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The anti-inflammatory effects of apigenin and genistein on the rat intestinal epithelial (IEC-6) cells with TNF-α stimulation in response to heat treatment.

ABSTRACT: The aims of the present study were to investigate the anti-inflammatory function of two flavonoids apigenin and genistein in rat intestinal epithelial (IEC-6) cells stimulated by tumor necrosis factor-alpha (TNF-α) and to clarify whether the heat treatment of the flavonoids might affect flavonoid activity. The flavonoids at lower dosage (e.g. 5 μmol/L) had no toxic effect but growth promotion on the cells. Meanwhile, the flavonoid pretreatment of the cells before TNF-α stimulation could maintain cellular morphology, decrease the production of prostaglandin E₂ and two pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-6, but increase the production of two anti-inflammatory cytokines IL-10 and transforming growth factor-β. Additionally, the flavonoids could block off the nuclear translocation of nuclear factor-kappaB (NF-κB) p65, and suppress the expression of phosphorylated IκBα and p65 induced by TNF-α. Meanwhile, the NF-κB inhibitor BAY 11-7082 shared a similar function with the flavonoids to mediate the production of IL-6/IL-10. Furthermore, in silico analysis also declared that the flavonoids could interact with the IκBα-NF-κB complex at the binding pockets to yield the binding energies ranging from -31.7 to -34.0 kJ/mol. However, the heated flavonoids were consistently less effective than the unheated counterparts to perform these anti-inflammatory effects. It is thus proposed that both apigenin and genistein have anti-inflammatory potential to the TNF-α-stimulated IEC-6 cells by inactivating the NF-κB pathway, while heat treatment of the flavonoids caused a negative impact on these assessed anti-inflammatory effects.

SUBMITTER: Cai SQ

PROVIDER: S-EPMC9846340 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The anti-inflammatory effects of apigenin and genistein on the rat intestinal epithelial (IEC-6) cells with TNF-α stimulation in response to heat treatment.

Cai Shi-Qing SQ Tang Zhi-Mei ZM Xiong Cen C Wu Fei-Fei FF Zhao Jun-Ren JR Zhang Qiang Q Wang Li L Zhang Xiao-Nan XN Zhao Xin-Huai XH

Current research in food science 20220531

The aims of the present study were to investigate the anti-inflammatory function of two flavonoids apigenin and genistein in rat intestinal epithelial (IEC-6) cells stimulated by tumor necrosis factor-alpha (TNF-α) and to clarify whether the heat treatment of the flavonoids might affect flavonoid activity. The flavonoids at lower dosage (e.g. 5 μmol/L) had no toxic effect but growth promotion on the cells. Meanwhile, the flavonoid pretreatment of the cells before TNF-α stimulation could maintain ...[more]

PMID: 36686365

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Project description:Background & aimsInducible heat shock proteins (iHsp), Hsp25/27 and Hsp70, play essential roles in protecting cells against stress and, in intestinal mucosal inflammation, potentially lessening the extent and severity of injury. We examined the expression and regulation of iHsp in human and experimental inflammatory bowel diseases (IBD) and in vitro.MethodsiHsp expression and regulation were assessed in normal and IBD colonic biopsy specimens, IL-10(-/-) mice, and young adult mouse colonic epithelial cells by immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR). Phosphorylation of double-stranded RNA-dependent protein kinase (PKR) and eukaryotic initiation factor-2alpha (eIF-2alpha) was determined by Western blot.ResultsHsp25/27 and Hsp70 levels were selectively reduced in areas of active mucosal inflammation associated with human IBD and IL-10(-/-) mice with colitis. Wild-type mice treated in vivo with interferon (IFN)-gamma + tumor necrosis factor (TNF)-alpha also demonstrated reduced colonic Hsp25/27 and Hsp70. In young adult mouse colonic epithelial cells, IFN-gamma+TNF-alpha inhibited heat induction of Hsp25/27 and Hsp70, an effect not associated with changes in iHsp messenger RNA or protein half-lives but caused by suppressed de novo iHsp synthesis. IFN-gamma+TNF-alpha cotreatment activated PKR, resulting in phosphorylation and inactivation of eIF-2alpha, an essential factor in protein translation. These effects were not due to induced apoptosis and could be negated by PKR-inhibitor and short interfering RNA to PKR. Increased phosphorylation of PKR and eIF-2alpha were also observed in active IBD tissues.ConclusionsMucosal inflammation is associated with iHsp down-regulation, an effect that appears mediated by translational down-regulation by proinflammatory cytokines. In the context of IBD, we propose that this mechanism contributes to the severity, extent, and persistence of inflammation-induced mucosal injury.

Project description:Background and Purpose: Novobiocin (NOVO), an ABC transporter inhibitor, decreases intestinal wall permeability of capsaicin (CAP), an ABC transporter substrate. However, the mechanism of this effect is not consistent with the action of NOVO as an ABC transporter inhibitor. We previously found that CAP can also be transported via TRPV1, which was site-specific in the permeability of CAP across the intestine. We explored the regulation by NOVO of TRPV1 in the present study. Methods: Rats and transfected IEC-6 cells were used as the models to assess intestinal permeability and expression of TRPV1. Ussing chamber and intracellular accumulation were used to evaluate the influence of NOVO on the transport of CAP in vitro. The expression of TRPV1 was detected after administration of NOVO by qRT-PCR, western blot and immunofluorescent imaging. In addition, MTT and lactate dehydrogenase (LDH) were used to evaluate the cytotoxicity of NOVO in both rat and cell models. Finally, the effect of NOVO on the absorption of CAP in vivo was studied by LC-MS/MS. Results: In vitro data showed that there existed a dose-dependent relationship in the range of concentration between 5 and 50 μM, and even 5 μM NOVO could decrease intestinal permeability of CAP across the intestine. Meanwhile, cytosolic accumulation of CAP decreased when NOVO was used simultaneously or 24 h in advance. NOVO exhibited an inhibition level similar to that of ruthenium red (RR) or SB-705498, a TRPV1-specific inhibitor. NOVO down-regulated TRPV1 expression in the intestine and in transfected cells in a concentration-dependent fashion, hinting that its inhibition of the permeability of CAP is due to its inhibition of TRPV1 expression. Immunofluorescent imaging data showed that the fluorescence intensity of TRPV1 was reduced after pre-treatment with NOVO and SB-705498. In vivo data further demonstrated that oral co-administration of NOVO decreased Cmax and AUC of CAP in dosage-dependent ways, consistent with its role as a TRPV1 inhibitor. Conclusion: NOVO could be a potential TRPV1 inhibitor by attenuating the expression of TRPV1 and may be used to attenuate permeability of TRPV1 substrates.

Dataset Information

The anti-inflammatory effects of apigenin and genistein on the rat intestinal epithelial (IEC-6) cells with TNF-α stimulation in response to heat treatment.

Publications

The anti-inflammatory effects of apigenin and genistein on the rat intestinal epithelial (IEC-6) cells with TNF-α stimulation in response to heat treatment.

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