Journal of Ginseng Research最新文献

{"title":"Korean red ginseng saponins ameliorate metabolic dysfunction-associated steatohepatitis in mice by inhibiting caspase-11 and NLRP3 inflammasomes","authors":"Eojin Kim,&nbsp;Hee Ryeong Lim,&nbsp;Deok-Hyeong Choi,&nbsp;Young-Su Yi","doi":"10.1016/j.jgr.2026.101075","DOIUrl":"10.1016/j.jgr.2026.101075","url":null,"abstract":"<div><h3>Background</h3><div>Although Korean red ginseng (KRG) has been investigated in various liver disorders, its role in Metabolic dysfunction-associated steatohepatitis (MASH) remains unclear. This study aimed to evaluate the pharmacological effects of the KRG saponin fraction (KRGSF) in MASH and to elucidate its underlying mechanisms in hepatocytes, macrophages, and an <em>in vivo</em> MASH animal model.</div></div><div><h3>Methods</h3><div>C57BL/6 mice were fed a methionine/choline-deficient (MCD) diet to induce MASH and were orally administered KRGSF at varying doses for 8 weeks. HepG2 cells were treated with free fatty acids (FFA) to induce steatosis and inflammation. RAW264.7 cells were stimulated with either palmitic acid (PA) or lipopolysaccharide (LPS) to model inflammatory responses.</div></div><div><h3>Results</h3><div>KRGSF ameliorated hepatic steatosis in MASH mice by downregulating lipogenic gene expression. It further attenuated liver injury, macrophage infiltration, and fibrosis, concomitant with reduced pro-inflammatory cytokine production, pyroptosis, and serum ALT and AST levels. Mechanistically, KRGSF suppressed the expression of caspase-11 and NLRP3 and inhibited the proteolytic activation of gasdermin D (GSDMD) in MASH mice. <em>In vitro</em>, KRGSF decreased lipid accumulation and lipogenic gene expression in FFA-treated HepG2 cells, while also reducing pro-inflammatory cytokine production and lowering ALT and AST levels. Additionally, KRGSF inhibited pro-inflammatory cytokine production in PA- or LPS-stimulated RAW264.7 cells.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that KRGSF exerts protective effects against MASH by mitigating hepatic steatosis, inflammation, and injury, highlighting its potential as a therapeutic candidate for the prevention and treatment of MASH.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101075"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rb1: From basic mechanisms to therapeutic applications in diabetic complications","authors":"Yinli Zhao,&nbsp;Lusha Wei,&nbsp;Junwen Gong,&nbsp;Shuanghua Zheng,&nbsp;Dan Li,&nbsp;Zhiqiang Ke","doi":"10.1016/j.jgr.2026.101070","DOIUrl":"10.1016/j.jgr.2026.101070","url":null,"abstract":"<div><div>Diabetes is a globally prevalent chronic metabolic disorder characterized by defective insulin secretion and/or insulin resistance, often leading to various severe complications. As a traditional Chinese medicine, <em>Panax ginseng</em> has a long-standing history in the adjunctive treatment of diabetes, with ginsenoside Rb1 being one of its most important active constituents. This review systematically summarizes recent advances in basic and clinical research concerning ginsenoside Rb1 in the prevention and treatment of diabetes, with a focus on its pharmacological effects and molecular mechanisms in improving insulin resistance, protecting pancreatic β-cell function, and delaying diabetic complications. Accumulated evidence demonstrates that ginsenoside Rb1 exerts anti-diabetic effects through multi-target and multi-pathway mechanisms, specifically involving the regulation of glucose and lipid metabolism, inhibition of oxidative stress and inflammatory responses, and modulation of autophagy, exhibiting significant therapeutic potential. Based on its favorable pharmacological activities, ginsenoside Rb1 holds promise as a lead compound for diabetes drug development. Future research should further focus on the validation of its molecular targets and the exploration of pathways for clinical translation.