The effects of lemon flavonoids, as crude flavonoids prepared from lemon juice, were investigated in diabetic rats. The oxidative stress of eriocitrin (eriodictyol 7-O-beta-rutinoside) and hesperidin (hesperetin 7-O-beta-rutinoside) on streptozotocin-induced diabetic rats was investigated. Diabetic rats were given a diet which contained 0.2% crude flavonoids, 0.2% eriocitrin, and 0.2% hesperidin. After the 28-d feeding period, the concentration of the thiobarbituric acid-reactive substance in the serum, liver, and kidney of diabetic rats administered crude flavonoids, eriocitrin, and hesperidin significantly decreased as compared with that of the diabetic group. The levels of 8-hydroxydeoxyguanosine, which is exchanged from deoxyguanosine owing to oxidative stress, in the urine of diabetic rats administered eriocitrin and hesperidin significantly decreased as compared with that of the diabetic rat group. Crude flavonoids, eriocitrin, and hesperidin suppressed the oxidative stress in the diabetic rats. These results demonstrated that dietary lemon flavonoids of eriocitrin and hesperidin play a role as antioxidant in vivo.

Eriocitrin, a flavonoid glycoside present in lemon fruit, is metabolized in vivo to a series of eriodictyol, methylated eriodictyol, 3,4-dihydroxyhydrocinnamic acid, and their conjugates. Plasma antioxidant activity increased following oral administration of aqueous eriocitrin solutions to rats. Eriocitrin metabolites were found in plasma and renal excreted urine through HPLC and LC-MS analyses. Eriocitrin was not detected in plasma and urine, but eriodictyol, homoeriodictyol, and hesperetin in their conjugated forms were detected in plasma of 4.0 h following administration of eriocitrin. In urine for 24 h, both nonconjugates and conjugates of these metabolites were detected. 3,4-Dihydroxyhydrocinnamic acid, which is metabolized from eriodictyol by intestinal bacteria, was detected in slight amounts with each form in 4.0-h plasma and 24-h urine. Eriocitrin was suggested to be metabolized by intestinal bacteria, and then eriodictyol and 3,4-dihydroxyhydrocinnamic of its metabolite were absorbed. Following administration of eriocitrin, plasma exhibited an elevated resistance effect to lipid peroxidation. Eriocitrin metabolites functioning as antioxidant agents are discussed.

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Two antioxidative two C-glucosylflavones were isolated from the peel of lemon fruit (Citrus limon BURM. f.). They were identified as 6,8-di-C-β-glucosyldiosmin (LE-B) and 6-C-β-glucosyldiosmin (LE-C) by UV, IR, FAB-MS, 1H NMR, and 13C NMR analyses. The antioxidative activities of LE-B, LE-C, and flavonoid compounds (eriocitrin, diosmin, hesperidin, and narirutin) in lemon fruit were examined using linoleic acid autoxidation, the liposome oxidation system, and the low-density lipoprotein (LDL) oxidation system. LE-B and LE-C showed antioxidative activity in these autoxidation systems but exhibited weaker activity than eriocitrin, its eriodictyol of its aglycon. Eriocitrin and its metabolites by intestinal bacteria (eriodictyol, 3,4-dihydroxyhydrocinnamic acid, and phloroglucinol) exhibited stronger antioxidative activity than α-tocopherol in the LDL oxidation system and had approximately the same activity as (−)-epigallocatechin gallate. Eriocitrin and its metabolites are powerful antioxidants using an in vitro oxidation model for heart disease. Keywords: Lemon fruit; Citrus limon; antioxidant; eriocitrin; flavonoid; 6,8-di-C-β-glucosyldiosmin; 6-C-β-glucosyldiosmin

An antioxidant was isolated from the peel and juice of lemon fruit (Citrus limon BURM. f.). It was identified as eriocitrin (eriodictyol 7-rutinoside) of the flavanone glycoside by HPLC, IH-NMR and *3C-NMR analyses. The purified eriocitrin was readily soluble in water, methanol, and ethanol. A water solution of 0.05% eriocitrin was weakly acidic (pH 4.2). Eriocitrin was found to be stable even at high temperature (121'C, 15 min) in acidic solution (pH 3.5). The distribution of eriocitrin in citrus fruits was found to be especially abundant in lemons and limes, however, it was scarcely found in other citrus fruits. In the case of lemon fruit, eriocitrin was primarily distributed in the peel (about 1,500 ppm) composed of the albedo (mesocarp), flavedo (epicarp), and pulp vesicles. It was also significantly present in the juice (about 200 ppm) but was not detected in the seed. Two varieties of lemon fruits, eureka and lisbon, almost had the same eriocitrin content. The antioxidative activity of eriocitrin in the linoleic acid autoxidation system was equal to that of a-tocopherol, and it was enhanced when used together with citric acid.The eriocitrin had a synergistic effect on a-tocopherol.