Journal of Ginseng Research最新文献

{"title":"Ginsenoside Re increases human coronary artery endothelial SK_Ca current and nitric oxide release via glucocorticoid receptor-PI3K-Akt/PKB pathway.","authors":"Kitinat Rodthongdee, Wattana B Watanapa, Katesirin Ruamyod, Namoiy Semprasert, Pimchanok Nambundit, Suwattanee Kooptiwut, Luecha Boontaveekul","doi":"10.1016/j.jgr.2025.04.008","DOIUrl":"10.1016/j.jgr.2025.04.008","url":null,"abstract":"<p><strong>Background: </strong>Ginsenoside Re (Re) has been shown to activate small-conductance calcium-activated potassium (SK_Ca) current in human coronary artery endothelial cells (HCAECs). We aimed to investigate whether Re increased SK_Ca current via glucocorticoid receptor (GR), its non-genomic pathway phosphoinositide 3-kinase-protein kinase B (PI3K-Akt/PKB), and endothelial nitric oxide synthase (eNOS), and whether SK_Ca mediated Re-induced increase in nitric oxide (NO), prostacyclin (PGI₂), epoxyeicosatrienoic acid (EET), and/or hydrogen peroxide (H₂O₂).</p><p><strong>Methods: </strong>Whole-cell patch clamp technique was employed to study Re-activated HCAEC currents, using specific inhibitors of the proposed mediating pathway. NO and H₂O₂ were assayed with colorimetric methods; PGI₂ and EET were investigated using ELISA. eNOS phosphorylation was assessed using Western blot analysis.</p><p><strong>Results: </strong>Re (1 μM) significantly increased HCAEC whole-cell current at +80 mV to 173.73 ± 43.90 % (mean ± SD). Apamin (SK_Ca blocker) could virtually eliminate Re-induced current and apamin-insensitive current could not be increased by Re, while blockers of other endothelial potassium channels did not produce the same effects. Moreover, antagonists of GR, PI3K, Akt/PKB, and eNOS effectively prevented Re's action. Re-induced eNOS phosphorylation and NO production could be prevented by blockers of SK_Ca, GR, or Akt/PKB, but Re-induced PGI₂ production could not be prevented by apamin, while EET and H₂O₂ were not increased by Re.</p><p><strong>Conclusion: </strong>Re enhances SK_Ca current and NO production via GR-PI3K-Akt/PKB and eNOS activation; in turn, SK_Ca current is essential for Re-increased NO. However, Re-induced PGI₂ release is independent of SK_Ca current. These findings could facilitate further research about ginseng effects on coronary artery and possible use in cardiovascular diseases.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"523-531"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956747","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":"Notoginsenoside R2 attenuates hepatic fibrosis via STAT3-dependent hepatic stellate cells senescence induction and inflammatory microenvironment suppression.","authors":"Kaili Deng, Min Li, Yuanyuan Li, Liangliang Xiang, Yuhua Wang, Hechen Shi, Jiayi Cheng, Sha Huang, Zhiping Lv","doi":"10.1016/j.jgr.2025.05.007","DOIUrl":"10.1016/j.jgr.2025.05.007","url":null,"abstract":"<p><strong>Background: </strong>Hepatic fibrosis (HF) continues to be a significant global health concern, substantially contributing to morbidity and mortality due to the absence of effective therapeutic options. This study examines the pharmacological effectiveness and underlying mechanisms of Notoginsenoside R2 (R2) in mitigating HF, aiming to find a new multifunctional candidate for therapeutic application.</p><p><strong>Methods: </strong>An integrative methodology utilizing network pharmacology, molecular docking, and experimental validation was implemented. <i>In vitro</i> models (HSC-T6), <i>in vivo</i> systems (zebrafish), and microinjection of morpholinos were employed to corroborate the antifibrotic effects of R2 and transcription 3 (STAT3)-dependent processes.