'''Kaempferol''' (3,4′,5,7-tetrahydroxyflavone) is a natural [[flavonol]], a type of [[flavonoid]], found in a variety of plants and plant-derived foods including [[kale]], [[Bean|beans]], [[tea]], [[spinach]] and [[Broccoli|broccoli.]] <ref>{{Cite journal|last=Holland|first=Thomas M.|last2=Agarwal|first2=Puja|last3=Wang|first3=Yamin|last4=Leurgans|first4=Sue E.|last5=Bennett|first5=David A.|last6=Booth|first6=Sarah L.|last7=Morris|first7=Martha Clare|date=2020-01-29|title=Dietary flavonols and risk of Alzheimer dementia|url=http://www.neurology.org/lookup/doi/10.1212/WNL.0000000000008981|journal=Neurology|language=en|pages=10.1212/WNL.0000000000008981|doi=10.1212/WNL.0000000000008981|issn=0028-3878}}</ref> Kaempferol is a yellow crystalline solid with a melting point of {{convert|276-278|C|F}}. It is slightly soluble in water and highly soluble in hot [[ethanol]], [[ethers]], and [[Dimethyl sulfoxide|DMSO]]. Kaempferol acts as an [[antioxidant]] by reducing oxidative stress. Many studies suggest that consuming kaempferol may reduce the risk of various cancers, and it is currently under consideration as a possible cancer treatment {{Citation needed|date=April 2018}}. It is named for 17th-century German naturalist [[Engelbert Kaempfer]].<ref name=MW>[https://www.merriam-webster.com/dictionary/kaempferol Kaempferol] at [[Merriam-Webster]].com; retrieved October 20, 2017</ref>

Kaempferol is common in [[Pteridophyta]], [[Pinophyta]] and [[Angiospermae]]. Within Pteridophyta and Pinophyta, kaempferol has been found in diverse families. Kaempferol has also been identified in both [[Dicotyledons]] and [[Monocotyledons]] of Angiosperms.<ref name="calderon" /> The total average intake of flavonols and flavones in a normal diet is estimated as 23&nbsp;mg/day, to which kaempferol contributes approximately 17%.<ref name=liu>{{cite journal | vauthors = Liu RH | title = Health-promoting components of fruits and vegetables in the diet | journal = Advances in Nutrition | volume = 4 | issue = 3 | pages = 384S–92S | date = May 2013 | pmid = 23674808 | pmc = 3650511 | doi = 10.3945/an.112.003517 }}</ref> Common foods that contain kaempferol include: apples,<ref name=kim>{{cite journal | vauthors = Kim SH, Choi KC | title = Anti-cancer Effect and Underlying Mechanism(s) of Kaempferol, a Phytoestrogen, on the Regulation of Apoptosis in Diverse Cancer Cell Models | journal = Toxicological Research | volume = 29 | issue = 4 | pages = 229–34 | date = December 2013 | pmid = 24578792 | pmc = 3936174 | doi = 10.5487/TR.2013.29.4.229 }}</ref> grapes,<ref name="kim" /> tomatoes,<ref name="kim" /> green tea,<ref name="kim" /> potatoes,<ref name="liu" /> onions,<ref name="calderon" /> broccoli,<ref name="calderon" /> Brussels sprouts,<ref name="calderon" /> squash,<ref name="calderon" /> cucumbers,<ref name="calderon" /> lettuce,<ref name="calderon" /> green beans,<ref name="calderon" /> peaches,<ref name="calderon" /> blackberries,<ref name="calderon" /> raspberries,<ref name="calderon" /> and spinach.<ref name="calderon" /> Plants that are known to contain kaempferol include ''[[Aloe vera]]'',<ref name="calderon" /> ''[[Coccinia grandis]]'',<ref name="calderon" /> ''[[Cuscuta chinensis]]'',<ref>{{cite journal | vauthors = Donnapee S, Li J, Yang X, Ge AH, Donkor PO, Gao XM, Chang YX | title = Cuscuta chinensis Lam.: A systematic review on ethnopharmacology, phytochemistry and pharmacology of an important traditional herbal medicine | journal = Journal of Ethnopharmacology | volume = 157 | issue = C | pages = 292–308 | date = November 2014 | pmid = 25281912 | doi = 10.1016/j.jep.2014.09.032 }}</ref> ''[[Euphorbia pekinensis]]'',<ref name="calderon" /> ''[[Glycine max]]'',<ref name="calderon" /> ''[[Hypericum perforatum]]'',<ref name="calderon" /> ''[[Scots pine|Pinus sylvestris]]'',<ref>{{cite journal | vauthors = de la Luz Cádiz-Gurrea M, Fernández-Arroyo S, Segura-Carretero A | title = Pine bark and green tea concentrated extracts: antioxidant activity and comprehensive characterization of bioactive compounds by HPLC-ESI-QTOF-MS | journal = International Journal of Molecular Sciences | volume = 15 | issue = 11 | pages = 20382–402 | date = November 2014 | pmid = 25383680 | pmc = 4264173 | doi = 10.3390/ijms151120382 }}</ref> ''[[Moringa oleifera]]'',<ref>{{cite journal | vauthors = Anwar F, Latif S, Ashraf M, Gilani AH | title = Moringa oleifera: a food plant with multiple medicinal uses | journal = Phytotherapy Research | volume = 21 | issue = 1 | pages = 17–25 | date = January 2007 | pmid = 17089328 | doi = 10.1002/ptr.2023 }}</ref> ''[[Rosmarinus officinalis]]'',<ref name="calderon" /> ''[[Sambucus nigra]]'',<ref name="calderon" /> and ''[[Toona sinensis]],''<ref name="calderon" /> and ''[[Ilex]]''.<ref name="calderon" /> It also is present in [[endive]].<ref name="DuPont_2004">{{cite journal | vauthors = DuPont MS, Day AJ, Bennett RN, Mellon FA, Kroon PA | title = Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans | journal = European Journal of Clinical Nutrition | volume = 58 | issue = 6 | pages = 947–54 | date = June 2004 | pmid = 15164116 | doi = 10.1038/sj.ejcn.1601916 }}</ref>

