Oxymatrine alleviates symptoms in high-fat diet and STZ-induced SD rats with painful diabetic neuropathy by reducing inflammation and oxidative stress.

INTRODUCTION: Painful Diabetic Neuropathy (PDN) is a severe complication of diabetes, featured by intricate aetiology and multiple side effects of current therapeutic approaches. In recent years, the glymphatic system has attracted increasing attention for its role in PDN. This study investigated the regulatory effects and underlying mechanisms of Oxymatrine (OMT) on the spinal glymphatic system in PDN rat models, aiming to provide novel therapeutic insights for PDN. METHODS: The PDN rat model was established by high-fat and high-sugar diet combined with streptozotocin (STZ) induction. The 50% paw withdrawal threshold (50% PWT) was measured by Von Frey filaments to evaluate neuropathic pain. Spinal glymphatic system function was observed via Magnetic Resonance Imaging (MRI). Western blotting was used to detect the expression of Aquaporin-4 (AQP-4), Metalloproteinase-9 (MMP-9), NF-κB p65, p-p65, Nrf2 and HO-1. Immunofluorescence was performed to assess AQP4 polarization and nuclear expression of p65. In addition, the levels of oxidative stress indicators (GSH, SOD, MDA) and inflammatory factors (IL-1β, IL-6, TNF-α) were determined. RESULTS: OMT treatment significantly alleviated PDN-related symptoms and improved the detected indicators. It effectively reduced oxidative stress and inflammatory levels, upregulated the expression of Nrf2 and HO-1, downregulated MMP-9 expression, repaired AQP-4 polarisation, and restored the function of the spinal glymphatic system in PDN rats. DISCUSSION: This study provides a theoretical foundation for the potential application of OMT as a therapeutic agent for PDN, and its multi-target regulatory mechanism offers new directions for PDN treatment.