Compound XiongShao Capsule ameliorates streptozotocin-induced diabetic peripheral neuropathy in rats via inhibiting apoptosis, oxidative - nitrosative stress and advanced glycation end products.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound XiongShao Capsule (CXSC), a traditional herb formula, has been approved for using to treat diabetic peripheral neuropathy (DPN) by the Shanghai Food and Drug Administration, with significant efficacy in clinic.

AIM OF THE STUDY: This study aimed to investigate the multidimensional pharmacological mechanisms and synergism of CXSC against DPN in rats.

METHODS: The quality analysis of CXSC was performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography. Rats with DPNinduced by streptozotocin/high-fat diet for 4 weeks were treated with CXSC at three doses (1.2 g/kg, 0.36 g/kg, and 0.12 g/kg), or epalrestat (15 mg/kg) daily for 8 weeks continuously. During the treatment period, body weight, serum glucose levels, and nerve function, including nerve conduction velocity (NCV), and mechanical and thermal hyperalgesia were tested and assessed every 4 weeks. In the 13th week, the histopathological examination in the sciatic nerve was performed using a transmission electron microscope. The expression of apoptosis-related proteins of BAX, BCL2, and caspase-3 in the sciatic nerve was examined using hematoxylin and eosin staining. The serum levels of advanced glycation end products (AGEs), oxidative-nitrosative stress biomarkers of superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured using a rat-specific ELISA kit.

RESULTS: CXSC had no significant effect on body weight or serum glucose levels (P > 0.05), but it significantly improved mechanical hyperalgesia (F5,36  = 18.24, P < 0.0001), thermal hyperalgesia (F5,36  = 8.45, P < 0.0001), and NCV (motor NCV: F5,36  = 7.644, P < 0.0001, sensory NCV: F5,36  = 12.83, P < 0.0001). Besides, it maintained myelin and axonal structure integrity, downregulated the expression of apoptosis-related proteins in the sciatic nerve tissue, reduced AGEs and NOS levels, and enhanced antioxidant enzyme SOD activities in the serum.

CONCLUSION: CXSC exerted neuroprotective effects against rats with DPN through multidimensional pharmacological mechanisms including antiapoptotic activity in the sciatic nerve and downregulation of the level of serum NOS, SOD and AGEs.