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Anti-inflammatory and analgesic effects of the marine-derived compound comaparvin isolated from the crinoid Comanthus bennetti.
Chen LC
,
Lin YY
,
Jean YH
,
Lu Y
,
Chen WF
,
Yang SN
,
Wang HM
,
Jang IY
,
Chen IM
,
Su JH
,
Sung PJ
,
Sheu JH
,
Wen ZH
.
Abstract
To date, no study has been conducted to explore the bioactivity of the crinoid Comanthus bennetti. Here we report the anti-inflammatory properties of comaparvin (5,8-dihydroxy-10-methoxy-2-propylbenzo[h]chromen-4-one) based on in vivo experiments. Our preliminary screening for anti-inflammatory activity revealed that the crude extract of Comanthus bennetti significantly inhibited the expression of pro-inflammatory proteins in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Comaparvin isolated from crinoids significantly decreased the expression of inducible nitric oxide synthase (iNOS) protein and mRNA in LPS-stimulated macrophage cells. Moreover, our results showed that post-treatment with comaparvin significantly inhibited mechanical allodynia, thermal hyperalgesia and weight-bearing deficits in rats with carrageenan-induced inflammation. Comaparvin also attenuated leukocyte infiltration and iNOS protein expression in carrageenan-induced inflamed paws. These results suggest that comaparvin is a potential anti-inflammatory therapeutic agent against inflammatory pain.
Figure 1. Chemical structure and source of comaparvin. (A) Chemical structure of comaparvin. Molecular formula, C17H16O5; molecular weight, 300.11 Da; (B) The crinoid sample, Comanthus bennetti, was collected from Lamay Island, Taiwan.
Figure 3. Effect of comaparvin on the expression of the pro-inflammatory protein iNOS, in LPS-stimulated macrophage cells. (A) Western blot bands corresponding to the effects of comaparvin on iNOS and β-actin expression in LPS-stimulated macrophage cells; (B) The relative intensity of expression of iNOS protein in the LPS-alone group was set to 100%, and β-actin was used to verify that equivalent amounts of protein were loaded in each lane. Comaparvin significantly inhibited iNOS protein expression in LPS-stimulated macrophage cells. Data are the mean ± SEM values of 4 independent experiments. * p < 0.05, significant difference compared with the LPS-alone group.
Figure 8. Histopathologic analyses of the effects of comaparvin on cell infiltration in carrageen-injected paws. (A) Vehicle group (B) Carrageenan-alone group (C) Pre-treatment group (D) Post-treatment group. Pre-treatment or post-treatment of comaparvin (30 mg/kg) appeared to attenuate carrageenan-induced upregulation of immune cells. Numbers of neutrophils (E); macrophages (F); and fibroblasts (G) were analyzed in paw tissue from each group. Pre, comaparvin pre-treatment at 1 h before carrageenan injection. Post, comaparvin post-treatment at 4 h after carrageenan injection. Scale bar = 200 μm. Data are the mean ± SEM values. * p < 0.05, significant difference compared with the control group. #
p < 0.05, significant difference compared with the vehicle group.
Figure 9. Inhibitory effect of comaparvin on the expression of carrageenan-induced iNOS protein expression in rat paw tissue. Western blot analyses of expression of iNOS and β-actin protein in paw tissues after carrageenan injection. Intraplantar carrageenan injection induced significant iNOS protein expression in ipsilateral (carrageenan injection site) but not contralateral paw tissues at 24 h. Administration of a subcutaneous injection of comaparvin (30 mg/kg) significantly inhibited carrageenan-induced upregulation of iNOS protein expression. β-actin protein expression remained unchanged in all groups. Quantification data show the mean ± SEM values for four different experiments. Pre, comaparvin pre-treatment at 1 h before carrageenan injection. Post, comaparvin post-treatment at 4 h after carrageenan injection. Data are the mean ± SEM values. * p < 0.05 compared with the vehicle group. #
p < 0.05 compared with the carrageenan group.
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