2. Academic Validation
  3. Pheophytin a inhibits inflammation via suppression of LPS-induced nitric oxide synthase-2, prostaglandin E2, and interleukin-1β of macrophages

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 Dec 9;15(12):22819-34. doi: 10.3390/ijms151222819.
Chun-Yu Lin 1,  Chien-Hsing Lee 2,  Yu-Wei Chang 3,  Hui-Min Wang 4,  Chung-Yi Chen 5,  Yen-Hsu Chen 6
Affiliations

Affiliations

  • 1 Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. [email protected].
  • 2 Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan 736, Taiwan. [email protected].
  • 3 School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 4 Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. [email protected].
  • 5 School of Medical and Health Sciences, Fooyin University, Kaohsiung 831, Taiwan. [email protected].
  • 6 Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. [email protected].
PMID: 25501336 DOI: 10.3390/ijms151222819
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.

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