Naringenin

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Naringenin
Naringenin.svg
Names
IUPAC name
(2S)-4′,5,7-Trihydroxyflavan-4-one
Preferred IUPAC name
(2S)-5,7-Dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one
Other names
Naringetol; Salipurol; Salipurpol
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.006.865 Edit this at Wikidata
UNII
  • InChI=1S/C15H12O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-6,13,16-18H,7H2/t13-/m0/s1 ☒N
    Key: FTVWIRXFELQLPI-ZDUSSCGKSA-N ☒N
  • O=C2c3c(O[C@H](c1ccc(O)cc1)C2)cc(O)cc3O
Properties
C15H12O5
Molar mass 272.256 g·mol−1
Melting point 251 °C (484 °F; 524 K)[1]
475 mg/L[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Naringenin is a flavorless,[2] colorless[3] flavanone, a type of flavonoid. It is the predominant flavanone in grapefruit,[4] and is found in a variety of fruits and herbs.[5]

Structure[edit]

Naringenin has the skeleton structure of a flavanone with three hydroxy groups at the 4', 5, and 7 carbons. It may be found both in the aglycol form, naringenin, or in its glycosidic form, naringin, which has the addition of the disaccharide neohesperidose attached via a glycosidic linkage at carbon 7.

Like the majority of flavanones, naringenin has a single chiral center at carbon 2, although the optical purity is variable.[5][6] Racemization of S(-)-naringenin has been shown to occur fairly quickly.[7]

Sources and bioavailability[edit]

Naringenin and its glycoside has been found in a variety of herbs and fruits, including grapefruit,[8] bergamot,[9] sour orange,[10] tart cherries,[11] tomatoes,[12][13] cocoa,[14] Greek oregano,[15] water mint,[16] as well as in beans.[17] Ratios of naringenin to naringin vary among sources,[12] as do enantiomeric ratios.[6]

The naringenin-7-glucoside form seems less bioavailable than the aglycol form.[18]

Grapefruit juice can provide much higher plasma concentrations of naringenin than orange juice.[19] Also found in grapefruit is the related compound kaempferol, which has a hydroxyl group next to the ketone group.

Naringenin can be absorbed from cooked tomato paste. There are 3.8 mg of naringenin in 150 grams of tomato paste.[20]

Biosynthesis and metabolism[edit]

It is derived from malonyl CoA and 4-coumaroyl CoA. The latter is derived from phenylalanine. The resulting tetraketide is acted on by chalcone synthase to give the chalcone that then undergoes ring-closure to naringenin.[21]

The enzyme naringenin 8-dimethylallyltransferase uses dimethylallyl diphosphate and (−)-(2S)-naringenin to produce diphosphate and 8-prenylnaringenin. Cunninghamella elegans, a fungal model organism of the mammalian metabolism, can be used to study the naringenin sulfation.[22]

Potential biological effects[edit]

Alzheimer's disease[edit]

Naringenin is being researched as a potential treatment for Alzheimer's disease. Naringenin has been demonstrated to improve memory and reduce amyloid and tau proteins in a study using a mouse model of Alzheimer's disease.[23][24] The effect is believed to be due to a protein present in neurons known as CRMP2 that naringenin binds to.[25]

Antibacterial, antifungal, and antiviral[edit]

Naringenin has an antimicrobial effect on S. epidermidis, as well as Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, and Escherichia coli.[26] Further research has added evidence for antimicrobial effects against Lactococcus lactis,[27] lactobacillus acidophilus, Actinomyces naeslundii, Prevotella oralis, Prevotella melaninogencia, Porphyromonas gingivalis,[28] as well as yeasts such as Candida albicans, Candida tropicalis, and Candida krusei.[29] There is also evidence of antibacterial effects on H. pylori, though naringenin has not been shown to have any inhibition on urease activity of the microbe.[30]

Naringenin has also been shown to reduce hepatitis C virus production by infected hepatocytes (liver cells) in cell culture. This seems to be secondary to naringenin's ability to inhibit the secretion of very-low-density lipoprotein by the cells.[31] The antiviral effects of naringenin are currently under clinical investigation.[32] Reports of antiviral effects on polioviruses, HSV-1 and HSV-2 have also been made, though replication of the viruses has not been inhibited.[33][34] In in vitro experiments Naringenin also showed a strong antiviral activity against SARS-CoV-2. [35]

Anti-inflammatory[edit]

Despite evidence of anti-inflammatory activity of naringin,[36] the anti-inflammatory activity of naringenin has been observed to be poor to nonexistent.[37][38]

Antioxidant[edit]

Naringenin has been shown to have significant antioxidant properties.[39][40] It has been shown to reduce oxidative damage to DNA in vitro and in animal studies.[41][42]

Anticancer[edit]

Cytotoxicity has been induced reportedly by naringenin in cancer cells from breast, stomach, liver, cervix, pancreas, and colon tissues, along with leukaemia cells.[43][44] The mechanisms behind inhibition of human breast carcinoma growth have been examined, and two theories have been proposed.[45] The first theory is that naringenin inhibits aromatase, thus reducing growth of the tumor.[46] The second mechanism proposes that interactions with estrogen receptors is the cause behind the modulation of growth.[47] New derivatives of naringenin were found to be active against multidrug-resistant cancer.[48]

Additional reading[edit]

References[edit]

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  3. ^ Shin, W.; Kim, S.; Chun, K. S. (1987-10-15). "Structure of (R,S)-hesperetin monohydrate". Acta Crystallographica Section C. 43 (10): 1946–1949. doi:10.1107/s0108270187089510. ISSN 0108-2701.
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