Naringin Attenuates Diabetic Neuropathic Pain and Modulates TRPV1-Related Ca2+ Dysregulation and MAPK/NF-ΚB Signaling

Background/Objectives: Diabetic neuropathic pain (DNP) is a common complication of diabetes characterized by sensory abnormalities, including mechanical allodynia and thermal hyperalgesia. This study aimed to investigate the effects of naringin on experimental DNP and evaluate its association with dorsal root ganglion (DRG) neuronal injury, TRPV1-related calcium imbalance, and inflammatory signaling.

Methods

Primary rat DRG neurons were exposed to high-glucose/high-free-fatty-acid (HGHF) conditions (50 mM glucose and 0.60 mM free fatty acids) and treated with naringin (40 or 80 μM). Cell viability, apoptosis, intracellular Ca2+ levels, gene/protein expression, and signaling changes were assessed using CCK-8 assay, Annexin V-FITC/PI flow cytometry, Fluo-4 AM imaging, qRT-PCR, and Western blotting. Male Sprague–Dawley rats were fed a high-fat/high-sucrose diet for 4 weeks, injected with streptozotocin (35 mg kg−1), and treated with naringin (50 mg kg−1 day−1) by gavage for 2 weeks.