No abstract

Background and purpose: 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[ə]pentalene-2,3a-diol (GB9) exhibited antiinflammatory 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[ə]pentalen-2-yl ester (GB10). Experimental approach: Effects of GB9 or GB10 on the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in interferon-g (IFN-g)-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. Key results: In BV2 cells, GB9 and GB10 inhibited the expression of iNOS and COX-2, stimulated by IFN-g. 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. Conclusion and implications: Taken together, these data indicate that the marine-derived capnellenes, GB9 and GB10, had anti-neuroinflammatory and anti-nociceptive properties in IFN-g-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.

Our results indicate that treatment with oral glucosamine sulfate in a rat OA model (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cell p38 and JNK and increase of ERK expression.

We aimed to establish an animal model to investigate primary osteoarthritis of the lumbar facet joints after collagenase injection in rats and its effects on chondrocyte apoptosis. We hypothesized that osteoarthritic-like changes would be induced by collagenase injection and that apoptosis of chondrocytes would increase. Collagenase (1, 10, or 50 U) or saline (control) was injected into the lumbar facet joints. The histology and histochemistry of cartilage, synovium, and subchondral bone were examined at 1, 3, and 6 weeks after surgery. Apoptotic cells induced by 1 U of collagenase were quantified using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Degeneration of the cartilage and changes to the synovium and subchondral bone were dependent on both the doses of collagenase and the time after surgery. There were significantly more apoptotic chondrocytes in collagenase-treated joints than in control (P < 0.001 at 1 and 3 weeks and P < 0.05 at 6 weeks). Thus, lumbar facet joints subjected to collagenase developed osteoarthritic-like changes that could be quantified and compared. This model provides a useful tool for further study on the effects of compounds that have the potential to inhibit enzyme-associated damage to cartilage.