Anti-inflammatory properties of kaempferol via its inhibition of aldosterone signaling and aldosterone-induced gene expression

Abstract

Osteopontin (OPN), also called cytokine Eta-1, is a pro-inflammatory cytokine. Recent studies have shown that aldosterone increases OPN gene expression in endothelial cells. As a flavonoid compound, kaempferol has potent anti-inflammatory properties, but whether kaempferol regulates aldosterone signaling and aldosterone-induced gene expression is still unknown. Human umbilical vein endothelial cells (HUVECs) were pretreated with kaempferol (0, 1, 3, or 10 μmol/L) for 1 h prior to exposure to aldosterone (10(-6) mol/L) for 24 h. Aldosterone induced generation of reactive oxygen species; OPN and cluster of differentiation 44 gene expression; phospho-p38 MAPK and NF-κB binding activity. The effect of aldosterone was abrogated by kaempferol and spironolactone (10(-6) mol/L). The present results suggest that kaempferol exerts its anti-inflammatory properties via its inhibition of aldosterone signaling and aldosterone-induced gene expression in HUVECs.

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

“…However, chronic inflammation has been considered to be associated with the progression of various diseases, including cancer, arthritis, and neurodegeneration (Tuli, Chaudhary, Beniwal, & Sharma, 2015;Tuli, Kashyap, Bedi, et al, 2015;. KMF has been proven to be a potent inhibitor of proinflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (Kong, Luo, Li, Zhou, & He, 2013a, 2013bLiu, Xiao, & Fang, 2014). The anti-inflammatory mechanisms of KMF are mainly mediated (Fig.…”

“…Garcia-Mediavilla et al (2007) examined the anti-inflammatory potential of KMF in the human hepatocyte-derived cell line and proved that KMF was able to reduce the expression of C-reactive protein (CRP), COX-2, and iNOS via alterations in NF-jB pathway. Osteopontin (OPN), a reactive oxygen species (ROS)-dependent cytokine, which engenders and activates the p38 MAPK and NF-jB signaling, has been found to be down-regulated in aldosterone-induced human umbilical vein endothelial cells (HUVECs) by KMF (Liu et al, 2014). Comparably, KMF treatment in lipopolysaccharide (LPS)-induced macrophages revealed the consequential down-regulation of COX-2, iNOS and TNF-a (tumour necrosis factor-a) both at transcriptional and translational levels via inhibition of NF-jB and AP-1 transcription factor (Kim, Kim, Moh, & Kang, 2015; Kim, Park, et al, 2015).…”

Network Pharmacology-Based Pharmacological Mechanism of the Chinese Medicine Rhizoma drynariae Against Osteoporosis

“…Most of these ingredients possess potent pharmacological activity. For example, β-sitosterol has good anti-oxidation and anti-inflammatory effects [21,22], luteolin has antibacterial, anti-oxidant, and other broad biological and pharmacological properties [23], and kaempferol has an anti-inflammatory effect [24], and naringenin was determined to be the quality markers of Rhizoma drynariae in the Chinese Pharmacopoeia (the State Pharmacopoeia Commission of China, 2015). The OB of these compounds varies greatly, presenting an approximately normal distribution, mostly concentrated at about 40%, and the OB is generally inversely proportional to the molecular weight (MW).…”

Berries and Their Polyphenols as a Potential Therapy for Coronary Microvascular Dysfunction: A Mini-Review

“…Aldosterone also impacts ECs and may dimish endothelial function via the mineralocorticoid receptor (MR) by increasing NOX expression independent of blood pressure [118]. Preliminary evidence suggests that polyphenols, such as kaempferol, may also inhibit MR in human umbilical vein endothelial cells (HUVECs), resulting in the reduction of ROS and inflammatory signaling [119,120]. Thus, berries may target RAAS primarily via reduced ACE activity and decreased AT 1 R but may also inhibit the production and action of aldosterone.…”

“…Aldosterone ↓ [116,117,119,120] Caffeic acid, quercetin and kaempferol May decrease the synthesis of aldosterone in the adrenal cortex and decrease the action of aldosterone in the kidneys, resulting in reduced blood pressure, decreasing microcirculatory resistance. Additionally, polyphenols may decrease MR activity in the endothelium, resulting in reduced endothelial dysfunction.…”