Panax ginseng is a traditional medicine used in China to cure many diseases. Polysaccharide is the primary active component. It has many pharmacological effects. Gastric ulcer is one of the...
Type 2 diabetes mellitus (T2DM) is a major health concern which may cause cardiovascular complications. Insulin resistance (IR), regarded as a hallmark of T2DM, is characterized by endothelial dysfunction. Ginsenoside Rc is one of the main protopanaxadiol-type saponins with relatively less research on it. Despite researches confirming the potent anti-inflammatory and antioxidant activities of ginsenoside Rc, the potential benefits of ginsenoside Rc against vascular complications have not been explored. In the present study, we investigated the effects of ginsenoside Rc on endothelial IR and endothelial dysfunction with its underlying mechanisms using high glucose- (HG-) cultured human umbilical vein endothelial cells (HUVECs) in vitro and a type 2 diabetic model of db/db mice in vivo. The results showed that ginsenoside Rc corrected the imbalance of vasomotor factors, reduced the production of Ang (angiotensin) II, and activated angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas axis in HG-treated HUVECs. Besides, ginsenoside Rc improved the impaired insulin signaling pathway and repressed oxidative stress and inflammatory pathways which constitute key factors leading to IR. Interestingly, the effects of ginsenoside Rc on HG-induced HUVECs were abolished by the selective ACE2 inhibitor MLN-4760. Furthermore, ginsenoside Rc exhibited anti-inflammatory as well as antioxidant properties and ameliorated endothelial dysfunction via upregulation of ACE2 in db/db mice, which were confirmed by the application of MLN-4760. In conclusion, our findings reveal a novel action of ginsenoside Rc and demonstrate that ginsenoside Rc ameliorated endothelial IR and endothelial dysfunction, at least in part, via upregulation of ACE2 and holds promise for the treatment of diabetic vascular complications.
Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20[Formula: see text]mg/kg) doses were injected intraperitoneally 1[Formula: see text]h before and 23[Formula: see text]h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4[Formula: see text]h before CCl4 administration to explore the mechanism. The blood and liver were collected 24[Formula: see text]h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI.
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