Discovering the efficacy and mechanism of Chinese herbal medicine for distal symmetric polyneuropathy via integrating meta-analysis and network pharmacology analysis

Objective Chinese herbal medicine(CHM)has been commonly used in Distal Symmetric Polyneuropathy(DSPN)treatment with satisfactory clinical effects,but the underlying pharmacological mechanism of CHM on DSPN remains unclear.We aimed to identify frequently used clinically effective CHM and its potential pharmacological mechanisms for DSPN by conducting meta-analysis and network pharmacology analysis.Methods We searched both Chinese and English databases from March 1990 to October 2022.Studies that met the inclusion criteria were selected for meta-analysis.After extracting the relevant data,we performed meta-analysis and frequency analysis.The active compounds and predicted targets of high-frequency herbs and DSPN-related targets were extracted from public databases.Then we conducted network construction,Gene Ontology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to discover the potential pharmacological mechanisms.Results Sixteen articles were selected for meta-analysis,and nine high-frequency CHMs were identified,including Radix Astragali seu Hedysari,Rhizoma Ligustici,Caulis Spatholobi,Radix Salviae Miltiorrhizae,Radix Paeoniae Alba,Flos Carthami,Radix Notoginseng,Radix Rehmanniae Recens,Rhizoma Corydalis.Fourteen hub targets including STAT3,CTNNB1,MAPK14,SRC,AKT1,TP53,EGFR,JUN,RELA,MAPK1,FOS,CCND1,HSP90AA1,MYC,and ten active compounds including Quercetin,Kaempferol,Luteolin,Apigenin,beta-sitosterol,Stigmasterol,Caffeic Acid,Aeginetic Acid,Vanillin,and Lauric Acid were identified by network analysis.Enrichment analysis showed that the biological process of hub targets included transcriptional regulation,cell proliferation,redox processes,apoptosis processes,ERK1 and ERK2 cascades,hypoxia reactions,MAPK cascades,and inflammatory responses.The main signalling pathways included HIF,TNF,and PI3K-AKT pathways.Conclusion Nine herbs were involved in the clinical therapeutic effect of CHM on DSPN treatment,and they may exert an anti-DSPN effect by regulating cell proliferation,apoptosis,and redox processes.

Physical Exercise as Treatment for Type 2 Diabetes Distal Symmetric Polyneuropathy: A Systematic Review of Randomized and Controlled Studies

Pharmaceuticals targeting the pathogenesis of diabetic distal symmetric polyneuropathy have all failed in clinical trials, limiting recourse to palliative treatments. The American Diabetes Association regards the effectiveness of glycemic control and lifestyle modification therapies on diabetic neuropathies as inconclusive. The objective of this research was to determine if and how physical exercise influences distal symmetric polyneuropathic severity in type 2 diabetes patients. Embase, MEDLINE, and Google Scholar were searched to collect randomized and controlled studies published between January 1, 2012 and April 20, 2020. Titles had to mention diabetes, physical exercise of any type or lifestyle interventions in general, and neuropathy. Abstracts had to indicate satisfaction of PICOS criteria, whereas full-text reviews had to be fully confirmatory. Extracted data was thematically synthesized based primarily on relationships between exercise interventions and effects on distal symmetric polyneuropathic severity outcomes in type 2 diabetes patients. Qualitative analysis scoring criteria objectively mirrored PICO except for the bias and limitation score component, which assessed common markers of validity for randomized trials (as specified in the PRISMA statement). Database searches yielded 379 unique records, 15 of which passed eligibility screening. Thematic synthesis supported exercise as an ameliorative treatment of type 2 diabetes distal symmetric polyneuropathy through improved Michigan Diabetic Neuropathy Scores and increased sural sensory nerve conduction velocity, though efficacy may be limited by neuropathic severity. This is the first systematic review to acquire these results, and to do so within the context of neuropathic severity. This review protocol is registered on PROSPERO (CRD42020181211) at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020181211