3.6 Dihydromyricetin
Dihydromyricetin, a bioactive flavonoid isolated from Ampelopsis cantoniensis var. grossedentata Hand. -Mazz. and Ziziphus jujuba Mill., has been found to have a wide range of pharmacological activities, such as anti-inflammatory (Y. Sun et al., 2021), analgesic (Guan et al., 2019), anti-tumor (L. Chen et al., 2020) and hepatoprotective effects (Silva et al., 2020). Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), plays a key role in maintaining endothelial function, and impaired NO biosynthesis is a hallmark of atherosclerosis (Cyr, Huckaby, Shiva, & Zuckerbraun, 2020; Tousoulis, Kampoli, Tentolouris, Papageorgiou, & Stefanadis, 2012). There is evidence that overexpression of dimethylarginine dimethylaminohydrolase-1 (DDAH1) increases NO production through an asymmetric aimethlarginine (ADMA) manner (Pope, Karrupiah, Kearns, Xia, & Cardounel, 2009). Studies suggested that dihydromyricetin treatment inhibits atherosclerotic lesion formation by increasing NO production by endothelial cells. MiR-21 expression can be reduced by dihydromyricetin in endothelial cells, which increases DDAH1 and reduces ADMA levels (D. Yang et al., 2018; D. Yang et al., 2020). Taken together, dihydromyricetin activates endothelial DDAH1/ADMA/eNOS/NO pathway by reducing miR-21, which relieves the pathogenesis of atherosclerosis.