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

Abstract

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 (F_5,36 = 18.24, P < 0.0001), thermal hyperalgesia (F_5,36 = 8.45, P < 0.0001), and NCV (motor NCV: F_5,36 = 7.644, P < 0.0001, sensory NCV: F_5,36 = 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.

Keywords: Advanced glycation end products; BAX/BCL2–caspase-3; Compound XiongShao Capsule; Diabetic peripheral neuropathy; Oxidative - nitrosative stress.