Journal of Ginseng Research最新文献

Background: 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.

Methods: 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.

Results: 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 (Cd28 and Cd27) and increased expression of mitochondrial complex genes, supporting RGE's role in enhancing mitochondrial function.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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 de novo 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.

Conclusion: GS and Rb2 enhance mitochondrial function and delay hepatocyte senescence by modulating the IDO2/QPRT-mediated NAD ⁺ de novo biosynthesis pathway. This discovery provides new insights into the role of ginsenosides in antiaging.

Background: 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 Panax ginseng 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.

Methods: Using Caenorhabditis elegans (C. elegans) 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.

Results: Four ginsenoside derivatives showed different activities of delaying aging by improving muscle function, enhancing anti-oxidant stress, and reducing AChE activity in C. elegans. 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.

Conclusion: 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.

Background: 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.

Materials and methods: 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.

Results: 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 CDK4 and CDK6 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 in vitro and in vivo.

Conclusions: 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.

Background: 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.

Methods: We conducted an in vivo 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.

Results: 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 %) (p < 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.

Conclusions: 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.

Ginseng, a traditional herb with a history spanning thousands of years in Asian culture, has gained widespread recognition for its valuable pharmacological properties. The primary active constituents of ginseng, ginsenosides, are renowned for their diverse biological activities, including cardioprotective, anti-tumor, anti-inflammatory, and neuroprotective effects. However, the therapeutic potential of ginsenosides is often constrained by their low bioavailability in their native forms. During metabolism, ginsenosides undergo biotransformation by intestinal microbiota and enzymes, yielding metabolites with significantly enhanced bioavailability. Thus, to enhance the utility of ginsenosides as pharmaceutical agents and health products, it is essential to deepen our understanding of their metabolic processes and bioavailability in vivo. This review provides a comprehensive analysis of the ginsenoside content in ginseng and the modifications that occur during in vivo metabolism. Particular emphasis is placed on the plasma concentrations of ginsenoside metabolites, as well as the pivotal roles of specific microorganisms and enzymes in the metabolic process. Additionally, the pharmacokinetics of ginsenosides in the bloodstream following metabolism and their associated pharmacological activities are thoroughly examined. By offering a detailed exploration of ginsenosides' metabolism and pharmacodynamics, this review aims to advance our understanding of their therapeutic potential and support future research and drug development initiatives.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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).

Background: 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.

Methods: 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.

Results: 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, in vivo and in vitro CaN, NFATc4 and GATA4 overexpression was rectified.

Conclusion: Rb1 ameliorated post-doxorubicin treatment myocardial hypertrophy, which may be correlated with CaN/NFAT/GATA4 downregulation.

Background: Ginsenoside Rb1 is a prominent bioactive component in traditional Chinese medicine.

Purpose: This study investigated the molecular mechanisms underlying the protective effects of Ginsenoside Rb1 on endothelium during ischemia-reperfusion (I/R) injury.

Materials and methods: To enrich for marker genes and investigate the differential expression of DUSP1 and NDUFS4 in coronary artery disease, single-cell transcriptome sequencing was utilized. SIRT5^CKO/TG and NDUFS4^CKO/TG mouse models were established using gene modification techniques. Si-DUSP-1/ad-DUSP-1 and si-SIRT5/ad-SIRT5 cell models were constructed. Fluorescence detection, mitochondrial membrane potential assays, RT-PCR, and Western blotting were employed to detect the mitochondrial function.

Results: NDUFS4 and DUSP1 regulate the mitochondrial unfolded protein response (mtUPR), energy metabolism, and dynamics, and may be crucial regulatory genes in the development of coronary artery disease. Ginsenoside Rb1 modulates the NDUFS4-SIRT5-DUSP1 axis, regulates the mitochondrial quality control network, and alleviates coronary microvascular inflammatory injury.

Conclusions: Ginsenoside Rb1 regulates the NDUFS4-SIRT5-DUSP1 axis, modulating the mitochondrial quality control network, inhibiting the inflammatory cascade response, and improved myocardial function.