Naringenin

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]

Not to be confused with naringin.
Naringenin
Names
IUPAC name
5,7-Dihydroxy-2-(4-hydroxyphenyl)chroman-4-one
Other names
Naringetol; Salipurol; Salipurpol; 4',5,7-Trihydroxyflavanone
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.006.865
UNII
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 YN ?)
Infobox references

Structure

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

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 is 253 mg of naringenin in 10 grams of tomato paste.[20]

Biosynthesis and metabolism

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

Antibacterial, antifungal, and antiviral

Naringenin has an antimicrobial effect on S. epidermidis, as well as Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, and Escherichia coli.[23] Further research has added evidence for antimicrobial effects against Lactococcus lactis,[24] lactobacillus acidophilus, Actinomyces naeslundii, Prevotella oralis, Prevotella melaninogencia, Porphyromonas gingivalis,[25] as well as yeasts such as Candida albicans, Candida tropicalis, and Candida krusei.[26] 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.[27]

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.[28] The antiviral effects of naringenin are currently under clinical investigation.[29] Reports of antiviral effects on polioviruses, HSV-1 and HSV-2 have also been made, though replication of the viruses has not been inhibited.[30][31] In in vitro experiments Naringenin also showed a strong antiviral activity against SARS-CoV-2. [32]

Anti-inflammatory

Despite evidence of anti-inflammatory activity of naringin,[33] the anti-inflammatory activity of naringenin has been observed to be poor to nonexistent.[34][35]

Antioxidant

Naringenin has been shown to have significant antioxidant properties.[36][37] It has been shown to reduce oxidative damage to DNA in vitro and in animal studies.[38][39]

Anticancer

Cytotoxicity has been induced reportedly by naringenin in cancer cells from breast, stomach, liver, cervix, pancreas, and colon tissues, along with leukaemia cells.[40] The mechanisms behind inhibition of human breast carcinoma growth have been examined, and two theories have been proposed.[41] The first theory is that naringenin inhibits aromatase, thus reducing growth of the tumor.[42] The second mechanism proposes that interactions with estrogen receptors is the cause behind the modulation of growth.[43] New derivatives of naringenin were found to be active against multidrug-resistant cancer.[44]

Additional reading

References
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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.
  4. Felgines C, Texier O, Morand C, Manach C, Scalbert A, Régerat F, Rémésy C (December 2000). "Bioavailability of the flavanone naringenin and its glycosides in rats" (PDF). Am. J. Physiol. Gastrointest. Liver Physiol. 279 (6): G1148–54. doi:10.1152/ajpgi.2000.279.6.G1148. PMID 11093936.
  5. Yáñez, Jaime A.; Andrews, Preston K.; Davies, Neal M. (2007-04-01). "Methods of analysis and separation of chiral flavonoids". Journal of Chromatography B. 848 (2): 159–181. doi:10.1016/j.jchromb.2006.10.052. PMID 17113835.
  6. Yáñez, Jaime A.; Remsberg, Connie M.; Miranda, Nicole D.; Vega-Villa, Karina R.; Andrews, Preston K.; Davies, Neal M. (2008-01-01). "Pharmacokinetics of selected chiral flavonoids: hesperetin, naringenin and eriodictyol in rats and their content in fruit juices". Biopharmaceutics & Drug Disposition. 29 (2): 63–82. doi:10.1002/bdd.588. ISSN 1099-081X. PMID 18058792. S2CID 24051610.
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