</p><p><strong>Results: </strong>Network pharmacology identified 32 common targets between R2 and HF, with a particular emphasis on pathways critical for the activation of HSCs. Molecular docking confirmed strong interactions between R2 and signal transducer and activator of STAT3. <i>In vitro</i>, R2 inhibited HSCs proliferation and decreased the expression of α-SMA, COL-I, Desimin and TIMP1. <i>In vivo</i>, R2 mitigated thioacetamide-induced fibrosis in zebrafish, leading to decreased collagen deposition and suppression of pro-inflammatory cytokines. Mechanistically, R2 induced senescence in HSCs via the STAT3 pathway, characterized by increased expression of cyclin-dependent kinase inhibitor 2A (CDKN2A/p16) and cyclin-dependent kinase inhibitor 1A (CDKN1A/p21), as well as components of the senescence-associated secretory phenotypes (SASPs).</p><p><strong>Conclusion: </strong>This study identified R2 as a regulator of STAT3 with dual antifibrotic effects: reduction of the inflammatory microenvironment and induction of senescence. These findings position R2 as a viable treatment candidate for HF, necessitating additional clinical investigation.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"574-584"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956879","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":"Protopanaxatriol, a ginsenoside metabolite, induces apoptosis in colorectal cancer cells and arrests their cell cycle by targeting AKT.","authors":"Yuhao Wang, Jianmei Zhang, Canglang Mou, Yeye Hu, Ziliang He, Jongsung Lee, Jong-Hoon Kim, Jae Youl Cho","doi":"10.1016/j.jgr.2025.03.012","DOIUrl":"10.1016/j.jgr.2025.03.012","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is the third most common cancer worldwide and the fourth leading cause of cancer death. Protopanaxatriol (PPT), one of the main active metabolic ginsenosides of ginseng, has been found to have neuroprotective and anti-inflammatory effects, but its role in regulating colon cancer development remained unclear.</p><p><strong>Purpose: </strong>We sought to confirm the inhibitory effect of PPT on colon cancer cells and elucidate its target and mechanism.</p><p><strong>Methods: </strong>MTT assay, colony formation, invasion, migration assays, cell apoptosis, and cell-cycle analysis were performed. Quantitative real-time PCR, Western blotting, bioinformatic analysis using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology, and cellular thermal shift assay experiments were also employed.</p><p><strong>Results: </strong>PPT can inhibit the cloning, migration, invasion, and proliferation of colon cancer cells. PPT can increase the number of apoptotic bodies, promote the expression of the apoptotic proteins caspase-9 and caspase-3, induce apoptosis, and inhibit cell proliferation. In addition, by regulating cyclin, PPT can increase the expression of p21 and p27 proteins and inhibit the expression of the cyclin D1 protein, thereby inhibiting the G1/S transformation in the cell cycle. We further demonstrated that PPT can target AKT, reduce its protein expression, and reduce tumor progression and the expression of inflammatory factors caused by AKT high expression (TNF-α, IL-1β, and IL-6), thereby playing a role in inhibiting colon cancer progression.</p><p><strong>Conclusion: </strong>We are the first to demonstrate that the ginsenoside PPT can inhibit the activity of colon cancer cells by directly binding AKT.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"488-501"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956871","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":"Red ginseng extract enhances mitochondrial function and alleviates immunosenescence in T cells.","authors":"Ho Yeop Lee, Jingwen Tian, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Alfin Mohammad Abdillah, Jieun Lee, Sang Hyeon Ju, Seung Ho Lee, Hun Kun Ko, Minho Shong, Hyon-Seung Yi","doi":"10.1016/j.jgr.2025.05.004","DOIUrl":"10.1016/j.jgr.2025.05.004","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial function is essential for immune cell regulation, and its decline is linked to aging and chronic diseases. Impaired activity contributes to inflammation and reduced immunity. This study explores Red ginseng extract (RGE)'s potential in enhancing mitochondrial function and immune cell viability, offering benefits in mitigating immunosenescence.