Oral Administration of East Asian Herbal Medicine for Peripheral Neuropathy: A Systematic Review and Meta-Analysis with Association Rule Analysis to Identify Core Herb Combinations

This review aimed to comprehensively assess the efficacy and safety of oral East Asian herbal medicine (EAHM) for overall peripheral neuropathy (PN). In addition, an Apriori algorithm-based association rule analysis was performed to identify the core herb combination, thereby further generating useful hypotheses for subsequent drug discovery. A total of 10 databases were searched electronically from inception to July 2021. Randomized clinical trials (RCTs) comparing EAHM with conventional analgesic medication or usual care for managing PN were included. The RCT quality was appraised using RoB 2.0, and the random effects model was used to calculate the effect sizes of the included RCTs. The overall quality of evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation. By analyzing the constituent herb data, the potential association rules of core herb combinations were explored. A total of 67 RCTs involving 5753 patients were included in this systematic review. In a meta-analysis, EAHM monotherapy and combined EAHM and western medicine therapy demonstrated substantially improved sensory nerve conduction velocity, motor nerve conduction velocity, and response rate. Moreover, EAHM significantly improved the incidence rate, pain intensity, Toronto clinical scoring system, and Michigan diabetic neuropathy score. The evidence grade was moderate to low due to the substantial heterogeneity among the studies. Nine association rules were identified by performing the association rule analysis on the extraction data of 156 EAHM herbs. Therefore, the constituents of the herb combinations with consistent association rules were Astragali Radix, Cinnamomi Ramulus, and Spatholobi Calulis. This meta-analysis supports the hypothesis that EAHM monotherapy and combined therapy may be beneficial for PN patients, and follow-up research should be conducted to confirm the precise action target of the core herb.