.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116352","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":"Dieckol, a phlorotannin from Ecklonia cava, alleviates stress hormone-induced depressive-like behaviors through glucocorticoid receptor antagonism","authors":"Inhye Park ,&nbsp;Jung-Eun Lee ,&nbsp;Minji Kim ,&nbsp;Minseok Yoon ,&nbsp;Min Jung Kim ,&nbsp;Min-Sun Kim ,&nbsp;Suengmok Cho ,&nbsp;Min Young Um","doi":"10.1016/j.phymed.2026.157906","DOIUrl":"10.1016/j.phymed.2026.157906","url":null,"abstract":"<div><h3>Background</h3><div>Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from <em>Ecklonia cava</em> (PS) and its active compound dieckol (DK) exhibit various biological activities, their antidepressant- and anxiolytic-like effects and underlying mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study investigated the antidepressant- and anxiolytic-like potential of PS and DK in a corticosterone (CORT)-induced mouse model of depression and anxiety, focusing on glucocorticoid receptor (GR) signaling.</div></div><div><h3>Methods</h3><div>CORT-treated mice were orally administered PS or DK, and behavioral tests were performed to assess depressive- and anxiety-like behaviors. PS composition was analyzed using LC-MS/MS. Molecular docking predicted the binding of PS components to GR. GR nuclear translocation, target gene expression, and downstream signaling were examined using behavioral, molecular, and computational approaches.</div></div><div><h3>Results</h3><div>PS alleviated CORT-induced depressive- and anxiety-like behaviors, accompanied by reduced GR nuclear translocation, suppression of Mkp-1, and restoration of ERK–CREB–BDNF signaling. Molecular docking analysis predicted strong binding of DK to the GR ligand-binding domain. Consistently, DK reduced GR nuclear translocation and GRE binding, downregulated GR target genes (<em>Mkp-1, Sgk-1, Fkbp5</em>, and <em>Bdnf</em>), and restored ERK–CREB–BDNF signaling. In vivo, DK also improved CORT-induced behavioral deficits and normalized HPA axis activity and neurotransmitter levels.</div></div><div><h3>Conclusion</h3><div>Collectively, our results suggest that DK, a major bioactive phlorotannin from <em>E. cava</em>, exerts antidepressant- and anxiolytic-like effects in association with modulation antagonism of GR signaling, highlighting its therapeutic potential as a natural GR-modulating agent for stress-related mood disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157906"},"PeriodicalIF":8.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116351","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":"Ginsenosides remodel tumor immune microenvironment through metabolic reprogramming: Targets and mechanisms","authors":"Zhong-Wei Yao ,&nbsp;Yong-Qing Wang ,&nbsp;He Zhu","doi":"10.1016/j.phymed.2026.157901","DOIUrl":"10.1016/j.phymed.2026.157901","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic reprogramming is a hallmark of cancer development. By regulating energy and nutrient metabolism, it shapes an immunosuppressive tumor microenvironment (TME) that supports rapid tumor proliferation and promotes cancer progression. Ginsenosides, the major active components of <em>Panax ginseng</em>, have recently been found not only to directly inhibit tumor cell proliferation and induce apoptosis, but also to remodel the TME through metabolic regulation in both tumor and immune cells, thereby enhancing antitumor immune responses. However, the underlying mechanisms have not been fully elucidated.</div></div><div><h3>Purpose</h3><div>This study systematically summarizes the metabolic targets and regulatory mechanisms of ginsenosides in key pathways of metabolic reprogramming involving glucose, lipid, amino acid, and nucleotide metabolism, aiming to provide a theoretical basis and new perspectives for tumor metabolism-based immunotherapy.</div></div><div><h3>Methods</h3><div>Using \"ginsenoside\", \"glucose metabolism\", \"Warburg effect\", \"lipid metabolism\", \"fatty acid\", \"cholesterol\", \"amino acid metabolism\", \"nucleotide metabolism\", \" tumor\" and combinations of these keywords in PubMed, Web of Science, and CNKI.