</p><p><strong>Methods: </strong>T cells and macrophages from young (12-week-old) and aged (20-month-old) mice were treated with RGE to assess mitochondrial function and cell viability. Flow cytometry evaluated immune cell populations and cytokine expression in splenocytes, while single cell transcriptomics analyzed RGE-induced transcriptional changes in T cells and macrophages.</p><p><strong>Results: </strong>RGE treatment improved mitochondrial oxygen consumption rate and glycolytic function in CD4⁺ and CD8⁺ T cells from both young and old mice, though effects were more pronounced in young cells. In aged mice, RGE administration resulted in higher proportions of naive T cells and reduced expression of senescence and exhaustion markers. Flow cytometry analysis indicated a decrease in pro-inflammatory cytokines IFN-γ and TNF-α in T cells, along with a reduction in IL-17-producing T cells. Single cell transcriptome analysis revealed downregulation of aging markers (<i>Cd28</i> and <i>Cd27</i>) and increased expression of mitochondrial complex genes, supporting RGE's role in enhancing mitochondrial function.</p><p><strong>Conclusion: </strong>RGE treatment enhances mitochondrial function and attenuates T cell senescence and exhaustion in aged immune cells, likely contributing to immune resilience against age-associated inflammation. This study highlights the potential of RGE as a therapeutic intervention for improving immune function and reducing the effects of immunosenescence, offering valuable insights into mitigating age-related immune decline.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"564-573"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956952","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":"Total ginsenosides and ginsenoside Rb2 delay hepatocyte senescence by regulating NAD⁺ metabolism and promoting IDO2/QPRT expression.","authors":"Chen Guo, Ming-Xia Wu, Ze-Peng Zhang, Jing Li, Jin-Jin Chen, Hang Su, Kun Wei, Da-Qing Zhao, Xiang-Yan Li, Qing-Xia Huang","doi":"10.1016/j.jgr.2025.05.001","DOIUrl":"10.1016/j.jgr.2025.05.001","url":null,"abstract":"<p><strong>Background: </strong>Imbalances in nicotinamide adenine dinucleotide (NAD⁺) homeostasis accelerate aging, and targeting NAD⁺ metabolism is a potential strategy for delaying aging. Ginsenoside, as the main active ingredient of Panax ginseng Meyer, exert age-delaying effects. However, the potential molecular mechanism by which total ginsenosides (GS) affect NAD⁺ metabolism remains unclear.</p><p><strong>Methods: </strong>The ability of GS to improve the health status of aging mice was evaluated by water maze, new object recognition, cardiac ultrasound, biochemical analysis, and H&E staining. LC-MS was used to detect NAD⁺ metabolites. Senescence-associated secretory phenotypes (SASPs), NAD⁺ level and mitochondrial function were used to assess cellular senescence status. Screening of active components of GS in mouse hepatocytes (AML12) based on serum metabolites of GS. Targeted knockdown of IDO2 further validated the molecular mechanism.</p><p><strong>Results: </strong>GS administration significantly improved the health status of aging mice, as evidenced by improvements in body weight maintenance, skeletal muscle function, neurological performance, and hepatic/cardiac function. Furthermore, GS treatment effectively ameliorated age-associated pathological alterations in multiple organs, including the liver, lung, heart, and brain. In addition, GS affects mainly the <i>de novo</i> biosynthesis pathway in the liver. After performing a phenotype screen, ginsenoside Rb2 (Rb2) was found to promote NAD⁺ metabolism, improve mitochondrial function and relieve AML12 cell senescence. The results attributed to IDO2 knockdown were reversed by GS and Rb2.</p><p><strong>Conclusion: </strong>GS and Rb2 enhance mitochondrial function and delay hepatocyte senescence by modulating the IDO2/QPRT-mediated NAD ⁺ <i>de novo</i> biosynthesis pathway. This discovery provides new insights into the role of ginsenosides in antiaging.