Pinnisterols A–C, New 9,11-Secosterols from a Gorgonian Pinnigorgia sp.

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Abstract

Three new 9,11-secosterols, pinnisterols A–C ( 1– 3), were isolated from a gorgonian coral Pinnigorgia sp., collected off the waters of Taiwan. The structures of these compounds were elucidated on the basis of spectroscopic methods. The new sterols 1 and 3 displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils, and sterol 1 was found to show moderate cytotoxicity in hepatic stellate cells (HSCs).

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Propofol inhibits superoxide production, elastase release, and chemotaxis in formyl peptide-activated human neutrophils by blocking formyl peptide receptor 1.

Yen-Shou Kuo, Chiung-Yin Huang, Hon-Man Chan … (2013)

Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF. Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. In addition, propofol showed less inhibitory effects in non-FPR1-induced cell responses. The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells. To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.

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

Wen Wei, Ping-Jyun Sung, Chang-Yih Duh … (2013)

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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2-(2-Fluorobenzamido)benzoate ethyl ester (EFB-1) inhibits superoxide production by human neutrophils and attenuates hemorrhagic shock-induced organ dysfunction in rats.

Tsann-Long Hwang, Pei-Jen Chung, Wen-Chang Chang … (2011)

Neutrophil activation after trauma-hemorrhagic shock (T/H) has been implicated in the development of multiple organ dysfunction (MOD). In this study, we report that a small chemical compound, 2-(2-fluorobenzamido)benzoic acid ethyl ester (EFB-1), exhibited a potent inhibitory effect on the formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced superoxide anion (O2•-) release and CD11b expression by human neutrophils. Additionally, administration of EFB-1 in rats subjected to T/H caused a significant improvement in MOD. EFB-1 treatment induced an increase in cAMP formation and protein kinase (PK) A activity in FMLP-activated neutrophils, which occurred through the selective inhibition of cAMP-specific phosphodiesterase (PDE) activity but not an increase in adenylate cyclase function or cGMP-specific PDE activity. FMLP-induced phosphorylation of protein kinase B (AKT), but not calcium mobilization, was reduced by EFB-1. The inhibitory effects of EFB-1 on O(2•-) production, CD11b expression, and AKT phosphorylation were reversed by PKA inhibitors (H89 and KT5720). Significantly, administration of EFB-1 (1 mg/kg body wt) attenuated the myeloperoxidase activity of the intestines, lungs, and liver and reduced the wet/dry weight ratio of the intestines and lungs and plasma alanine aminotransferase and aspartate aminotransferase levels in Sprague-Dawley rats after T/H. Therefore, EFB-1 is a new inhibitor of cAMP-specific PDE that potently suppresses O(2•-) release and CD11b expression by human neutrophils and attenuates T/H-induced MOD in rats. Copyright © 2011 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Orazio Taglialatela-Scafati: Role: Academic Editor

Journal

Journal ID (nlm-ta): Mar Drugs

Journal ID (iso-abbrev): Mar Drugs

Journal ID (publisher-id): marinedrugs

Title: Marine Drugs

Publisher: MDPI

ISSN (Electronic): 1660-3397

Publication date (Electronic): 07 January 2016

Publication date Collection: January 2016

Volume: 14

Issue: 1

Electronic Location Identifier: 12

Affiliations

[1 ]Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 804, Taiwan; jay0404@ 123456gmail.com (Y.-C.C.); wzh@ 123456mail.nsysu.edu.tw (Z.-H.W.)

[2 ]National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan

[3 ]Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; kuo33410@ 123456yahoo.com.tw

[4 ]Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan

[5 ]Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan; htl@ 123456mail.cgu.edu.tw

[6 ]Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan

[7 ]Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 804, Taiwan; jessicayeh8912001@ 123456gmail.com

[8 ]Department of Sport, Health, and Leisure, Cheng Shiu University, Kaohsiung 833, Taiwan; lsfang@ 123456csu.edu.tw

[9 ]School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan; yachwu@ 123456mail.cmu.edu.tw

[10 ]Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan

[11 ]Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan

[12 ]Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan

[13 ]Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 944, Taiwan

Author notes

[* ]Correspondence: shinlin@ 123456mail.nsysu.edu.tw (C.-S.L.); sheu@ 123456mail.nsysu.edu.tw (J.-H.S.); pjsung@ 123456nmmba.gov.tw (P.-J.S.); Tel.: +886-7-525-2000 (ext. 5035) (C.-S.L.); +886-7-525-2000 (ext. 5030) (J.-H.S.); +886-8-882-5037 (P.-J.S.); Fax: +886-7-525-5020 (C.-S.L. & J.-H.S.); +886-8-882-5087 (P.-J.S)

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Publisher ID: marinedrugs-14-00012

DOI: 10.3390/md14010012

PMC ID: 4728509

PubMed ID: 26751457

SO-VID: 00453abb-e7a7-4c58-a3c0-021c6888c309

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This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Pinnisterols A–C, New 9,11-Secosterols from a Gorgonian Pinnigorgia sp.

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Neuropharmacology and Therapy

Most cited references 13

Propofol inhibits superoxide production, elastase release, and chemotaxis in formyl peptide-activated human neutrophils by blocking formyl peptide receptor 1.

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

2-(2-Fluorobenzamido)benzoate ethyl ester (EFB-1) inhibits superoxide production by human neutrophils and attenuates hemorrhagic shock-induced organ dysfunction in rats.

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