Biochem Biophys Res Commun 2022 Jun 7;610:49-55. Epub 2022 Apr 7.
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address:
Aims: Berberine hydrochloride (BBR) is efficacious in relieving alcoholic liver injury (ALI) in animal models, but its underlying mechanisms remains largely unclear.
Methods And Results: In the study, the rats were divided into control group, model group, model with BBR group, and control with BBR group, and given corresponding treatment for 4 weeks. RNA-Seq, ELISA and RT-PCR were performed to explore the potential mechanisms of BBR in ALI. Treatment of rats with BBR (200 mg/kg/d, gavage, once daily) over 4 weeks diminished 4 g/kg/d alcohol-induced inflammation and lipid deposition. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in BBR-treated rats. Hepatic gene expression profile detected that BBR suppressed ethanol-stimulated overexpression of thyroid hormone responsive gene-THRSP. And overexpression of THRSP-responsive genes (fatty acid synthase-FASN, adenosine monophosphate activated protein kinase α-AMPK-α, acetyl-CoA carboxylase-ACC, ATP-citrate lyase-ACLY) responsible for fatty acid synthesis was also downregulated by BBR. Additionally, BBR downregulated expression of cluster of differentiation 36-CD36 and upregulated expression of peroxisome proliferator-activated receptor α (PPARα) and its target genes (carnitine palmitoyltransferase 1 α-CPT1α and acyl-CoA oxidase 1-ACOX1). Meanwhile, BBR treatment suppressed systemic inflammation by mediating a reduction in IL-10, TNF-α, LPS, and ET, but elevated IL-6.
Conclusions: The results indicated that BBR alleviated alcoholism-induced hepatic injury by suppressing inflammation (IL-10, TNF-α, LPS, ET and IL-6), and regulating fatty acids uptake (CD36), lipid synthesis (THRSP, FASN, AMPK-α, ACC, ACLY) and lipid oxidation (PPARα, CPT1α, ACOX1), and THRSP may be its novel target.