</div></div><div><h3>Results</h3><div>Ginsenosides primarily restore immune cell function by reversing the Warburg effect, suppressing fatty acid synthesis and oxidation, downregulating cholesterol and arachidonic acid metabolism, and inhibiting the depletion of glutamine and tryptophan as well as the catabolism of arginine. In addition, ginsenosides downregulate purine and pyrimidine biosynthesis, thereby limiting tumor cell proliferation.</div></div><div><h3>Conclusions</h3><div>Ginsenosides alleviate the immunosuppressive state of the TME and restore immune effector cell functions through multidimensional metabolic regulation. In the future, it is necessary to conduct further clinical investigations and develop metabolism-targeted ginsenoside delivery systems to ultimately achieve precise cancer therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157901"},"PeriodicalIF":8.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116405","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":"2026-01-29","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":"Baitouweng decoction regulates ferroptosis-mediated mitophagy and apoptosis through the SLC7A11/GPX4/FTH1 pathway in ulcerative colitis","authors":"Liuliang Zhang ,&nbsp;Xiaolan Zhu ,&nbsp;Xiaochao Hu ,&nbsp;Hui Feng ,&nbsp;Guoqing Wang ,&nbsp;Ying Zhang ,&nbsp;Xuan Wang ,&nbsp;Jiayu Su ,&nbsp;Tongtong Liu ,&nbsp;Xingyue Du ,&nbsp;Huimin Zhu ,&nbsp;Limei Gu ,&nbsp;E-Hu Liu ,&nbsp;Shijia Liu","doi":"10.1016/j.phymed.2026.157898","DOIUrl":"10.1016/j.phymed.2026.157898","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of ulcerative colitis (UC) has increased recently, with severe cases potentially progressing to colon cancer. The classic herbal formula Baitouweng Decoction (BTW) has a centuries-long clinical application in UC treatment, but its underlying mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate BTW’s efficacy against Dextran Sodium Sulfate (DSS)-induced UC and clarify its mechanisms.</div></div><div><h3>Results</h3><div>Proteomic analysis identified ferroptosis as a key pathogenic mechanism in UC. <em>In vitro</em> and <em>in vivo</em> experiments showed that BTW reduced UC-associated inflammatory symptoms, normalized the levels of inflammatory factors, and maintained intestinal barrier integrity. Notably, BTW inhibited ferroptosis and restored the antioxidant capacity of the SCL7A11/GSH/GPX4 system, thereby suppressing UC inflammation. Transcriptomic analysis revealed apoptosis and ferroptosis as core pathways for BTW’s intervention in UC, with mitophagy serving as a pivotal hub connecting these processes. BTW regulated the PINK1/PARKIN-mediated mitophagy pathway and apoptosis, and this regulation was closely linked to ferroptosis.</div></div><div><h3>Conclusion</h3><div>BTW alleviates UC-related inflammation and intestinal barrier damage by modulating apoptosis, mitophagy, and ferroptosis, while mitigating oxidative stress.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157898"},"PeriodicalIF":8.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116348","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":"Magnolol inhibits the resistance of ESBLs E. coli to fourth-generation cephalosporins in vitro and in vivo","authors":"Yin-Chao Tong ,&nbsp;Huan Lin ,&nbsp;Yang Yang ,&nbsp;Zhi-fu Zhou ,&nbsp;Yi-Ning Zhang ,&nbsp;Juan Wang ,&nbsp;Wu-ren Ma ,&nbsp;Yongsheng Wang ,&nbsp;Wei-Min Zhang ,&nbsp;Su-Zhu Qing","doi":"10.1016/j.phymed.2026.157889","DOIUrl":"10.1016/j.phymed.2026.157889","url":null,"abstract":"<div><h3>Background</h3><div>Antimicrobial resistance (AMR) infection is attracting increasing attention, especially superbug infections. As a result, finding ways to reduce AMR is essential. For the time being, natural compound therapy for reducing AMR is an ideal choice.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the mechanism of magnolol reducing the AMR of <em>E. coli</em> in <em>vitro</em> and <em>vivo</em>.</div></div><div><h3>Methods</h3><div>The morphology and function of <em>E. coli</em> under magnolol treatment were assessed using a scanning electron microscope, qPCR, RNA-seq, and other methods. Moreover, the in vivo treatment effects of magnolol combined with antibiotics were evaluated by HE and IHC staining.