*2.1. Ameliorative Effect of SR, CR, and Combined Extracts on Hyperglycemia, Dyslipidemia, and Insulin Resistance in T2DM Rats*

To evaluate the compatibility effects of SR and CR, a favorable T2DM rat model with a notable glycolipid metabolism disorder was established by HFD along with low dose of STZ. The significant increase of FBG, FINS, TG, TC, LDL-C, and FFA levels in T2DM rats was observed. By contrast, compared with T2DM rats, the levels of the above biochemical factors were decreased to a range from 51.1% to 85.4% after oral administration of individual and combined extracts. Furthermore, LSC or HSC extracts exerted better effects than the single drug, and the levels of these biochemical indexes declined remarkably after treatment. Metformin demonstrated a similar regulation as HSC in T2DM rats (Figure 1). These results indicated the better effects of combined extracts on the regulation of glucose and lipid homeostasis.

**Figure 1.** The levels of fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) in serum of the normal group (N), model group (M), and groups gavaged with metformin (P), scutellaria Radix (SR), coptidis Rhizome (CR), low dose of combined extracts group (LSC) and high dose of combined extracts (HSC). The values were shown as mean ± SD. # *p* < 0.05, ## *p* < 0.01, ### *p* < 0.001 vs. normal group; \* *p* < 0.05, \*\* *p* < 0.01, \*\*\* *p* < 0.001 vs. model group. Data were analyzed by One-way-ANOVA.

#### *2.2. Pathological Assessment of Some Tissues Related to Insulin Resistance*

The liver tissues of normal rats exhibited normal cellular structure with neat liver lobule, liver cords, liver sinusoid, and a clear three pipeline structure of the portal area. While notable changes with severe fatty degeneration were observed in the liver tissues of T2DM rats, this indicated that the model had been successfully established. Compared to model rats, SR and CR group rats showed moderate fatty degeneration, while LSC, HSC, and P group rats showed mild fatty degeneration by HE staining observation. The islet cells of T2DM rats showed severe atrophy. After treatment, SR and CR group rats showed moderate atrophy, however, LSC, HSC, and P group rats showed mild atrophy. The mean adipocyte diameter of T2DM rats compared with normal rats was seriously increased. After treatment, the mean adipocyte diameter was decreased and HSC showed a normalized effect. The skeletal muscle of T2DM rats was notably infiltrated with inflammatory cells, but P, SR, CR, LSC, and HSC group rats were normalized (Figure 2). The histological examination results were consistent with biochemical data, which further confirmed the synergistic effect of SR and CR.

**Figure 2.** Histopathological observation of liver, pancreas, skeletal muscle and adipose tissue in the normal group (N), model group (M), and groups gavaged with metformin (P), scutellaria Radix (SR), coptidis Rhizome (CR), low dose of combined extracts group (LSC) and high dose of combined extracts

(HSC). Liver tissues of M: notable changes with severe fatty degeneration can been seen as shown by the black arrow; Pancreas of M: severe atrophy of pancreatic islet cells is shown by the black arrow; Skeletal muscle of M: notably inflammatory cells infiltration is indicated by the black arrow; Adipose tissues of M: mean adipocyte diameter was seriously increased, as indicated by the black arrow. Samples were stained with H&E and photographed at 400× magnification.
