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, we focused to determine whether lemnalol has in vivo antinociceptive and anti-inflammatory effects on carrageenan-induced rat paw edema and the hyperalgesia model using the thermal hyperalgesia test, paw edema assay, and histological examination. Furthermore, we also explored the possible cellular mechanisms of lemnalol on carrageenan-induced inflammatory responses by immunohistochemistry. The present results show that both systemic and central administration of lemnalol significantly inhibits carrageenan-evoked thermal hyperalgesia behavior. Moreover, intramuscular injection of lemnalol also significantly decreases paw edema and improves the inflammatory status of the tissues with reduced neutrophil infiltration. From behavioral and immunohistological observations, we found that lemnalol exerts its anti-inflammatory and analgesic effects on carrageenan-induced inflammatory responses; the cellular mechanisms of these effects involved the inhibition of elevated inflammatory mediators, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial cell growth factor (VEGF), tumor necrosis factor-£\ (TNF-£\), and deletion of phosphatase and tensin homologues on chromosome 10 (PTEN).
Since 1962, the carrageenan-induced rat model of inflammation has been widely used as an animal model to investigate inflammatory mechanisms and anti-inflammatory activity of drugs and has been fully characterized. However, the use of rats as an animal model has certain limitations such as those associated with breeding, economy, efficiency, and higher dosage. Recently, many studies have demonstrated zebrafish (Danio rerio) to be a valuable animal model for the investigation of bioactive compounds and molecular mechanisms of various diseases. In the present study, we attempted to establish an inflammatory animal model in zebrafish. Our research results showed that intraperitoneal (i.p.) administration of carrageenan significantly increased body edema and caused death of zebrafish resulting in a decrease in the cumulative survival rate. These effects were significantly inhibited by i.p. administration of methylprednisolone. Immunohistochemical observations revealed i.p. carrageenan-induced upregulation of iNOS, heat shock protein 25 (Hsp25), heat shock protein 90 (Hsp90), and PTEN; however, heat shock protein 70 (Hsp70) was observed to be downregulated. The present study provides a new in vivo inflammatory model for the screening of small volumes of drugs or compounds.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0825108-060451 |
| Date | 25 August 2008 |
| Creators | Huang, Shi-Ying |
| Contributors | Yen-Hsuan Jean, Chan-Shing Lin, Zhi-Hong Wen, Wu-Fu Chen |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0825108-060451 |
| Rights | not_available, Copyright information available at source archive |
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