Changes of body weight, food intake and blood chemistry.

<p>Changes of body weight, food intake and blood chemistry.</p

<i>In vivo</i> therapeutic effect of combination treatment with metformin and <i>Scutellaria baicalensis</i> on maintaining bile acid homeostasis

<div><p>The radix of <i>Scutellaria baicalensis</i> (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 <i>FXR</i>, <i>CYP7A1</i> and <i>LDLR</i> genes and repression of <i>HMGCR</i> 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.</p></div

Western blot analysis of CYP7A1, HMG CoA reductase, LDL receptor and FXR in liver tissues.

<p>MetSB: Metformin co-administered with <i>Scutellaria baicalensis</i> extract. Each protein samples are obtained by pooling liver tissues from each group. Numbers denotes fold changes compared to LETO group. Y-axis denotes fold changes compared to LETO group.</p

Functional composition of metagenome related to metabolism was predicted with PICRUSt algorithm.

<p>#: <i>p</i> < 0.05 compared to LETO group. MetSB: Metformin co-administered with <i>Scutellaria baicalensis</i> extract.</p

Predicted functional composition of metagenome related to primary and secondary bile acid biosynthesis was analyzed with PICRUSt algorithm.

<p>There was no significant difference between groups. MetSB: Metformin co-administered with <i>Scutellaria baicalensis</i> extract.</p

Relative abundance of intestinal microbial community after 12 weeks of drug intervention shown at the phylum level and family level.

<p>MetSB: Metformin co-administered with <i>Scutellaria baicalensis</i> extract. Data are from stool samples from 5 rats/group.</p

Effect of metformin and metformin plus <i>Scutellaria baicalensis</i> (SB) extract on the glucose homeostasis and insulin sensitivity in OLETF rats.

<p>(A, B) Oral glucose tolerance test (OGTT) and (C, D) intraperitoneal insulin tolerance test (IPITT). #: <i>p</i> < 0.05 compared to LETO group. *: <i>p</i> <0.05 compared to OLETF group. **: <i>p</i> <0.001 compared to OLETF group. MetSB: Metformin co-administered with <i>Scutellaria baicalensis</i> extract.</p

Quantitative analysis of total cholesterol and total bile acids in feces and liver.

<p>Values are means ± Standard deviations. #: <i>p</i> < 0.05 compared to LETO group. *: <i>p</i> <0.05 compared to OLETF group. **: <i>p</i> < 0.001 compared to OLETF group. MetSB: Metformin co-administered with <i>Scutellaria baicalensis</i> extract. Liver and fecal samples were obtained from individual rats from each group.</p

Genes related to bile acid secretion from RT² Profiler PCR array analysis.

<p>Genes related to bile acid secretion from RT² Profiler PCR array analysis.</p