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      Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Comaparvin Isolated from the Crinoid Comanthus bennetti

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          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.

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          Origin and physiological roles of inflammation.

          Ruslan Medzhitov (2008)
          Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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            A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.

            Mark Brown, Sonia Flores, R Dubner … (1987)
            A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.
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              Marine natural products.

              Michele Prinsep, Murray H. G. Munro, John Blunt … (2009)
              This review covers the literature published in 2007 for marine natural products, with 948 citations(627 for the period January to December 2007) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, cnidarians,bryozoans, molluscs, tunicates, echinoderms and true mangrove plants. The emphasis is on new compounds (961 for 2007), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.1 Introduction, 2 Reviews, 3 Marine microorganisms and phytoplankton, 4 Green algae, 5 Brown algae, 6 Red algae, 7 Sponges, 8 Cnidarians, 9 Bryozoans, 10 Molluscs, 11 Tunicates (ascidians),12 Echinoderms, 13 Miscellaneous, 14 Conclusion, 15 References.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 16 September 2014
                Publication date Collection: September 2014
                Volume: 19
                Issue: 9
                Pages: 14667-14686
                Affiliations
                [1 ]Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; E-Mails: pharmacy@ 123456mail.ngh.com.tw (L.-C.C.); chas6119@ 123456gmail.com (Y.-Y.L.); snakefoot5052@ 123456gmail.com (Y.L.); hawkiyc@ 123456gmail.com (I.-Y.J.); 99001@ 123456mail.wzu.edu.tw (I.-M.C.); sheu@ 123456mail.nsysu.edu.tw (J.-H.S.)
                [2 ]Department of Pharmacy of Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan
                [3 ]Section of Orthopedic Surgery, Pingtung Christian Hospital, Pingtung 90059, Taiwan; E-Mail: jean.tang@ 123456msa.hinet.net
                [4 ]Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; E-Mail: ma4949@ 123456cgmh.org.tw
                [5 ]School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 84001, Taiwan; E-Mail: y520729@ 123456gmail.com
                [6 ]Department of Fragrance and Cosmetic Science, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; E-Mail: davidw@ 123456kmu.edu.tw
                [7 ]General Education Center, Wenzao Ursuline University of Languages, Kaohsiung 80793, Taiwan
                [8 ]Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 94450, Taiwan; E-Mails: x2219@ 123456nmmba.gov.tw (J.-H.S.); pjsung@ 123456nmmba.gov.tw (P.-J.S.)
                [9 ]Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan
                [10 ]Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: wzh@ 123456mail.nsysu.edu.tw ; Tel.: +886-7-5252000 (ext. 5038); Fax: +886-7-5252021.
                Article
                Publisher ID: molecules-19-14667
                DOI: 10.3390/molecules190914667
                PMC ID: 6271468
                PubMed ID: 25230122
                SO-VID: 4531f5f7-9049-4357-9e78-0aeb37639312
                Copyright © © 2014 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 29 July 2014
                Date revision received : 09 September 2014
                Date accepted : 10 September 2014
                Categories
                Subject: Article

                Keywords: comaparvin,crinoids,comanthus bennetti,inducible nitric oxide synthase,lipopolysaccharide,carrageenan
                Data availability:
                Keywords: comaparvin, crinoids, comanthus bennetti, inducible nitric oxide synthase, lipopolysaccharide, carrageenan

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