Diosgenin alleviates neuropathic pain based on the enhancement of autophagy and promotion of M2 polarization

IF 4.8 2区 医学 Q2 IMMUNOLOGY
Shuli Man , Yaxue Zhou , Xinghao Zhang , Xiaoqin Tang , Lu Xie , Long Ma , Wenyuan Gao
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Abstract

Neuropathic pain has serious impacts on the quality of people's life. Diosgenin extracted from yams has shown significant potential in the treatment of nervous system diseases. To investigate the potential mechanism of diosgenin fighting against neuropathic pain, we established a chronic compression injury (CCI) model. The pain-related behaviors were determined by Von Frey, hot plate, and sciatic nerve index test. As a result, diosgenin significantly lowered the pain threshold, improved the sciatic nerve index, and decreased the damage of sciatic nerve structure in CCI model mice. It increased the protein levels of LC3-II and Beclin-1, the number of the lysosomes, decreased the protein level of P62 and the number of the autophagosomes, and therefore activated autophagy. Diosgenin also inhibited the proliferation of microglia cells and the translocation of NF-κB p65, while promoting promoted M2 polarization of microglia cells. Autophagy inhibitor like chloroquine inhibited the M2 polarization of microglia cells, and reversed the therapeutic effect of diosgenin. All in all, diosgenin alleviated neuropathic pain in CCI mice based on the enhancement of autophagy and the promotion of M2 polarization.
薯蓣皂苷元通过增强自噬和促进M2极化来减轻神经性疼痛
神经性疼痛严重影响人们的生活质量。从山药中提取的薯蓣皂苷元在神经系统疾病的治疗中显示出巨大的潜力。为了探讨薯蓣皂苷元抗神经性疼痛的可能机制,我们建立了慢性压迫性损伤(CCI)模型。采用Von Frey法、热板法、坐骨神经指数法测定疼痛相关行为。结果表明,薯蓣皂苷元能显著降低CCI模型小鼠的痛觉阈值,改善坐骨神经指数,减轻坐骨神经结构损伤。升高LC3-II和Beclin-1蛋白水平和溶酶体数量,降低P62蛋白水平和自噬体数量,从而激活自噬。薯蓣皂苷元还能抑制小胶质细胞的增殖和NF-κB p65的易位,同时促进小胶质细胞的M2极化。自噬抑制剂如氯喹抑制小胶质细胞的M2极化,逆转薯蓣皂苷元的治疗作用。综上所述,薯蓣皂苷元对CCI小鼠神经性疼痛的缓解是基于增强自噬和促进M2极化。
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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