Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Center of Pharmacological Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, 200025, China.
J Ethnopharmacol. 2021 Mar 25;268:113560. doi: 10.1016/j.jep.2020.113560. Epub 2020 Nov 5.
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.
This study aimed to investigate the multidimensional pharmacological mechanisms and synergism of CXSC against DPN in rats.
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.
CXSC had no significant effect on body weight or serum glucose levels (P > 0.05), but it significantly improved mechanical hyperalgesia (F = 18.24, P < 0.0001), thermal hyperalgesia (F = 8.45, P < 0.0001), and NCV (motor NCV: F = 7.644, P < 0.0001, sensory NCV: F = 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.
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.
熊绍胶囊（CXSC）是一种传统的草药配方，已被上海市食品药品监督管理局批准用于治疗糖尿病周围神经病变（DPN），在临床上有显著疗效。
本研究旨在探讨 CXSC 对糖尿病大鼠多维度的药理机制及协同作用。
采用高效液相色谱法（HPLC）和薄层色谱法对 CXSC 进行质量分析。用链脲佐菌素/高脂饮食诱导大鼠 4 周，建立 DPN 模型，连续 8 周给予 CXSC 三个剂量（1.2g/kg、0.36g/kg 和 0.12g/kg）或依帕司他（15mg/kg）治疗。在治疗期间，每 4 周测试和评估一次体重、血清葡萄糖水平以及神经功能，包括神经传导速度（NCV）和机械性及热痛觉过敏。在第 13 周，使用透射电子显微镜对坐骨神经进行组织病理学检查。采用苏木精-伊红染色法检测坐骨神经中凋亡相关蛋白 BAX、BCL2 和 caspase-3 的表达。采用大鼠特异性 ELISA 试剂盒测定血清中晚期糖基化终产物（AGEs）、超氧化物歧化酶（SOD）和一氧化氮合酶（NOS）的氧化-硝化应激生物标志物的水平。
CXSC 对体重或血清葡萄糖水平无显著影响（P>0.05），但能显著改善机械性痛觉过敏（F=18.24，P<0.0001）、热痛觉过敏（F=8.45，P<0.0001）和 NCV（运动 NCV：F=7.644，P<0.0001；感觉 NCV：F=12.83，P<0.0001）。此外，它还能维持髓鞘和轴突结构的完整性，下调坐骨神经组织中凋亡相关蛋白的表达，降低血清 AGEs 和 NOS 水平，并增强血清抗氧化酶 SOD 的活性。
CXSC 通过多维度的药理机制发挥神经保护作用，包括坐骨神经的抗凋亡活性以及降低血清 NOS、SOD 和 AGEs 水平，从而对 DPN 大鼠产生治疗作用。