==Pharmacokinetics==

Kaempferol is ingested as a [[glycoside]], absorbed in the small intestine, usually by passive diffusion due to kaempferol’s lipophilicity, and metabolized in various areas of the body. In the small intestine, kaempferol is metabolized to [[glucuronide]]s and [[sulfoconjugate]]s by intestinal enzymes. It can also be metabolized by colon microflora which can hydrolyze the glycosides to aglycones or form simple phenolic compounds. These compounds can be absorbed or excreted. Kaempferol is also extensively metabolized in the liver to form glucurono-conjugated and sulfo-conjugated forms. These forms of kaempferol, and kaempferol itself, can then be excreted in urine. About 2.5% of kaempferol ingested is excreted as urine. Much of the rest of ingested kaempferol is present in the plasma and tissues in nanomolar concentrations.<ref name="calderon" />

== Potential pharmacology ==

{{medical citations needed|section|date=March 2015}}

Numerous preclinical studies have shown kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, antiosteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic, and antiallergic activities.<ref name="calderon"/>

===Anti-cancer effects===

''[[In vitro]]'' studies along with some [[animal testing]] has demonstrated the wide range of potential anti-cancer properties of kaempferol. It has been shown in malignant cancer cells to interrupt cell growth, limit angiogenesis, induce apoptosis, and to reduce their available energy and ability to metastasize. Kaempferol has also been shown to reduce MMP-3 protein activity inferring potential ability to reduce metastasis.<ref name="calderon" />

====Breast cancer====

[[Estrogen receptors]] are important in both maintaining a normal mammary gland, and in the development of primary and secondary breast cancer. Kaempferol has been shown to interact with the estrogen receptor pathway and alter signaling in order to help slow growth. This compound exhibits ability to lower levels of [[aromatase]].<ref>{{cite journal | vauthors = Wang C, Mäkelä T, Hase T, Adlercreutz H, Kurzer MS | title = Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 50 | issue = 3–4 | pages = 205–12 | date = August 1994 | pmid = 8049151 | doi = 10.1016/0960-0760(94)90030-2 }}</ref> Kaempferol has also been found to induce apoptosis in breast cancer cells through [[extracellular signal-regulated kinase]] ½ activation <ref>{{cite journal | vauthors = Aiyer HS, Warri AM, Woode DR, Hilakivi-Clarke L, Clarke R | title = Influence of berry polyphenols on receptor signaling and cell-death pathways: implications for breast cancer prevention | journal = Journal of Agricultural and Food Chemistry | volume = 60 | issue = 23 | pages = 5693–708 | date = June 2012 | pmid = 22300613 | pmc = 3383353 | doi = 10.1021/jf204084f }}</ref> and up-regulation of [[p53]].<ref name="calderon" />

