Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology

Wang, Jin; Wang, Lin; Lou, Guan-Hua; Zeng, Hai-Rong; Hu, Ju; Huang, Qin-Wan; Peng, Wei; Yang, Xiang-Bo

Atherosclerosis (AS) commonly occurs in the subendothelial space (intima) of arteries and is triggered by endothelial dysfunction and subendothelial lipoprotein retention (Tabas et al. 2015) . It has been reported that CR and its main alkaloids, such as berberine and coptisine, could effectively prevent the development of AS, and the potential mechanisms are correlated with suppressing ROS mediated oxidation (Xu RX et al. 2017) , and halting chronic inflammatory reactions via inhibition of intracellular inflammation signaling pathways . In particular, berberine could inhibit atherogenesis by reducing oxidative stress and the expression of adhesion molecules in the aorta, and increasing the levels of uncoupling protein 2 (UCP2) . Another CR component, magnoflorine, could inhibit the copper-mediated (Cu 2þ ) oxidation of various lowdensity lipoprotein (LDL) forms by increasing the lag time of conjugated diene formation and suppressing the generation of thiobarbituric acid reactive substances (TBARS) (Hung et al. 2007 ). The accumulation of foam cells in the subendothelial space is an indispensable step for the initiation and progression of AS. Berberine treatment could suppress foam cell formation, as well as the accumulation of lipid and cholesterol. The mechanism involves the activation of adenosine 5-monophosphate (AMP)-activated protein kinase (AMPK)-SIRT1-peroxisome proliferators-activated receptor c2 (PPAR-c) pathway and a decrease in ox-LDL uptake (Chi et al. 2014) . Berberine can stabilize atherosclerotic plaques by inhibiting the expressions of matrix metalloproteinase 9 (MMP-9) and extracellular matrix metalloproteinase inducer (EMMPRIN) by suppressing activation of the p38 pathway .