Phytomedicine最新文献

{"title":"Panax notoginseng saponins ameliorate spinal cord injury by inhibiting JAK2/STAT3-mediated macrophage polarization: Enhanced delivery by ultrasound-targeted microbubble destruction","authors":"Yin Shi ,&nbsp;Xuelian Chen ,&nbsp;Shu Luo ,&nbsp;Anjie Chen ,&nbsp;Keyu Xie ,&nbsp;Miao Fang ,&nbsp;Jiaojiao Zhou","doi":"10.1016/j.phymed.2026.157856","DOIUrl":"10.1016/j.phymed.2026.157856","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) causes abnormal macrophage polarization, worsening inflammation and neuronal apoptosis, with current therapies showing limited efficacy. Panax Notoginseng Saponins (PNS) has anti-inflammatory and neuroprotective potential but is limited by low bioavailability. Ultrasound-targeted microbubble destruction (UTMD) can open the blood-spinal cord barrier to improve drug delivery.</div></div><div><h3>Aim</h3><div>To clarify the role of PNS and molecular mechanisms in regulating macrophage polarization for SCI and explore the effect of UTMD on enhancing PNS efficacy.</div></div><div><h3>Methods</h3><div>RAW264.7 macrophages and rat SCI models were used. Flow cytometry, RT-qPCR, Western blotting (WB), TUNEL staining, BBB scoring, and MRI were applied to detect polarization markers, JAK2/STAT3 pathway proteins, neuronal apoptosis, and neurological recovery.</div></div><div><h3>Results</h3><div>PNS dose-dependently promoted macrophage M2 polarization, inhibited the JAK2/STAT3 pathway, and reduced neuronal apoptosis. These effects were enhanced by the JAK2/STAT3 inhibitor AG490, while PNS also antagonized the pro-apoptotic action of the pathway activator colivelin. UTMD strengthened PNS’s effects in vitro. In rats, compared with the SCI-only group, the SCI+PNS group already showed therapeutic effects, with improved BBB scores, less M1 infiltration, suppressed JAK2/STAT3, and reduced apoptosis and cyst areas. Notably, the SCI+UTMD+PNS group exhibited even more pronounced improvements in these aspects and superior efficacy to both the SCI and SCI+PNS groups.</div></div><div><h3>Conclusion</h3><div>PNS inhibits JAK2/STAT3 to promote M2 polarization and reduce apoptosis. UTMD amplifies PNS’s efficacy, providing a novel SCI therapy strategy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157856"},"PeriodicalIF":8.3,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126177","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":"Nelumbo nucifera extract alleviates UVB-induced hyperpigmentation via NOX4-mediated AMPK-YAP-ATG5 signaling pathway","authors":"Cailing Wen ,&nbsp;Jiaying Li ,&nbsp;Canye Li ,&nbsp;Xiuhan Song ,&nbsp;Pingping Lv ,&nbsp;Jieli Chen ,&nbsp;Dong Wang ,&nbsp;Shuyue Zhao ,&nbsp;Meiling Tai ,&nbsp;Xiaoyan Shen","doi":"10.1016/j.phymed.2026.157857","DOIUrl":"10.1016/j.phymed.2026.157857","url":null,"abstract":"<div><h3>Background</h3><div>Hyperpigmentation is primarily caused by ultraviolet (UV) radiation, which triggers oxidative stress and melanin accumulation in the skin. Moderate UVB exposure activates autophagy, which facilitates cell repair, while prolonged UVB exposure disrupts this process, worsening skin damage and pigmentation. <em>Nelumbo nucifera</em> extract (NnE) drew our attention in our preliminary screening experiments for its potential to regulate keratinocyte autophagy. Nevertheless, the molecular mechanisms underlying the extract of NnE’s therapeutic effects and its bioactive constituents remain incompletely characterized.</div></div><div><h3>Purpose</h3><div>The aim of this study was to evaluate the effects of NnE on UVB-induced hyperpigmentation and to explore the mechanisms underlying its autophagy-promoting activity of bioactive ingredients.</div></div><div><h3>Methods</h3><div>B16 murine melanoma cells and human epidermal keratinocytes (HEKa) exposed to UVB radiation were used to model autophagy inhibition and melanosome accumulation. 3D pigmented skin organoid model and UVB-exposed guinea pigs were used to assess the effects of NnE on pigmentation. Various techniques, including western blot, immunofluorescence, and transcriptome sequencing, were employed to analyze autophagy regulation and melanosome clearance. Furthermore, we used molecular docking and <em>in vitro</em> enzyme activity detection methods to search for the active substances of NnE acting on the target.