{"title":"Ginsenoside Rb1 inhibits oxidative stress and ferroptosis to alleviate salpingitis infertility by down-regulating PTGS2 and up-regulating GPX4","authors":"Yuhan Wang, Jilin Kuang","doi":"10.1016/j.jgr.2026.101057","DOIUrl":"10.1016/j.jgr.2026.101057","url":null,"abstract":"<div><h3>Background</h3><div>Salpingitis infertility (SI) is a common disease among women of childbearing age, referring secondary infertility caused by acute or chronic salpingitis. Ginsenoside Rb1 (Rb1) has been confirmed to be an effective drug agent SI. Nevertheless, the underlying mechanism by which Rb1 acts on SI remains unclear.</div></div><div><h3>Methods</h3><div>Female mice and FT194 cells were employed as experimental subjects to establish SI models. HE staining was performed to evaluate the morphology changes of fallopian tube tissues. ELISA assays were conducted to determine the levels of inflammatory factors. Commercial kits were performed to examine the contents of MDA, SOD and Fe<sup>2+</sup>. Western blot and IHC were used to determine protein levels. Cell viability and proliferation were assessed via CCK-8 and EdU assay, respectively.</div></div><div><h3>Results</h3><div>Rb1 alleviated pathological lesions in fallopian tubal tissues, improved the pregnancy rate and litter size of SI mice and mitigated inflammation, oxidative stress and ferroptosis in both in vivo mouse and in vitro cell models of SI. In SI models, PTGS2 expression was upregulated while GPX4 expression was downregulated and these abnormal expression patterns were reversed by Rb1 treatment. PTGS2 knockdown inhibited ferroptosis and elevated the pregnancy rate and litter size of SI mice, whereas GPX4 knockdown abolished the above beneficial effects. Moreover, PTGS2 was found to downregulate GPX4 expression in SI models under Rb1 intervention.</div></div><div><h3>Conclusion</h3><div>Rb1 treatment decreased PTGS2 expression and increased GPX4 expression, thereby enhancing cell viability and proliferation, alleviating oxidative stress and ferroptosis, and ultimately ameliorating SI.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101057"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147912513","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":"Valorizing ginseng residues using dimethyl ether: Recovering functional lipids and ginsenosides","authors":"Sabrinna Wulandari, Ruqian Cao, Jongho Choi, Aye Aye Myint, Jaehoon Kim","doi":"10.1016/j.jgr.2026.101067","DOIUrl":"10.1016/j.jgr.2026.101067","url":null,"abstract":"<div><h3>Background</h3><div>Red ginseng marc (RGM), a byproduct of hot water extraction, contains valuable lipid fractions and bioactive compounds. Conventional extraction methods often require harsh processing conditions and additional solvent removal steps, leading to high operational costs.</div></div><div><h3>Methods</h3><div>Dimethyl ether (DME) was used as a green solvent to extract ginseng oil from RGM. Response surface methodology (RSM) was employed to investigate the effects of temperature (303–333 K), pressure (3–7 MPa), and extraction time (20–80 min) on extraction yield, total ginsenoside content, antioxidant activity, and total phenolic content (TPC) of the extracted oil.</div></div><div><h3>Results</h3><div>Under optimal conditions (333 K, 7 MPa, 80 min), the extraction yield reached 3.37%, with total ginsenoside content of 4.22 mg g<sup>−1</sup> dry RGM, and TPC of 1.09 mg GAE g<sup>−1</sup> RGM. DME-extracted ginseng oil also exhibited higher antioxidant activity (9.04 mmol TE g<sup>−1</sup> extract) and FAME content (14.93 mg g<sup>−1</sup> dry RGM) compared to ethanol and hexane extracts. Notably, DME enabled direct extraction from wet RGM without prior drying.</div></div><div><h3>Conclusion</h3><div>Extraction from wet RGM using DME resulted in higher ginsenoside content and extraction yield, but lower FAME content, compared to dry RGM. These findings highlight the potential of DME as a versatile, energy-efficient solvent for extracting bioactive ginseng oil from both dry and wet RGM, offering practical applications in the food and cosmetic industries.