Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Abstract

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

“…Venkataraman et al [ 82 ] used thymoquinone, a bioactive molecule from the quinone-monoterpene family present in the volatile oil of Nigella sativa L. seeds, in a model of induced colitis. After treatment, there was a reduction in the expression of chemokine (C-X-C motif) ligand 1 (CXCL-1), IL-8, and COX-2, and an increased expression of PPAR-γ.…”

α-Bisabolol Mitigates Colon Inflammation by Stimulating Colon PPAR-γ Transcription Factor: In Vivo and In Vitro Study

“…CMV vectors were purchased from Promega (Cat# N1021 & N1101, Madison, WI, USA), and the PPRE-pNL1.3 plasmid was purchased from Addgene (Cat#84394, Watertown, MA, USA). Other reagents were obtained from the suppliers listed in our previous publication [ 18 ].…”

“…The plasmid was extracted using the Plasmid Purification Maxiprep Kit (Cat# 12162, Qiagen, Germany) following the manufacturers' instructions. The plasmid DNA and Lipofectamine LTX mixture wer prepared in serum and antibiotic-free DMEM media as described previously [ 18 ]. The transient transfection with PPRE-pNL1.3 or pNL1.3 basic secreted luciferase reporter used as control.…”

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

“…In vivo, TQ significantly reduced the disease activity index (DAI) and myeloperoxidase (MPO) activity, protecting the internal microenvironment of the colon. In vitro experiments demonstrated that TQ mediates COX-2 expression and exerts anti-inflammatory function by inhibiting MAPK and NF-κB signaling [ 27 ]. In 2013, the relationship between TQ and COX-2 was verified in the skin of female HR-1 hairless mice.…”