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101070"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural characterization of a novel low-molecular-weight β-fructan from Panax quinquefolius and its effect on ameliorating hyperuricemia","authors":"Jinqian Yu,&nbsp;Chuangchuang Wang,&nbsp;Min Jiang,&nbsp;Tao Li,&nbsp;Yingjian Guo,&nbsp;Kai Zhong,&nbsp;Lei Zhao,&nbsp;Xiao Wang","doi":"10.1016/j.jgr.2026.101103","DOIUrl":"10.1016/j.jgr.2026.101103","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia (HUA), a widespread metabolic disorder, is closely associated with renal injury, tubulointerstitial fibrosis, and uric acid nephrolithiasis, posing a significant global health burden. In this study, we investigated the anti-hyperuricemic effects and underlying mechanisms of a novel low-molecular-weight β-fructan (AGP-W) derived from <em>Panax quinquefolius</em> L.</div></div><div><h3>Methods</h3><div>AGP-W was extracted from <em>P. quinquefolius</em> using ultra-high pressure extraction. Its structural characteristics were determined by molecular weight analysis, monosaccharide composition, and glycosidic linkage assays. Its therapeutic effects were evaluated in hyperuricemic mice by assessing serum parameters, renal transporters, intestinal barrier integrity, and gut microbiota.</div></div><div><h3>Results</h3><div>AGP-W was characterized as a novel low-molecular-weight β-fructan. AGP-W administration significantly and dose-dependently reduced serum uric acid, creatinine, and blood urea nitrogen levels (P &lt; 0.01), while ameliorating lipid metabolic disorders against the hyperuricemic mouse model. Mechanistically, AGP-W restored the expression of renal urate exporters ABCG2, OAT1/3, and OCT and suppressed the expression of URAT1, GLUT9. As for its effects on the intestines, it restored intestinal barrier integrity by upregulating tight junction proteins of ZO-1, Occludin, Claudin-1, reduced villus atrophy, and modulated gut microbiota by enriching <em>Lactobacillus</em> and suppressing HUA-associated bacteria.</div></div><div><h3>Conclusion</h3><div>AGP-W exerts potent anti-hyperuricemic effects by modulating renal urate transporters, and restoring intestinal barrier function with gut microbiota regulation. These findings highlight AGP-W as a promising natural candidate for hyperuricemia treatment.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101103"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1226845326001296/pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenosides Rh2 and Rg3 in first-line combination therapy: Prospects for rapid clinical translation in drug-resistant triple-negative breast cancer","authors":"Sungpil Yoon,&nbsp;Jae Youl Cho","doi":"10.1016/j.jgr.2026.101073","DOIUrl":"10.1016/j.jgr.2026.101073","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC), defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), remains one of the most aggressive breast cancer subtypes, characterized by high metastatic potential, poor prognosis, and limited therapeutic options. Despite extensive clinical efforts, durable improvements in survival have been limited due to the intrinsic heterogeneity of TNBC and the rapid emergence of multidrug resistance (MDR), primarily mediated by P-glycoprotein (P-gp) overexpression. P-gp–enriched cancer stem cells frequently survive initial chemotherapy, repopulate tumors, and drive relapse. Therefore, effective first-line strategies capable of eliminating heterogeneous, drug-resistant populations are urgently needed.</div><div>Ginsenosides derived from <em>Panax ginseng</em> have gained increasing attention as natural compounds with potent anticancer activity and excellent safety profiles. Among them, the panaxadiol-type ginsenosides Rg3 and Rh2 exhibit strong translational potential and are being actively explored as candidate adjuvant or first-line agents. Their multifaceted activities—anticancer efficacy in TNBC, inhibition of P-gp, MDR sensitization, cytoprotection of normal cells, compatibility with nanoparticle delivery systems, and availability of preclinical and clinical data—underscore their promise in overcoming resistance in TNBC. This review summarizes the evidence supporting Rg3 and Rh2 as multi-targeted agents capable of enhancing therapeutic efficacy and accelerating clinical application in drug-resistant TNBC.