Pharmacological effects
Kaempferol (3,5,7‐trihydroxy‐2‐[4‐hydroxyphenyl]‐4H‐1‐benzopyran‐4‐one) is a yellow bioactive flavonoid, which is present inmany edible plants such as tea, cabbage, broccoli, endive, kale, beans, tomato, strawberries, leek, and grapes. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Its efficacy, a broad range of activity, and low toxicity compared with other examined compounds, make it an attractive chemical in the fight against diseases (including cancer).
Mechanism of action
Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3‐kinase (PI3K)/AKT (protein kinase B) and human T‐cell leukemia/lymphoma virus‐I (HTLV-I) signaling pathways, suppresses protein expression of epithelial‐mesenchymal transition (EMT)‐related markers including N‐cadherin, E‐cadherin, Slug, and Snail, and metastasis‐related markers such as matrix metallopeptidase 2 (MMP-2).
Bioactivity
As an anti‐oxidant, kaempferol counteracts production of superoxide ions and lowers the formation of reactive oxygen and nitrogen species. It also scavenges Fenton‐generated hydroxyl radical, peroxynitrite, and hydroxyl radicals. Furthermore, kaempferol suppresses the activity of xanthine oxidase and enhances the activities of catalase, heme oxygenase‐1, and superoxide dismutase.
Chemical Properties
Yellow Solid
Uses
Chromogenic reagent for antimony in the low ppm range and for gallium and indium in the sub-ppm range.
Uses
antidepressant, inhibits fatty acid amide hydrolase
Uses
Kaempferol, is used as an inhibitor of Fatty Acid Synthase, Cox-1 activity, and Topo I. It also Induces caspase-9-mediated apoptosis in a variety of cancer cell lines via downregulation of polo-like kinase 1 (PLK1) expression. Exhibits antioxidant activity and attenuates osteoclastic bone reabsorption in vitro. Also blocks EGF-induced histone H3Ser10 phosphorylation in mouse epidermal JB6 C141 cells.
Definition
ChEBI: Kaempferol is a tetrahydroxyflavone in which the four hydroxy groups are located at positions 3, 5, 7 and 4'. Acting as an antioxidant by reducing oxidative stress, it is currently under consideration as a possible cancer treatment. It has a role as an antibacterial agent, a plant metabolite, a human xenobiotic metabolite, a human urinary metabolite, a human blood serum metabolite and a geroprotector. It is a member of flavonols, a 7-hydroxyflavonol and a tetrahydroxyflavone. It is a conjugate acid of a kaempferol oxoanion.
General Description
Kaempferol is a polyphenolic antioxidant abundantly present in vegetables and fruits. It has a diphenylpropane structure. In many plants, it is present as a glycosidic form namely, kaempferol-3-
O-glucoside.
Biological Activity
Naturally occurring flavonoid found in Gingko biloba and red wines that activates the mitochondrial Ca 2+ uniporter (EC 50 = 7 μ M). Induces caspase-9-mediated apoptosis in a variety of cancer cell lines via downregulation of polo-like kinase 1 (PLK1) expression. Exhibits antioxidant activity and attenuates osteoclastic bone reabsorption in vitro .
Biochem/physiol Actions
Potent inhibitor of osteoclastic bone resorption. The effect is believed to be attributable to both the antioxidant and estrogenic activities of kaempferol.
Anticancer Research
Kaempferol is one of the secondary metabolites found in some plants, plant-derivedfoods, and traditional medicines. It is a flavonoid compound obtained from someedible plants including grapes, tea, strawberries, broccoli, tomato, cabbage, leek,kale, endive, and beans. It inhibits growth and migration of pancreatic cancer cellsby acting on proto-oncogene tyrosine kinase (Src), ERK1/2, and AKT pathways(Singh et al. 2016a). It is being investigated in pancreatic and lung cancers toevaluate its antiangiogenic, anticancer, and radical scavenging activities. It showsmoderate cytostatic activity in PC3, HeLa, and K562 human cancer cells. It isidentified as aryl hydrocarbon receptor antagonist and acts against ABCG2 (ATP-bindingcassette subfamily G member 2)-mediated multidrug resistance bypreventing the ABCG2 upregulation in esophageal carcinoma. It induces theapoptosis of ovarian cancer cell by activating p53 in intrinsic pathway mechanism.It is an inhibitor of breast cancer resistance protein (BCRP), quinine reductase-2,and a substrate of BCRP (Calderon-Montano et al. 2011; Wang et al. 2012).
Synthesis
Kaempferol is synthesized from dihydromyricetin in three steps. 1) Hydrolysis to prepare a hydroxyacetophenone intermediate: Dihydromyricetin is hydrolyzed with NaOH solution. After acidification, a light yellow solid is obtained, which is purified by slurrying with ethanol to yield the intermediate. 2) Catalytic cyclization to prepare crude dihydrokaempferol: The intermediate reacts with proline and p-hydroxybenzaldehyde in DMF under catalysis. Glacial acetic acid is added to precipitate a solid. Filtration and drying give the crude product. 3) Oxidation to prepare kaempferol: The crude product is oxidized by refluxing in ethanol under oxygen with K2CO3 as base. Work-up and purification by refluxing with water yield kaempferol.
