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Int. J. Mol. Sci. 2014, 15(12), 22819-22834; doi:10.3390/ijms151222819

Pheophytin a Inhibits Inflammation via Suppression of LPS-Induced Nitric Oxide Synthase-2, Prostaglandin E2, and Interleukin-1β of Macrophages

1
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
2
School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3
Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
4
Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan 736, Taiwan
5
Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7
School of Medical and Health Sciences, Fooyin University, Kaohsiung 831, Taiwan
8
Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 13 October 2014 / Revised: 26 November 2014 / Accepted: 27 November 2014 / Published: 9 December 2014
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Abstract

Inflammation is a serious health issue worldwide that induces many diseases such as sepsis. There has been a vast search for potentially effective drugs to decrease mortality from sepsis. Pheophytin a is a chlorophyll-related compound derived from green tea. We found that pre-treatment with pheophytin a suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-1β in RAW 264.7 macrophages. NO synthase-2 (NOS2) and cyclooxygenase-2 (COX-2) expression levels were repressed by pre-treatment with pheophytin a at both the transcriptional and translational levels. Pheophytin a inhibited NOS2 promoter activity, but not its mRNA stability, through extracellular signal-regulated kinase (ERK1/2). This suppression was reversed by ERK1/2 inhibitor (U0126). Pheophytin a reduced signal transducers and activators of transcription 1 (STAT-1) activation, without an obvious influence on activator protein-1 (AP-1) and nuclear factor κB (NF-κB). These results suggest that pheophytin a functions by down-regulating the transcriptional levels of inflammatory mediators and blocking the ERK and STAT-1 pathways. View Full-Text
Keywords: pheophytin a; NO; signal transducers and activators of transcription 1 (STAT-1); anti-inflammation pheophytin a; NO; signal transducers and activators of transcription 1 (STAT-1); anti-inflammation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lin, C.-Y.; Lee, C.-H.; Chang, Y.-W.; Wang, H.-M.; Chen, C.-Y.; Chen, Y.-H. Pheophytin a Inhibits Inflammation via Suppression of LPS-Induced Nitric Oxide Synthase-2, Prostaglandin E2, and Interleukin-1β of Macrophages. Int. J. Mol. Sci. 2014, 15, 22819-22834.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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