Hesperetin
DESCRIPTION
Hesperetin belongs to the flavanone class of flavonoids. Hesperetin, in the form of its glycoside hesperidin, is the predominant flavonoid in lemons and oranges.
Hesperetin is a solid substance that is poorly soluble in water. Its molecular formula is C16H14O6, and its molecular weight is 302.28 daltons. It is also known as 3',5,7-trihydroxy-4'-methoxyflavanone and (S)-2,3- dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-H-1-benzopy- ran-4-one. Hesperetin is the aglycone (aglucon) of hesperedin. Hesperetin has the following structural formula:
Hesperetin
ACTIONS AND PHARMACOLOGY
ACTIONS
Hesperetin may have antioxidant, anti-inflammatory, anti-allergic, hypolipidemic, vasoprotective and anticarcinogenic actions.
MECHANISM OF ACTION
Hesperetin is a phenolic antioxidant. It may scavenge such reactive oxygen species as superoxide anions and may protect against peroxidation.
Hesperetin's possible anti-inflammatory activity may be accounted for by its interference with the metabolism of arachidonic acid and histamine release. There is evidence that hesperetin inhibits phospholipase A2, lipoxygenase and cyclo-oxygenase. Hesperetin may inhibit histamine release from mast cells.
Hesperetin may reduce plasma cholesterol levels by inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase as well as acylcoenzyme A: cholesterol acyltransferase (ACAT). Inhibition of these enzymes has been demonstrated in rats fed a high-cholesterol diet.
The mechanism of hesperetin's possible vasoprotective action is unclear. Hesperetin has been shown to decrease microvascular permeability. It may protect endothelial cells from hypoxia by stimulating certain mitochondrial enzymes such as succinate dehydrogenase.
The mechanism of hesperetin's possible anticarcinogenic action is also unclear. It may be accounted for, in part, by hesperetin's possible antioxidant activity. Other possibilities include inhibition of polyamine biosynthesis and inhibition of lipoxygenase and cyclo-oxygenase.
PHAMACOKINETICS
Hesperetin is typically administered as hesperidin. See Hesperidin.
INDICATIONS AND USAGE
Hesperetin may be helpful in lowering cholesterol and, possibly, otherwise favorably affecting lipids. In vitro and animal research also suggests the possibility that hesperetin might have some anticancer effects and that it might have some anti-aromatase activity, as well as activity against Helicobacter pylori. More research will be required before hesperetin is indicated for any of these situations.
RESEARCH SUMMARY
Like hesperidin, hesperetin has shown some favorable effects on lipids, but, unlike hesperidin, this research has so far been confined to in vitro and animal studies. In the best-designed of the animal studies to date, hesperetin significantly lowered plasma cholesterol levels (but not triglyceride levels) in rats fed a high-cholesterol diet.
No conclusions can yet be drawn from early animal work that suggests hesperetin-induced anticancer effects. Similarly, isolated studies showing anti-aromatase and anti-Helicobacter pylori activity in vitro need follow-up.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
See Hesperidin.
DOSAGE AND ADMINISTRATION
Hesperetin is typically administered as hesperidin. See Hesperidin.
LITERATURE
Ameer B, Weitraub RA, Johnson JV, et al. Flavanone absorption after naringinin, hesperidin and citrus administration. Clin Pharmacol Ther. 1996; 60:34-40.
Bae EA, Han MJ, Kim DH. In vitro anti-Helicobacter pylori activity of some flavonoids and their metabolites. Planta Med. 1999; 65:442-443.
Borradaile NM, Carroll KK, Kurowaska EM. Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin. Lipids. 1999; 34:591-598.
Choi JS, Park KV, Moon SH, et al. Antimutagenic effect of plant flavonoids in the Salmonella assay system. Arch Pharm Res. 1994; 17:71-75.
Franke AA, Cooney RV, Custer LJ, et al. Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents. Adv Exp Med Biol. 1998; 439:237-248.
Jeong HJ, Shin YG, Kim IH, Pezzuto JM. Inhibition of aromatase activity by flavonoids. Arch Pharm Res. 1999; 22:309-312.
Lee S-H, Jeong T-S, Park YB, et al. Hypocholesterolemic effect of hesperetin mediated by inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A: cholesterol acyltransferase in rats fed high-cholesterol diet. Nutr Res. 1999; 19:1245-1258.