</div></div><div><h3>Results</h3><div>In this study, we found that magnolol reduced the resistance of ESBL <em>E. coli</em> to the fourth-generation cephalosporin in <em>vitro</em> via two main mechanisms. Firstly, magnolol disrupts iron ion metabolism by increasing environmental iron uptake significantly (P ≤ 0.01), leading to a significant increase in intracellular ROS (P ≤ 0.01) and membrane damage. Secondly, magnolol significantly inhibits the relative mRNA expression of blaCTX-M-1 (P ≤ 0.01) and the CTX-M-1 enzyme activity in ESBL <em>E. coli.</em> Furthermore, we find that magnolol can inhibit ESBL E. coli in vivo by significantly reducing the TLR4-NFκB p65 pathway (<em>P</em> ≤ 0.01).</div></div><div><h3>Conclusion</h3><div>In a word, our results indicate that magnolol is a natural antibacterial adjuvant with potent inhibitory activity against bacterial resistance and exerts this activity through multiple pathways, which has particular significance for the further study of the AMR mechanism.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157889"},"PeriodicalIF":8.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106873","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":"Vitex negundo Linn.: A decade of advances in phytochemistry, pharmacological activities, and biotechnological interventions (2015–2025) - A comprehensive review","authors":"Pratik Vinayak Phate,&nbsp;Anita Surendra Patil","doi":"10.1016/j.phymed.2026.157895","DOIUrl":"10.1016/j.phymed.2026.157895","url":null,"abstract":"<div><h3>Relevance</h3><div><em>Vitex negundo</em> Linn. is an important medicinal plant widely used in traditional medicine, particularly for inflammatory and pain-related conditions. Recent advances in phytochemical characterization, mechanistic pharmacology, and biotechnological interventions have strengthened its potential as a phytopharmaceutical candidate; however, translational gaps remain.</div></div><div><h3>Objectives</h3><div>This review aims to critically summarize and evaluate research published between 2015 and 2025 on the phytochemistry, pharmacological activities, analytical standardization, and biotechnological advancements of <em>V. negundo</em>, with emphasis on mechanistic relevance and evidence-based application.</div></div><div><h3>Materials and Methods</h3><div>A systematic literature survey was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed studies published between 2015 and 2025 were screened using predefined inclusion criteria, focusing on phytochemical profiling, pharmacological evaluation, analytical characterization, and metabolite enhancement strategies.</div></div><div><h3>Results</h3><div>&gt;25 phytochemicals, including vitexin, isovitexin, luteolin derivatives, iridoids, lignans, and phenolic acids, were identified using HPLC, LC–MS/MS, and NMR techniques. Pharmacological studies demonstrated anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, nephroprotective, neuroprotective, antimicrobial, and antiviral activities. These effects were mediated through key molecular pathways such as COX-2, NF-κB, MAPK, AMPK, and Nrf2/ARE. Advances in plant tissue culture and metabolite-enhancement approaches have contributed to improved production of bioactive constituents. However, inconsistencies in experimental design, lack of biomarker-based standardization, and limited pharmacokinetic data were evident.</div></div><div><h3>Conclusion</h3><div>Recent scientific evidence supports the pharmacological relevance of <em>V. negundo</em> and validates several of its traditional uses. Nevertheless, future research should prioritize biomarker-guided standardization, pharmacokinetic and toxicological evaluation, and clinically relevant study designs to enable the rational development of standardized <em>V. negundo</em>-based phytomedicines.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157895"},"PeriodicalIF":8.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132928","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":"Albiflorin alleviates osteoporosis through suppression of osteoclast mitophagy via the Rap1a/ERK signaling pathway","authors":"Cheng Tang ,&nbsp;Jingxian Yu ,&nbsp;Dong Sheng ,&nbsp;Yong Gu ,&nbsp;Donglong Xia ,&nbsp;Kuibing Lan ,&nbsp;Yajun Li ,&nbsp;Yunshang Yang ,&nbsp;Chengcheng Feng ,&nbsp;Yu Gong ,&nbsp;Long Xiao ,&nbsp;Zhirong Wang","doi":"10.1016/j.phymed.2026.157893","DOIUrl":"10.1016/j.phymed.2026.157893","url":null,"abstract":"<div><h3>Objectives</h3><div>Dysregulated mitophagy coupled with osteoclast activation orchestrates the development and progression of osteoporosis.Although albiflorin (ALB) exhibits bone-protective effects through anti-inflammatory and antioxidant activities, its precise mechanism—particularly regarding mitochondrial regulation—remains unknown. This study therefore investigates ALB as a novel osteoclast inhibitor by examining its molecular mechanism in regulating mitophagy via the Rap1a/ERK signaling pathway.