A Critical Review of Kaempferol in Intestinal Health and Diseases

Abstract

Kaempferol, a secondary metabolite found in plants, is a naturally occurring flavonoid displaying significant potential in various biological activities. The chemical structure of kaempferol is distinguished by the presence of phenyl rings and four hydroxyl substituents, which make it an exceptional radical scavenger. Most recently, an increasing number of studies have demonstrated the significance of kaempferol in the regulation of intestinal function and the mitigation of intestinal inflammation. The focus of the review will primarily be on its impact in terms of antioxidant properties, inflammation, maintenance of intestinal barrier function, and its potential in the treatment of colorectal cancer and obesity. Future research endeavors should additionally give priority to investigating the specific dosage and duration of kaempferol administration for different pathological conditions, while simultaneously conducting deeper investigations into the comprehensible mechanisms of action related to the regulation of aryl hydrocarbon receptor (AhR). This review intends to present novel evidence supporting the utilization of kaempferol in the regulation of gut health and the management of associated diseases.

Keywords: antioxidant; intestinal barrier function; intestinal health; intestinal inflammation; kaempferol.

Figure 1

Chemical structure of kaempferol. (A). Two-dimensional structure; (B). Three-dimensional structure (Source from ChemSpider).

Figure 2

The beneficial effects of kaempferol on the intestine and the proposed mechanism of action based on current knowledge. Abbreviations: BCRP, breast cancer resistance protein; COX-2, cyclooxygenase-2; CRP, C-reaction protein; DR5, death receptor 5; eWAT, epididymal white adipose tissue; FXR, farnesoid X receptor; GSR, glutathione reductase; GSTA4, glutathione S-transferase 4; HO-1, heme oxygenase-1; ICAM-1, intercellular adhesion molecule-1; IFN-γ, interferon-γ; IL-1β, interleukin-1β; IL-6, interleukin-6; IL-10, interleukin-10; iONS, inducible nitric oxide synthase; iWAT, inguinal white adipose tissue; LDH, lactate dehydrogenase; LTB₄, leukotriene B₄; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein-1; MIP-3α, macrophage inflammatory protein-3 alpha; MPO, myeloperoxidase; MRP2, multi-drug resistance-associated protein 2; NF-κB, nuclear factor kappa-B; NLRP3, nucleotide oligomerization domain (NOD)-like receptor 3; Nrf2, nuclear factor-E2-related factor 2; PARP, poly ADPribose polymerase; PGE₂, prostaglandin E₂; PKA, protein kinase A; pWAT, perirenal white adipose tissue; RhoA/ROCK, Ras homolog gene family member A/Rho-associated protein kinase; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; TEER, transepithelial electrical resistance; TFF3, trefoil factor family 3; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor-α; VCAM-1, vascular cell adhesion molecule-1.

Figure 3

AhR signaling pathway. Abbreviations: AhR, aryl hydrocarbon receptor; AhRE, aryl hydrocarbon receptor responsive elements; Ahrr, AhR repressor; AIP, AhR-interacting protein; ARNT, aryl hydrocarbon receptor nuclear translocator; Cyp1a1, cytochrome P450 family 1 subfamily A member 1; Cyp1b1; cytochrome P450 family 1 subfamily B member 1; HSP90, heat shock protein 90; Ido1, indoleamine 2,3-dioxygenase 1; P23, co­chaperone P23; SRC, SRC protein kinase; Tdo, tryptophan 2,3-dioxygenase.