Hydrochloride Berberine ameliorates alcohol-induced liver injury by regulating inflammation and lipid metabolism

• Published in: Biochemical and biophysical research communications 2022-06, Vol.610, p.49-55
• Main Authors: Ke, Xiumei, Zhang, Ruoyu, Li, Pan, Zuo, Ling, Wang, Meng, Yang, Junxuan, Wang, Jianwei
• Format: Article
• Language: English
• Subjects: acetyl coenzyme A; acyl-CoA oxidase; adenosine monophosphate; Alcoholic liver injury; AMP-Activated Protein Kinases - metabolism; Animals; berberine; Berberine - pharmacology; Berberine - therapeutic use; Berberine hydrochloride; carnitine palmitoyltransferase; Chemical and Drug Induced Liver Injury, Chronic - pathology; Ethanol - adverse effects; Ethanol - metabolism; fatty acids; histology; inflammation; Inflammation - pathology; Inflammatory; interleukin-10; Interleukin-10 - metabolism; interleukin-6; Interleukin-6 - metabolism; Lipid Metabolism; lipid peroxidation; Lipopolysaccharides - metabolism; liver; Liver - metabolism; Non-alcoholic Fatty Liver Disease - metabolism; PPAR alpha - genetics; PPAR alpha - metabolism; protein kinases; Rats; sequence analysis; Thyroid hormone responsive gene; thyroid hormones; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.04.009

Berberine hydrochloride (BBR) is efficacious in relieving alcoholic liver injury (ALI) in animal models, but its underlying mechanisms remains largely unclear. 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. 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. •Overexpression of THRSP in ALD was found for the first time.•BBR suppressed THRSP and its related genes expression involved in lipid synthesis.•BBR suppressed expression of lipid metabolism-related genes.•BBR attenuated ALD by regulating inflammation and lipid metabolism disorders.