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101067"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376021","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":"Panax ginseng as a proteome–metabolome medicinal ecosystem: Reframing pharmacology beyond a strictly saponin-centric paradigm","authors":"Byong Chul Yoo, Jae Youl Cho, Mi-Yeon Kim","doi":"10.1016/j.jgr.2026.101064","DOIUrl":"10.1016/j.jgr.2026.101064","url":null,"abstract":"<div><div>The pharmacological understanding of <em>Panax ginseng</em> has traditionally focused on ginsenosides (saponins) as the principal bioactive determinants for its anti-inflammatory, metabolic, and anticancer effects. However, advances in multi-omics, high-resolution proteomics, spatial metabolomics, and microbiome analysis are expanding this view beyond a metabolite-exclusive framework. Emerging evidence shows that the ginseng proteome undergoes dynamic remodeling in response to ecological stress, development, and processing, generating glycosylated proteoforms, stress-responsive proteins, and peptide derivatives with biological relevance. Concurrently, microbiome-mediated biotransformation reshapes metabolite bioactivity and immune–metabolic homeostasis. These observations support the consideration of <em>P. ginseng</em> as an expanded, multi-layered system built on the established saponin-centered architecture. While saponins remain the primary signaling axis, the peptide tier, including small proteins, may exert complementary influences through redox buffering, receptor-proximal modulation, and localized stress-response mechanisms. These distinct molecular tiers are thought to converge on shared regulatory hubs, such as nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), nuclear factor erythroid 2–related factor 2 (Nrf2), inflammasome signaling, and mitochondrial stress pathways. Although some catalytic stress mechanisms need experimental validation, structural and proteomic findings suggest that additional regulatory layers beyond classical signaling modulation merit systematic study. Modern technologies like data-independent acquisition proteomics, peptidomics, spatial omics, and AI-assisted network modeling now enable comprehensive interrogation of this cross-tier structure. Integrating proteomic, metabolomic, and microbiome axes is essential to refine mechanistic understanding, improve multidimensional standardization, and expand translational exploration in botanical pharmacology.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101064"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375865","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":"Ginseng-containing Shentao Ruangan (STR) formula alleviates hepatic fibrosis via hepatocellular Nrf2-ROS-TGF-β axis regulating hepatocyte-HSC crosstalk: Integrating single-cell RNA sequencing and multi-tiered validation","authors":"Shangyi Huang, Ruisheng Zhou, Jing Li, Yi Zheng, Lunwei Yang, Tianqi Gao, Yi Yuan, Dailin Wu, Yafei Shi, Dayong Zheng, Daihan Zhou, Ying Tang","doi":"10.1016/j.jgr.2026.101053","DOIUrl":"10.1016/j.jgr.2026.101053","url":null,"abstract":"<div><h3>Background</h3><div>The ginseng-containing Shentao Ruangan (STR) formula is clinically used for chronic liver conditions, including hepatic fibrosis. Guided by traditional Chinese medicine (TCM) principles, it targets the “deficiency leading to accumulation (Xu Sun Sheng Ji)\" pathology in hepatic fibrosis via the “strengthening healthy qi and dispelling pathogenic factors (Fu Zheng Qu Xie)\" mechanism.</div></div><div><h3>Aims</h3><div>To elucidate how STR attenuates hepatic fibrosis, focusing on its regulation of the fibrotic liver microenvironment.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing profiled the fibrotic liver microenvironment; GEO analysis confirmed reactive oxygen species (ROS) as a central fibrotic driver. <em>In vitro/in vivo</em> experiments assessed STR's effects on ROS and fibrosis. Mechanisms were explored via RNA sequencing, network pharmacology, molecular docking, Nrf2 inhibitors and Nrf2-knockout (Nrf2<sup>−/−</sup>) mice.</div></div><div><h3>Results</h3><div>Single-cell sequencing identified hepatocyte-hepatic stellate cell (HSC) crosstalk as a core fibrotic feature, with hepatocellular metabolic dysfunction and elevated ROS promoting fibrosis (GEO-validated). STR alleviated fibrosis and suppressed excessive hepatic ROS in vitro and <em>in vivo</em>. Integrated analyses identified ROS modulation as STR's key anti-fibrotic mechanism, with Nrf2 as the critical target. STR activated hepatocellular Nrf2, alleviating oxidative stress, reducing TGF-β expression and secretion, and thus inhibiting HSC activation and extracellular matrix deposition. Molecular docking, Nrf2 inhibitors and Nrf2<sup>−/−</sup> mouse studies confirmed Nrf2's essential role.