Inhibition of lipopolysaccharide-induced inflammatory responses by piperine

• Published in: European journal of pharmacology 2010-09, Vol.642 (1), p.154-162
• Main Authors: Bae, Gi-Sang, Kim, Min-Sun, Jung, Won-Seok, Seo, Sang-Wan, Yun, Seung-Won, Kim, Sung Gyu, Park, Rae-Kil, Kim, Eun-Cheol, Song, Ho-Joon, Park, Sung-Joo
• Format: Article
• Language: English
• Subjects: Alkaloids - pharmacology; Alkaloids - therapeutic use; Animals; Benzodioxoles - pharmacology; Benzodioxoles - therapeutic use; Biological and medical sciences; Endotoxin shock; Female; Gene Knockout Techniques; Inflammation - drug therapy; Inflammation - immunology; Inflammation - metabolism; Interferon regulatory factor; Interferon Type I - biosynthesis; Lipopolysaccharides - pharmacology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Miscellaneous; Pharmacology. Drug treatments; Piper; Piper nigrum; Piperidines - pharmacology; Piperidines - therapeutic use; Piperine; Polyunsaturated Alkamides - pharmacology; Polyunsaturated Alkamides - therapeutic use; Shock, Septic - drug therapy; Signal transducer and activator of transcription; STAT1 Transcription Factor - metabolism; Tumor Necrosis Factor-alpha - deficiency; Tumor Necrosis Factor-alpha - genetics; Type 1 interferon
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.05.026

Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medical use. Piperine exhibits anti-inflammatory activity; however, the underlying mechanism remains unknown. We examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory responses. Administration of piperine inhibited LPS-induced endotoxin shock, leukocyte accumulation and the production of tumor necrosis factor-α (TNF-α), but not of interleukin (IL)-1β and IL-6. In peritoneal macrophages, piperine inhibited LPS/poly (I:C)/CpG-ODN-induced TNF-α production. Piperine also inhibited LPS-induced endotoxin shock in TNF-α knockout (KO) mice. To clarify the inhibitory mechanism of LPS-induced endotoxin shock, type 1 interferon (IFN) mRNA expression was determined. Piperine inhibited LPS-induced expression of type 1 IFN mRNA. Piperine inhibited the levels of interferon regulatory factor (IRF)-1 and IRF-7 mRNA, and the phosphorylation and nuclear translocation of IRF-3. Piperine also reduced activation of signal transducer and activator of transcription (STAT)-1. In addition, activation of STAT-1 was inhibited in IFN-α/β-treated cells by piperine. These results suggest that piperine inhibits LPS-induced endotoxin shock through inhibition of type 1 IFN production.