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Title: Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum

Abstract

Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl) -1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O{sub 2}{sup ·−}) production, elastase release, and CD11b expression in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O{sub 2}{sup ·−} production. The peak cytosolic calcium concentration ([Ca{sup 2+}]{sub i}) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca{sup 2+}]{sub i} was significantly shortened. In a calcium-free solution, changes in [Ca{sup 2+}]{sub i} caused by the addition of extracellular Ca{sup 2+} were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca{sup 2+}]{sub i} changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibitionmore » of SOCE. Highlights: ► Bractelactone isolated from Fissistigma bracteolatum. ► Bractelactone inhibited FMLP-induced human neutrophil activations. ► Bractelactone had no effect on IP3 formation. ► Bractelactone did not alter MAPKs, AKT, and cAMP pathways. ► Bractelactone inhibited store-operated calcium entry.« less

Authors:
 [1];  [2]; ; ;  [3];  [4];  [1];  [3];  [3];  [2]
  1. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)
  2. (China)
  3. Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China)
  4. School of Pharmacy, China Medical University, Taichung 404, Taiwan (China)
Publication Date:
OSTI Identifier:
22216053
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 266; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; ADENOSINE; AMP; ANIONS; CALCIUM; GTP-ASES; INFLAMMATION; INHIBITION; INOSITOL; LACTATE DEHYDROGENASE; NEUTROPHILS; PHENYLALANINE; PHOSPHORYLATION; RECEPTORS; SUPEROXIDE DISMUTASE; TETRAZOLIUM

Citation Formats

Wu, Yang-Chang, Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan, Sureshbabu, Munisamy, Fang, Yao-Ching, Wu, Yi-Hsiu, Lan, Yu-Hsuan, Chang, Fang-Rong, Chang, Ya-Wen, Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan. Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2012.11.021.
Wu, Yang-Chang, Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan, Sureshbabu, Munisamy, Fang, Yao-Ching, Wu, Yi-Hsiu, Lan, Yu-Hsuan, Chang, Fang-Rong, Chang, Ya-Wen, Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw, & Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan. Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum. United States. doi:10.1016/J.TAAP.2012.11.021.
Wu, Yang-Chang, Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan, Sureshbabu, Munisamy, Fang, Yao-Ching, Wu, Yi-Hsiu, Lan, Yu-Hsuan, Chang, Fang-Rong, Chang, Ya-Wen, Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan. Fri . "Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum". United States. doi:10.1016/J.TAAP.2012.11.021.
@article{osti_22216053,
title = {Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum},
author = {Wu, Yang-Chang and Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan and Sureshbabu, Munisamy and Fang, Yao-Ching and Wu, Yi-Hsiu and Lan, Yu-Hsuan and Chang, Fang-Rong and Chang, Ya-Wen and Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan},
abstractNote = {Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl) -1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O{sub 2}{sup ·−}) production, elastase release, and CD11b expression in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O{sub 2}{sup ·−} production. The peak cytosolic calcium concentration ([Ca{sup 2+}]{sub i}) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca{sup 2+}]{sub i} was significantly shortened. In a calcium-free solution, changes in [Ca{sup 2+}]{sub i} caused by the addition of extracellular Ca{sup 2+} were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca{sup 2+}]{sub i} changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibition of SOCE. Highlights: ► Bractelactone isolated from Fissistigma bracteolatum. ► Bractelactone inhibited FMLP-induced human neutrophil activations. ► Bractelactone had no effect on IP3 formation. ► Bractelactone did not alter MAPKs, AKT, and cAMP pathways. ► Bractelactone inhibited store-operated calcium entry.},
doi = {10.1016/J.TAAP.2012.11.021},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 266,
place = {United States},
year = {Fri Feb 01 00:00:00 EST 2013},
month = {Fri Feb 01 00:00:00 EST 2013}
}