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"541-552"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956990","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":"Structure-activity relationship of ginsenoside derivatives with different glycosides and double bond position on anti-aging bioactivities.","authors":"Juntao Zhang, Weimin Wang, Daidi Fan, Jianjun Deng, Haixia Yang","doi":"10.1016/j.jgr.2025.05.002","DOIUrl":"10.1016/j.jgr.2025.05.002","url":null,"abstract":"<p><strong>Background: </strong>Aging is a complex and inevitable biological process that involves the decline of function in multiple systems and organs, and it is possible to delay aging process and improve health conditions through diet. Ginsenosides, the major active compounds in <i>Panax ginseng</i> Meyer, exhibit anti-oxidant, anti-cancer, and anti-aging properties. However, the relationship between bioactivities and structures of ginsenoside derivatives with same molecular formula remain unclear.</p><p><strong>Methods: </strong>Using <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) model, we evaluated the anti-aging activities of 4 ginsenoside derivatives (Rg5, Rg6, Rk1, and F4), which differ in glycoside composition and double bond position. Their effects on lifespan, physiological functions, locomotion ability, lipofuscin accumulation, stress resistance, and acetylcholinesterase (AChE) activity were assessed.</p><p><strong>Results: </strong>Four ginsenoside derivatives showed different activities of delaying aging by improving muscle function, enhancing anti-oxidant stress, and reducing AChE activity in <i>C. elegans</i>. Particularly, Rg5 and Rk1, which contain two glucose residues, demonstrated superior activity compared to Rg6 and F4, which possess glucose-(2-1)-rhamnose residues. Meanwhile, Rg5 and F4, with a double bond at Δ²⁰⁽²²⁾ had better effects than Rk1 and Rg6 with a double bond at Δ²⁰⁽²¹⁾. Molecular docking analysis showed that Rg5 and Rk1 formed more hydrogen bonds and hydrophobic interactions with amino acid residues at the AChE active site compared to Rg6 and F4, Rg5 exhibited the most favorable binding energy, while Rg6 formed only a hydrogen bond and F4 showed no hydrogen bonding; both had the same binding energy.</p><p><strong>Conclusion: </strong>These findings suggest that glycoside types and double bond position are key structural determinants of the anti-aging activities of ginsenoside derivatives. This provides a theoretical foundation for the development of ginsenoside-based therapeutics for aging and aging-related chronic diseases.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"553-563"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957027","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 Rg5 enhances Abemaciclib sensitivity in ER+ breast cancer by modulating cell cycle proteins via transcriptional and post-translational levels.","authors":"Jie Chen, Dongxu Liao, Chong Wu, Liangquan Liu, Jing Luo, Gang Li, Lei Cao","doi":"10.1016/j.jgr.2025.06.004","DOIUrl":"10.1016/j.jgr.2025.06.004","url":null,"abstract":"<p><strong>Background: </strong>The development of resistance to CDK4/6 inhibitors is a significant challenge in treating estrogen receptor-positive (ER+) breast cancer. This study aimed to explore the regulatory mechanisms of ginsenoside Rg5 in enhancing Abemaciclib sensitivity in ER+breast cancer.</p><p><strong>Materials and methods: </strong>Abemaciclib-resistant ER + breast cancer cell lines were established. Cell viability, colony formation, cell cycle progression, and apoptosis were evaluated following treatment with ginsenoside Rg5 and/or Abemaciclib. Molecular mechanisms were investigated using Western blot analysis, qRT-PCR, co-immunoprecipitation, and cycloheximide chase assays. The therapeutic efficacy of ginsenoside Rg5 was further validated in xenograft models.