====Ovarian cancer====

Available evidence has shown that kaempferol can “inhibit VEGF production and suppress ovarian cancer cell metastasis in vitro”.<ref>{{cite journal | vauthors = Chen SS, Michael A, Butler-Manuel SA | title = Advances in the treatment of ovarian cancer: a potential role of antiinflammatory phytochemicals | journal = Discovery Medicine | volume = 13 | issue = 68 | pages = 7–17 | date = January 2012 | pmid = 22284780 }}</ref>

====Leukemia====

Kaempferol has been shown to reduce growth in pro-myelocytic leukemia cells through altering the cell cycle.<ref>{{cite journal | vauthors = Jaganathan SK, Mandal M | title = Antiproliferative effects of honey and of its polyphenols: a review | journal = Journal of Biomedicine & Biotechnology | volume = 2009 | pages = 1–13 | year = 2009 | pmid = 19636435 | pmc = 2712839 | doi = 10.1155/2009/830616 }}</ref>

====Bladder, prostate, and colorectal cancer ====

Various studies have shown that intake of kaempferol containing foods is associated with decreased bladder cancer, prostate cancer, or colorectal cancer risk.<ref name="calderon" />

====Gastric cancer====

A case controlled study found that “consumption of kaempferol-containing foods was associated with a reduced gastric cancer risk”.<ref name="calderon" />

====Pancreatic cancer====

An eight-year study found the consumption of three [[flavonol]]s (kaempferol, [[quercetin]], and [[myricetin]]) correlated with a lower risk of [[pancreatic cancer]] among current smokers, but not non-smokers or ex-smokers.<ref>{{cite journal | vauthors = Nöthlings U, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN | title = Flavonols and pancreatic cancer risk: the multiethnic cohort study | journal = American Journal of Epidemiology | volume = 166 | issue = 8 | pages = 924–31 | date = October 2007 | pmid = 17690219 | doi = 10.1093/aje/kwm172 }}</ref>

====Lung cancer====

In A549 lung cancer cells, kaempferol up-regulated pro-apoptotic [[Bcl-2-associated X protein|bax]] and [[Bcl-2-associated death promoter|bad]] genes, while it down-regulated anti-apoptotic bcl-2 and bcl-xL expression. This resulted in an increase in apoptosis of the cancer cells.<ref name="kim" />

===Diabetes===

A correlation was found between increased levels of kaempferol in the diet and a reduced relative risk of type 2 diabetes in a cohort study in 2005.<ref name="calderon" /> Additionally, 6-methoxykaempferol-3-O-β-D-robinobioside was shown to have significant inhibitory activity of aldose reductase, which plays an important role in diabetic complications.<ref>{{cite journal | vauthors = Veeresham C, Rama Rao A, Asres K | title = Aldose reductase inhibitors of plant origin | journal = Phytotherapy Research | volume = 28 | issue = 3 | pages = 317–33 | date = March 2014 | pmid = 23674239 | doi = 10.1002/ptr.5000 }}</ref>

===Cardiovascular disorders===

A cohort study in men showed that consumption of flavonoid containing food decreased the risk of mortality from coronary heart disease. Another cohort study showed that high intake of tea is inversely associated with myocardial infarction.<ref name="calderon" />

Kaempferol has also been shown to have a protective effect on the apoptosis induced by the ischemia/reperfusion of cardiac cells. Due to this, it has a promising pharmacological role in preventing cardiovascular disease.<ref>{{cite journal | vauthors = Khalil MI, Sulaiman SA | title = The potential role of honey and its polyphenols in preventing heart diseases: a review | journal = African Journal of Traditional, Complementary and Alternative Medicines | volume = 7 | issue = 4 | pages = 315–21 | year = 2010 | pmid = 21731163 | pmc = 3005390 | doi = 10.4314/ajtcam.v7i4.56693 }}</ref>

===Anti-bacterial activity===

In a four-week study, kaempferol and its glycosides decreased the number of ''[[Helicobacter pylori]]'' colonies in [[gerbil]]s. It also has been shown to work synergistically with antibiotics.<ref name="calderon" />

===Anti-viral activity===

Kaempferol has been shown to inhibit or decrease the activity of enzymes that partake in viral infection such as reverse transcriptase, viral proteases and neuraminidase.<ref name="calderon" />

===Antioxidant effects===

Kaempferol has been shown to have an array of antioxidant effects in vitro and in vivo. At low concentrations, its acts as a super-oxide scavenger, specifically against the highly reactive hydroxyl radical and peroxynitrite species. At high concentrations it increases the activity or expression of antioxidant enzymes such as [[superoxide dismutase]], [[catalase]], and [[heme oxygenase-1]]. Kaempferol can prevent the oxidation of low-density lipid proteins indicating a potential protective role in atherosclerosis.<ref name="calderon" />