interleukin-8 and piperine

The anti-inflammatory effect of piperine has been largely investigated in macrophages, but its activity on epithelial cells in inflammatory settings is unclear. The present study aimed to investigate the effect of piperine on the expression of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human epithelial-like SW480 and HT-29 cells. Our data showed that although piperine inhibited the proliferation of SW480 and HT-29 cells in a dose-dependent manner, it had low cytotoxicity on these cell lines with 50 % inhibiting concentration (IC50) values greater than 100 μM. As epithelial-like cells, SW480 and HT-29 cells secreted high levels of the chemokine CXCL8 upon LPS stimulation. Importantly, piperine dose-dependently suppressed LPS-induced secretion of CXCL8 and the expression of CXCL8 messenger RNA (mRNA). Although piperine failed to affect the critical inflammatory nuclear factor-κB pathway, it attenuated the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling. Consistent with previous reports, p38 signaling seemed to play a more pronounced role on the CXCL8 expression than JNK signaling since inhibition of p38, instead of JNK, greatly suppressed LPS-induced CXCL8 expression. Collectively, our results indicated that piperine could attenuate the inflammatory response in epithelial cells via downregulating the MAPK signaling and thus the expression of CXCL8, suggesting its potential application in anti-inflammation therapy.

Topics: Alkaloids; Anti-Inflammatory Agents; Benzodioxoles; Cell Line; Cell Proliferation; Cell Survival; Down-Regulation; Epithelial Cells; HT29 Cells; Humans; Inflammation; Inflammatory Bowel Diseases; Interleukin-8; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Piperidines; Polyunsaturated Alkamides; RNA, Messenger

Leukocyte infiltration, up-regulation of proinflammatory cytokines and severe oxidative stress caused by increased amounts of reactive oxygen species are characteristics of inflammatory bowel disease. The catechin (2R,3R)-2-(3,4,5-Trihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol-3-(3,4,5-trihydroxybenzoate), named epigallocatechin-3-gallate, EGCG, has been demonstrated to exert anti-inflammatory and antioxidative properties, reducing reactive oxygen species in the inflamed tissues. The aim of this study was to evaluate the therapeutic effects of EGCG in a murine model of colitis induced by oral administration of dextran sodium sulfate.. Mice received a daily oral administration of 6.9 mg/kg body weight EGCG or Piper nigrum (L.) alkaloid (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylpenta-2,4-dien-1-one, named piperine (2.9 mg/kg body weight) or the combination of the both - piperine was used in this combination to enhance the bioavailability of EGCG.. In vivo data revealed the combination of EGCG and piperine to significantly reduce the loss of body weight, improve the clinical course and increase overall survival in comparison to untreated groups. The attenuated colitis was associated with less histological damages to the colon and reduction of tissue concentrations of malondialdehyde, the final product of lipid peroxidation. Neutrophils accumulation indicator myeloperoxidase was found to be reduced in colon tissue, while antioxidant enzymes like superoxide dismutase and glutathione peroxidase showed an increased activity. In vitro, the treatment with EGCG plus piperine enhanced the expression of SOD as well as GPO and also reduced the production of proinflammatory cytokines.. These data support the concept of anti-inflammatory properties of EGCG being generally beneficial in the DSS-model of colitis, an effect that may be mediated by its strong antioxidative potential.

Topics: Alkaloids; Analysis of Variance; Animals; Antioxidants; Benzodioxoles; Catechin; Colitis; Dextran Sulfate; Female; Glutathione Peroxidase; HT29 Cells; Humans; Interleukin-8; Malondialdehyde; Mice; Mice, Inbred C57BL; Oxidative Stress; Peroxidase; Piperidines; Polyunsaturated Alkamides; Reactive Oxygen Species; Superoxide Dismutase; Weight Loss