The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty liver disease by activating AMPKα

Abstract

An effective treatment for non-alcoholic fatty liver disease (NAFLD) is urgently needed. In the present study, we investigated whether the Chinese medicine Chai Hu Li Zhong Tang (CHLZT) could protect against the development of NAFLD. Rats in an animal model of NAFLD were treated with CHLZT, and their serum levels of cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were detected with an automatic biochemical analyzer. A cellular model of NAFLD was also established by culturing HepG2 cells in a medium that contained a long chain fat emulsion. Those cells were treated with CHLZT that contained serum from rats. After treatment, the levels of adenylate-activated protein kinase (AMPK) α (AMPKα), p-AMPKα, acetyl coenzyme A carboxylase (ACC) α (ACCα), pACCα, PPARγ, and SREBP-2 were detected. The AMPK agonist, acadesine (AICAR), was used as a positive control compound. Our results showed that CHLZT or AICAR significantly decreased the serum levels of TG, TC, LDL-C, AST, ALT, and insulin in NAFLD rats, and significantly increased their serum HDL-C levels. Treatments with CHLZT or AICAR significantly decreased the numbers of lipid droplets in NAFLD liver tissues and HepG2 cells. CHLZT and AICAR increased the levels of p-AMPKα and PPARγ in the NAFLD liver tissues and HepG2 cells, but decreased the levels of ACC-α, p-ACC-α, SREBP-2, and 3-hydroxyl-3-methylglutaryl-coenzyme A reductase (HMGR). CHLZT protects against NAFLD by activating AMPKα, and also by inhibiting ACC activity, down-regulating SREBP2 and HMGR, and up-regulating PPAR-γ. Our results suggest that CHLZT might be useful for treating NAFLD in the clinic.

Apigenin reduces the excessive accumulation of lipids induced by palmitic acid via the AMPK signaling pathway in HepG2 cells

“…Notably, increases in lipid metabolism is mainly observed in the liver, which can lead to chronic diseases related to hepatocytes (2). If left untreated, this increase in metabolism can lead to hepatocellular carcinoma therefore, it is necessary to investigate the underlying molecular mechanism (3). Adipogenesis is regulated via a complex process involving coordinated changes in hormone sensitivity and gene expression regulated by various transcription factors (4).…”

Primary Broiler Hepatocytes for Establishment of a Steatosis Model

“…Similar to humans, the liver is the main site of fat synthesis in broilers [ 4 , 17 , 18 ]. Although the liver can store some energy for nutritional needs, excessive nutrient levels accelerate the accumulation of fatty acids in liver tissues [ 13 , 19 ]. A high-energy diet during rapid growth is the main reason for FLHS in broilers [ 20 , 21 , 22 ].…”

“…Hepatocyte steatosis models induced by oleic acid, sodium oleate, fat emulsion, and ethanol have been successfully used to study the disease in human and other animals [ 8 , 9 , 10 , 11 ]. Fat emulsion, a known steatosis inducer, is high in energy and contains essential fatty acids, which provide biosynthetic materials for hepatocyte steatosis [ 12 , 13 , 14 ]. Commercial fat emulsion does not need to be prepared, and the proportion of components is stable, which is better than other inducers of hepatocyte steatosis.…”

Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine

“…erefore, nephron warming can calm the liver and strengthen the spleen to further improve the therapeutic effect. e basic methods for NAFLD differentiation treatment include: lipid-regulating and liverstrengthening decoction, herba artemisiae scopariae Yueju decoction, dachaihu decoction, modified sini powder, qili preparation, lipid-lowering decoction, liver-soothing, spleen-strengthening and blood-quickening decoction, turbid-eliminating and liver-clearing decoction, fat-eliminating and liver-protecting decoction, Shennong liver lipideliminating pills, yang-warming and turbid-eliminating decoction, Wuchong prescription, Tiluo powder, Ganzhikang capsule, dampness-resolving and fat-eliminating decoction, liver-controlling-dredging and lipid-lowering decoction, fat-reducing decoction, lipid-regulating capsule, liver-soothing, circulation-promoting and stasis-removing decoction, and lipid-lowering and liver-benefiting pills [48][49][50][51][52][53] (Table 1). Furthermore, according to the literature and clinical experience, the Chinese medicinal herbs commonly used for treatment of NAFLD in clinical practice can be divided into the following types ( Table 2).…”