</p><p><strong>Results: </strong>Ginsenoside Rg5 significantly enhanced Abemaciclib sensitivity in both parental and resistant ER+breast cancer cells. The combination treatment induced G1 arrest and apoptosis more effectively than either agent alone. Mechanistically, Rg5 suppressed the PI3K/Akt signaling pathway, downregulated <i>CDK4</i> and <i>CDK6</i> mRNA expression, and disrupted the HSP90-CDC37 chaperone complex. This disruption promoted proteasomal degradation of CDK2, CDK4, and CDK6 proteins. Introduction of an HSP90α-Y61A mutant, which resists Rg5 binding, abrogated these effects both <i>in vitro</i> and <i>in vivo.</i></p><p><strong>Conclusions: </strong>Ginsenoside Rg5 increases the sensitivity of ER+breast cancer cells by modulating cell cycle proteins via transcriptional and post-translational levels. These findings provide insights into novel combination therapies to circumvent CDK4/6 inhibitor resistance in ER+breast cancer.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"594-603"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956711","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":"Korean Red ginseng supplements improve quality of life in patients with mild chronic pancreatitis symptoms: A prospective clinical trial.","authors":"Joongyu Kang, Jin Ho Choi, Sang Hyub Lee, Junyeol Kim, Tae Seung Lee, Sung Hoon Chang, Yong Soo Song, In Rae Cho, Woo Hyun Paik, Ji Kon Ryu","doi":"10.1016/j.jgr.2025.04.003","DOIUrl":"10.1016/j.jgr.2025.04.003","url":null,"abstract":"<p><strong>Background: </strong>Managing symptoms of chronic pancreatitis (CP) remains a significant challenge. Korean Red ginseng (KRG), a well-known herbal supplement, has shown potential benefits in various health conditions, prompting its investigation in CP patients.</p><p><strong>Methods: </strong>We conducted a single-arm, prospective clinical trial to evaluate the effect of KRG on quality of life in CP patients exhibiting mild symptoms, as defined by a Clinical Global Impression (CGI) score of 0 or 1. 40 patients were enrolled and assessed at baseline, as well as at 30, 90, and 180 days. The primary outcome was an improvement in CGI scores, with secondary outcomes including changes in Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) scores.</p><p><strong>Results: </strong>A total of 40 patients were enrolled in this study, and 39 participants were analyzed. Results showed significant improvements in CGI scores at all examined intervals (days 0-30, 0-90, 0-180; p < 0.05). The PEI-Q score also significantly improved from day 0 to day 180 (p < 0.05). Two adverse events (AEs) probably related to KRG were reported, and all AEs were improved with conservative managements.</p><p><strong>Conclusion: </strong>KRG supplementation significantly improves quality of life in CP patients with mild symptoms. These findings suggest that KRG may be a beneficial adjunct therapy in this patient population. Further research is needed to explore KRG's pharmacological mechanisms, its use in combination with other treatments, and its effects in patients with more severe symptoms. (CRIS number: KCT0009681).</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"502-508"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956816","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 post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4.","authors":"Jin-Jin Chang, Li-Xia Xu, Wen-Jing Yi, Huan-Huan Zhang, Jun-Wei Zhang, Bin Zheng, Ping-Ying Fu, Rui-Lan He, Rui-Xing Wang, Jian-Feng Jiang, Long-Xin Gui, Min-Xia Wu, Jun-Jin Lin, Zhi-Hong Huang, Jia-Lin Song, Mo-Jun Lin, Hai-Xia Jiao, Zhi-Juan Wu","doi":"10.1016/j.jgr.2025.06.003","DOIUrl":"10.1016/j.jgr.2025.06.003","url":null,"abstract":"<p><strong>Background: </strong>Myocardial hypertrophy is a crucial pathological change that occurs during post-anthracycline treatment cardiomyopathy. The effects of ginsenoside Rb1 (Rb1) on anthracycline-induced hypertrophy remain unclear. This study aimed to explore the antihypertrophic effect of Rb1 on post-doxorubicin (DOX) treatment myocardial hypertrophy and underlying mechanism.