Mudan Granules for Diabetic Peripheral Neuropathy: A Systematic Review of Preclinical and Clinical Evidence

BackgroundMudan granules has been used in China to treat diabetic peripheral neuropathy (DPN), but there is a lack of systematic review of reports in this area. The aim of this systematic review was to evaluate the efficacy and safety of Mudan granules in the treatment of diabetic peripheral neuropathy. MethodsInitial studies were searched from PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), VIP database, Wanfang electronic databases. The Cochrane Risk of Bias tool was used to evaluate the risk of bias. The meta-analysis was performed by Stata 16.0 software. For dichotomous and continuous outcomes, the relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) were conducted, respectively. Results51 randomized controlled trials (RCTs) involving 5,416 patients were included. In the meta-analysis, compared with routine treatment (RT) alone, Mudan granules plus RT reduced Toronto clinical scoring system (TCSS) score (SMD, -0.52; 95% CI, -0.66 to -0.38; P < 0.01), total symptoms score (TSS) (SMD, -1.44; 95% CI, -2.88 to -0.00; P = 0.05), serum homocysteine (Hcy) levels (SMD, - 3.84; 95% CI, -5.99 to -1.70; P < 0.01), serum high sensitive C-reactive protein (hs-CRP) levels (SMD, -1.68; 95% CI, -3.29 to -0.08; P = 0.04), and improved total clinical efficacy (RR, 1.23; 95% CI, 1.19 to 1.27; P < 0.01) and serum superoxide dismutase (SOD) levels (SMD, 1.54; 95% CI, 1.13 to 1.95; P < 0.01). Besides, Mudan granules presented an adjuvant efficacy on median motor nerve conduction velocity (SMD, 1.61; 95% CI, 1.16 to 2.07), median sensory nerve conduction velocity (SMD, 1.73; 95% CI, 1.26 to 2.20), common peroneal motor nerve conduction velocity (SMD, 1.48; 95% CI, 1.10 to 1.86), common peroneal sensory nerve conduction velocity (SMD, 1.57; 95% CI, 1.23 to 1.92), tibial motor nerve conduction velocity (SMD, 1.34; 95% CI, 0.82 to 1.87), and tibial sensory nerve conduction velocity (SMD, 1.03; 95% CI, 0.86 to 1.20). In terms of adverse events, there was no statistically significant difference between the trial group and the control group (P =0.87). Five preclinical studies were also retrieved for the study. Animal studies have shown that Mudan granules have anti-oxidative stress effects and could reduce the inflammatory response. It may improve peripheral nerve injury in diabetic rats by modulating the TLR4/MyD88/NF-{kappa}B pathway, TLR4/p38 MAPK pathway and PI3K/AKT pathway. ConclusionsMudan granules presented an adjuvant efficacy on patients with DPN and could improve the oxidative stress and inflammatory levels in preclinical models. However, high-quality original studies are needed to further prove the evidence.