Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice.

Abstract

Berberine compounds (BC), consisting of berberine (BBR), oryzanol and vitamin B6, have been used to treat diabetes and hyperlipidemia in recent years, but the potential mechanisms under the effects have not been well determined. In this study, we evaluated the effect of BC in db/db mice, and found that BC treatment reversed the increased levels of fasting glucose and hemoglobin A1c in db/db mice, which was superior to BBR treatment. Fecal 16S rRNA gene sequencing indicated that BC increased relative abundance of microbiomes Bacteroidaceae and Clostridiaceae, which may promote conversion of primary bile acid cholic acid (CA) into secondary bile acid deoxycholic acid (DCA). Gas chromatography/mass spectrometry (GC/MS)-based metabolomics revealed that BC treatment increased fecal DCA level. Since DCA processes the potential to activate bile acid receptor-takeda G protein-coupled receptor 5 (TGR5) and induce glucagon-like peptide (GLP) secretion, we detected TGR5 expression, and found that BC-treatment significantly increased the colonic TGR5 and serum GLP-1/-2 levels in db/db mice. Modulation of TGR5-GLP pathway may also affect metabolomic profiles of serum and liver, and BC treatment showed effects on restoring the altered carbohydrate, lipid, amino acid and nucleotide metabolism. Our study suggested that BC improved hyperglycemia, the effect might attribute to the increased microbiome mediated DCA production, which up-regulated colonic TGR5 expression and GLP secretion, and improved glucose, lipid and energy metabolism in db/db mice.

• Authors: Meng Li, Wenjun Zhou, Yanqi Dang, Chunlin Li, Guang Ji, Li Zhang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 132 Pg. 110953 (Dec 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 33254441 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Gpbar1 protein, mouse
• Receptors, G-Protein-Coupled
• Berberine
• Glucagon-Like Peptides

Topics

• Animals
• Berberine (pharmacology, therapeutic use)
• Colon (drug effects, metabolism)
• Gastrointestinal Microbiome (drug effects, physiology)
• Glucagon-Like Peptides (agonists, metabolism)
• Hyperglycemia (drug therapy, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Receptors, G-Protein-Coupled (agonists, metabolism)