The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550005, China; Gansu University of Chinese Medicine, Lanzhou 730000, China.
Department of Diagnostics of Traditional Chinese Medicine, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Gansu University of Chinese Medicine, Lanzhou 730000, China.
J Chem Neuroanat. 2022 Dec;126:102182. doi: 10.1016/j.jchemneu.2022.102182. Epub 2022 Nov 2.
Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus. Oxidative stress is implicated in DPN progression, suggesting that antioxidant therapy could be a viable anti-DPN method. Hedysarum polysaccharide (HPS) is an active component of Radix Hedysari, a plant that has been widely used as food and a herb for treating multiple diseases. Here, we evaluated the mechanisms of action of anti-DPN effects of HPS in genetically obese (ob/ob) mice. Schwann cells (SCs) were exposed to glucose (100 mM) in vitro and then treated with HPS at concentrations of 30, 60, 120, and 240 mg/L. Notably, HPS significantly inhibited high glucose-mediated cytotoxicity and oxidative stress by reducing malondialdehyde (MDA) levels and upregulating the expression of antioxidant enzymes (γ-glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione reductase (GR)) in SCs. Moreover, HPS increased the expression of nerve growth factor, stimulated Nrf2 signaling, and decreased Keap1 expression levels. Analysis of DPN mice models gavaged with HPS at 50, 100, and 200 mg/kg/d or lipoic acid (LA) at 30 mg/kg/d (positive control) for 8 weeks revealed that HPS markedly increased motor nerve conduction velocity (MNCV), shortened thermal withdrawal latency (TWL), and inhibited oxidative stress in serum and sciatic nerves of DPN mice models. Mechanistically, HPS suppressed Keap1 signaling and enhanced Nrf2 signaling in sciatic nerves. These findings imply that HPS ameliorates DPN via antioxidant mechanisms and by activating Keap1/Nrf2 signaling, suggesting that HPS is a potential treatment option for DPN.
糖尿病周围神经病变（DPN）是糖尿病的一种慢性并发症。氧化应激与 DPN 的进展有关，这表明抗氧化治疗可能是一种可行的抗 DPN 方法。黄耆多糖（HPS）是一种植物的活性成分，该植物已被广泛用作食物和治疗多种疾病的草药。在这里，我们评估了 HPS 对遗传性肥胖（ob/ob）小鼠抗 DPN 作用的作用机制。体外将雪旺细胞（SCs）暴露于葡萄糖（100mM）中，然后用浓度为 30、60、120 和 240mg/L 的 HPS 处理。值得注意的是，HPS 通过降低丙二醛（MDA）水平和上调抗氧化酶（γ-谷氨酰半胱氨酸连接酶催化亚基（GCLC）和谷胱甘肽还原酶（GR）的表达）显著抑制高葡萄糖介导的细胞毒性和氧化应激。此外，HPS 增加了神经生长因子的表达，刺激了 Nrf2 信号通路，并降低了 Keap1 的表达水平。分析用 HPS 以 50、100 和 200mg/kg/d 或硫辛酸（LA）以 30mg/kg/d（阳性对照）灌胃 8 周的 DPN 小鼠模型表明，HPS 显著增加了运动神经传导速度（MNCV），缩短了热撤退潜伏期（TWL），并抑制了 DPN 小鼠模型血清和坐骨神经中的氧化应激。在机制上，HPS 抑制了坐骨神经中的 Keap1 信号通路并增强了 Nrf2 信号通路。这些发现表明，HPS 通过抗氧化机制和激活 Keap1/Nrf2 信号通路来改善 DPN，表明 HPS 是治疗 DPN 的一种潜在选择。
