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

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Review

Anti-Inflammatory Activities of Natural Products

Isolated from Soft Corals of Taiwan between 2008

and 2012

Wen-Chi Wei 1, Ping-Jyun Sung 2,3, Chang-Yih Duh 4, Bo-Wei Chen 4, Jyh-Horng

Sheu 4,5,6,* and Ning-Sun Yang 1,7,8,*

1 Agricultural Biotechnology Research Center, Academia Sinica, Taipei 128, Taiwan;

E-Mail: [email protected]

2 National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan; E-Mail:

[email protected]

3 Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung

944, Taiwan

4 Department of Marine Biotechnology and Resources, National Sun Yat-sen University,

Kaohsiung 804, Taiwan; E-Mails: [email protected] (C.-Y.D.); [email protected] (B.-W.C.)

5 Department of Medical Research, China Medical University Hospital, China Medical

University, Taichung 404, Taiwan

6 Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807,

Taiwan

7 Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan 8 Department of Life Science, National Central University, Taoyuan 320, Taiwan

* Authors to whom correspondence should be addressed; E-Mails:

[email protected] (J.-H.S.); [email protected] (N.-S.Y.); Tel./Fax: +886-7525-2000 (ext. 5030) (J.-H.S.), +886-2-2787-2067 (N.-S.Y.).

Received: 30 July 2013; in revised form: 12 September 2013 / Accepted: 13 September 2013 / Published: 23 October 2013

Abstract: 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.

Keywords: soft coral; anti-inflammatory activity; iNOS; COX-2; superoxide anion;

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1. Introduction

Marine natural products, especially those from stationary or slow moving marine organisms, are used naturally as a chemical defense to protect the organisms from dangerous predators, stressful local environments, and/or the encroachment of competitors. Due to the biological and chemical diversity of marine habitats, and the identification and greater understanding of marine secondary metabolites with unique chemical structures and biological activities, natural products from marine organisms are increasingly being considered as a major source of new therapeutics [1–3]. More than 20,000 novel compounds have been isolated and identified from marine organisms since the 1960s [4]. At least two current drugs and a series of anti-tumor drug candidates in preclinical or clinical trials have been developed from marine natural products [2–4]. The soft corals or Alcyonacea, an order of Anthozoa widely distributed in warm seawaters, have been a particular focus of attention. An abundance of unique secondary metabolites including sesquiterpenoids, diterpenoids, steroids and other chemical compounds have been isolated and identified from various species of soft corals [5–7]. It has been estimated that the percentage of new metabolites discovered from soft corals represents up to 22% of the total new marine natural products reported from 2010 to 2011 [5,6]. Importantly, many of the natural products discovered from soft corals have been demonstrated to exhibit a spectrum of biological activities such as anti-tumor, antiviral, antifouling and anti-inflammatory [5–8].

Inflammation processes often constitute an initial activation of the mammalian immune system, and the body’s normal defense or protective mechanisms in response to microbial infection or irritation or injury of tissues/organs. Increasing evidence suggests a critical link between inflammation and the chronic promotion/progression of various human diseases, including atherosclerosis, diabetes, arthritis, inflammatory bowel disease, cancer and Alzheimer. Proinflammatory enzymes, particularly the inducible nitric oxide synthase (iNOS) for nitric oxide production and cyclooxygenase (COX-2) for prostaglandin production, have been demonstrated to play central roles in the development of

inflammatory diseases. In addition, it is also known that during the initial phase of acute inflammation, neutrophils are one of the first leukocyte populations to migrate towards the damaged tissue sites [9]. Neutrophils play a key role in the pathogenesis of various chronic inflammation diseases such as rheumatoid arthritis [10,11]. Activated neutrophils can secrete the superoxide anion, reactive oxygen species (ROS) and enzymes that are associated with the killing of invading pathogens [12]. Furthermore, elastase secreted by stimulated neutrophils has been recognized to play a key contribution in the demolition of tissues affected by chronic inflammatory disease [13]. Therefore, evaluation of the inhibition of iNOS and COX-2 expression, the production of superoxide anion, and the release of elastase in inflammatory cells/tissues by various natural products have been

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extensively employed in a spectrum of in vitro preliminary screening systems for lead compound or drug discovery. Recently, a number of marine biology and chemistry researchers in Taiwan (including our laboratory) have systematically screened several marine natural products isolated from soft corals for such in vitro anti-inflammatory activities, mainly by measuring the inhibition of iNOS, COX-2, superoxide anion or elastase in murine immune cells. Animal models were further used to evaluate the potential therapeutic activities of candidate compounds in specific disease models. This report reviews some recent representative studies and examples of marine natural products with anti-inflammatory and other related bioactivities that have been isolated from soft corals of Taiwan. Soft corals areabundant in the off-shore environment of the island of Taiwan, and have hence become a focus of local studies of marine nature products. We hope that this review will provide a useful data for the further study of marine natural products.

2. Results and Discussion

In the reports reviewed here, anti-inflammatory activities of natural products from the soft corals of Taiwan were generally determined in vitro by their inhibition of LPS-induced expression of iNOS and COX-2 in murine macrophage cells (RAW264.7) or by their inhibition of the production of superoxide anion and the release on the elastase from human neutrophils in response to FMLP/CB.

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