Phytomedicine最新文献

{"title":"Trigonelline regulates glycolysis and energy metabolism during hepatic fibrosis via Glut-1-HIF-1α axis: Focusing the interaction of macrophages and HSCs","authors":"Chong Gao ,&nbsp;Wei Liu ,&nbsp;Sai-Hu Liu ,&nbsp;Shuang Zheng ,&nbsp;Chen-Yu Wang ,&nbsp;Xu Dai ,&nbsp;Li-Hua Lian ,&nbsp;Zhen-Yu Cui ,&nbsp;Ji-Xing Nan ,&nbsp;Yan-Ling Wu","doi":"10.1016/j.phymed.2026.157854","DOIUrl":"10.1016/j.phymed.2026.157854","url":null,"abstract":"<div><h3>Background</h3><div>Reprogramming of aerobic glycolysis occurs with HSCs activation and is associated with regression of liver fibrosis. Trigonelline (TRG), a plant alkaloid extracted from <em>Trigonella foenum-graecum L</em> seeds, has a variety of pharmacological effect.</div></div><div><h3>Purpose</h3><div>The current study investigated the hepatoprotective effect and mechanism of TRG against hepatic fibrosis by regulating glycolysis.</div></div><div><h3>Methods</h3><div>Anti-hepatic fibrosis effects of TRG were detected in thioacetamide (TAA)-induced hepatic fibrosis mice. HSCs or LX-2 were stimulated with TGF-β or conditioned medium (CM) from LPS-stimulated THP-1, then incubated with TRG, phloretin (PHL), rosiglitazone (RGZ), siRNA Glut-1 or plasmid with Glut-1.</div></div><div><h3>Results</h3><div>TRG significantly reduced serum transaminase levels, liver histopathological changes, excessive collagen deposition, inflammatory response, and neutrophil recruitment in TAA-induced mice. TAA increased hepatic Glut-1, HIF-1α and key enzymes of glycolysis expressions, while TRG completely reversed this effect. TRG also obviously regulated the combination of Glut-1 and HIF-1α to affect glycolysis in activated HSCs. TRG could inhibit α-SMA, IL-6, IL1R1, and HIF-1α expressions accompanying inhibition of Glut-1, function as PHL (Glut-1 inhibitor). Glut-1 silencing weakened α-SMA, IL-6, IL1R1, and HIF-1α expressions and enhanced the effect of TRG in activated LX-2. TRG inhibited LX-2 activation caused by Glut-1 overexpression, even demonstrated in interaction between LX-2 and macrophages. Further, TRG shown that improved fibrogenesis and inflammatory response by inhibiting Glut-1 compared with PHL in <em>vivo</em>.</div></div><div><h3>Conclusion</h3><div>TRG could ameliorate hepatic fibrosis through inhibiting ECM excessive deposition and inflammatory response. Inhibiting Glut-1-HIF-1α axis and glycolysis was a potential therapeutic strategy for TRG ameliorating liver microenvironment, further against hepatic fibrosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157854"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039454","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":"Arnicolide C induces ferroptosis in liver cancer through modulation of the HMOX1-TRC8 axis","authors":"Xuqi Zhao ,&nbsp;Jinrui Wei ,&nbsp;Yuxin Xie ,&nbsp;Zhenkai Tan ,&nbsp;Yuhan Jiang ,&nbsp;Lichuan Wu","doi":"10.1016/j.phymed.2026.157859","DOIUrl":"10.1016/j.phymed.2026.157859","url":null,"abstract":"<div><div>Liver cancer remains a significant therapeutic challenge, underscoring the urgent need for novel treatment strategies. Recently, induction of ferroptosis has emerged as a promising approach for treating malignant tumors. In this study, we identified Arcnicolide C (ArC) as an effective ferroptosis inducer in liver cancer. ArC markedly suppressed viability and clonogenic growth across multiple liver cancer cell lines. Notably, these anti-proliferative effects were selectively ameliorated by ferroptosis inhibitors. ArC treatment triggered characteristic ferroptotic events, including iron accumulation, lipid peroxidation, glutathione depletion, reactive oxygen species (ROS) generation, and loss of GPX4 enzymatic activity. Multi-omics analysis revealed HMOX1 as a key target, with ArC upregulating HMOX1 protein expression without altering its transcription. Functional studies confirmed the critical role of HMOX1 in ArC-induced ferroptosis, as HMOX1 knockdown attenuated ferroptotic cell death and restored proliferative capacity. Mechanistically, ArC