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101073"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context-dependent modulation of the TAK1–MAPK axis by ginsenoside-based formulations along the NAFLD–HCC continuum","authors":"Hyun Kyung Lim,&nbsp;Jae-Yong Oh,&nbsp;Kyu Nung Chung,&nbsp;Byong Chul Yoo,&nbsp;Jae Youl Cho","doi":"10.1016/j.jgr.2026.101024","DOIUrl":"10.1016/j.jgr.2026.101024","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) is a dynamic metabolic liver disorder that can progress to hepatocellular carcinoma (HCC). Stress-responsive signaling pathways, particularly the transforming growth factor-β–activated kinase 1 (TAK1)–mitogen-activated protein kinase (MAPK) axis, play context-dependent roles in hepatocyte survival, disease adaptation, and tumorigenesis.</div></div><div><h3>Methods</h3><div>Two ginseng-derived formulations with distinct biological properties were investigated: a non-cytotoxic Rg5/Rk1–triterpene complex and a cytotoxic Rg3/paclitaxel liposomal formulation. Cytotoxicity and signaling responses were evaluated in HepG2 hepatocellular carcinoma cells, MKN1 gastric cancer cells, and HEK293T cells. Cell viability was assessed using MTT assays. TAK1–MAPK signaling was analyzed by Western blotting and overexpression experiments, and cellular thermal shift assays were performed to examine target engagement.</div></div><div><h3>Results</h3><div>Rg5/Rk1–triterpene enhanced TAK1 autophosphorylation and activated downstream MAPK signaling without inducing cytotoxicity, consistent with an adaptive stress-response profile. This modulation was accompanied by selective upregulation of the RNA editing enzyme ADAR2, while global translational regulators such as eIF6 remained unchanged. In contrast, Rg3/paclitaxel liposomes induced cytotoxic stress and suppressed MEK–ERK signaling in hepatic and gastric cancer cells, supporting a pro-apoptotic mechanism. These opposing effects demonstrate formulation-dependent regulation of the TAK1–MAPK signaling axis.</div></div><div><h3>Conclusion</h3><div>These findings suggest that ginseng-derived formulations differentially modulate the TAK1–MAPK pathway and may represent a context-dependent signaling framework relevant to different stages of liver disease progression.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101024"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A combined extract of Salvia miltiorrhiza and Panax notoginseng enhances collateral flow and protects the neurovascular unit after ischemic stroke","authors":"Tae Woo Kwon,&nbsp;Minho Jung,&nbsp;Won Myoung Lee,&nbsp;Da Yeon Park,&nbsp;Han-Gyul Lee,&nbsp;Seungwon Kwon,&nbsp;Sanghyun Lee,&nbsp;Sang-Kwan Moon,&nbsp;Ik-Hyun Cho","doi":"10.1016/j.jgr.2026.101077","DOIUrl":"10.1016/j.jgr.2026.101077","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke remains a major cause of mortality and disability, with few therapeutic options outside the narrow time window for reperfusion. Collateral circulation critically sustains penumbral viability, yet no pharmacological agent is approved to enhance collateral flow. <em>Salvia (S.) miltiorrhiza</em> and <em>Panax (P.) notoginseng</em> possess complementary vascular, anti-inflammatory, and neuroprotective actions, suggesting potential synergy in acute ischemia.</div></div><div><h3>Methods</h3><div>A combined extract of <em>S. miltiorrhiza</em> and <em>P. notoginseng</em> (SM/PN) was tested in a permanent middle cerebral artery occlusion (pMCAO) mouse model and <em>in vitro</em> systems. Endpoints included infarct volume, anterior cerebral artery (ACA) perfusion, vascular endothelial growth factor (VEGF) expression, microglial activation, inflammatory mediators, and endothelial barrier integrity.