Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model

Abstract

Qing Sun, Chao Wang, Bin Yan, Xiaohu Shi, Yue Shi, Ling Qu, Xiaochun Liang Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People’s Republic of ChinaCorrespondence: Xiaochun LiangPeking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Jinmaitong (JMT) has been used to prevent and treat diabetic peripheral neuropathy (DPN) for decades. The present study aimed to elucidate the effects of JMT on thioredoxin-interacting protein (TXNIP) and Nod-like receptor protein 3 (NLRP3) inflammasome activation in the streptozotocin (STZ)-induced rat model.Methods: The diabetic rat model was induced by a single intraperitoneal injection of 55 mg/kg STZ. The rats were divided into 3 groups (n = 8–10 per group): diabetic control, JMT (0.876 g/kg/d), and alpha-lipoic acid (ALA; 100 mg/kg/d). Body weight and blood glucose levels were monitored every 4 weeks for 12 weeks. Mechanical allodynia and myelin sheath injury of sciatic nerves (SNs) were assessed using the mechanical withdrawal threshold (MWT) test and Luxol fast blue staining. Serum T-superoxide dismutase (T-SOD), malondialdehyde (MDA), and catalase (CAT) levels were measured using commercially available kits. TXNIP/NLRP3 inflammasome proteins, including TXNIP, NLRP3, pro-caspase-1, and cleaved -caspase-1, and the downstream protein interleukin (IL)-1β, were measured using immunohistochemistry and Western blot. Gasdermin D (GSDMDC1) protein expression was analyzed using Western blot, and serum IL-1β and IL-18 levels were detected using ELISA.Results: JMT did not significantly affect body weight or level of fasting blood glucose but improved mechanical allodynia and myelin sheath injury of SNs at 12 weeks following treatment. Moreover, JMT increased serum levels of the anti-oxidative enzymes CAT and T-SOD, and decreased MDA levels. Both JMT and ALA decreased expression of TXNIP, NLRP3, and cleaved-caspase-1 protein. JMT and ALA also decreased IL-1β, IL-18, and GSDMDC1 protein expression.Conclusion: The current study demonstrated that TXNIP/NLRP3 inflammasome activation is involved in the molecular mechanisms underlying JMT’s protective effects in the STZ-induced diabetic rat model, which provides novel evidence to support the future clinical use of JMT.Keywords: Jinmaitong, diabetic peripheral neuropathy, TXNIP/NLRP3 inflammasome, diabetic rat model, alpha lipoic acid

Keywords

• Jinmaitong
• diabetic peripheral neuropathy
• TXNIP/NLRP3 inflammasome
• diabetic rat model
• alpha lipoic acid