interacted with HMOX1 protein, disrupted its binding to the E3 ubiquitin ligase TRC8, and thereby inhibited HMOX1 ubiquitination, leading to protein stabilization. In vivo, ArC potently inhibited the growth of liver cancer xenografts, exhibiting anti-tumor efficacy comparable to sorafenib but with an improved safety profile. This anti-tumor activity was also demonstrated to depend on the ferroptosis pathway. Collectively, our findings establish ArC as a ferroptosis inducer that acts through direct interaction with and stabilization of HMOX1, highlighting its potential as a novel therapeutic candidate for liver cancer.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157859"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039916","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":"Linggui Zhugan Decoction mitigates post-myocardial infarction heart failure through modulation of cardiomyocyte F-actin cytoskeletal organization","authors":"Maojun Cheng ,&nbsp;Liyang Li ,&nbsp;Xing Huang ,&nbsp;Fang Ding ,&nbsp;Chengxun He ,&nbsp;Changmao Dai ,&nbsp;Jia Xu ,&nbsp;Xiangyu He ,&nbsp;Yayi Jiang ,&nbsp;Guangmin Xu ,&nbsp;Xueping Li","doi":"10.1016/j.phymed.2026.157851","DOIUrl":"10.1016/j.phymed.2026.157851","url":null,"abstract":"<div><h3>Background</h3><div>Linggui Zhugan Decoction (LGZGD), a traditional Chinese formula for spleen-strengthening and yang-warming to resolve fluid retention, has consistently shown efficacy in preventing and treating heart failure. However, its underlying biological mechanisms remain incompletely understood.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the therapeutic efficacy of LGZGD in a rat model of heart failure and in H9C2 cardiomyocytes, as well as to elucidate its effects on F-actin remodeling and the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A rat model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery, followed by treatment with LGZGD for 4 weeks. The chemical constituents of the decoction and drug-containing serum were characterized using ultra-performance liquid chromatography. Network pharmacology analysis identified potential key therapeutic targets of LGZGD for heart failure treatment. An in <em>vitro</em> hypoxia/reoxygenation injury model was constructed in H9C2 cardiomyocytes. Additionally, siRNA-mediated ROCK knockdown was performed to investigate the mechanisms underlying LGZGD–mediated regulation of F-actin remodeling in cardiomyocytes.</div></div><div><h3>Results</h3><div>The results showed that LGZGD significantly improved cardiac function and pathological morphology in heart failure rats. Network pharmacology analysis identified RhoA as a key potential target for LGZGD in regulating F-actin in heart failure. Both in <em>vivo</em> and in <em>vitro</em> experiments further confirmed that LGZGD modulates F-actin cytoskeletal remodeling.</div></div><div><h3>Conclusion</h3><div>The present findings indicate that LGZGD significantly improves cardiac function in rats with heart failure. Furthermore, it enhances the stability of F-actin cytoskeletal organization and function in both heart tissues from rats with heart failure and H9C2 cardiomyocytes.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157851"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143272","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":"Coniferyl aldehyde in ginger-Eucommiae Cortex enhances osteoarthritis treatment by modulating ALDOA and H3K23la histone lactylation","authors":"Yijing Pan ,&nbsp;Xinyue Liu ,&nbsp;Shunshun Wang ,&nbsp;Lin Chen ,&nbsp;Anzheng Li ,&nbsp;Qingjia Chi ,&nbsp;Xiong Ku ,&nbsp;Kang Xu ,&nbsp;Chunli Wang","doi":"10.1016/j.phymed.2026.157852","DOIUrl":"10.1016/j.phymed.2026.157852","url":null,"abstract":"<div><h3>Background and purpose</h3><div><em>Eucommiae Cortex</em> (EC), a traditional Chinese medicinal herb, has been utilized to treat osteoarthritis (OA). The therapeutic efficacy of EC can be augmented by combining it with ginger juice. OA is often linked to metabolic disorders, with lactate accumulation contributing to its progression. Notably, the concentration of coniferyl aldehyde (CFA) markedly increases during the processing of EC with ginger juice. This study seeks to investigate whether CFA ameliorates OA via lactylation and to develop a non-invasive machine-learning model for the rapid diagnosis of OA utilizing lactate and other metabolic markers.