Physiological effects of tangeretin and heptamethoxyflavone on obese C57BL/6J mice fed a high‐fat diet and analyses of the metabolites originating from these two polymethoxylated flavones

Abstract

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.

Differential Effect of Nobiletin and Tangeretin on the Antioxidant Activity and Levels of α-Tocopherol and Retinol in Rats

“…Compared to the current experiment, these doses were 4.6 to 9.1 times higher, the initial body weight was 50% higher and, the intervention was longer (6 wk). In contrast, Nery et al [27] found similar results to the current study in mice fed a highfat diet plus 100 mg/kg bw TAN for 4 weeks. The authors showed an increase in weight gain compared to the standard diet, but no change in animals fed a high-fat diet without TAN.…”

Tangeretin-a special polymethoxyflavones: An insight into its pharmacological and therapeutic effects on diabetes

“…The result shows that the blood serum glucose levels, leptin, resistin, and TBARS in these diabetic mice were considerably lower after four weeks of supplementation with 100 mg/kg b.w. of tangeretin than in the healthy control and non-supplemented HFD groups [43]. Shin et al 2017 examined the effects of tangeretin on inflammatory changes and glucose absorption in a coculture of RAW 264.7 cells (a mouse macrophage cell line) and 3T3-L1 adipocytes (a mouse adipocyte cell line), whereby they observed that tangeretin (100 µM) treatment reduced the expression of interleukin IL-6, TNF-α and IL-1, inducible nitric oxide synthase, and cyclooxygenase-2 as well as the synthesis of nitric oxide, and also increase in glucose absorption in the coculture was observed.…”

“…In C57BL/6J mice with pre-existing obesity, Marina et al [43] looked into the ability of tangeretin to restore metabolic damage brought on by a high-fat diet (HFD). The result shows that the blood serum glucose levels, leptin, resistin, and TBARS in these diabetic mice were considerably lower after four weeks of supplementation with 100 mg/kg b.w.…”

Three polymethoxyflavones from the peel of Citrus reticulata “Chachi” inhibits oxidized low-density lipoprotein-induced macrophage-derived foam cell formation

“…In addition, the metabolite of nobiletin, 3′,4′-dihydroxy-5,6,7,8-tetramethoxyflavone, reduced LDL oxidation and attenuated the differentiation of monocytes to macrophages and diminished the uptake of modified LDL by macrophages ( 27 ). Both tangeretin and heptamethoxyflavone reduced lipid peroxidation (TBARS) in the serum of HFD mice and had a significant therapeutic effect on obesity and hyperlipidemia ( 28 – 30 ). Furthermore, some PMFs from Citrus peel regulate lipid homeostasis via suppressing multiple scavenger receptors ( 25 , 31 – 33 ).…”