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Open AccessArticle

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.
Int. J. Mol. Sci. 2014, 15(12), 22819-22834; https://doi.org/10.3390/ijms151222819
Received: 13 October 2014 / Revised: 26 November 2014 / Accepted: 27 November 2014 / Published: 9 December 2014
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
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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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