</div></div><div><h3>Conclusion</h3><div>This study links hepatocyte-HSC crosstalk/ROS-TGF-β-driven activation in hepatic fibrosis to TCM's “Xu Sun Sheng Ji”, while STR's Nrf2-mediated antioxidant and anti-fibrotic actions embody “Fu Zheng Qu Xie”, integrating TCM with modern medicine. STR, a ginseng-containing formula, is a promising targeted fibrosis therapy, advancing TCM-modern medicine integration.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101053"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375868","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":"Corrigendum to “GinDB-AI: An integrated database of Panax-derived compounds and an AI-driven platform for multidimensional information and biological activity prediction” [J Ginseng Res 50/3 (2026) 100986]","authors":"Nguyen Doan Hieu Nguyen, Vinoth Kumar Sangaraju, Duong Thanh Tran, Nhat Truong Pham, Jae Youl Cho, Balachandran Manavalan","doi":"10.1016/j.jgr.2026.101074","DOIUrl":"10.1016/j.jgr.2026.101074","url":null,"abstract":"","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101074"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375935","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}
Yannan Zheng, Mingyue Lv, Hongxi Xu, Errui Zhang, Min Zheng, Trinh Thach Thi Nguyen, Shijie Wan, Man Yuan, Weiliang Gu
{"title":"Korean red ginseng extract ameliorates high-fat diet-induced hyperlipidemia by modulating the gut microbiota-liver metabolic axis","authors":"Yannan Zheng, Mingyue Lv, Hongxi Xu, Errui Zhang, Min Zheng, Trinh Thach Thi Nguyen, Shijie Wan, Man Yuan, Weiliang Gu","doi":"10.1016/j.jgr.2026.100977","DOIUrl":"10.1016/j.jgr.2026.100977","url":null,"abstract":"<div><h3>Background</h3><div>Korean Red Ginseng is recognized for its ability to modulate immune responses, alleviate fatigue, and combat aging, and shows promise in treating hyperlipidemia. However, comprehensive insights into its gut–liver axis mechanisms remain limited.</div></div><div><h3>Methods</h3><div>Rats were assigned to a normal control group, an HFD-fed model group, and four groups treated with Korean Red Ginseng extract (RGE) at doses of 125 mg/kg, 250 mg/kg, 500 mg/kg, and 1000 mg/kg. The treatment groups administered RGE by gavage for 60 days while on an HFD. The study evaluated RGE's effects on hyperlipidemia and gut microbiota through serum biochemical analysis, hepatic histopathology, cecal metabolomics, 16S rRNA sequencing, and further investigated hepatic regulatory mechanisms using molecular biology techniques.</div></div><div><h3>Results</h3><div>After 60 days of treatment, RGE significantly reduced serum lipid levels and liver injury markers. Histological analysis using H&E and Oil Red O staining showed that RGE significantly reduced hepatic steatosis in comparison to the model group. LC-MS and 16S rRNA sequencing of cecal contents revealed that RGE remodeled gut microbiota composition, enhancing microbiota-derived metabolite production. Molecular analysis indicated that RGE activated hepatic PPARα, downregulated SREBP-1c, and partially restored basal cholesterol biosynthesis by upregulating HMGCR mRNA. These changes collectively reduced hepatic triglyceride accumulation and promoted cholesterol excretion.</div></div><div><h3>Conclusions</h3><div>RGE alleviates HFD-induced hyperlipidemia and hepatic steatosis through a coordinated gut-liver axis mechanism, involving microbiota modulation, metabolic reprogramming, and regulation of hepatic lipid factors. These findings support RGE as a potential therapeutic option for hyperlipidemia and related metabolic disorders, using an \"excretion-centric\" strategy.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 100977"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376011","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}
Keun-Tae Park, Heejoon Jo, Seung-Yeol Nah, Young-Ho Jin, Ik-Hyun Cho, Woojin Kim
