Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells

Microglial-mediated neuroinflammation has recently been implicated as one of the important mechanisms responsible for the progression of neurodegenerative diseases. Activated microglia cells produce various neurotoxic factors that are harmful to neurons. Therefore, suppression of the inflammatory re...

Full description

Bibliographic Details
Main Authors: Sandeep Vasant More, Ju-Young Park, Byung-Wook Kim, Hemant Kumar, Hyung-Woo Lim, Seong-Mook Kang, Sushruta Koppula, Sung-Hwa Yoon, Dong-Kug Choi
Format: Article
Language:English
Published: Elsevier 2013-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319303871
_version_ 1811228613430738944
author Sandeep Vasant More
Ju-Young Park
Byung-Wook Kim
Hemant Kumar
Hyung-Woo Lim
Seong-Mook Kang
Sushruta Koppula
Sung-Hwa Yoon
Dong-Kug Choi
author_facet Sandeep Vasant More
Ju-Young Park
Byung-Wook Kim
Hemant Kumar
Hyung-Woo Lim
Seong-Mook Kang
Sushruta Koppula
Sung-Hwa Yoon
Dong-Kug Choi
author_sort Sandeep Vasant More
collection DOAJ
description Microglial-mediated neuroinflammation has recently been implicated as one of the important mechanisms responsible for the progression of neurodegenerative diseases. Activated microglia cells produce various neurotoxic factors that are harmful to neurons. Therefore, suppression of the inflammatory response elicited by activated microglia is considered a potential therapeutic target for neurodegenerative diseases. The cannabinoid (CB) system is widespread in the central nervous system and is very crucial for modulating a spectrum of neurophysiological functions such as pain, appetite, and cognition. In the present study, we synthesized and investigated a novel CB derivative (CD-101) for its ability to suppress lipopolysaccharide (LPS)-mediated activation of BV-2 microglial cells and subsequent release of various inflammatory mediators. CD-101 significantly inhibited the production of inflammatory markers such as nitric oxide, cyclooxygenase-2, and pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. The anti-neuroinflammatory effect of this novel cannabinoid derivative occurred by inhibiting p38MAPK phosphorylation and by decreasing nuclear translocation of p65 subunit of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells. These results suggest that the use of the cannabinoid derivative CD-101 might be a potential therapeutic target against neuroinflammatory disorders. Keywords:: lipopolysaccharide, microglia, neuroinflammation, cannabinoid signaling
first_indexed 2024-04-12T10:00:08Z
format Article
id doaj.art-9703c51b73154e899b042a0c9813829b
institution Directory Open Access Journal
issn 1347-8613
language English
last_indexed 2024-04-12T10:00:08Z
publishDate 2013-01-01
publisher Elsevier
record_format Article
series Journal of Pharmacological Sciences
spelling doaj.art-9703c51b73154e899b042a0c9813829b2022-12-22T03:37:35ZengElsevierJournal of Pharmacological Sciences1347-86132013-01-011212119130Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial CellsSandeep Vasant More0Ju-Young Park1Byung-Wook Kim2Hemant Kumar3Hyung-Woo Lim4Seong-Mook Kang5Sushruta Koppula6Sung-Hwa Yoon7Dong-Kug Choi8Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of KoreaDepartment of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of KoreaDepartment of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of KoreaDepartment of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of KoreaDepartment of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of KoreaDepartment of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of KoreaDepartment of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea; Corresponding author. choidk@kku.ac.krMicroglial-mediated neuroinflammation has recently been implicated as one of the important mechanisms responsible for the progression of neurodegenerative diseases. Activated microglia cells produce various neurotoxic factors that are harmful to neurons. Therefore, suppression of the inflammatory response elicited by activated microglia is considered a potential therapeutic target for neurodegenerative diseases. The cannabinoid (CB) system is widespread in the central nervous system and is very crucial for modulating a spectrum of neurophysiological functions such as pain, appetite, and cognition. In the present study, we synthesized and investigated a novel CB derivative (CD-101) for its ability to suppress lipopolysaccharide (LPS)-mediated activation of BV-2 microglial cells and subsequent release of various inflammatory mediators. CD-101 significantly inhibited the production of inflammatory markers such as nitric oxide, cyclooxygenase-2, and pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. The anti-neuroinflammatory effect of this novel cannabinoid derivative occurred by inhibiting p38MAPK phosphorylation and by decreasing nuclear translocation of p65 subunit of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells. These results suggest that the use of the cannabinoid derivative CD-101 might be a potential therapeutic target against neuroinflammatory disorders. Keywords:: lipopolysaccharide, microglia, neuroinflammation, cannabinoid signalinghttp://www.sciencedirect.com/science/article/pii/S1347861319303871
spellingShingle Sandeep Vasant More
Ju-Young Park
Byung-Wook Kim
Hemant Kumar
Hyung-Woo Lim
Seong-Mook Kang
Sushruta Koppula
Sung-Hwa Yoon
Dong-Kug Choi
Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells
Journal of Pharmacological Sciences
title Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells
title_full Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells
title_fullStr Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells
title_full_unstemmed Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells
title_short Anti-neuroinflammatory Activity of a Novel Cannabinoid Derivative by Inhibiting the NF-κB Signaling Pathway in Lipopolysaccharide-Induced BV-2 Microglial Cells
title_sort anti neuroinflammatory activity of a novel cannabinoid derivative by inhibiting the nf κb signaling pathway in lipopolysaccharide induced bv 2 microglial cells
url http://www.sciencedirect.com/science/article/pii/S1347861319303871
work_keys_str_mv AT sandeepvasantmore antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT juyoungpark antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT byungwookkim antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT hemantkumar antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT hyungwoolim antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT seongmookkang antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT sushrutakoppula antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT sunghwayoon antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells
AT dongkugchoi antineuroinflammatoryactivityofanovelcannabinoidderivativebyinhibitingthenfkbsignalingpathwayinlipopolysaccharideinducedbv2microglialcells