Tags

Type your tag names separated by a space and hit enter

Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats.
Front Pharmacol. 2018; 9:989.FP

Abstract

Koumine, an indole alkaloid, is a major bioactive component of Gelsemium elegans. Previous studies have demonstrated that koumine has noticeable anti-inflammatory and analgesic effects in inflammatory and neuropathic pain (NP) models, but the mechanisms involved are not well understood. This study was designed to explore the analgesic effect of koumine on chronic constriction injury (CCI)-induced NP in rats and the underlying mechanisms, including astrocyte autophagy and apoptosis in the spinal cord. Rats with CCI-induced NP were used to evaluate the analgesic and anti-inflammatory effects of koumine. Lipopolysaccharide (LPS)-induced inflammation in rat primary astrocytes was also used to evaluate the anti-inflammatory effect of koumine. We found that repeated treatment with koumine significantly reduced and inhibited CCI-evoked astrocyte activation as well as the levels of pro-inflammatory cytokines. Meanwhile, we found that koumine promoted autophagy in the spinal cord of CCI rats, as reflected by decreases in the LC3-II/I ratio and P62 expression. Double immunofluorescence staining showed a high level of colocalization between LC3 and GFAP-positive glia cells, which could be decreased by koumine. Intrathecal injection of an autophagy inhibitor (chloroquine) reversed the analgesic effect of koumine, as well as the inhibitory effect of koumine on astrocyte activation in the spinal cord. In addition, TUNEL staining suggested that CCI-induced apoptosis was inhibited by koumine, and this inhibition could be abolished by chloroquine. Western blot analysis revealed that koumine significantly increased the level of Bcl-xl while inhibiting Bax expression and decreasing cleaved caspase-3. In addition, we found that koumine could decrease astrocyte-mediated neuroinflammation and enhance autophagy in primary cultured astrocytes. These results suggest that the analgesic effects of koumine on CCI-induced NP may involve inhibition of astrocyte activation and pro-inflammatory cytokine release, which may relate to the promotion of astrocyte autophagy and the inhibition for apoptosis in the spinal cord.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China. Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China.Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China.Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China.Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China.Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China. Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China.Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China. Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30214411

Citation

Jin, Gui-Lin, et al. "Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats." Frontiers in Pharmacology, vol. 9, 2018, p. 989.
Jin GL, Yue RC, He SD, et al. Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats. Front Pharmacol. 2018;9:989.
Jin, G. L., Yue, R. C., He, S. D., Hong, L. M., Xu, Y., & Yu, C. X. (2018). Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats. Frontiers in Pharmacology, 9, 989. https://doi.org/10.3389/fphar.2018.00989
Jin GL, et al. Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats. Front Pharmacol. 2018;9:989. PubMed PMID: 30214411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats. AU - Jin,Gui-Lin, AU - Yue,Rong-Cai, AU - He,Sai-di, AU - Hong,Li-Mian, AU - Xu,Ying, AU - Yu,Chang-Xi, Y1 - 2018/08/30/ PY - 2018/05/28/received PY - 2018/08/10/accepted PY - 2018/9/15/entrez PY - 2018/9/15/pubmed PY - 2018/9/15/medline KW - apoptosis KW - astrocyte KW - autophagy KW - koumine KW - neuropathic pain KW - rats SP - 989 EP - 989 JF - Frontiers in pharmacology JO - Front Pharmacol VL - 9 N2 - Koumine, an indole alkaloid, is a major bioactive component of Gelsemium elegans. Previous studies have demonstrated that koumine has noticeable anti-inflammatory and analgesic effects in inflammatory and neuropathic pain (NP) models, but the mechanisms involved are not well understood. This study was designed to explore the analgesic effect of koumine on chronic constriction injury (CCI)-induced NP in rats and the underlying mechanisms, including astrocyte autophagy and apoptosis in the spinal cord. Rats with CCI-induced NP were used to evaluate the analgesic and anti-inflammatory effects of koumine. Lipopolysaccharide (LPS)-induced inflammation in rat primary astrocytes was also used to evaluate the anti-inflammatory effect of koumine. We found that repeated treatment with koumine significantly reduced and inhibited CCI-evoked astrocyte activation as well as the levels of pro-inflammatory cytokines. Meanwhile, we found that koumine promoted autophagy in the spinal cord of CCI rats, as reflected by decreases in the LC3-II/I ratio and P62 expression. Double immunofluorescence staining showed a high level of colocalization between LC3 and GFAP-positive glia cells, which could be decreased by koumine. Intrathecal injection of an autophagy inhibitor (chloroquine) reversed the analgesic effect of koumine, as well as the inhibitory effect of koumine on astrocyte activation in the spinal cord. In addition, TUNEL staining suggested that CCI-induced apoptosis was inhibited by koumine, and this inhibition could be abolished by chloroquine. Western blot analysis revealed that koumine significantly increased the level of Bcl-xl while inhibiting Bax expression and decreasing cleaved caspase-3. In addition, we found that koumine could decrease astrocyte-mediated neuroinflammation and enhance autophagy in primary cultured astrocytes. These results suggest that the analgesic effects of koumine on CCI-induced NP may involve inhibition of astrocyte activation and pro-inflammatory cytokine release, which may relate to the promotion of astrocyte autophagy and the inhibition for apoptosis in the spinal cord. SN - 1663-9812 UR - https://www.unboundmedicine.com/medline/citation/30214411/Koumine_Decreases_Astrocyte_Mediated_Neuroinflammation_and_Enhances_Autophagy_Contributing_to_Neuropathic_Pain_From_Chronic_Constriction_Injury_in_Rats_ L2 - https://doi.org/10.3389/fphar.2018.00989 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.