{"title":"Gintonin prevents paclitaxel-induced neuropathic pain via spinal LPA3 receptors and oligodendrocyte precursor cells in mice","authors":"Keun-Tae Park, Heejoon Jo, Seung-Yeol Nah, Young-Ho Jin, Ik-Hyun Cho, Woojin Kim","doi":"10.1016/j.jgr.2026.101047","DOIUrl":"10.1016/j.jgr.2026.101047","url":null,"abstract":"<div><h3>Background</h3><div>Chemotherapy-induced peripheral neuropathy (CIPN) remains a major clinical challenge with limited treatment options. Gintonin, a glycolipoprotein complex derived from <em>Panax ginseng</em> Meyer<em>,</em> acts as a ligand for lysophosphatidic acid (LPA) receptors and has been reported to exert neuroprotective effects. This study investigated gintonin's actions in paclitaxel-induced neuropathic pain (8 mg/kg, i.p.), focusing on a previously unreported LPA<sub>3</sub>–OPC mechanism.</div></div><div><h3>Methods</h3><div>Gintonin (50–200 mg/kg, p.o.) was repeatedly administered in a paclitaxel-induced neuropathic pain model. Mechanical and cold allodynia were assessed, and spinal tissues were analyzed for LPA receptor expression. Receptor-specific siRNAs were intrathecally delivered to identify the subtype involved. Immunofluorescence and Cy5.5-labeled gintonin were used to examine LPA<sub>3</sub> receptor localization in NG2<sup>+</sup> oligodendrocyte precursor cells (OPCs).</div></div><div><h3>Results</h3><div>Gintonin attenuated paclitaxel-induced mechanical and cold allodynia, with the greatest effects observed at 100 and 200 mg/kg, and upregulated spinal gene expression of LPA<sub>1</sub> and LPA<sub>3</sub>, but not LPA<sub>2</sub> receptor. <em>LPA</em><sub><em>3</em></sub>-specific siRNA abolished its analgesic effect, confirming LPA<sub>3</sub> receptor dependence. Gintonin also preserved NG2<sup>+</sup> OPCs, with immunofluorescence and Cy5.5-labeled gintonin demonstrating co-localization with LPA<sub>3</sub> receptors.</div></div><div><h3>Conclusion</h3><div>These findings suggest that gintonin prevents paclitaxel-induced neuropathic pain through LPA<sub>3</sub> receptor–mediated regulation of spinal OPCs.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101047"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376038","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}
Yifan Cheng, Ha Thanh Tung Pham, Pengfei Tu, Luqi Huang, Xiuming Cui
{"title":"Mechanisms of yield and quality enhancement in Panax Vietnamensis: A comparison of three artificial cultivation models","authors":"Yifan Cheng, Ha Thanh Tung Pham, Pengfei Tu, Luqi Huang, Xiuming Cui","doi":"10.1016/j.jgr.2026.101056","DOIUrl":"10.1016/j.jgr.2026.101056","url":null,"abstract":"<div><h3>Background</h3><div><em>Panax vietnamensis</em> is a medicinally valuable species whose wild populations are threatened by overexploitation, necessitating the development of sustainable, high-yielding cultivation systems.</div></div><div><h3>Method</h3><div>A six-year systematic assessment was conducted on three artificial cultivation models: standard field (SF), artificial forest (AF), and wild forest (WF). Growth parameters, biomass production, and saponin content (via HPLC-ELSD) were measured. Furthermore, non-targeted metabolomic analysis (LC-MS/MS) was employed to elucidate the metabolic mechanisms underlying yield and quality in SF-grown plants.</div></div><div><h3>Results</h3><div>The SF model produced the highest biomass at year five, significantly outperforming the AF and WF systems, while achieving competitive total saponin content.Metabolomic profiling identified the fifth year as a pivotal developmental transition, characterized by the coordinated upregulation of secondary metabolite biosynthesis and stress adaptation pathways, alongside a significant enrichment of the key saponin precursor dimethylallyl diphosphate in taproots. Moreover, a functional division of labor was observed: rhizomes primarily synthesized precursors, whereas taproots functioned as the primary sink for saponin storage, indicating an efficient resource allocation strategy.</div></div><div><h3>Conclusion</h3><div>This study establishes the five-year SF model as a scientifically grounded and sustainable cultivation protocol for <em>P. vietnamensis</em>. These findings advance our understanding of how cultivation-driven metabolic shifts mediate quality enhancement, providing a framework that integrates agricultural productivity with species conservation.