Tang Wang Ming Mu Granule Attenuates Diabetic Retinopathy in Type 2 Diabetes Rats

Abstract

Aims: This study aimed to determine the influence of Tang Wang Ming Mu granule (TWMM) on the diabetic retinopathy of diabetic rats. Methods: Male Wistar rats were divided into seven groups: normal control, diabetes model(DM), diabetes with TWMM (3.6, 7.2, and 14.4 g/kg) treatment, the positive control treatment groups of Qi Ming granules and Calcium dobesilate capsules. All rats were treated for 8 weeks. The levels of body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of TWMM. Furthermore, malondialdehyde (MDA), intracellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) in serum were measured to study effects of TWMM on oxidative stress and inflammatory in DM2 rats. VEGF, JAK/STAT signaling pathway and SOCS3 in retina was detected by immunohistochemistry. Results: TWMM and the positive control drugs Qi Ming and Calcium dobesilate showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, TWMM significantly decreased HbA1c, MDA, ICAM-1, and VEGF levels in serum of diabetic rats. However, Qi Ming granules showed significantly reduced MDA and VEGF levels (P < 0.01, and P < 0.05, respectively), Calcium dobesilate showed significantly reduced MDA and ICAM-1levels (P < 0.01 and P < 0.05, respectively) in serum. All drug- treated DM2 rats showed significantly lower levels of VEGF, JAK2, P-JAK2, STAT3, and P-STAT3 in retina than DM group, while TWMM and Calcium dobesilate significantly increased SOCS3 in retina. Conclusion: Our data suggest that the diabetic retina protective effect of TWMM might be related to antiinflammatory, antioxidative, upregulation of SOCS3 expression, inhibition of the JAK/STAT/VEGF signaling pathway.

Keywords: JAK2/STAT3 pathway; SOCS3; Tang Wang Ming Mu Granule; VEGF; antihyperglycemic activity; diabetic retinopathy; oxidative stress.

Figure 1

Effects of TWMM on blood glucose and weight levels in type 2 diabetic rats. Control group and model group were treated with the same volume of vehicle. Blood glucose (A) and weight (B) levels were recorded every week throughout the study. DM+H-TWMM group was treated with 14.4 g/kg TWMM. DM+M-TWMM group was treated with 7.2 g/kg TWMM. DM+L-TWMM group was treated with 3.6 g/kg TWMM. DM+QM group was treated with 1.4 g/kg Qi Ming granules. DM+CD group was treated with 150 mg/kg Calcium dobesilate capsules. Data are presented as mean. n = 8.

Figure 2

Effect of TWMM on hemoglobin A1c (HbA1c) of type 2 diabetic rats. Data are presented as mean ± SD. n = 8. ^**Indicate significant differences compared to the Control group at ^**P < 0.01. ^#,##Indicate significant differences compared to the DM group at ^#P < 0.05 and ^##P < 0.01.

Figure 3

Effect of TWMM on MDA (A), ICAM-1 (B), and VEGF (C) of type 2 diabetic rats. Data are presented as mean ± SD. n = 8. ^*, ^**Indicate significant differences compared to the Control group at ^*P < 0.05 and ^**P < 0.01. ^#,##Indicate significant differences compared to the DM group at ^#P < 0.05 and ^##P < 0.01.

Figure 4

Effect of TWMM on the number of endotheliocytes (A), the number of pericytes (B), the ratio of endotheliocytes/ pericytes (C) of type 2 diabetic rats. Data are presented as mean ± SD n = 8. ^**Indicate significant differences compared to the Control group at ^**P < 0.01. ^#,##Indicate significant differences compared to the DM group at ^#P < 0.05 and ^##P < 0.01.

Figure 5

Immunohistochemistry for VEGF (A), JAK (B), p-JAK (B), STAT3 (C), p-STAT3 (C), and SOCS3 (D) expression in the retina. Data are presented as mean ± SD n = 8. ^*, ^**Indicate significant differences compared to the Control group at ^*P < 0.05 and ^**P < 0.01. ^#,##Indicate significant differences compared to the DM group at ^#P < 0.05 and ^##P < 0.01.