</div></div><div><h3>Results</h3><div>Pre-ischemic SM/PN (15–60 mg/kg) significantly reduced cortical infarct volume and sustained ACA perfusion during the first 15 min after occlusion without increasing VEGF in brain or endothelial cells. SM/PN decreased Iba-1 immunoreactivity in peri-infarct regions and suppressed inducible nitric oxide synthase, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated BV2 microglia. It also reduced endothelial PECAM-1 upregulation while restoring occludin and partially recovering claudin-5, accompanied by reduced phosphorylation of STAT3 and p38.</div></div><div><h3>Conclusions</h3><div>SM/PN provides early neurovascular protection through non-angiogenic collateral enhancement, microglial modulation, and blood–brain barrier stabilization. This integrated mechanism distinguishes SM/PN from conventional pro-collateral or angiogenic strategies and supports its potential as an adjunctive therapy for acute ischemic stroke, especially for patients who cannot undergo reperfusion.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101077"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gintonin protects hematopoietic stem cells and accelerates bone marrow recovery following cyclophosphamide-induced injury","authors":"Ajay Vijayakumar,&nbsp;BaiCheng Chen,&nbsp;Jun Hong Park,&nbsp;Seung-Yeol Nah,&nbsp;Jong-Hoon Kim","doi":"10.1016/j.jgr.2026.101109","DOIUrl":"10.1016/j.jgr.2026.101109","url":null,"abstract":"<div><div>Gintonin administration to mice with hematopoietic injury induced by cyclophosphamide (CY) demonstrated that, gintonin promotes hematopoietic recovery as evidenced by restored count of blood cells, alleviated bone marrow suppression and reduced apoptosis of hematopoietic stem cells indicating the potential of gintonin as an adjunct therapeutic agent in chemotherapy.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101109"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nrf2 as a therapeutic target of ginseng: A comprehensive review from preclinical evidence to clinical applications","authors":"Bella Rhea Lavifa Sanjaya,&nbsp;Lilik Duwi Wahyudia,&nbsp;Min Kyung Cho","doi":"10.1016/j.jgr.2026.101079","DOIUrl":"10.1016/j.jgr.2026.101079","url":null,"abstract":"<div><div>Ginseng is a traditional herb that has been widely used for centuries to treat various diseases. A key mechanism of ginseng is the activation of nuclear factor erythroid 2-like 2 (Nrf2), a master regulator of antioxidant gene expressions. Activation of Nrf2 helps maintain redox homeostasis, which is crucial for chronic disease management. This review aims to summarize the pleiotropic role of Nrf2 in mediating the biological effects of bioactive compounds, extracts, and formulations of ginseng. It provides a comprehensive overview of current research on the medicinal applications of ginseng for treating various diseases and highlights the mechanisms involved in Nrf2 regulation. The literature published from 2018 to 2025 were reviewed using a PubMed search to assess recent studies on the therapeutic applications of ginseng mediated by Nrf2. Ginseng activates the Nrf2 signaling pathway and modulates its upstream signaling, including Kelch-like ECH-associated protein 1 (Keap1), p62, and glycogen synthase kinase-3β (GSK-3β). It exhibits anti-oxidative stress, anti-inflammation, anti-apoptosis, anti-ferroptosis, and anti-pyroptosis properties in both <em>in vitro</em> and <em>in vivo</em> disease models. The causal relationship between Nrf2 regulation and the protective effects of ginseng was demonstrated in Nrf2/its upstream regulators knockout and knockdown models. Clinical studies including those on Korean red ginseng (KRG) and Shenmai Injection (SMI) have validated the safety and efficacy of ginseng in improving several pathological conditions. The pleiotropic pharmacological effects of ginseng are attributed to Nrf2 activation and stabilization. These findings offer significant potential for the therapeutic applications of ginseng.