Loganin prevents CXCL12/CXCR4-regulated neuropathic pain via the NLRP3 inflammasome axis in nerve-injured rats

被引：29

作者：

Cheng, Kuang-, I ^{[1
,2
]}

Chen, Sin-Lan ^{[3
]}

Hsu, Jong-Hau ^{[4
,5
]}

Cheng, Yu-Chi ^{[3
]}

Chang, Yu-Chin ^{[3
]}

Lee, Chien-Hsing ^{[3
,6
]}

Yeh, Jwu-Lai ^{[3
,6
]}

Dai, Zen-Kong ^{[4
,5
]}

Wu, Bin-Nan ^{[3
,6
]}

机构：

[1] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Anesthesiol, Kaohsiung, Taiwan

[2] Kaohsiung Med Univ Hosp, Dept Anesthesiol, Kaohsiung, Taiwan

[3] Kaohsiung Med Univ, Drug Dev & Value Creat Res Ctr, Coll Med, Dept Pharmacol,Grad Inst Med, Kaohsiung, Taiwan

[4] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Pediat, 100 Shih Chuan 1st Rd, Kaohsiung 807, Taiwan

[5] Kaohsiung Med Univ Hosp, Dept Pediat, Div Pediat Cardiol & Pulmonol, Kaohsiung, Taiwan

[6] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung, Taiwan

来源：

PHYTOMEDICINE | 2021年 / 92卷

关键词：

Loganin; Chronic constriction injury; CXCL12/CXCR4; Neuropathic pain; NLRP3; inflammasome; Spinal dorsal horn; PROTEIN; ACTIVATION; MECHANISMS; GLYCOSIDE; SYSTEM; MODEL;

D O I：

10.1016/j.phymed.2021.153734

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Background: Neuropathic pain has been shown to be modulated by the activation of the chemokine C-X-C motif ligand 12 (CXCL12)/chemokine CXC receptor 4 (CXCR4) dependent nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. Loganin, an iridoid glycoside, was proven to prevent neuropathic pain, but its underlying mechanisms related to NLRP3 activation are still unknown. Purpose: This study investigated the underlying mechanisms of loganin's effect on chronic constriction injury (CCI)-induced NLRP3 inflammasome activation in the spinal cord. Methods: Sprague-Dawley rats were randomly divided into four groups: sham, CCI, sham + loganin, and CCI + loganin. Loganin (5 mg/kg/day) was administered intraperitoneally starting the day after surgery. Paw withdrawal threshold (PWT) and latency (PWL) were assessed before CCI and on days 1, 3, 7 and 14 after CCI. Spinal cords were collected for western blots and immunofluorescence studies. Results: Loganin prevented CCI-attenuated PWT and PWL, suggesting improved mechanical allodynia and thermal hyperalgesia. The expression of CXCL12, CXCR4, thioredoxin-interacting protein (TXNIP), NLRP3 inflammasome (NLRP3, ASC, and caspase-1), IL-1 beta, and IL-18 were enhanced on day 7 after CCI, and all were reduced after loganin treatment. Dual immunofluorescence also showed that increased CXCL12, CXCR4, and NLRP3 were colocalized with NeuN (neuronal marker), GFAP (astrocyte marker), and Iba1 (microglial marker) on day 7 in the ipsilateral spinal dorsal horn (SDH). These immunoreactivities were attenuated in loganin-treated rats. Moreover, loganin decreased the assembly of NLRP3/ASC inflammasome after CCI in the ipsilateral SDH. Loganin appears to attenuate CCI-induced neuropathic pain by suppressing CXCL12/CXCR4-mediated NLRP3 inflammasome. Conclusion: Our findings suggest that loganin might be a suitable candidate for managing CCI-provoked neuropathic pain.

引用

页数：11

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