AMERICAN JOURNAL OF CHINESE MEDICINE
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2025
·Vol. 53
·期 03
·909-930
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IF 5.5
Ke Li,Ya-Jun Wang,Kun Wei,Wen-Lin Li,Yong-Bo Liu,Jun-Nan Hu,Wen-Guang Chang,Wen-Xuan Zhang,Long Chen,Wei Li
Diabetes mellitus (DM) is considered to be the most widespread epidemic worldwide, and diabetic nephropathy (DN) is one of the most serious diabetic complications. Its complex pathogenesis makes treatment of DN an ongoing medical challenge. Ginseng ( Panax ginseng . C. A Meyer) is a valuable medicinal herb with a long medicinal and culinary history. Ginsenoside Rg2 (Rg2), an important active component in ginseng, has effective inhibitory effects on lipogenesis and hepatic glucose production. However, the potential effect and mechanism of Rg2 on DN remain unclear. In this study, we investigated the effect of Rg2 on DN in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice and high glucose (HG)-induced human kidney 2 (HK-2) cells. The results demonstrated that Rg2 significantly improved the levels of FBG, dyslipidemia and impaired kidney function in DN mice. Additionally, Rg2 decreased the phosphorylation levels of IKKβ, IκBα, and NF-κB p65, inhibited the activation of NLRP3 inflammasomes (NLRP3, ASC, and Caspase 1), and restrained release of inflammatory factors (IL-18 and IL-1 β ) . In HG-induced HK-2 cells, Rg2 showed similar inhibitory effects on pyroptosis via NF-κB/NLRP3 signaling pathways. Moreover, the effect of Rg2 on inhibiting the activation of NF-κB/NLRP3 signaling pathways may have a relationship to reducing the overproduction of reactive oxygen species (ROS), which is further supported by the ROS inhibitor N-acetylcysteine (NAC). In conclusion, our findings clearly indicated that Rg2 could prevent the progress of DN by inhibiting the activation of pyroptosis-related NF-κB/NLRP3 signaling pathways in vivo and in vitro , suggesting that Rg2 may be a novel and promising therapeutic agent in the treatment of DN.
研究领域:
药理学
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分子生物学
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糖尿病研究
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DOI
PubMed
高影响因子
Journal of Ginseng Research
·
2025
·
IF 5.6
Ji Zhang,Jing Xie,Zhiqiang Niu,Long You,Yanan Liu,Rui Guo,Guigui Yang,Ziliang He,Ting Shen,Honggang Wang,Qi Yan,Weicheng Hu
Background Ginsenoside Rg2 (G-Rg2), a major active compound of Panax ginseng , exhibits a wide range of pharmacological properties, including anticancer, antioxidant and neuroprotective effects. However, the mechanisms by which G-Rg2 mitigates ulcerative colitis (UC) have not been clearly elucidated. Aims In the present study, we aimed to elucidate the underlying mechanisms by which G-Rg2 mitigated UC. Methods In this study, we investigated the efficacy of G-Rg2 in ameliorating dextran sulfate sodium (DSS)-induced UC and its potential mechanisms using a DSS-induced UC mouse model and Lipopolysaccharides (LPS)/ nigericin (Nig)-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation on immortalized bone marrow-derived macrophages (iBMDMs). Results Oral administration of G-Rg2 at doses of 10 and 20 mg/kg significantly mitigated weight loss, normalized food and water intake, and improved colon histopathology in DSS-induced UC mice. G-Rg2 also restored mRNA expression levels of occludin, claudin-3, zona occluden (ZO)-1 and mucin 2, thereby enhancing intestinal barrier integrity. G-Rg2 significantly suppressed the nuclear translocation of p65, the subunit of nuclear factor kappa-B (NF-κB), as well as downregulated NLRP3, cleaved IL-1β and caspase1 p20 expression induced by LPS/Nig in iBMDMs. Conclusion G-Rg2 effectively reduced colon inflammation in DSS-induced UC mice and diminishes inflammatory responses under LPS/Nig conditions by regulating NF-κB/NLRP3 pathway, thereby inhibiting NLRP3 inflammasome activation, which may serve as a potent therapeutic agent for UC.
研究领域:
药理学
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免疫学
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消化系统疾病
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DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6074
·
IF 1.7
Qinghai Dong,Fei Shi,Fang Lin,Yaqi Wang,Yang An,Hongliu Xie,Jihua Liu
Previous studies have suggested that ginsenoside Rg 2 glycine ester derivative (RG) exhibits therapeutic potential in mitigating hypoxia. This study aimed to elucidate the potential mechanism of RG in hypoxia injury through a combined approach of metabolomics and network pharmacology. Initially, a CoCl 2 -induced cell hypoxia model was established, and the therapeutic impact of RG on biochemical indices was evaluated. Subsequently, metabolomics analysis of cell samples was conducted to identify biomarkers, and network pharmacology was employed to identify potential targets of RG for hypoxia treatment. Finally, the key target and pathway were verified. The study revealed that RG could reverse CoCl 2 -induced abnormalities in biochemical indicators. Metabolomics analysis identified 13 biomarkers and seven metabolic pathways associated with RG treatment. Utilizing network pharmacology, five key targets and five metabolic pathways were identified, partially aligning with the metabolomics results. Molecular docking results demonstrated the effective binding of RG to the key targets. Enzyme linked immunosorbent assay verified that RG could exert antihypoxia effect by activated PI3K/Akt pathway. In conclusion, this integrated strategy, combining metabolomics with network pharmacology, sheds light on the protective mechanism of RG against hypoxia-induced cellular damage. The findings offer valuable insights for future research and potential applications of RG in the field.
研究领域:
药理学
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代谢组学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Ginseng Research
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2019
·
IF 4.029
Dongxia Gou,Xuejing Pei,Jiao Wang,Yue Wang,Chenxing Hu,Chengcheng Song,Sisi Cui,Yifa Zhou
Background Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride–induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase II. Conclusion Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.
研究领域:
药理学
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心脏病学
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毒理学
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DOI
PubMed
高影响因子
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