</div></div><div><h3>Results</h3><div>In HEKa cells, NnE effectively reversed UVB irradiation-induced inhibition of autophagy and promoted melanosome clearance. NnE also reduced the melanin content in HEKa cells. In MelaKutis® and UVB-exposed guinea pigs, topical application of NnE effectively alleviated pigmentation. Mechanistically, NnE suppressed the interaction between AMPK and YAP, thereby promoting nuclear translocation of YAP and upregulation of key autophagy-related genes, including ATG5, and ultimately enhancing autophagic activity. Finally, through molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability assay (DARTS), in vitro enzyme activity detection, and RNA interference, we demonstrated that quercetin-3-O-glucuronide, the major active constituent of NnE, exerts anti-photoaging effects by inhibiting NOX4 and subsequently regulating the AMPK/YAP/ATG5 signaling axis.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that the anti-pigmentation effect of NnE and its bioactive compound, quercetin 3-O-glucuronide, is mediated through the YAP-ATG5 signaling axis and Q3Q-driven NOX4 inhibition, which establishes the mechanistic basis for their potential application in preventing UVB-induced skin pigmentation and provides a novel perspective for the development of anti-photoaging interventions.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157857"},"PeriodicalIF":8.3,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047140","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":"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":"2026-01-20","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":"Parthenolide ameliorates inflammation in sepsis via covalently targeting Trim33 and inhibiting NF-κB pathway.","authors":"Xueling He, Chen Wang, Ruihao Zhang, Yuanyuan Wang, Ying Zhang, Tong Yang, Junzhe Zhang, Shuan Rao, Huan Tang, Xin Peng, Jigang Wang","doi":"10.1016/j.phymed.2026.157862","DOIUrl":"https://doi.org/10.1016/j.phymed.2026.157862","url":null,"abstract":"<p><strong>Background: </strong>Sepsis, a life-threatening condition, arises from an aberrant or uncontrolled immune response of the host to severe infection. Timely and precise control of this inflammatory response is of paramount importance in sepsis prevention and constitutes the core of sepsis prevention efforts. Parthenolide (PA), recognized as an NF-κB inhibitor, has previously demonstrated its capacity to mitigate the inflammatory response. This study aimed to investigate whether and how PA can inhibit inflammation, thereby alleviating sepsis, and to profile functional target proteins using chemoproteomics strategy.</p><p><strong>Methods: </strong>The cecal ligation and puncture (CLP) procedure was performed to induce a mouse model of sepsis, and lipopolysaccharide (LPS) was employed to establish a model of cellular inflammation in mouse mononuclear macrophage cells (RAW264.7) in vitro. Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin (H&E) staining were utilized to evaluate the therapeutic effects of PA on septic mice. In the in vitro experiments, streamlined cysteine activity-based protein profiling (SLC-ABPP) and proteomics techniques were employed to identify potential protein targets and molecular pathways responsible for the anti-inflammatory properties of PA.</p><p><strong>Results: </strong>We demonstrated that PA could enhance the survival rate, reduce inflammatory cytokines release, ameliorate histopathological changes, and balance macrophage polarization in a sepsis model. Similarly, PA could effectively alleviate the inflammatory response in LPS-stimulated RAW264.7 cells. Chemoproteomics profiling revealed that the Trim33 protein was a potential covalent target of PA via cysteine engagement, and the expression changes of global proteins indicated by proteomics analysis suggested that PA mitigated inflammation by inhibiting the NF-κB pathway. Finally, through a series of molecular biology experiments, we confirmed that PA suppresses the NF-κB pathway by functionally binding to Trim33 and subsequently reducing the ubiquitin dependent degradation of Smad4, thereby exhibiting anti-inflammatory activity.