</div></div><div><h3>Methods</h3><div>Differences in the chemical composition of EC before and after processing with ginger were investigated using an untargeted metabolomics strategy and database integration. Active components were screened using network pharmacology to examine CFA's effect on inflammation in tumor necrosis factor-α (TNF-α) -induced C28/I2 and primary mouse chondrocytes. Biomarkers and molecular mechanisms were identified using metabolomics, interpretable machine learning, and RNA sequencing. In-cell western blotting and expression correlation analysis confirmed the correlation between inflammation and H3 histone lactylation improvement in C28/I2 cells treated with CFA. Molecular docking analysis identified targets, and the overexpression (oe) and silencing (si) of ALDOA validated the inhibitory effect of CFA on lactylation. The in vivo efficacy of CFA was assessed using a mouse destabilization of the medial meniscus (DMM) model of OA.</div></div><div><h3>Results</h3><div>CFA, a principal component in G-EC, exhibited significant anti-inflammatory effects both in vitro and in vivo. A non-invasive diagnostic model utilizing machine learning was developed by analyzing 44 OA urine samples from the Metabolomics Workbench database. This model employed SHapley Additive exPlanations in conjunction with a random forest algorithm and identified lactate as a significant potential diagnostic metabolite for OA. Metabolomic analysis of C28/I2 cells indicated that CFA influences the glycolysis pathway.</div></div><div><h3>Conclusions</h3><div>This study identified the basis for the synergistic effect of ginger juice on EC and supported the scientific rationale for G-EC processing. In this study, CFA improved OA by affecting glycolysis and modulating lactylation at the H3K23la site of H3 histones, highlighting the critical role of CFA in its anti-OA effects. A non-invasive diagnostic model for OA was developed, which facilitated the rapid prediction of OA risk in patients, and interpretable machine-learning methodologies enabled the analysis of key metabolic markers.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157852"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080564","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":"Bee propolis for inflammatory bowel disease: A review of its gastroprotective effects, mechanisms, and translation strategies","authors":"Yuxuan Lu ,&nbsp;Daniel Granato ,&nbsp;Lin Hu ,&nbsp;Kai Wang","doi":"10.1016/j.phymed.2026.157849","DOIUrl":"10.1016/j.phymed.2026.157849","url":null,"abstract":"<div><h3>Background</h3><div>Propolis is a natural bee product containing diverse botanicals-derived active compounds. Its bioactive constituents vary to its geographical origin and botanical sources. Bee propolis has been effectively shown as a potent modulator for different inflammatory-related diseases.</div></div><div><h3>Purpose and methods</h3><div>We systematically reviewed literature from PubMed and Web of Science to evaluate the gastroprotective effects of propolis in experimental colitis models. Additionally, we analysed innovative strategies, such as nano-delivery systems, to enhance its therapeutic and preventive potential.</div></div><div><h3>Results</h3><div>Regardless of botanical origin, propolis demonstrates efficacy in several preclinical inflammatory bowel disease (IBD) models. Several active constituents, including caffeic acid phenethyl ester and artepillin C, protected against colitis by regulating the Nrf2, NF-κB, JAK-STAT, and NLRP3 pathways, and by restoring the intestinal barrier and gut microbiota. Novel delivery systems address bioavailability limitations, enhancing the clinical viability of propolis and its active compounds.