Notoginsenoside-R1 ameliorates palmitic acid-induced insulin resistance and oxidative stress in HUVEC via Nrf2/ARE pathway.

Panax notoginseng , a Chinese traditional food and herb medicine, possesses notable cardiovascular health-promoting properties, with notoginsenoside (NG)-R1 being a key active compound. Insulin resistance represents a global health concern associated with various metabolic disorders. This study investigated the effects of NG-R1 on palmitic acid (PA)-induced insulin resistance and oxidative stress in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that NG-R1 significantly alleviated impaired glucose uptake, enhanced the phosphorylation of protein kinase B (PKB/Akt) at Ser473, and reduced the phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser307 in PA-treated HUVECs. Furthermore, NG-R1 treatment significantly lowered the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), while increasing the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Additionally, NG-R1 activated the Nrf2/ARE signaling pathway, leading to a substantial increase in the expression of antioxidant enzymes. Notably, knockdown of Nrf2 attenuated the beneficial effects of NG-R1 on PA-induced insulin resistance and oxidative stress in HUVECs, suggesting that NG-R1 exerts its effects through the Nrf2/ARE pathway. In summary, our study reveals that NG-R1 ameliorated PA-induced insulin resistance in HUVECs via Nrf2/ARE pathway, providing novel insights into its potential for alleviating metabolic disorders and cardiovascular disease.