首页|Salidroside alleviates diabetic neuropathic pain through regulation of the AMPK-NLRP3 inflammasome axis

Salidroside alleviates diabetic neuropathic pain through regulation of the AMPK-NLRP3 inflammasome axis

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  • NSTL
  • Elsevier
High glucose (HG)-induced nucleotide-binding and oligomerization (NACHT) domain, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome activation leads to diabetic neuropathic pain. We recently showed that salidroside could suppress NLRP3 inflammasome activation in hepatocytes exposed to HG. The aim of this study was to evaluate the analgesic effect of salidroside on diabetic rats and to explore its underlying mechanisms. Rat models with diabetic neuropathic pain were induced by high-fat diet feeding combined with low dose streptozotocin injections. Doses of salidroside at 50 and 100 mg.kg(-1).day(-1) were administered by gavage to diabetic rats for 6 weeks. Mechanical allodynia test, thermal hyperalgesia test and biochemical analysis were performed to evaluate therapeutic effects. Primary dorsal root ganglion (DRG) cells exposed to HG at 45 mM were used to further study the effects of salidroside on the AMP-activated protein kinase (AMPK)-NLRP3 inflammasome axis and insulin sensitivity in vitro. Salidroside administration improved hyperglycemia, ameliorated insulin resistance, and alleviated neuropathic pain in diabetic rats. Moreover, salidroside induced AMPK activation and suppressed NLRP3 inflammasome activation in the DRGs of diabetic rats. In addition, salidroside treatment relieved oxidative stress, improved insulin sensitivity and regulated the AMPK-NLRP3 inflammasome axis in HG-treated DRGs in vitro. Furthermore, AMPK inhibition in vivo or AMPK silencing in vitro abolished the beneficial effects of salidroside on diabetic neuropathic pain. Together, these results indicate that salidroside alleviates diabetic neuropathic pain through its regulation of the AMPK-NLRP3 inflammasome axis in DRGs.

Diabetes mellitusNeuropathic painSalidrosideAMP-activated protein kinaseNLRP3 inflammasome

Zheng, Tao、Wang, Qibin、Bian, Fang、Zhao, Yan、Ma, Weidong、Zhang, Yonghong、Lu, Wei、Lei, Pan、Zhang, Lulu、Hao, Xincai、Chen, Li

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Hubei Univ Med, Inst Wudang Tradit Chinese Med, Taihe Hosp, Shiyan, Hubei, Peoples R China

Hubei Univ Med, Taihe Hosp, Dept Pharm, Shiyan, Hubei, Peoples R China

Hubei Univ Arts & Sci, Xiangyang Cent Hosp, Dept Pharm, Affiliated Hosp, Xiangyang, Hubei, Peoples

Hubei Univ Med, Taihe Hosp, Dept Hematol, Shiyan, Hubei, Peoples R China

Hubei Univ Med, Hubei Key Lab Wudang Local Chinese Med Res, Shiyan, Hubei, Peoples R China

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2021

10.1016/j.taap.2021.115468

Toxicology and Applied Pharmacology

Toxicology and Applied Pharmacology

SCI
ISSN：0041-008X
年,卷(期)：2021.416
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