(±)-Naringenin

Naringenin is a citrus-derived flavonoid that inhibits CYP3A4 activity in human liver microsomes (IC₅₀s = 139-188 μM).^1,2 At 100 mg/kg/day, naringenin selectively inhibits the transcription of Smad3 and directly down-regulates TGF-β1, significantly reducing lung metastasis in mice with bleomycin-induced pulmonary fibrosis.³ Naringenin demonstrates both lipid lowering and insulin-like properties in low-density lipoprotein (LDL) receptor-deficient mice fed a Western diet containing 1-3% naringenin by correcting VLDL overproduction, ameliorating hepatic steatosis, and attenuating dyslipidemia without affecting caloric intake or fat absorption.⁴

1.Fuhr, U., Klittich, K., and Staib, A.H.Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in manBr. J. Clin. Pharmacol.35(4)431-436(1993) 2.Ho, P.C., and Saville, D.J.Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compoundsJ. Pharm. Pharm. Sci.4(3)217-227(2001) 3.Du, G., Jin, L., Han, X., et al.Naringenin: A potential immunomodulator for inhibiting lung fibrosis and metastasisCancer Res.69(7)3205-3212(2009) 4.Mulvihill, E.E., Allister, E.M., Sutherland, B.G., et al.Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistanceDiabetes58(10)2198-2210(2009)