</p><p><strong>Conclusion: </strong>Our findings demonstrated that PA significantly mitigated inflammation in sepsis by targeting the Trim33 protein and consequently suppressing ubiquitination on Smad4 as well inhibiting the NF-κB pathway, thus providing new insights into the clinical use of PA in treatment of inflammation related diseases.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"157862"},"PeriodicalIF":8.3,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213898","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":"Functional calibration of PPARγ by baicalein reverses bone-lipid imbalance in type 2 diabetic osteoporosis","authors":"Hua Zhang ,&nbsp;Bai hao Chen ,&nbsp;Jianan Huang ,&nbsp;Junzheng Yang ,&nbsp;Jiacong Xiao ,&nbsp;Peng Chen","doi":"10.1016/j.phymed.2026.157850","DOIUrl":"10.1016/j.phymed.2026.157850","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetic osteoporosis (T2DOP) is characterized by excessive bone marrow adiposity and impaired osteogenesis, a pathology driven primarily by PPARγ-mediated dysregulation of the osteogenic–adipogenic differentiation balance in BMSCs under hyperglycemic conditions. Baicalein (BCL) is a natural flavonoid and a key active constituent of Gegen Qinlian Decoction (GQD), has shown regulatory potential in various metabolic disorders. However, its specific role and underlying mechanisms in T2DOP remain to be fully elucidated.</div></div><div><h3>Methods</h3><div>We treated <em>db/db</em> mice with BCL for 8 weeks. Micro-CT and histomorphometric analyses evaluated bone microarchitecture, while histochemical staining assessed marrow adiposity. Immunohistochemistry and Western blot analysis examined the expression of osteogenic and adipogenic markers. In <em>vitro</em>, we subjected high glucose-treated BMSCs to osteogenic/adipogenic induction in the presence of BCL. Differentiation was evaluated by ARS and Oil Red O staining. Furthermore, we employed molecular docking, CETSA, and molecular dynamics simulations to confirm direct binding between BCL and PPARγ.</div></div><div><h3>Results</h3><div>BCL significantly increased bone mineral density and trabecular number in <em>db/db</em> mice, while reducing marrow fat accumulation. In <em>vitro</em>, it promoted mineralization and suppressed lipid droplet formation. BCL downregulated PPARγ and adipogenic genes and enhanced osteogenic markers (Runx2, COL1A, OCN). Mechanistically, it bound strongly to the PPARγ ligand-binding domain, acting as a microenvironment-dependent modulator that recalibrates its transcriptional activity toward osteogenesis.</div></div><div><h3>Conclusion</h3><div>BCL attenuates T2DOP by directly targeting PPARγ and restoring its bone-lipid balance.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157850"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047144","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":"Spermidine alleviates ethanol-induced hepatocyte ferroptosis by restoring hepatic iron homeostasis via the gut-liver axis","authors":"Yan-Jing Zhang ,&nbsp;Dong Cheng ,&nbsp;Wen-Huan Yao ,&nbsp;Hui Li ,&nbsp;Ming-Bao Zhang ,&nbsp;Ying-Wen Mu ,&nbsp;Xiu-Ning Zhang ,&nbsp;Ge Song ,&nbsp;Tao Zeng","doi":"10.1016/j.phymed.2026.157853","DOIUrl":"10.1016/j.phymed.2026.157853","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Alcohol-related liver disease (ALD) remains a global public health challenge, highlighting the urgent need to uncover novel pathophysiological mechanisms and therapeutic targets. Spermidine, a natural polyamine abundant in dietary plant sources and present in all eukaryotic cells, exhibits versatile biological activities, yet its role in ALD development remains unclear. This study aimed to investigate the changes of spermidine metabolism and evaluate the hepatoprotective potential of spermidine in ALD.