Naringenin

Not to be confused with naringin.
Naringenin
Systematic (IUPAC) name
5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one
Identifiers
CAS Number 480-41-1 YesY
ATC code None
PubChem CID 439246
CID 932
DrugBank DB03467 N
ChemSpider 388383 N
UNII HN5425SBF2 N
ChEBI CHEBI:50202 N
ChEMBL CHEMBL9352 N
Synonyms 4',5,7-trihydroxyflavanone
Chemical data
Formula C15H12O5
Molar mass 272.257 g/mol
 NYesY (what is this?)  (verify)

Naringenin is a flavanone, a type of flavonoid, that is considered to have a bioactive effect on human health as antioxidant, free radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, and immune system modulator. It is the predominant flavanone in grapefruit.[1]

Biological effects

This substance has also been shown to reduce oxidative damage to DNA in vitro. Scientists exposed cells to 80 micromoles of naringenin per liter, for 24 hours, and found that the amount of hydroxyl damage to the DNA was reduced by 24% in that very short period of time.

Naringenin found in grapefruit juice has been shown to have an inhibitory effect on the human cytochrome P450 isoform CYP1A2, which can change pharmacokinetics in a human (or orthologous) host of several popular drugs in an adverse manner, even resulting in carcinogens of otherwise harmless substances.[2]

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.[3] The antiviral effects of naringenin are currently under clinical investigation.[4]

Naringenin seems to protect LDLR-deficient mice from the obesity effects of a high-fat diet.[5]

Naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet.[6]

The National Research Institute of Chinese Medicine in Taiwan conducted experiments on the effects of the grapefruit flavanones naringin and naringenin on CYP450 enzyme expression. Naringenin proved to be a potent inhibitor of the benzo(a)pyrene metabolizing enzyme benzo(a)pyrene hydroxylase (AHH) in in vitro experiments in mice.[7] This suggests, but does not conclusively prove, that naringenin would elicit the same response when administered to humans. More research will be needed to determine if naringenin has any clinically significant effects (including medical applications) in human subjects.

It also produces BDNF-dependent antidepressant-like effects in mice.[8]

Like many other flavonoids, naringenin has been found to possess activity at the opioid receptors.[9] It specifically acts as a non-selective antagonist of all three opioid receptors, albeit with somewhat weak affinity.[9]

Sources and bioavailability

It can be found in grapefruits, oranges and tomatoes (skin).[10]

This bioflavonoid is difficult to absorb on oral ingestion. In the best-case scenario, only 15% of ingested naringenin will get absorbed in the human gastrointestinal tract. A full glass of orange juice will supply about enough naringenin to achieve a [blood plasma?] concentration of about 0.5 micromoles per liter.

The naringenin-7-glucoside form seems less bioavailable than the aglycol form.[11]

Grapefruit juice can provide much higher plasma concentrations of naringenin than orange juice.[12] 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.[13]

Metabolism

The enzyme naringenin 8-dimethylallyltransferase uses dimethylallyl diphosphate and (−)-(2S)-naringenin to produce diphosphate and sophoraflavanone B (8-prenylnaringenin).

Biodegradation

Cunninghamella elegans, a fungal model organism of the mammalian metabolism, can be used to study the naringenin sulfation.[14]

References

  1. ↑ 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". Am. J. Physiol. Gastrointest. Liver Physiol. 279 (6): G1148–54. PMID 11093936.
  2. ↑ Fuhr U, Klittich K, Staib AH (April 1993). "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man". Br J Clin Pharmacol 35 (4): 431–6. doi:10.1016/0024-3205(96)00417-1. PMC 1381556. PMID 8485024.
  3. ↑ Nahmias Y, Goldwasser J, Casali M, van Poll D, Wakita T, Chung RT, Yarmush ML (May 2008). "Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin". Hepatology 47 (5): 1437–45. doi:10.1002/hep.22197. PMID 18393287.
  4. ↑ A Pilot Study of the Grapefruit Flavonoid Naringenin for HCV Infection
  5. ↑ Mulvihill EE, Allister EM, Sutherland BG, Telford DE, Sawyez CG, Edwards JY, Markle JM, Hegele RA, Huff MW (October 2009). "Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance". Diabetes 58 (10): 2198–210. doi:10.2337/db09-0634. PMC 2750228. PMID 19592617.
  6. ↑ Lee SH, Park YB, Bae KH, Bok SH, Kwon YK, Lee ES, Choi MS (1999). "Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase in rats". Ann. Nutr. Metab. 43 (3): 173–80. doi:10.1159/000012783. PMID 10545673.
  7. ↑ Ueng YF, Chang YL, Oda Y, Park SS, Liao JF, Lin MF, Chen CF (1999). "In vitro and in vivo effects of naringin on cytochrome P450-dependent monooxygenase in mouse liver". Life Sci. 65 (24): 2591–602. doi:10.1016/s0024-3205(99)00528-7. PMID 10619367.
  8. ↑ Yi LT, Liu BB, Li J, Luo L, Liu Q, Geng D, Tang Y, Xia Y, Wu D (October 2013). "BDNF signaling is necessary for the antidepressant-like effect of naringenin". Prog. Neuropsychopharmacol. Biol. Psychiatry 48C: 135–141. doi:10.1016/j.pnpbp.2013.10.002. PMID 24121063.
  9. 1 2 Katavic PL, Lamb K, Navarro H, Prisinzano TE (August 2007). "Flavonoids as opioid receptor ligands: identification and preliminary structure-activity relationships". J. Nat. Prod. 70 (8): 1278–82. doi:10.1021/np070194x. PMC 2265593. PMID 17685652.
  10. ↑ Vallverdú-Queralt, A; Odriozola-Serrano, I; Oms-Oliu, G; Lamuela-Raventós, RM; Elez-Martínez, P; Martín-Belloso, O (2012). "Changes in the polyphenol profile of tomato juices processed by pulsed electric fields". J Agric Food Chem. 60 (38): 9667–9672. doi:10.1021/jf302791k. PMID 22957841.
  11. ↑ Choudhury R, Chowrimootoo G, Srai K, Debnam E, Rice-Evans CA (November 1999). "Interactions of the flavonoid naringenin in the gastrointestinal tract and the influence of glycosylation". Biochem. Biophys. Res. Commun. 265 (2): 410–5. doi:10.1006/bbrc.1999.1695. PMID 10558881.
  12. ↑ Erlund I, Meririnne E, Alfthan G, Aro A (February 2001). "Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice". J. Nutr. 131 (2): 235–41. PMID 11160539.
  13. ↑ Bugianesi R, Catasta G, Spigno P, D'Uva A, Maiani G (November 2002). "Naringenin from cooked tomato paste is bioavailable in men". J. Nutr. 132 (11): 3349–52. PMID 12421849.
  14. ↑ Ibrahim AR (January 2000). "Sulfation of naringenin by Cunninghamella elegans". Phytochemistry 53 (2): 209–12. doi:10.1016/S0031-9422(99)00487-2. PMID 10680173.


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