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      New Anti-Inflammatory Cembranes from the Cultured Soft Coral Nephthea columnaris

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          Abstract

          Two new cembranes, columnariols A ( 1) and B ( 2), were isolated from the cultured soft coral Nephthea columnaris. The structures of cembranes 1 and 2 were elucidated by spectroscopic methods. In the anti-inflammatory effects test, cembranes 1 and 2 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Compound 1 exhibited moderate cytotoxicity toward LNCaP cells with an IC 50 value of 9.80 μg/mL.

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          Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.

          For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.
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            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.

            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.
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              Anti-Inflammatory Activities of Natural Products Isolated from Soft Corals of Taiwan between 2008 and 2012

              This review reports details on the natural products isolated from Taiwan soft corals during the period 2008–2012 focusing on their in vitro and/or in vivo anti-inflammatory activities. Chemical structures, names, and literature references are also reported. This review provides useful and specific information on potent anti-inflammatory marine metabolites for future development of immune-modulatory therapeutics.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                29 May 2015
                June 2015
                : 13
                : 6
                : 3443-3453
                Affiliations
                [1 ]Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 944, Taiwan; E-Mails: hsiaoinon@ 123456gmail.com (T.-H.H.); jinx6609@ 123456nmmba.gov.tw (M.-C.L.)
                [2 ]National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan
                [3 ]Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 112, Taiwan; E-Mail: sung6119@ 123456gmail.com
                [4 ]School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
                [5 ]School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan; E-Mail: lanyh@ 123456mail.cmu.edu.tw
                [6 ]Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 804, Taiwan; E-Mails: cvyc.wang@ 123456gmail.com (Y.-C.W.); wzh@ 123456mail.nsysu.edu.tw (Z.-H.W.)
                [7 ]Division of Cardiology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
                [8 ]Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan
                [9 ]Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [10 ]Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Authors to whom correspondence should be addressed; E-Mails: yachwu@ 123456mail.cmu.edu.tw (Y.-C.W.); pjsung@ 123456nmmba.gov.tw (P.-J.S.); Tel.: +886-4-220-57513 (Y.-C.W.); +886-8-882-5037 (P.-J.S.); Fax: +886-4-220-60248 (Y.-C.W.); +886-8-882-5087 (P.-J.S.).
                Article
                marinedrugs-13-03443
                10.3390/md13063443
                4483638
                26035022
                586030ff-aacd-49d2-a53c-8c1499bfd73f
                © 2015 by the authors; 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/4.0/).

                History
                : 19 April 2015
                : 21 May 2015
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                nephthea columnaris,cembrane,octocoral,antiinflammatory,inos,cox-2,cytotoxicity

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