</p><p><strong>Methods: </strong>Post-DOX treatment myocardial hypertrophy was induced 12 days or 22 h after 15 mg/kg DOX injection in C57BL/6 mice or 2 h DOX (2 μM) incubation in H9c2 cardiomyoblasts. Rb1 was administered 2 days before DOX exposure for 14 consecutive days or 6 h before DOX incubation for 30 h. Heart weight/Body weight (HW/BW), heart weight/tibia length (HW/TL) ratios, echocardiography, WGA staining and the contents of α-SMA, BNP and β-MCH were used to validate myocardial hypertrophy. HE staining, Masson staining, and transmission electron microscopy were performed to assess changes in cardiac morphology. Fluo-3/AM fluorescence was applied to measure the cytosolic free calcium concentration. Western blot, immunohistochemical and immunofluorescence staining were used to assess the expression of CaNBβ/NFATc4/GATA4 signaling.</p><p><strong>Results: </strong>Rb1 significantly decreased the HW/BW, HW/TL and LVd mass/BW ratios, reduced the cardiomyocyte area and the expression of BNP, β-MHC and α-SMA. Rb1 also relieved myocardial fibrosis and subcellar structure changes and improved the cardiac hemodynamics of post-DOX treatment mice. Rb1 decreased post-DOX treatment calcium overload. Consistent with these findings, <i>in vivo</i> and <i>in vitro</i> CaN, NFATc4 and GATA4 overexpression was rectified.</p><p><strong>Conclusion: </strong>Rb1 ameliorated post-doxorubicin treatment myocardial hypertrophy, which may be correlated with CaN/NFAT/GATA4 downregulation.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"585-593"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956985","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":"Crude saponin from Korean red ginseng alleviates di(2-ethylhexyl) phthalate-induced urogenital damage via regulating p38 MAPK/NF-κB signaling.","authors":"Ji Hye Oh, Seung Hwa Baek, Hee Won Seo, Seung Ho Lee, Seock Yeon Hwang","doi":"10.1016/j.jgr.2025.04.009","DOIUrl":"10.1016/j.jgr.2025.04.009","url":null,"abstract":"<p><strong>Background: </strong>Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer and environmental pollutant that continuously accumulates in the body, causing urogenital toxicity. Further, DEHP accumulation can cause glomerulonephritis due to nephrotoxicity as well as infertility by disturbing reproductive function. Crude saponin is the main active ingredient of ginseng and acts effectively to protect against oxidative stress by activating signaling pathways, such as NF-κB, AP-1 and IRF. Here we investigated the effect of crude-saponin on p38 MAPK/NF-κB signaling against DEHP-induced genitourinary damage in rats.</p><p><strong>Methods: </strong>We conducted an <i>in vivo</i> reproductive toxicity study in 4-week-old prepubertal SD rats. DEHP was administered orally at 1000 mg/kg/b.w., for 28 days and crude saponin was administered intraperitoneally at 10, 20, and 40 mg/kg/b.w. for 21 days from 1 wk after DEHP exposure. Four weeks later, extensive analysis of the mice's blood and tissues was performed to characterize their response to DEHP and the protective effects of crude saponin.</p><p><strong>Results: </strong>DEHP induced inflammation, decreased testicular germ cells, and caused damage to renal tubular epithelial cells and infiltration of inflammatory cells. The expression of MCP-1, a chemokine upregulated by MAPK signaling, was significantly increased in the testicular tissue of DEHP-treated rats (68.3 % ± 4.3 %) compared with the NC group (47.3 % ± 9.8 %) (<i>p</i> < 0.05). In contrast, the high-dose crude saponin group showed a decrease of 60.8 % ± 3.3 %, increased testicular germ cells, and alleviated damage to seminiferous tubule epithelial cells. crude saponin alleviated inflammation by regulating MCP-1 and thereby modulating p38 MAPK/NF-κB signaling.</p><p><strong>Conclusions: </strong>While the precise mechanism underlying the favorable effects of crude saponin remains to be determined, present study provides a basis for the preventive and therapeutic potential of Korean red ginseng against urogenital disorders induced by phthalate-related plasticizer.</p>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"49 5","pages":"532-540"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957014","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}