Inhibition of lipopolysaccharide-induced inflammatory responses by piperine.
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-alpha (TNF-alpha), but not of interleukin (IL)-1beta and IL-6. In peritoneal macrophages, piperine inhibited LPS/poly (I:C)/CpG-ODN-induced TNF-alpha production. Piperine also inhibited LPS-induced endotoxin shock in TNF-alpha 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-alpha/beta-treated cells by piperine. These results suggest that piperine inhibits LPS-induced endotoxin shock through inhibition of type 1 IFN production.
Bae
Gi-Sang
GS
Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, 540-749 Jeonbuk, South Korea.
Kim
Min-Sun
MS
Jung
Won-Seok
WS
Seo
Sang-Wan
SW
Yun
Seung-Won
SW
Kim
Sung Gyu
SG
Park
Rae-Kil
RK
Kim
Eun-Cheol
EC
Song
Ho-Joon
HJ
Park
Sung-Joo
SJ
D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000494:pharmacology* / Q000627:therapeutic use; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics
D000470:Alkaloids; D052117:Benzodioxoles; D007370:Interferon Type I; D008070:Lipopolysaccharides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; C008922:piperine