In vivo therapeutic effect of combination treatment with metformin and Scutellaria baicalensis on maintaining bile acid homeostasis.

Abstract

The radix of Scutellaria baicalensis (SB) is a herb widely used in traditional Chinese medicine to treat metabolic diseases. Several main components, including baicalin and wogonoside, possess anti-dyslipidemia, anti-obesity and anti-diabetic effects. We hypothesized that co-administration of SB extract and metformin exerts a better effect on obesity-induced insulin resistance and lipid metabolism than treatment with metformin alone. We compared the effect of metformin (100 mg/10 mL/kg/day) alone with co-administration of metformin (100 mg/5 mL/kg/day) and SB extract (200 mg/5 mL/kg/day) on Otsuka Long Evans Tokushima Fatty rats, a useful model of type II diabetes with obesity, and used Long-Evans Tokushima Otsuka rats as a control. Weight, fasting glucose, oral glucose tolerance test, intraperitoneal insulin tolerance test, and serum total cholesterol were measured after 12 weeks of drug administration. We observed a synergetic effect of metformin and SB on lowering cholesterol level by excretion of bile acid through feces. We found that this accompanied activation of FXR, CYP7A1 and LDLR genes and repression of HMGCR in the liver. Although there were no significant changes in BSH-active gut microbiota due to high variability, functional prediction with 16S sequences showed increased primary and secondary bile acid biosynthesis in the combination treatment group. Further study is needed to find the specific strains of bacteria which contribute to FXR-related cholesterol and bile acid regulations.

• Authors: Kyungsun Han, Shambhunath Bose, Jing-Hua Wang, Soo-Kyoung Lim, Young-Won Chin, Young-Mi Kim, Han-Seok Choi, Hojun Kim
• Journal: PloS one (PLoS One) Vol. 12 Issue 9 Pg. e0182467 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28877164 (Publication Type: Journal Article)

Chemical References

• Bile Acids and Salts
• Blood Glucose
• Plant Extracts
• Receptors, Cytoplasmic and Nuclear
• Scutellaria baicalensis extract
• farnesoid X-activated receptor
• Metformin
• Cholesterol
• CYP7A1 protein, rat
• Cholesterol 7-alpha-Hydroxylase

Topics

• Algorithms
• Animals
• Bile Acids and Salts (metabolism)
• Blood Glucose (metabolism)
• Blotting, Western
• Body Weight (drug effects)
• Cholesterol (blood)
• Cholesterol 7-alpha-Hydroxylase (genetics, metabolism)
• Combined Modality Therapy
• Feces (chemistry)
• Feeding Behavior (drug effects)
• Gastrointestinal Microbiome (drug effects)
• Homeostasis (drug effects)
• Insulin Resistance
• Liver (drug effects, metabolism)
• Male
• Metagenome
• Metformin (administration & dosage, pharmacology)
• Phylogeny
• Plant Extracts (administration & dosage, pharmacology)
• Principal Component Analysis
• Rats, Inbred OLETF
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Scutellaria baicalensis
• Up-Regulation (drug effects, genetics)