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

Obesity is a pathological condition characterized by excessive body fat that often leads to cardiovascular diseases (Ashraf and Baweja 2013) . 3T3-L1 cells are commonly used to detect fat metabolism. Previous studies revealed that five CR alkaloids (berberine, coptisine, palmatine, epiberberine and magnoflorine) could inhibit adipocyte differentiation and cellular triglyceride accumulation in 3T3-L1 cells, and downregulated adipocyte marker genes [including PPAR-c and CCAAT/enhancer binding protein (C/EBP)] (Choi et al. 2014 Zhang et al. 2015) . Lipolysis is the process of breaking down lipids and has been regarded as a target for treating obesity. Adiponectin, which is involved in the regulation of metabolic processes, binds to two main receptors (AdipoR1 and AdipoR2), whose expression levels are decreased during the development of obesity. Berberine treatment upregulated the expression of AdipoR1 and AdipoR2, which consequently elevated adiponectin production and induced lipolysis. Berberine could also directly upregulate lipolysis-related genes such as those encoding LPL, PPARa, carnitine palmitoyltransferase 1 (CPT1), and medium-chain acyl-CoA dehydrogenase (MCAD) . Nonalcoholic fatty liver disease is a type of hepatic steatosis, which is always involved in obesity. It was reported that mice gut microbiota could be restored by gavage of 200 mg/kg of berberine for 8 weeks, resulting in alleviation of the predisposing factors for liver steatosis. These effects could be mediated by decreasing endotoxin receptor CD14 and inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumour necrosis factor alpha (TNF-a) ). This finding is consistent with another study that suggested that berberine's actions are largely based on suppressing inflammation, independent of AMPK . Berberine could also attenuate hepatic steatosis and enhance energy expenditure in mice by inducing autophagy and fibroblast growth factor 21 (FGF21) expression; however, these effects were abolished by a deficiency of the nutrient sensor SIRT1 . Furthermore, increasing evidence suggests that the mechanism may correlate with global modulation of hepatic mRNA and long noncoding RNA (lncRNA) expression profiles, reducing endoplasmic reticulum stress (ER) stress through the ATF6/SREBP-1c pathway Zhang et al. 2016) .