Exploring the Impact of Electroacupuncture on Diabetic Peripheral Neuropathy in Mice through Untargeted Metabolomics Analysis

Objective: Diabetic peripheral neuropathy (DPN) is a common diabetic complication that affects the peripheral nerves, leading to symptoms such as pain, numbness, and tingling in the extremities. Electroacupuncture (EA) is effective in treating DPN, albeit the underlying mechanisms are not well understood. This study employed a metabolomics approach to investigate the metabolic alterations induced by EA therapy for DPN in mice along with the exploration of the mechanisms of EA’s therapeutic effects in DPN treatment. Materials and Methods: DPN was induced in mice with streptozotocin, after which the mice were treated with EA for 2 weeks. To evaluate the neurological function in mice, their sensory and motor nerve conduction velocities were measured, and the responses of mice to mechanical and thermal stimuli were analyzed. Sciatic nerve samples were collected and analyzed using an untargeted metabolomics methodology based on liquid chromatography-mass spectrometry. Results: EA treatment improved peripheral nerve function in DPN mice. The metabolomics analysis revealed 53 potential biomarkers (including L-methionine S-oxide, prostaglandin E1, vanillylmandelic acid, sphinganine, etc.) related to EA treatment. Pathway analysis revealed that changes in these metabolites were mainly related to beta-alanine metabolism, nicotinate and nicotinamide metabolism, taste transduction, phenylalanine, tyrosine, and tryptophan metabolism, vitamin digestion and absorption, ATP-binding cassette transporters, and serotonergic synapses. Conclusions: EA therapy exhibited a significant neuroprotective effects against DPN, which may be mediated by ameliorating metabolic disorders in DPN mice. Thus, EA treatment may be a promising complementary approach for DPN management.