Cardioprotective Properties of Kaempferol: A Review

Abstract

Cardiac diseases, such as myocardial infarction and heart failure, have become a major clinical problem globally. The accumulating data demonstrate that bioactive compounds with antioxidant and anti-inflammatory properties have favorable effects on clinical problems. Kaempferol is a flavonoid found in various plants; it has demonstrated cardioprotective properties in numerous cardiac injury models. This review aims to collate updated information regarding the effects of kaempferol on cardiac injury. Kaempferol improves cardiac function by alleviating myocardial apoptosis, fibrosis, oxidative stress, and inflammation while preserving mitochondrial function and calcium homeostasis. However, the mechanisms of action of its cardioprotective properties remain unclear; therefore, elucidating its action could provide insight into directions for future studies.

Keywords: anti-inflammatory; antiapoptosis; antifibrosis; antioxidant; calcium regulation; cardiac disease; cardiac function; flavonoid.

Figure 1

The molecular structure of kaempferol, consisting of benzene rings A and B, as well as a heterocyclic ring C.

Figure 2

Sites of action of kaempferol in myocardial injury. Akt, protein kinase B; APAF1, apoptotic protease activating factor 1; ARE, antioxidant response element; ATF6, activating transcription factor 6; CHOP, C/EBP homologous protein; CTGF, connective tissue growth factor; cyt. c, cytochrome c; eIF2, eukaryotic initiation factor 2α; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; GRP78, glucose regulatory protein 78; GSK3, glycogen synthase kinase-3; HO-1, heme oxygenase-1; IKB, inhibitor of κB kinase; NF-κB, nuclear factor kappa B; IKKα, inhibitor of NF-κB kinase α; IKKβ, inhibitor of NF-κB kinase β; IKKγ, inhibitor of NF-κB kinase γ; IRE1, inositol-requiring transmembrane kinase endoribonuclease-1α; JNK, c-Jun N-terminal kinase; Keap1, Kelch-like ECH-associated protein 1; MAPK, mitogen-activated protein kinase; MCUC, mitochondrial Ca²⁺ uniporter complex; MICU1, mitochondrial Ca²⁺ uptake 1; MMP, matrix metalloproteinase; mPTP, mitochondrial permeability transition pore; NQO1, NAD(P)H dehydrogenase (quinone 1); Nrf2, nuclear factor erythroid 2 p45-related factor 2; p38, p38 MAPK; p53, p53 tumor suppressor gene; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator 1α; PI3K, phosphoinositide 3-kinase; PTEN, phosphatase and tensin homolog; ROS, reactive oxygen species; SIRT1, silent information regulator type 1; α-SMA, α-smooth muscle actin; Smad, small mothers against decapentaplegic; STING, stimulator of interferon genes; TFAM, mitochondrial transcription factor A; TGFβ, transforming growth factor β; TIMP; TNFα, tumor necrosis factor α; TNFR, tumor necrosis factor receptor; XBP1, X-box binding protein 1.