</div></div><div><h3>Approach &amp; results</h3><div>The effects of ethanol on hepatic spermidine homeostasis and the hepatoprotective effects of spermidine were examined in clinical sample analysis, ethanol-fed mouse models, and <em>in vitro</em> systems (AML12 hepatocytes and Caco-2 monolayers). In this study, we provided the first comprehensive evidence from clinical samples, animal models, and cell culture systems demonstrating that ethanol consumption significantly reduced spermidine levels. Ethanol feeding induced an increase in serum aminotransferase activities, liver steatosis, oxidative stress, iron accumulation, and hepatocyte ferroptosis, which were significantly ameliorated by exogenous spermidine supplementation and exacerbated by the spermidine synthesis inhibitor DFMO. Mechanistically, spermidine inhibited iron uptake, prevented ferritin heavy chain (FTH) degradation likely by suppressing ferritinophagy, promoted iron export in hepatocytes, and reduced intestinal iron absorption. Notably, these protective effects were abolished in both global and hepatocyte-specific <em>Nrf2</em>-knockout mice, indicating dependence on NRF2 signaling.</div></div><div><h3>Conclusions</h3><div>These results identify ethanol-induced spermidine reduction as a previously unrecognized molecular event in the pathogenesis of ALD and highlight dietary spermidine supplementation as a promising strategy to counteract ethanol-driven iron dysregulation and hepatocyte ferroptosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157853"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039918","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":"American ginseng-derived extracellular vesicle-like nanoparticles (AGELNs) mitigate doxorubicin-induced cardiotoxicity by inhibiting GPX4-mediated ferroptosis","authors":"Teng Liu ,&nbsp;Huan Wang ,&nbsp;Ruifen Wang ,&nbsp;Yumeng Jin ,&nbsp;Yihan Wang ,&nbsp;Shijie Wang ,&nbsp;Xinrui Li ,&nbsp;Yaru Wang ,&nbsp;Zeyang Zhang ,&nbsp;Ping Su ,&nbsp;Songsong Wang ,&nbsp;Huangge Zhang ,&nbsp;Liwen Han","doi":"10.1016/j.phymed.2026.157861","DOIUrl":"10.1016/j.phymed.2026.157861","url":null,"abstract":"<div><h3>Background</h3><div>Panacis Quinquefolii Radix (American ginseng, AG) has a well-documented history of use in cardiac protection. Nevertheless, the therapeutically active components responsible for its cardioprotective properties have not been fully elucidated. Extracellular vesicle-like nanoparticles (ELNs) have recently emerged as a promising class of natural nanocarriers with diverse applications in medicine and biology. However, it remains uncertain whether American Ginseng-derived extracellular vesicle-like nanoparticles (AGELNs) exhibit cardioprotective effects.</div></div><div><h3>Purpose</h3><div>This investigation aims to analyze the effects of AGELNs on Doxorubicin-induced cardiotoxicity (DIC) and the mechanisms.</div></div><div><h3>Methods</h3><div>Gradient ultracentrifugation was employed to isolate and purify AGELNs, while HPLC was employed for both qualitative and quantitative analysis of saponin molecules in AGELNs. Fluorescently labeled AGELNs were used to assess their uptake in cardiac tissue and cardiomyocytes. DIC models in mice and zebrafish were employed to evaluate the effect of AGELNs against DIC. Transcriptomics, RT-PCR, immunofluorescence, Western blotting, and pharmacological agonist and antagonist treatments were used to elucidate the molecular mechanisms of AGELNs <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Results</h3><div>AGELNs significantly enhanced cardiac function in mice and zebrafish models, evidenced by increased fractional shortening (FS), stroke volume, heart rate, and pericardial sac areas. Concomitantly, AGELNs demonstrated pronounced cardiac accumulation in Dox-treated mice, zebrafish, and cardiomyocytes. Transcriptomic and cellular analyses demonstrated AGELNs attenuate DIC by suppressing lipid peroxidation and ferroptosis. Mechanistically, AGELNs predominantly inhibit cardiomyocyte ferroptosis by targeting GPX4 and activating the NRF2/HO-1/GPX4 pathway. Furthermore, the cardioprotective effect of AGELNs against DIC has been found to be closely linked to its specific combination of bioactive saponins, including Rb1, Rg1, Re, and Rd.</div></div><div><h3>Conclusions</h3><div>AGELNs significantly mitigated DIC by activating GPX4 and suppressing cardiomyocyte ferroptosis <em>in vitro</em> and <em>in vivo</em>. These insights are valuable for the formulation of AGELNs therapies aimed at combating DIC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157861"},"PeriodicalIF":8.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080632","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":"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}