Eriocitrin plays a role in the reduction of oxidative stress and inflammation linked to the development of diabetes mellitus and atherosclerosis. We investigated the pharmacokinetics and distribution of eriocitrin metabolites in rats orally administered with eriocitrin. Plasma, urine, and organs were collected at 12 different time points from 0 to 24 h and analyzed by HPLC-PDA-MS. For the first time, the metabolism and distribution of orally administered eriocitrin were shown. Nine metabolites of eriocitrin were identified in rat urine, and seven in various tissues (eriodictyol, homoeriodictyol, hesperetin, and glucuronidated metabolites), and preliminary identifications of these metabolites are suggested. Overall, eriocitrin metabolites were widely distributed in the rat tissues, where homoeriodictyol and homoeriodictyol-7-O-glucuronide were the major metabolites. The halflives of the metabolites in plasma were between 3 and 3.2 h, and the total bioavailability of eriocitrin was less than 1%.
Eriocitrin is a citrus flavonoid with a high capacity to reduce the oxidative stress related to metabolic disorders and obesity. We assessed the effects of low doses of eriocitrin on the oxidative stress, inflammation, and metabolism of glucose and lipids of high-fat diet (HFD)-fed obese mice. Fifty male C57BL/6J mice were randomly assigned into five groups (n 10). The mice were fed an HFD (45 % kcal from fat, i.e. lard) for 4 weeks for obesity induction. After this period, the mice continued receiving the same HFD, but supplemented with eriocitrin at 10, 25 or 100 mg/kg body weight (bw) for an additional 4 weeks. Control groups were fed with standard diet (10 % kcal of fat, i.e. soy oil) or with HFD without eriocitrin, for eight consecutive weeks. At the end of the study, mice supplemented with eriocitrin showed lower levels of blood serum glucose and blood and liver triacylglycerols (P < 0⋅05). There was also improved levels of insulin, HOMA-IR, total-cholesterol, resistin and lipid peroxidation in the supplemented mice. It was concluded that the 25 mg dose of eriocitrin improved all the parameters studied and had positive effects on oxidative stress, systemic inflammation and metabolism of lipids and glucose in general.
Two compounds from citrus peel, tangeretin (TAN) and 3′,4′,3,5,6,7,8‐heptamethoxyflavone (HMF), were investigated for their abilities to repair metabolic damages caused by an high‐fat diet (HFD) in C57BL/6J mice. In the first 4 weeks, mice were fed either a standard diet (11% kcal from fat) for the control group, or a HFD (45% kcal from fat) to establish obesity in three experimental groups. In the following 4 weeks, two groups receiving the HFD were supplemented with either TAN or HMF at daily doses of 100 mg/kg body weight, while the two remaining groups continued to receive the standard healthy diet or the nonsupplemented HFD. Four weeks of supplementation with TAN and HMF resulted in intermediate levels of blood serum glucose, leptin, resistin, and insulin resistance compared with the healthy control and the nonsupplemented HFD groups. Blood serum peroxidation (TBARS) levels were significantly lower in the TAN and HMF groups compared with the nonsupplemented HFD group. Several differences occurred in the physiological effects of HMF versus TAN. TAN, but not HMF, reduced adipocyte size in the mice with pre‐existent obesity, while HMF, but not TAN, decreased fat accumulation in the liver and also significantly increased the levels of an anti‐inflammatory cytokine, IL‐10. In an analysis of the metabolites of TAN and HMF, several main classes occurred, including a new set of methylglucuronide conjugates. It is suggested that contrasts between the observed physiological effects of TAN and HMF may be attributable to the differences in numbers and chemical structures of TAN and HMF metabolites.
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