*4.9. Statistical Analysis*

Statistical analysis was assessed by SPSS 19.0 (SPSS Inc., Chicago, IL, USA). All data were given as mean ± SD, and comparison of mean values was evaluated using One-way-ANOVA with Dunnett. In all experiments, *p* values <0.05 were considered significant difference.

#### **5. Conclusions**

Previous studies suggested that macrophage-specific TGR5 signaling in kupffer cells protected liver from inflammation and insulin resistance.An increase of cholic acid and deoxycholic acid was found, while glycocholic acid was decreased in T2DM rats. So combined SR and CR could better modulate inflammation and improve insulin resistance by increasing the levels of glycocholic aid and decreasing the levels of cholic acid and deoxycholic acid. In conclusion, the present studies suggested that combined extracts exerted significant amelioration on T2DM by modulation of proinflammatory cytokines, key target protein expressions in MAPK, and insulin signaling pathways as well as enzymatic activities related to glycometabolism. Thus, administration of combined extract could improve the symptoms of T2DM rats more effectively than the single drug. These results might provide useful hints for T2DM treatment and deserve further clinical investigations.

**Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/19/11/ 3634/s1.

**Author Contributions:** X.C. designed the study, performed experiments, analyzed the data, and drafted the manuscript. D.-W.Q., E.-X.S. and Z.-H.Z. contributed significantly to perform experiments and analyze data. S.J. and J.-A.D. designed the study and critically reviewed the manuscript. All authors reviewed and approved the final manuscript. X.C. and S.J. were the guarantors of this work.

**Funding:** This research received the Nature Science Foundation of China (No. 81673831) and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (No. ZDXM-1-10).

**Acknowledgments:** This work was financially supported by the Nature Science Foundation of China (No. 81673831) and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (No. ZDXM-1-10).

**Conflicts of Interest:** The authors declare no conflict of interest.