</div></div><div><h3>Conclusions</h3><div>This review moves beyond a generic description of propolis, establishing a rationale for the precise usage of natural products in IBD. By matching geographically distinct propolis types to specific pathological stages, this work provides up-to-date data towards a standardised, targeted propolis-based interventions for IBD. Using advanced delivery systems and precision nutrition strategies hold great promise for advancing propolis into practical clinical therapeutic applications in the future.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157849"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192657","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":"Salvia miltiorrhiza Bunge promotes osteogenesis and angiogenesis by activating HIF-1α/VEGF and Slit3 pathways","authors":"Gaiyue Yue ,&nbsp;Shan Wang ,&nbsp;Xuan Dai ,&nbsp;Yongqi Li ,&nbsp;Kun Zhu ,&nbsp;Fan Xue ,&nbsp;Ling Huang ,&nbsp;Sihua Gao ,&nbsp;Lili Wang ,&nbsp;Dongwei Zhang","doi":"10.1016/j.phymed.2026.157842","DOIUrl":"10.1016/j.phymed.2026.157842","url":null,"abstract":"<div><h3>Background</h3><div>Osteogenesis and angiogenesis are closely coupled during bone modeling and remodeling, providing a potential direction for treating osteoporosis. <em>Salvia miltiorrhiza</em> Bunge (SM) has been preclinically and clinically used to treat skeletal and cardiovascular diseases in traditional Chinese medicine, but its mechanisms in bone formation and vascularization remain poorly understood.</div></div><div><h3>Purpose</h3><div>To elucidate the actions and mechanisms of SM against osteoporosis.</div></div><div><h3>Methods</h3><div>Osteoporotic mice established by bilateral ovariectomy were orally administered SM aqueous extracts for 14 weeks. Bone quality was evaluated by micro-CT, histomorphometry, and three-point bending assay. Immunofluorescence staining was performed to quantify the proportions of type H vessels (CD31^hiEMCN^hi) in the femurs. <em>In vitro</em>, SM medicated serum was applied to MC3T3-E1 preosteoblasts and EA.hy926 endothelial cells to evaluate osteogenic and angiogenic capacities. Mechanistic studies involved HIF-1α inhibition and Slit3 knockdown in both cell lines. Moreover, the ingredients of SM aqueous extracts and SM medicated serum were characterized by an UPLC-MS/MS.</div></div><div><h3>Results</h3><div>SM treatment improved bone mass and strength, promoted bone formation and type H vessels formation, and upregulated the expressions of HIF-1α, VEGF and Slit3 in the bones of ovariectomized mice. In vitro, SM enhanced osteogenic and angiogenic activities in MC3T3-E1 and EA.hy926 cells. These actions were dependent on HIF-1α/VEGF and Slit3 pathways, as their inhibition abolished the beneficial outcomes. Additionally, salvianolic acid B (Sal B) was identified as a key bioactive component contributing to these processes.</div></div><div><h3>Conclusion</h3><div>SM improves bone quality in osteoporosis by concurrently stimulating osteogenesis and angiogenesis through the HIF-1α/VEGF and Slit3 signaling pathways. These results provide a mechanistic basis for the application of SM in osteoporosis treatment and highlight its potential as a multi-target therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157842"},"PeriodicalIF":8.3,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080055","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":"Phaseoloidin, a homogentisic acid glucoside from Entada phaseoloides, suppresses gout inflammation via NLRP3 inflammasome","authors":"Yin-Jing Jiang ,&nbsp;Hao-Qing Zhu ,&nbsp;Yong-Hong Cheng ,&nbsp;Yan-Ling Wu ,&nbsp;Zi-Ying Zhan ,&nbsp;Ji-Xing Nan ,&nbsp;Li-Hua Lian","doi":"10.1016/j.phymed.2026.157848","DOIUrl":"10.1016/j.phymed.2026.157848","url":null,"abstract":"<div><h3>Background</h3><div>Gout is an arthritic disorder caused by the deposition of sodium urate crystals in the joints. Phaseoloidin (PHA), a β-glucoside of homogentisic acid isolated from the seeds of the legume “<em>Entada phaseoloides (L.) Merr.”