Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms rem...

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Main Authors: Gui-Lin Jin, Sai-Di He, Shao-Mei Lin, Li-Mian Hong, Wan-Qing Chen, Ying Xu, Jian Yang, Su-Ping Li, Chang-Xi Yu
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2018/9347696
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author Gui-Lin Jin
Sai-Di He
Shao-Mei Lin
Li-Mian Hong
Wan-Qing Chen
Ying Xu
Jian Yang
Su-Ping Li
Chang-Xi Yu
author_facet Gui-Lin Jin
Sai-Di He
Shao-Mei Lin
Li-Mian Hong
Wan-Qing Chen
Ying Xu
Jian Yang
Su-Ping Li
Chang-Xi Yu
author_sort Gui-Lin Jin
collection DOAJ
description Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI) neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR) were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.
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spelling doaj-art-06eda0ff378b4662a067426d5eb1666f2025-02-03T01:11:17ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/93476969347696Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic PainGui-Lin Jin0Sai-Di He1Shao-Mei Lin2Li-Mian Hong3Wan-Qing Chen4Ying Xu5Jian Yang6Su-Ping Li7Chang-Xi Yu8Department of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDepartment of Pharmacology and College of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350004, ChinaDespite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI) neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR) were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.http://dx.doi.org/10.1155/2018/9347696
spellingShingle Gui-Lin Jin
Sai-Di He
Shao-Mei Lin
Li-Mian Hong
Wan-Qing Chen
Ying Xu
Jian Yang
Su-Ping Li
Chang-Xi Yu
Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain
Neural Plasticity
title Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain
title_full Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain
title_fullStr Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain
title_full_unstemmed Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain
title_short Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain
title_sort koumine attenuates neuroglia activation and inflammatory response to neuropathic pain
url http://dx.doi.org/10.1155/2018/9347696
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