Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways.
It is hypothesized that Rhizoma Coptidis (RC) alkaloids exert their hypolipidemic effects primarily by targeting the gastrointestinal tract and liver. Thus, this study was conducted to evaluate the antihyperlipidemic mechanisms of RC alkaloids (at a daily dose of 140mg/kg for 35days) in high-fat and high-cholesterol induced hyperlipidemic B6 mice. After treatment, serum lipid parameters were determined, the expression of lipid metabolism related genes and pathways such as the sterol regulatory element binding proteins (SREBPs) and bile acid signaling in mice were also investigated. Meanwhile, Illumina sequencing was used to investigate the differences in gut microbiota of B6 mice. The results indicated that RC alkaloids reduced the body weight gain and serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA) and lipopolysaccharide of B6 mice. Liver fat deposition and epididymal adipose cell size were also deceased in therapy group. RC alkaloids feeding significantly promoted the abundance of Sporobacter termitidis, Alcaligenes faecalis, Akkermansia muciniphila in the gut of mice, whereas, the abundance of Escherichia coli, Desulfovibrio C21_c20, Parabacteroides distasonis was suppressed. The observed antihyperlipidemic effects of RC alkaloids can also be attributed to their action as agonists of FXR and TGR5, activators for SREBP2, LDLR, UCP2 and CYP7A1, inhibitors of HMGCR, TXNIP, TLR4 and JNK. Therefore, this study expands current knowledge on hypolipidemic mechanisms of RC alkaloids and presents new evidence supporting a key role for RC alkaloids as regulators of lipid homeostasis by modulation gut microbiota and hepatic lipid metabolism.
Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Department of Clinical Laboratory, Hunan University of Medicine, Hunan 418000, China.
Kai
K
He
Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Yinran
Y
Hu
Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Hang
H
Ma
Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Zongyao
Z
Zou
Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Yubo
Y
Xiao
Department of Clinical Laboratory, Hunan University of Medicine, Hunan 418000, China.
Yong
Y
Yang
Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Min
M
Feng
Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China. Electronic address: xuegangli@swu.edu.cn.
Xuegang
X
Li
School of Life Sciences, Southwest University, Chongqing 400715, China. Electronic address: yexiaoli@swu.edu.cn.
Xiaoli
X
Ye
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D039323:Coptis / Q000737:chemistry; D000089042:Coptis chinensis; D059305:Diet, High-Fat / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000382:microbiology; D010946:Plants, Medicinal / Q000737:chemistry
D000470:Alkaloids; D001647:Bile Acids and Salts; D004365:Drugs, Chinese Herbal; D008055:Lipids; C107393:Coptidis rhizoma extract
Alkaloids; Antihyperlipidemic; B6 mice; Gut microbiota; Mechanisms; Rhizoma Coptidis