Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

A review on the dietary flavonoid kaempferol.

Bioactive flavonoids in medicinal plants: Structure, activity and biological fate.

Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.

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Flavonoids as Anticancer Agents

Estrogenic endocrine disruptors: Molecular mechanisms of action.

Kaempferol, a potential cytostatic and cure for inflammatory disorders.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2009.01.030

Kaempferol is an estrogen-related receptor α and γ inverse agonist.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2009.11.026

Structural activity relationship of flavonoids with estrogen-related receptor gamma.

Objective Although oestrogen-related receptor alpha (ERRalpha) is primarily thought to regulate energy homeostasis, it also serves as a prognostic marker for cancer. The aim of this study was to investigate any connection between ERRalpha activity and cell population growth. Materials and methods XCT-790, an ERRa specific inverse agonist, was employed to suppress ERRa activity in human non-small cell lung cancer cells (NSCLC) A549. Gene expressions were detected using quantitative real-time PCR and Western blot analysis. Mitochondrial mass, membrane potential and reactive oxygen species (ROS) production were measured by staining with Mitotracker green, JC-1 and CM-H(2)DCFDA dyes respectively. Rate of progression through the tricarboxylic acid (TCA) cycle was analysed by measuring activities of citrate synthase and succinate dehydrogenase. Cell cycle analysis was performed by using flow cytometry. Results We found that XCT-790 treatment reduced mitochondrial mass but enhanced mitochondrial ROS production by increasing rate through the TCA cycle, elevating mitochondrial membrane potential (DeltaPsi(m)) and down-regulating expression of superoxide dismutase. It was further demonstrated that XCT-790-induced ROS modulated p53 and Rb signalling pathways and suppressed cell replication. Conclusions ERRalpha affects cell cycle mechanisms through modulating mitochondrial mass and function. Dysregulation of this essential pathway leads to elevation in mitochondrial ROS production, which in turn modulates activities of tumour suppressors, resulting in cell cycle arrest.

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Oestrogen-related receptor alpha inverse agonist XCT-790 arrests A549 lung cancer cell population growth by inducing mitochondrial reactive oxygen species production

Chi-Wai Wong

Papers

Kaempferol is an estrogen-related receptor α and γ inverse agonist.

Structural activity relationship of flavonoids with estrogen-related receptor gamma.

Oestrogen-related receptor alpha inverse agonist XCT-790 arrests A549 lung cancer cell population growth by inducing mitochondrial reactive oxygen species production

Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist.