Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats.
OBJECTIVE
Natural compounds obtained from marine organisms have received considerable attention as potential sources of novel drugs for treatment of human inflammatory diseases. Capnellene, isolated from the marine soft coral Capnella imbricate, 4,4,6a-trimethyl-3-methylene-decahydro-cyclopenta[]pentalene-2,3a-diol (GB9) exhibited anti-inflammatory actions on activated macrophages in vitro. Here we have assessed the anti-neuroinflammatory properties of GB9 and its acetylated derivative, acetic acid 3a-hydroxy-4,4,6a-trimethyl-3-methylene-decahydro-cyclopenta[]pentalen-2-yl ester (GB10).


METHODS
Effects of GB9 or GB10 on the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in interferon-gamma (IFN-gamma)-stimulated mouse microglial BV2 cells were measured by Western blot. The in vivo effects of these compounds were examined in the chronic constriction injury (CCI) rat model of neuropathic pain, measuring thermal hyperalgesia, and microglial activation and COX-2 protein in lumbar spinal cord, by immunohistochemistry.


RESULTS
In BV2 cells, GB9 and GB10 inhibited the expression of iNOS and COX-2, stimulated by IFN-gamma. Intrathecal administration of GB9 and GB10 inhibited CCI-induced nociceptive sensitization and thermal hyperalgesia in a dose-dependent manner. Intraperitoneal injection of GB9 inhibited CCI-induced thermal hyperalgesia and also inhibited CCI-induced activation of microglial cells and up-regulation of COX-2 in the dorsal horn of the lumbar spinal cord ipsilateral to the injury.


CONCLUSIONS
Taken together, these data indicate that the marine-derived capnellenes, GB9 and GB10, had anti-neuroinflammatory and anti-nociceptive properties in IFN-gamma-stimulated microglial cells and in neuropathic rats respectively. Therefore, capnellene may serve as a useful lead compound in the search for new therapeutic agents for treatment of neuroinflammatory diseases.
Jean
Yen-Hsuan
YH
Section of Orthopedic Surgery, Pingtung Christian Hospital, Pingtung, Taiwan.
Chen
Wu-Fu
WF
Sung
Chun-Sung
CS
Duh
Chang-Yih
CY
Huang
Shi-Ying
SY
Lin
Chan-Shing
CS
Tai
Ming-Hon
MH
Tzeng
Shun-Fen
SF
Wen
Zhi-Hong
ZH
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D003251:Constriction, Pathologic / Q000150:complications; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy; D007371:Interferon-gamma / Q000494:pharmacology; D008161:Lumbosacral Region; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D015854:Up-Regulation
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D012717:Sesquiterpenes; C546411:delta9(12)-capnellene-8beta,10alpha-diol; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2