3.3 Notoginsenoside R1
Notoginsenoside R1, the monomer extracted from Panax notoginseng(Burkill) F.H.Chen, has a unique effect of promoting blood circulation and has been used on clinical treatment of cardiovascular diseases (Lei et al., 2022). Matrix Gla Protein (MGP), an important inhibitor of vascular and cartilage calcification, is highly expressed in human atherosclerotic plaques (Shanahan, Cary, Metcalfe, & Weissberg, 1994). Recently, a study found a targeting relationship between miR-132 and MGP, which showed that notoginsenoside R1 treatment down-regulates miR-132 and up-regulates MGP, subsequently inhibiting ox-LDL-induced endothelial cell apoptosis, migration, and release of adhesion factors (C. Fu, Yin, Nie, & Sun, 2018). Myeloid differentiation primary response gene 88 (MyD88) is an important immunoregulatory factor, and studies have found that inhibiting MyD88 has a good effect on diabetes (Androulidaki, Wachsmuth, Polykratis, & Pasparakis, 2018). Notoginsenoside R1 was found to relieve high glucose-induced endothelial cell inflammation and oxidative stress by down-regulating the MyD88 via up-regulating miR-147a (X. Q. Li & Huang, 2021). The Toll-like receptor 4 (TLR4)/Nuclear factor-κB (NF-κB) pathway participates in oxidative stress and induces atherosclerosis in ApoE−/− mice by up-regulating inflammatory cytokines (Tang et al., 2015). A study revealed that notoginsenoside R1 could up-regulate the expression of miR-221-3p to target TLR4/NF-κB pathway, thereby inhibiting ox-LDL-induced endothelial cell apoptosis, oxidative stress, and inflammation (L. Zhu et al., 2020). Notoginsenoside R1 may also play a role in delaying senescence of endothelial cells. Notoginsenoside R1 can decrease the expressions of miR-34a and p53, while increase the expression of SIRT1, thus enhancing the intracellular superoxide dismutase (SOD) activity and cell proliferation capacity in hydrogen peroxide-induced endothelial cell aging model (Lai, Lei, Yang, & Xiu, 2018). These studies suggest that notoginsenoside R1 has a strong and multifaceted endothelial protective effect through regulating ncRNAs.