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101079"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated LC–HRMS and in silico prediction discovery a hydroxylated protopanaxatriol metabolite in vivo with enhanced anti-inflammatory activity","authors":"Longchan Liu,&nbsp;Haizhen Zhang,&nbsp;Haoyue Zhang,&nbsp;Wenxiang Fan,&nbsp;Yingbo Yang,&nbsp;Yingmin Zhang,&nbsp;Aizhen Xiong,&nbsp;Linnan Li,&nbsp;Yuqing Zhao,&nbsp;Zhengtao Wang,&nbsp;Li Yang","doi":"10.1016/j.jgr.2026.101081","DOIUrl":"10.1016/j.jgr.2026.101081","url":null,"abstract":"<div><h3>Background</h3><div>Protopanaxatriol (PPT), a key aglycone of ginsenosides, exhibits significant anti-inflammatory potential but suffers from poor oral bioavailability. After oral administration, PPT is transformed by gastric acid, gut microbiota, and liver enzymes into metabolites with enhanced bioactivity.</div></div><div><h3>Methods</h3><div>We employed an integrated metabolomics strategy combining LC–HRMS, in silico prediction, and molecular networking to systematically characterize PPT metabolism in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Metabolites were identified across serum, urine, and feces samples.</div></div><div><h3>Results</h3><div>A total of 20 metabolites were identified, including the novel 25-hydroxy-PPT (25OH-PPT), discovered for the first time. Mechanistic in vitro assays demonstrated that 25OH-PPT was exclusively generated under simulated gastric conditions via an acid-catalyzed, non-enzymatic hydroxylation pathway. Functional evaluation showed that 25OH-PPT exhibited significantly stronger anti-inflammatory activity than PPT (IC₅₀ = 1.52 μM vs. 40.34 μM in RAW 264.7 cells).</div></div><div><h3>Conclusions</h3><div>These findings uncover a new metabolic activation pathway of PPT, providing mechanistic insights into its pharmacological effects and offering new perspectives for designing PPT-based therapeutics.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101081"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rb1 ameliorates endothelial dysfunction in sepsis: Targeting the RhoA/ROCK pathway to modulate mitochondrial homeostasis and inflammation","authors":"Shixi Shang,&nbsp;Jingju Wang,&nbsp;Ying Huang,&nbsp;Lihua Sun,&nbsp;Junsong Yin,&nbsp;Jiayao Shi,&nbsp;Guangzhao Cao,&nbsp;Hongjun Yang,&nbsp;Xiaolu Shi","doi":"10.1016/j.jgr.2026.101080","DOIUrl":"10.1016/j.jgr.2026.101080","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced endothelial dysfunction drives organ injury through microcirculatory failure, characterized by barrier disruption and heterogeneous blood flow. Ginsenoside Rb1 (G-Rb1), a bioactive ginseng constituent, exhibits potent anti-inflammatory and antioxidant properties. This study investigates whether G-Rb1 ameliorates sepsis by preserving endothelial barrier integrity via modulating mitochondrial homeostasis and inhibiting the RhoA/ROCK pathway.</div></div><div><h3>Methods</h3><div>A murine cecal ligation and puncture (CLP) sepsis model and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) were employed. Endothelial barrier function, mitochondrial dynamics, and inflammatory responses were assessed via histology, flow cytometry, Western blot, and Seahorse XF analysis. RhoA/ROCK inhibitor (Fasudil) and Drp1 inhibitor (Mdivi-1) served as mechanistic controls.</div></div><div><h3>Results</h3><div>G-Rb1 significantly improved survival in CLP mice and attenuated lung injury. It suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in bronchoalveolar lavage fluid and rebalanced T cell percentage. In HUVECs, G-Rb1 restored endothelial junction proteins (VE-cadherin, ZO-1, Claudin-5), reduced ROS/MDA, and enhanced SOD/GSH/ATP levels. Mechanistically, G-Rb1 inhibited RhoA activation and ROCK-mediated Drp1 phosphorylation (Ser616), normalizing mitochondrial fission, membrane potential, and oxidative phosphorylation.</div></div><div><h3>Conclusion</h3><div>G-Rb1 alleviates sepsis-induced endothelial dysfunction by suppressing the RhoA/ROCK/Drp1 axis, thereby restoring mitochondrial homeostasis and barrier integrity. These findings highlight G-Rb1 as a promising therapeutic candidate for sepsis management via dual modulation of cytoskeletal dynamics and mitochondrial quality control.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 5","pages":"Article 101080"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148859243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}