Supplementary Table 1. Blood glucose levels in male Zucker fa/fa rat during 1 month treatment with either vehicle or Chinese medicine (JCU).

Transcription

1 Supplementary Table 1. Blood glucose levels in male Zucker fa/fa rat during 1 month treatment with either vehicle or Chinese medicine (JCU). JCU (4g/kg) n=7 Vehicle (water 10 ml/kg) n=5 P value (between groups) Day 0 Day 15 Day 30 Day 0 Day 15 Day 30 Day 0 Day 15 Day 30 Trend of change* Age (week) 29.8± ± Body weight (g) 427.1± ± ± ± ± < ± Oral glucose tolerance test 0 min (mmol/l) 5.5± ± ± ± ± ± min (mmol/l) 12.7± ± ± ± ± ± min (mmol/l) 14.3± ± ± ± ± ± min (mmol/l) 12.1± ± ± ± ± ± AUC 30.6± ± ± ± ± ± <0.001 Insulin tolerance test 0 min (mmol/l) 6.1± ± ± ± ± ± < min (mmol/l) 7.0± ± ± ± ± ± < min (mmol/l) 6.2± ± ± ± ± ± < min (mmol/l) 6.2± ± ± ± ± ± <0.001 AUC 15.8± ± ± ± ± ± <0.001 Data are mean±sd; * p value of trend test between groups.

2 Supplementary Table 2. P-value of terms related to lipid metabolism generated by DAVID tool. Term Count p-value Lipid biosynthetic E-13 Cholesterol metabolic E-08 Fatty acid metabolic E-06 Bile acid metabolic E-02 Supplementary Table 3. P-value of terms related to lipid metabolism generated by Chi-square test. Terms Lists Counts Negative counts Lipid biosynthetic Our list Fatty acid metabolic Cholesterol metabolic Bile acid metabolic Union Background Our list Background Our list Background Our list Background Our list Background Chi-square with Yates' correction

3 Supplementary Figure 1. The berberine-containing 3-herb formula JCU. The phytochemical profiles of JCU were identified by high performance liquid chromatography (HPLC) A. The three herbs and their main chemicals in the berberine-containing JCU. B. HPLC graphs of the three herbs JCU-1, JCU-2 and JCU-3. C. HPLC graphs of JCU extract preparations after 5 and 16 months of storage.

4 Supplementary Figure 2. The time line of the three sets of animal experiments. Note: the upward arrows indicate the days when OGTT were performed. A. Single-dose treatment and 1-week follow up study. B. Two-week treatment and 2-month follow up study. C. One-month treatment and 12-month follow-up study.

5 Supplementary Figure 3. Characterization and validation of the male Zucker diabetic fatty (ZDF) rats. Note: data are mean±sd, * p<0.05. A. Genotyping of Zucker rats by PCR. B. Body weight gain of aging male Zucker fatty rats (dark line, n=6) and their lean littermates (light line n=9). C. One obese and one lean rat at 3 months of age. D. Blood glucose levels of male Zucker fatty (solid line), lean (light line) and normal (dash line) rats during OGTT (2.5g/kg glucose). Each group contained 6 animals of 14- to 16- week old. E. Blood glucose levels of male Zucker fatty (solid line), lean (light line) and normal (dash line) rats during ITT (0.5 U/kg, i.p.). Each group contained 6 animals of 14- to 16- weeks old. F. Blood glucose levels of male Zucker fatty rats during OGTT (2.5g/kg glucose). Each group contained 6 animals of 6 (dash line), 12 (light line) and 18 (solid line) weeks of age. G. Blood glucose levels of male Zucker diabetic fatty rats (n=6) before (solid line) and after (dash line) one-week oral treatment with metformin (50 mg/kg).

6 Supplementary Figure 4. Global gene expression in liver by microarray and candidate gene validation by quantitative real-time PCR. A. Reconstructed gene network and biological. Hepatic genes corrected by the JCU treatment in ZDF rats were annotated by GeneSpring GX software version (solid lines) or literature (dashed lines) for gene network construction. B. Quantitative expression of IGFBP1 and CYP7a1 genes in the liver. Fresh liver specimens were obtained from male Zucker normal rats (ZN, n=3) and male ZDF rats at the end of the 2-month observation period after discontinuing the 2-week treatment with JCU (ZDF-JCU, n=3) or vehicle (ZDF-V, n=3). The Y-axis is the relative expression level normalized against the mean expression level in ZDF-V rats.