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101056"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147967083","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":"Ginseng nonsaponins: New insights into their pharmacological potentials in inflammasome-driven inflammation and immunopathology","authors":"Young-Su Yi","doi":"10.1016/j.jgr.2026.101030","DOIUrl":"10.1016/j.jgr.2026.101030","url":null,"abstract":"<div><div>The inflammatory response comprises a priming phase that prepares for inflammation and a subsequent triggering phase that activates and amplifies inflammatory signaling in cells. A critical event during the triggering phase is the activation of inflammasomes, cytosolic multiprotein complexes that function as signaling platforms to promote inflammatory responses. Although canonical and noncanonical inflammasomes are activated by distinct ligands, both play pivotal roles in inflammatory processes and contribute to the development of a wide range of human diseases. Consequently, inflammasomes have emerged as promising therapeutic targets for the regulation of inflammation and the treatment of inflammatory diseases. Ginseng and its major saponin constituents, ginsenosides, have been extensively reported to exhibit anti-inflammatory functions, at least in part, through the inhibition of inflammasome activation, emphasizing their therapeutic potential in inflammasome-associated diseases. Beyond ginsenosides, accumulating evidence has highlighted the biological relevance of ginseng-derived nonsaponin components and has begun to elucidate their mechanisms of action in inflammatory conditions, particularly through the modulation of inflammasome activation. This review summarizes current findings on the regulatory roles of ginseng nonsaponins in inflammasome-mediated inflammatory responses and highlights their potential as novel herbal therapeutics to prevent and treat inflammasome-driven human diseases.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101030"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375929","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 RK3 attenuates isoproterenol-induced heart failure in mice through AMPK/Sirt1/PGC-1α pathway activation","authors":"Chongyang Zhang, Yuning chen, Wei Liu, Rong-chang Chen","doi":"10.1016/j.jgr.2026.101063","DOIUrl":"10.1016/j.jgr.2026.101063","url":null,"abstract":"<div><h3>Background</h3><div>Ginsenoside RK3 was first isolated from heat-processed ginseng. Our study aimed to explore the underlying mechanism of RK3 in combating isoproterenol (ISO)-induced heart failure (HF) in mice.</div></div><div><h3>Methods</h3><div>HF was induced in mice by subcutaneous injection of ISO (80 mg/kg/d) 1 h after intraperitoneal administration of RK3 (10 and 20 mg/kg/d) for 28 days. Cardiac function and heart injury were assessed and comprehensive metabolic alterations in the serum were profiled. Western blot analysis was conducted. In vitro experiments, H9c2 cells were pretreated with RK3 before hypoxia exposure. Cell viability and LDH release were determined.</div></div><div><h3>Results</h3><div>In vivo experiments demonstrated that RK3 treatment prevented ISO-induced myocardial damage. Additionally, RK3 reduced serum inflammatory factors and levels of myocardial fibrosis. Metabolomics data indicated that RK3 mitigated the ISO-induced increase in glycolytic intermediates, including 3-phenyllactic acid, D-glucose-6-phosphate, D-glucose-1-phosphate, and D-fructose-6-phosphate and the decrease in intermediates of the TCA cycle, such as citric acid. Treatment with RK3 also inhibited the expression of MCT4 while enhancing the expression of MPC2, PGC-1α, Sirt1, and p-AMPK in heart tissues. In vitro investigations revealed that the protective effect of RK3 on H9c2 cells was abolished by AMPK inhibition.</div></div><div><h3>Conclusions</h3><div>Our study, for the first time, confirmed that RK3 protects against ISO-induced HF, which may be related to the restoration of balance in the pyruvate-lactate axis through the activation of the AMPK/Sirt1/PGC1 pathway.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 4","pages":"Article 101063"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375981","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}