</em>, has previously showed anti-inflammatory properties, but its effects on gout and underlying mechanisms remain unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the novel therapeutic potential of PHA in gout, with a focus on its multi-target actions against NLRP3 inflammasome activation and associated inflammatory cascades—areas not yet addressed for this compound.</div></div><div><h3>Method</h3><div>In vivo, arthritis models include the acute gouty arthritis model by injecting sodium urate crystals into the paws of mice, as well as the air pouch acute gout model by injecting sodium urate crystals into the subcutaneous tissue of the back of mice. In vitro, mouse peritoneal macrophages (MPM) and rat articular chondrocytes were stimulated with LPS plus sodium urate crystals, both with and without pre-treatment of PHA. Through a combination of pathological analysis, Western blot, network pharmacology analysis, immunofluorescence, immunohistochemistry, and ELISA, the anti-inflammatory activity of PHA and its therapeutic effects mediated via NLRP3 targeting were comprehensively demonstrated.</div></div><div><h3>Results</h3><div>In vivo and in vitro GA models, PHA significantly suppressed NLRP3 inflammasome activation by inhibiting caspase-1-dependent IL-1β maturation and blocking the caspase-11–GSDMD pyroptotic axis, and attenuated inflammatory cascades through reduced NETosis formatted. Notably, PHA also uniquely preserved cartilage matrix integrity by downregulating collagen-degrading enzymes.</div></div><div><h3>Conclusion</h3><div>These findings reveal, for the first time, the multi-target anti-gout activity of PHA, highlighting its dual role in modulating NLRP3 inflammasome-driven inflammation and protecting joint structure. These results position PHA as a promising and innovative natural lead compound for the development of multi-mechanistic therapies against gout and related inflammatory arthritis diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157848"},"PeriodicalIF":8.3,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039860","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":"Gentiopicroside attenuates lupus arthritis by targeting galectin-mediated macrophage activation","authors":"Yihong Gan ,&nbsp;Shihui Zhou ,&nbsp;Ke Lin ,&nbsp;Yijing Bai ,&nbsp;Jingqun Liu ,&nbsp;Meng Jin ,&nbsp;Shuo Huang ,&nbsp;Qice Sun ,&nbsp;Chao Sun ,&nbsp;Yilin Zhang ,&nbsp;Shengyu Chen ,&nbsp;Xinchang Wang ,&nbsp;Yongsheng Fan ,&nbsp;Jie Bao ,&nbsp;Li Xu","doi":"10.1016/j.phymed.2026.157843","DOIUrl":"10.1016/j.phymed.2026.157843","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory arthritis represents a common and clinically challenging manifestation of systemic lupus erythematosus (SLE), with current therapeutic options often exhibiting limited efficacy.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-arthritic effects and underlying mechanism of gentiopicroside (GPS), a key bioactive constituent of the Jiawei Baihu Jia Guizhi Decoction (JBH), with a specific focus on its interaction with galectin-9-mediated pathways in macrophage activation.</div></div><div><h3>Study design</h3><div>The anti-arthritic efficacy of GPS was investigated using a pristane-induced arthritis (PIA) mouse model, which recapitulates key features of SLE-associated arthritis. Integrated transcriptomic and network pharmacology approaches were employed for mechanistic exploration, followed by experimental validation in vitro and in vivo.</div></div><div><h3>Methods</h3><div>The PIA mouse model was treated with GPS to evaluate its effects on joint inflammation, synovial pathology, and bone remodeling. Transcriptomic profiling of joint tissues and network pharmacology analysis were conducted to identify potential targets. The interaction between GPS and Galectin-9 (Gal-9) was characterized using molecular docking and biophysical assays (determining a Kd of ∼350 nM). The functional impact of GPS on Gal-9-dependent NF-κB signaling, pro-inflammatory cytokine secretion, and macrophage activation was assessed in cellular models and PIA mice.