ABSTRACT
Objective:To study the effect of Huangqi Guizhi Wuwutang on receptor of advanced glycation end products(AGEs)/advanced glycation endproducts (RAGE)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway in the diabetic peripheral neuropathy rats through an animal modeling experiment, and discuss the mechanism of Huangqi Guizhi Wuwutang in alleviating diabetic peripheral neuropathy. Method:Rat model of diabetic peripheral neuropathy was established by high-fat diet and intraperitoneal injection with streptozotocin (STZ). After successful modeling, Huangqi Guizhi Wuwutang intervention began in the fifth week. The patients in high-dose group (19.40 g∙kg-1∙d-1), middle-dose group (4.85 g∙kg-1∙d-1) and low-dose group (2.43 g∙kg-1∙d-1) were given by gavage continuously for 12 weeks. The western medicine control group was given 25 mg∙kg-1∙d-1 by gavage. After the experiment, serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect RAGE and NF-κB p65 mRNA expressions in sciatic nerve tissue. The expressions of RAGE, NF-κB and phosphorylation(p)-NF-κB p65 proteins in sciatic nerve tissues were detected by Western blot (WB). Result:Compared with the normal group, serum IL-1β and TNF-α protein levels, RAGE mRNA and NF-κB p65 mRNA levels, RAGE protein, NF-κB p65 protein and p-NF-κB p65 protein levels were significantly increased in the model group (P<0.01), the ratio of p-NF-κB p65 to NF-κB p65 was increased, and the phosphorylation of NF-κB p65 was enhanced (P<0.01). After the intervention of Huangqi Guizhi Wuwutang, compared with the model group, serum IL-1β and TNF-α protein levels, RAGE and NF-κB p65 mRNA levels, RAGE protein, NF-κB p65 protein and p-NF-κB p65 protein levels were all decreased (P<0.01), the ratio of p-NF-κB p65 to NF-κB p65 was decreased in high-dose group (P<0.01). The effect was obvious with the increase of dose of astragalus cassia twig. Conclusion:Huangqi Guizhi Wuwutang can alleviate diabetic peripheral neuropathy, and its mechanism may be related to blocking the expression of RAGE on tissue cell surface in AGEs/RAGE/NF-κB signaling pathway, inhibiting the activation of NF-κB and inducing TNF-α triggered oxidative stress and excessive inflammatory response, so as to avoid cell damage and dysfunction.
ABSTRACT
BACKGROUND@#Traditional Chinese exercises (TCEs) have a positive effect on glycemic control and hemoglobin A1c (HbA1c), but there is no consensus on the benefits of TCEs for patients with prediabetes.@*OBJECTIVE@#The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes.@*SEARCH STRATEGY@#Comprehensive retrieval of randomized controlled trials (RCTs) was carried out using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China Biology Medicine disc, Google Scholar and Baidu academic databases. The retrieval window ranged from the establishment of the database to December 2018, and references related to the included trials were searched without language restrictions.@*INCLUSION CRITERIA@#The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs.@*DATA EXTRACTION AND ANALYSIS@#Literature screening, data extraction and literature quality assessment were performed independently by two researchers. In the case of disagreement, a third party was invited to negotiate and make a decision. Standardized mean difference (SMD) was used to estimate the therapeutic effect. Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0. Heterogeneity was assessed using Q test and I, and the source of heterogeneity was determined using Galbraith diagram and sensitivity analysis. A Q test resulting in P 50% indicated significant difference and random effect model analysis was performed. Otherwise, a fixed effect model was applied. Begg's and Egger's tests were used to assess publication bias.@*RESULTS@#Nine RCTs involving 485 participants were included in this study. The results showed that TCEs could reduce fasting blood glucose (FBG), 2 h blood glucose (2hPBG) and HbA1c in patients with prediabetes. The treatment subgroup showed that an intervention of 6 months had better results, while the Gongfa subgroup showed that the TCE Baduanjin yielded better results. (1) FBG: SMD = -0.73, 95% confidence interval (CI) [-0.97, -0.50], P < 0.00001; Baduanjin: SMD = -0.83, 95% CI [-1.13, -0.53], P < 0.00001; 6 month treatment: SMD = -0.73, 95% CI [-1.20, -0.26], P = 0.002. (2) 2hPBG: SMD = -0.75, 95% CI [-0.94, -0.57], P < 0.00001; Baduanjin: SMD = -0.62, 95% CI [-0.91, -0.32], P < 0.00001; 6 month treatment: SMD = -0.91, 95% CI [-1.39, -0.44], P = 0.0002. (3) HbA1c: SMD = -0.56, 95% CI [-0.89, -0.23], P = 0.00008; Baduanjin: SMD = -0.46, 95% CI [-0.83, -0.08], P = 0.02; 6 month treatment: SMD = -0.77, 95% CI [-1.24, -0.29], P = 0.002.@*CONCLUSION@#TCEs had positive effects in improving blood glucose levels in patients with prediabetes. Hence, TCEs may be of potential therapeutic value for patients with prediabetes, as an adjuvant therapy along with other treatments. Although the evidence suggests that the intervention is effective for 6 months, the mechanism of TCEs on glycemic control, the minimum exercise dose and their safety remain to be further studied.