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.