title: Protective effects of Garcinol against neuropathic pain - Evidence from in vivo and in vitro studies.
abstract: Neuroinflammatory processes have a vital role in the pathogenesis of neuropathic pain. Garcinol, harvested from Garcinia indica, is known to exert potent anti-inflammatory properties. Recent studies have indicated that Garcinol may inhibit activation of nuclear factor-κB (NF-κB) by inhibiting NF-κB/p65 acetylation. These findings prompted us to evaluate the protective effects of Garcinol in the lumbar fifth spinal nerve ligation (SNL)-induced rat model of neuropathic pain and Lipopolysaccharide(LPS)-stimulated primary cultured microglia. In the present study, we found that intrathecal administration of Garcinol significantly attenuated SNL-induced nociceptive behaviors. Garcinol suppressed microglial activation as well as the expression of interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS)/nitric oxide (NO), and cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) in the spinal cord of SNL rats. It also reduced the nuclear translocation of NF-κB by decreasing acetyl-p65 protein expression. Similarly, in the in vitro study, Garcinol decreased the production of NO/iNOS, PGE2/COX-2, and proinflammatory cytokines in LPS-exposed microglia. Likewise, Garcinol inhibited the NF-κB signaling pathway by downregulating acetyl-p65 levels in LPS-challenged microglia. Our findings suggest that Garcinol may have protective effects against neuropathic pain that are associated with the inhibition of neuroinflammation in microglia. Therefore, Garcinol could be a promising agent in the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210002, PR China.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210002, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Nanjing General Hospital, Nanjing 210002, PR China.
authors.forename: Chun-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210002, PR China; Department of Anesthesiology, Nanjing General Hospital, Nanjing 210002, PR China.
authors.forename: Qing-Zhen
authors.initials: QZ
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210002, PR China.
authors.forename: Jia-Wen
authors.initials: JW
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210002, PR China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Qian
authors.affiliation: Department of Anesthesiology, Nanjing General Hospital, Nanjing 210002, PR China. Electronic address: weiyanlee65@163.com.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210002, PR China. Electronic address: yanning_qian@163.com.
authors.forename: Yan-Ning
authors.initials: YN
authors.lastname: Qian
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries; D013729:Terpenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013729:Terpenes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C054597:garcinol
keywords: Acetylation; Garcinol; Microglia; NF-κB; Neuroinflammation; Neuropathic pain