Abstract
Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH), which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques. Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group): (i) normal control group; (ii) high-fat diet- (HFD-) induced NASH model group; and (iii) HFD berberine-treated group (i.d. 200 mg/kg). The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH. Key Findings. (i) According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii) Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM), phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE), eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine. Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized disease state in which lipids accumulate in the hepatocytes in the absence of excessive alcohol consumption [1, 2]
The results showed that HFD caused a marked accumulation of fat in hepatocytes (red O oil staining demonstrated steatosis affected most of the hepatocytes, Figure 1(b)) and an evident infiltration of inflammatory cells in foci or in surrounding groups of hepatocytes as evidenced by arrows (Figure 1(a))
The results showed that serum levels of ALT, AST, CHO, TG, and low density lipoprotein cholesterol (LDL-C) were significantly higher in high-fat diet- (HFD-)fed rats (P < 0.05 or P < 0.01)
Summary
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized disease state in which lipids (triglycerides) accumulate in the hepatocytes in the absence of excessive alcohol consumption [1, 2]. The earliest stage of NAFLD is hepatic steatosis, which is often contained. It can progress to nonalcoholic steatohepatitis (NASH) if inadequate treatment or poor prognosis occurs. The operational definitions for NASH have remained uncertain until now. NASH is distinguished from simple steatosis by the presence of hepatocyte ballooning, cell death, inflammatory infiltrate, and/or collagen deposition in liver tissue [3]. As the worldwide trend currently continues towards an increased prevalence of NAFLD [4,5,6,7], the pathogenesis, diagnosis, and specific therapeutic strategies have duly gained the critical attention of researchers
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