Kaempferol inhibits multiple pathways involved in the secretion of inflammatory mediators from LPS‑induced rat intestinal microvascular endothelial cells

Abstract

Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory disease of the small and/or large intestine. Endothelial expression of inflammatory mediators, including cytokines and adhesion molecules, serves a critical role in the initiation and progression of IBD. The dietary flavonoid, kaempferol, has been reported to inhibit expression of inflammatory mediators; however, the underlying mechanisms require further investigation. In the present study, a novel molecular mechanism of kaempferol against IBD was identified. The potential anti-inflammatory effect of kaempferol in a cellular model of intestinal inflammation was assessed using lipopolysaccharide (LPS)-induced rat intestinal microvascular endothelial cells (RIMVECs), and an underlying key molecular mechanism was identified. RIMVECs were pretreated with kaempferol of various concentrations (12.5, 25 and 50 µM) followed by LPS (10 µg/ml) stimulation. ELISA was used to examine the protein levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the supernatant. Protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, inhibitor of NF-κB, mitogen-activated protein kinase p38 and signal transducer and activator of transcription (STAT) in cells were measured by western blotting. Kaempferol significantly reduced the overproduction of TNF-α, IL-1β, interleukin-6, ICAM-1 and VCAM-1 induced by LPS, indicating the negative regulation of kaempferol in TLR4, NF-κB and STAT signaling underlying intestinal inflammation. The present results provide support for the potential use of kaempferol as an effective therapeutic agent for IBD treatment.

Bioactivity and Bioavailability of the Major Metabolites of Crocus sativus L. Flower

“…Kaempferol can inhibit the inflammatory response induced due to endotoxins in acute lung injury in mice as well as in cellular models [172]. The inhibition of the expression of inflammatory mediators was demonstrated in a cellular model of intestinal inflammation in rats [173]; further, anti-inflammatory effects were observed on the inflammation induced by Helicobacter pylori [174]. In addition, antidepressant effects [175] and improvement of wound healing in diabetic and non-diabetic rats [176] have also been attributed to kaempferol.…”

Network Pharmacology‐Based Approach to Investigate the Mechanisms of Mahai Capsules in the Treatment of Cardiovascular Diseases

“…Various pharmacological studies showed that isorhamnetin protects against cardiac hypertrophy and can exhibit positive effect on hypoxia/reoxygenation-induced injury by attenuating apoptosis and oxidative stress [25,26]. Kaempferol can inhibit inflammatory responses and exert protective effect in LPS-induced microvascular endothelial cells [27]. Besides, the protective effect of kaempferol on heart in isoproterenol-induced heart failure has also been proven [28,29].…”

An Investigation of the Mechanism of Rapid Relief of Ulcerative Colitis Induced by Five-flavor Sophora Flavescens Enteric-coated Capsules Based on Network Pharmacology

“…The level of TFF3 mRNA as a functional marker of goblet cells was also up-regulated [ 35 ]. Similarly, the intestinal inflammatory cell model induced by LPS also showed that kaempferol significantly reduced the excessive secretion of TNF-α, IL-1β, IL-6 and ICAM-1, indicating the negative regulation of TLR4, NF-kappaB and STAT signal transduction pathways [ 36 ].…”