title: Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory and analgesic effects of the natural marine compound lemnalol from Formosan soft coral Lemnalia cervicorni.
abstract: Lemnalol (8-isopropyl-5-methyl-4-methylene-decahydro-1,5-cyclo-naphthalen-3-ol) is a natural compound isolated from the marine soft coral Lemnalia cervicorni. In the present study, the anti-inflammatory and anti-nociceptive properties of lemnalol were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and carrageenan-injected rats, respectively. Our results demonstrate that lemnalol significantly inhibited the expression of the pro-inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-stimulated RAW 264.7 cells. An in vivo inflammation model was induced by intraplantar injection of carrageenan into rat hind paws. An intramuscular injection of lemnalol (15 mg/kg) 10 min before carrageenan injection resulted in significant inhibition of carrageenan-induced rat paw edema and thermal hyperalgesia behavior. Western blot experiments revealed that the carrageenan-induced expression of iNOS and COX-2 in paw tissue was significantly down-regulated by lemnalol. Moreover, post-intrathecal injection of lemnalol produced a dose-dependent anti-nociceptive effect in carrageenan-injected rats (1 and 5 microg). The present results indicate that the marine-derived compound lemnalol had anti-inflammatory and analgesic effects in LPS-stimulated RAW 264.7 cells and carrageenan-injected rats, respectively. In addition, inhibition of elevated iNOS and COX-2 protein expression as well as neurophil infiltration of carrageenan-injected paws may be involved in the beneficial effects of lemnalol.
authors.affiliation: Section of Orthopedic Surgery, Pingtung Christian Hospital, #60 Da-Lan Road, Pingtung 900, Taiwan.
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Jean
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Duh
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.forename: Chi-Hsin
authors.initials: CH
authors.lastname: Hsu
authors.forename: Chan-Shing
authors.initials: CS
authors.lastname: Lin
authors.forename: Chun-Sung
authors.initials: CS
authors.lastname: Sung
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Chen
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D037421:Anthozoa / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002351:Carrageenan; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007278:Injections, Spinal; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; C038776:lemnalol; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2