</div></div><div><h3>Results</h3><div>GPS treatment significantly alleviated joint inflammation, synovial hyperplasia, and bone erosion in PIA mice, while also restoring the balance of bone remodeling. Integrative analyses pinpointed Gal-9 as a critical target, and GPS was confirmed to bind Gal-9 with high affinity. Functionally, GPS inhibited Gal-9-triggered NF-κB activation, suppressed the production of pro-inflammatory cytokines, and reduced macrophage infiltration and activation. Furthermore, GPS ameliorated systemic inflammation, lowered autoantibody levels, and improved joint integrity in PIA mice, demonstrating efficacy comparable to methotrexate.</div></div><div><h3>Conclusion</h3><div>Gentiopicroside, a key active constituent of the JBH, attenuates lupus arthritis by specifically targeting Galectin-9 and subsequently disrupting galectin-driven macrophage activation. These findings highlight GPS as a promising targeted therapeutic candidate for the management of SLE-related joint damage.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157843"},"PeriodicalIF":8.3,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047147","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":"Hemoglobin adduction and impaired oxygen transport define the etiology of pyrrolizidine alkaloid-induced pulmonary arterial hypertension","authors":"Caibin Zhang ,&nbsp;Tianyang Huang ,&nbsp;Xiaokai Guo ,&nbsp;Yujian Fan ,&nbsp;Zijing Song ,&nbsp;Jiang Ma ,&nbsp;Yisheng He","doi":"10.1016/j.phymed.2026.157847","DOIUrl":"10.1016/j.phymed.2026.157847","url":null,"abstract":"<div><h3>Background</h3><div>Pyrrolizidine alkaloids (PAs), particularly monocrotaline (MCT), are common phytotoxins known to induce pulmonary arterial hypertension (PAH), a progressive and fatal cardiopulmonary disease. However, the specific mechanism initiating PAH and the basis for the differing toxic potencies among PAs, such as MCT and retrorsine (RTS), remain undefined.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the mechanistic basis for the marked difference in pulmonary toxicity between two representative PAs, MCT and RTS. We specifically tested the hypothesis that the severity of PA-induced lung injury is determined by the extent of hemoglobin adduction within red blood cells (RBCs) and the consequent impairment of oxygen transport.</div></div><div><h3>Study Design</h3><div>We employed a comparative toxicological design using rat models, treating them with equimolar doses of MCT and RTS, to assess and compare their respective toxicological pathways and resulting pulmonary injury.</div></div><div><h3>Methods</h3><div>Rats were administered MCT or RTS. Dehydropyrrolizidine alkaloid (DHPA) adduct formation on RBC hemoglobin was profiled using proteomics. Pulmonary hemodynamics, pulmonary vascular remodeling, and systemic hypoxia levels were subsequently measured.</div></div><div><h3>Results</h3><div>DHPAs selectively and covalently bound to specific residues (D74, E91, H93, K133) on the hemoglobin β-1 chain, critically impairing the oxygen-carrying capacity of RBCs. MCT exposure resulted in significantly higher levels of pyrrole-hemoglobin adducts (approximately 95% binding) compared to RTS (approximately 70% binding). This higher adduction rate led to more severe systemic hypoxia, which was consistently associated with greater pulmonary arterial endothelial activation and more severe PAH in the MCT group.</div></div><div><h3>Conclusion</h3><div>The severity of PA-induced PAH is directly correlated with the degree of hemoglobin adduction and resulting hypoxia. Hemoglobin adduction and impaired oxygen transport are critical, upstream events that define the etiology of PA-induced pulmonary arterial hypertension.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157847"},"PeriodicalIF":8.3,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119583","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":"2026-01-17","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}