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.
Ginsenoside Rg3 (Rg3), a natural product abundantly present in Korean Red Ginseng, is widely known for its anti-tumor activity. In our previous studies, we had further demonstrated that Rg3 has protective effects on the hearts, kidneys, and aortas of animals with hypertension or hypercholesterolemia, and its main mechanisms include down-regulation of angiotensin II (Ang II) levels and activation of peroxisome proliferator-activated receptor gamma (PPARγ) pathway in those tissues. In this study, the protective effects of Rg3 on liver were determined in db/db mice, a most recognized type II diabetes (T2DM) animal model with nonalcoholic fatty liver disease (NAFLD). The results showed that Rg3 did not have obvious effects to the body weight, blood glucose, and lipids of db/db mice. According to the results of histology examination, Rg3 could not improve steatosis in the hepatic tissue, too. But Rg3 did attenuate alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation in serum and collagen deposition in hepatic tissue. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) showed that Rg3 upregulated PPARγ and downregulated Ang II in hepatic tissue in db/db mice, which resulted in reducing activities of transforming growth factor β (TGF-β)/connective tissue growth factor (CTGF) pathway, downregulating the levels of inflammatory cytokines and attenuating collagen accumulation. In conclusion, although it has no obvious effect on steatosis in the hepatic tissue, Rg3 indeed attenuates early hepatic injury from NAFLD via inhibiting PPARγ- and Ang II-related inflammation and fibrosis in T2DM db/db mice. These effects are independent of reducing blood glucose and lipids, and the mechanisms are similar to the protective effects of Rg3 in hypertension and hypercholesterolemia animals in our previous studies.
Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons. To avoid inconvenience of frequent administration caused by short half life and recurrence of symptoms such as tremor and bradykinesia incurred by drug elimination, a novel long-acting pramipexole transdermal patch has been made. In the present study, we evaluated the neuroprotective effects and underlying mechanisms of pramipexole patch (PPX patch) in a subacute PD mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PPX patch treatment improved dyskinesia. MPTP-induced reduction of DA as well as its metabolites DOPAC and HVA in the striatum were prevented by PPX patch in a dose-dependent manner. PPX patch also restored the activity of antioxidant enzymes including SOD, GSH-Px and CAT in the striatum while reduced the content of MDA. Furthermore, PPX patch upregulated Nrf2/HO-1 expression. The protective effects of PPX patch was also associated with downregulation of the Bax/Bcl-2 ratio and Apaf-1, inhibition of cytochrome c release and inactivation of caspase-9 and caspase-3. In conclusion, our studies demonstrated that the long-acting pramipexole patch exerts its neuroprotective effects, at least in part, by inhibiting oxidative stress and mitochondrial apoptosis pathway and holds promise as a candidate drug.
At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called “no-reflow (NR),” and there is still no effective therapy for NR. Studies showed Panax quinquefolius L. saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes’ aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome via TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.
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