Effect of Baihu and Renshen Decoction on intestinal TLR4/NF-κB signaling pathway and intestinal barrier in type 2 diabetes MKR mice / 中草药

ABSTRACT

Objective: To observe the effect of Baihu and Renshen Decoction on intestinal barrier and TLR4/NF-κB inflammatory signaling pathway in type 2 diabetes MKR mice. Methods: A total of 32 MKR mice were randomly divided into model group, low dose Baihu and Renshen Decoction group, high dose Baihu and Renshen Decoction group and metformin group after 4 weeks with the high-fat diet. Another eight FVB/N mice were served as control group. After 4-week intragastric administration, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) in serum were examined. The morphological changes of colon tissue were observed by hematoxylin-eosin (HE) staining. The mRNA expression of TLR4, NF-κB, ZO-1, Claudin-1 and Occludin were measured by qRT-PCR method. The protein expression of ZO-1, Claudin-1 and Occludin in colon were measured by Western blotting. Results: Compared with model group, FBG in each administration group were significantly decreased (P < 0.01), serum IL-6, IL-1β, TNF-α, LPS and TLR4, NF-κB mRNA expressions were decreased (P < 0.05, P < 0.01) in high dose Baihu and Renshen Decoction group and metformin group. The mucosal epithelium integrity was improved. The mRNA and protein expression levels of ZO-1, Claudin-1, Occludin were increased (P < 0.05, P < 0.01) in high dose Baihu and Renshen Decoction group and metformin group; The mRNA expression levels of ZO-1, Claudin-1, Occludin were increased (P < 0.05) in low dose Baihu and Renshen Decoction group, while protein expressions showed no statistical difference. Conclusion: Baihu and Renshen Decoction can consequently reduce the levels of LPS and pro-inflammatory cytokines in MKR mice, regulate TLR4/NF-κB signaling pathway. It can significantly improve insulin resistance and reduce blood glucose levels by improving endotoxaemia, ameliorating intestinal injury and attenuating inflammation.