Hedysarum polysaccharide alleviates oxidative stress to protect against diabetic peripheral neuropathy via modulation of the keap1/Nrf2 signaling pathway

• Published in: Journal of chemical neuroanatomy 2022-12, Vol.126, p.102182-102182, Article 102182
• Main Authors: He, Liu, Huan, Pengfei, Xu, Jing, Chen, Yanxu, Zhang, Lei, Wang, Jun, Wang, Li, Jin, Zhisheng
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - pharmacology; Antioxidants - therapeutic use; Diabetes Mellitus; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - metabolism; Diabetic peripheral neuropathy; Glucose; Hedysarum polysaccharide; Keap1/Nrf2 pathway; Kelch-Like ECH-Associated Protein 1 - metabolism; Mice; NF-E2-Related Factor 2 - metabolism; Oxidative Stress; Polysaccharides - pharmacology; Polysaccharides - therapeutic use; Signal Transduction
• ISSN: 0891-0618; 1873-6300
• DOI: 10.1016/j.jchemneu.2022.102182

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. •HPS ameliorates DPN through antioxidant mechanisms and by initiating Keap1/Nrf2 signaling, suggesting that HPS is a potential treatment option for DPN.•This study is the first to explore the possible mechanism of HPS treatment for DPN through cell experiments.•The possible mechanism of HPS treatment of diabetic peripheral neuropathy was further elucidated by combining in vitro and in vivo experiments.