</div></div><div><h3>Materials and Methods</h3><div>ALB was evaluated using murine models of postmenopausal osteoporosis. Key methodologies included RNA sequencing (RNA-seq) for gene expression pathway analysis, transmission electron microscopy (TEM) for visualization of mitochondrial and autophagic structures, MitoTracker/LysoTracker co-staining for assessment of mitophagy, and Western blotting for protein signaling validation. The impact of ALB on osteoclast differentiation and the prevention of bone loss was evaluated in both laboratory and live animal studies..</div></div><div><h3>Results</h3><div>ALB significantly inhibited osteoclastogenesis and osteoclast differentiation, thereby effectively reducing osteoporosis in murine models. RNA-seq analysis revealed that ALB modulated mitophagy by regulating the expression of Rap1a and components of the ERK signaling pathway. Validation through TEM demonstrated suppressed mitochondrial autophagy, while MitoTracker/LysoTracker co-staining confirmed a reduction in mitophagy. Furthermore, Western blot analysis showed that ALB inhibited osteoclast activation via the Rap1a/ERK signaling axis.</div></div><div><h3>Conclusion</h3><div>ALB mitigates postmenopausal osteoporosis by suppressing osteoclast activation through Rap1a/ERK-dependent inhibition of mitophagy. These findings identify ALB as a promising therapeutic strategy for osteoporosis, addressing the need for safer long-term treatment options.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157893"},"PeriodicalIF":8.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166391","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":"Ginkgetin alleviates sepsis-induced acute lung injury by promoting autophagy via inhibiting ubiquitination of Laptm5 in macrophages","authors":"Haoxuan Liang ,&nbsp;Ziyi Yuan ,&nbsp;Ruimeng Liu ,&nbsp;Hongfei Hu ,&nbsp;Qinghui Chen ,&nbsp;Zhaoying Lin ,&nbsp;Zheng Gu ,&nbsp;Yuetan Qiu ,&nbsp;Qirui Wang ,&nbsp;Bowen Zhu ,&nbsp;Yifan Deng ,&nbsp;Shiwei Huang ,&nbsp;Zhiyong Peng ,&nbsp;Xuedi Zhang ,&nbsp;Youtan Liu","doi":"10.1016/j.phymed.2026.157894","DOIUrl":"10.1016/j.phymed.2026.157894","url":null,"abstract":"<div><h3>Background</h3><div>Excessive inflammatory responses mediated by innate immunity are a significant cause of sepsis-induced acute lung injury (SI-ALI), underscoring the need for further drug development to improve therapeutic outcomes. Ginkgetin (GK), a natural flavone, has demonstrated potential anti-inflammatory and antioxidative effects. However, it remains unclear whether GK can ameliorate SI-ALI and what the underlying mechanisms might be.</div></div><div><h3>Purpose</h3><div>We aimed to investigate the therapeutic effects and mechanisms of GK on SI-ALI.</div></div><div><h3>Study design/methods</h3><div>We established SI-ALI models using lipopolysaccharide or cecal ligation and puncture to assess the impact of GK. An autophagy agonist and inhibitor were applied to detect the effect of GK on autophagy. Proteomics and targeted gene knockdown experiments were employed to validate lysosomal-associated transmembrane protein 5 (Laptm5) as the key protein. Co-immunoprecipitation and site mutation assays were used to identify the site where GK inhibited Laptm5 ubiquitination. Biotin pulldown coupled with mass spectroscopy, molecular docking, and drug affinity responsive target stability (DARTS) were performed to elucidate the direct target and underlying mechanisms.</div></div><div><h3>Results</h3><div>We demonstrated that GK activated the autophagosome-lysosome pathway by increasing the protein level of Laptm5. This process facilitated autophagy-mediated degradation of tank-binding kinase 1 (TBK1) and inhibited the signal transduction of downstream inflammatory pathways. Further, we found that GK inhibited the K48-linked ubiquitination of Laptm5 and revealed the ubiquitination sites of Laptm5 (K86 and K122) for the first time. Biotin pulldown and DARTS identified ubiquitin-protein ligase E3C (Ube3c) as a target of GK in inhibiting Laptm5 ubiquitination, with TYR707 and ASN832 being the key residues.