Abstract:

AIM: To analyze the effects of angelica sinensis polysaccharides on TLR4/MyD88/NF-κB signaling pathway in the inhibition of diabetic neuropathy (DPN) in rats. METHODS: A total of 105 SPF-level Wistar male rats were randomly selected and 15 were selected as the normal group, and the remaining 90 rats were used to prepare the DPN model. Seventy-five models were successfully established and were randomly divided into 5 groups, i.e. the model group, the angelica polysaccharide low, medium and high dose groups and positive control group, with 15 rats in each group. The rats in the model group and the normal group were intragastrically administered with 2 mL/100 g normal saline. The rats in the low, middle and high doses of angelica polysaccharide were given the polysaccharide of angelica sinensis polysaccharide, and the positive control group was given the Mi Kebao + metformin solution. The administration volume was 2 mL/100 g once a day for a continuous gavage of 10 days. After 3 and 10 days of administration, the mechanical contraction threshold (PWT) and heat-shrinking reflex latency (PWL) were measured. After the last administration, the rats were tested for fasting blood glucose, serum malondialdehyde (MDA) and superoxide dismutase. (SOD), catalase (CAT) activity, glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), myelin basic protein (MBP), TNF-α And C-reactive protein (CRP) content, detecting motor motor conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), rat sciatic nerve factor-κB (NF-κB) mRNA, myeloid molecular factor 88 (MyD88) mRNA and Toll-like receptor 4 (TLR4) mRNA expression. RESULTS: The fasting blood glucose and MDA content in the model group and the low dose group of angelica polysaccharide were significantly higher than those in the normal group. The contents of CAT, SOD and GSH-Px were significantly lower than those in the normal group. The fasting blood glucose and MDA content in the middle and high dose groups of angelica polysaccharide were significant. The levels of CAT, SOD and GSH-Px in the model group and the positive control group were significantly higher than those in the model group and the positive control group, and the difference was statistically significant (P＜0.05). The levels of serum IL-6, MBP, TNF-α and CRP in the model group and angelica polysaccharide low dose group were significantly higher than those in the normal group, and the serum IL-6, MBP and TNF-α in the middle and high dose groups of angelica sinensis polysaccharide. The CRP content was significantly lower than that of the model group and the positive control group, and the difference was statistically significant (P＜0.05).The expressions of NF-κB mRNA, MyD88 mRNA and TLR4 mRNA in the model group and the low dose group of angelica sinensis polysaccharide were significantly higher than those in the normal group, and the expression of NF-κB mRNA, MyD88 mRNA and TLR4 mRNA in the middle and high dose groups of angelica sinensis polysaccharide. Both were significantly lower than the model group and the positive control group, and the difference was statistically significant (P＜0.05). CONCLUSION: Angelica sinensis polysaccharides can significantly reduce the serum inflammatory factors and oxidative stress response in DPN rats. The mechanism may be that it inhibits the expression of TLR4, which affects the downstream gene expression of MyD88 signaling pathway, which is related to the inhibition of NF-κB activation.

Key words: diabetic peripheral neuropathy, toll-like receptor 4, myeloid molecule factor 88, nuclear transcription factor-κB, angelica sinensis polysaccharide