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that GK exerts its anti-inflammatory effect on macrophages by promoting autophagy via suppressing the ubiquitination of Laptm5, thus offering a promising therapeutic approach for SI-ALI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157894"},"PeriodicalIF":8.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158197","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":"Microbiota-dependent mechanism of Jianpiyifei II in treating experimental virus-induced acute exacerbation of chronic obstructive pulmonary disease","authors":"Xuhua Yu ,&nbsp;Huameng Li ,&nbsp;Miaona Zhang ,&nbsp;Ting Cao ,&nbsp;Zhihang Liu ,&nbsp;Ziyao Liang ,&nbsp;Jingyu Quan ,&nbsp;Long Fan ,&nbsp;Lin Lin ,&nbsp;Lei Wu","doi":"10.1016/j.phymed.2026.157891","DOIUrl":"10.1016/j.phymed.2026.157891","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Numerous studies have shown that infections caused by respiratory viruses, particularly influenza A virus, contribute to the triggering and worsening of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, targeted therapies remain lacking. Our previous research indicated that the Jianpiyifei II (JPYF II) formulation, composed of &lt;em&gt;Codonopsis pilosula, Astragalus membranaceus, Bupleurum chinense, Cimicifuga foetida, Atractylodes macrocephala, Vitex trifolia, Cynomorium songaricum, and Prunus persica&lt;/em&gt;, may serve as a potential treatment for virus-induced AECOPD, although the precise mechanisms involved remain unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This research sought to explore the effects of JPYF II on AECOPD and uncover the mechanisms driving its action.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A murine model of AECOPD was established by exposing animals to cigarette smoke and then infecting them with influenza A virus. The efficacy of JPYF II was comprehensively evaluated by assessing cell counts in bronchoalveolar lavage fluid (BALF), histopathologic changes of the lungs, lung function, Micro-CT imaging features of the lungs, and RT-qPCR analysis. Additionally, the intestinal microbiota and metabolites from cecal contents were systematically analyzed using 16S rDNA sequencing, non-targeted metabolomics, and MetOrigin metabolite traceability analysis to explore potential mechanisms of action. Furthermore, a microbiota depletion experiment was performed to demonstrate whether JPYF II's effects depend on gut microbiota. Finally, network pharmacology, western blotting, and transcriptomics analyses revealed the pathways affected by JPYF II.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;This study found that JPYF II treatment notably reduced the recruitment of white blood cells in both BALF and lung tissue, mitigated pulmonary inflammation, enhanced lung function, and alleviated emphysema. JPYF II also modulated the diversity and composition of intestinal flora, partially reversing dysbiosis in AECOPD mice. It promoted the presence of beneficial bacteria and simultaneously suppressed the growth of pathogenic microbes. These changes were associated with changes in metabolites such as α-ketoglutarate, sphingolipids, and bile acids. Further studies indicated that depleting gut microbiota with antibiotics partially limited the therapeutic effects of JPYF II on AECOPD. This mechanism is associated with the suppression of the Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;JPYF II alleviated pulmonary inflammation, enhanced lung function, and reduced damage to lung structure and viral replication in a virus-induced AECOPD mouse model. The mechanisms involved the improvement of gut microbiota composition. Furthermore, JPYF II suppressed immune responses and the formation of emphysema by inhibiting the JAK-STAT signaling pathway","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157891"},"PeriodicalIF":8.3,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166451","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}