Abstract:Polymethoxyflavones
(PMFs) have been shown to prevent obesity,
ameliorate type 2 diabetes, and regulate lipid metabolism in vitro and in vivo. However, little is
known about the contribution of 3,5,6,7,8,3′,4′-heptamethoxyflavone
(HMF) to prevent obesity and regulate lipid metabolism in
vivo. We aimed to investigate the potential efficacy of HMF
on preventing obesity and hyperlipidemia in rats fed a high-fat diet
(HFD) and its underlying mechanisms. Male Sprague–Dawley rats
were fed a normal diet or an HFD wit… Show more
“…Our study provides evidence suggesting that HMF attenuates hepatic damage and steatosis caused by HFDs, with concurrent reductions in oxidative stress. A recent transcriptome analysis demonstrated that HMF supplementation markedly down-regulated hepatic genes related to adipogenesis and inflammatory responses, while increasing fatty acid oxidation and energy expenditure (Feng et al, 2019), and we hypothesize that this can contribute to the observed effect of HMF on the steatosis mitigation. that biological actions of the PMFs are largely due to their various metabolites.…”
Section: Discussionmentioning
confidence: 63%
“…(Kim et al, 2012) TAN ingestion mediated activities of enzymes important for carbohydrate metabolism and reduced glycosylated hemoglobin in diabetic rats (Sundaram et al, 2014). HMF has been also reported to regulate body weight, lipid profiles, and blood serum lipid levels in rats continuously fed a high-fat diet (HFD; Feng et al, 2019). Nobiletin (3′,4′,5,6,7,8-hex amethoxyflavone), a structurally related polymethoxylated flavone (PMF), improves adiposity, dyslipidemia, hyperglycemia, and insulin resistance in obese mice and also regulates glucose transport in muscles and white adipose tissue (Lee et al, 2010(Lee et al, , 2013.…”
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.
“…Our study provides evidence suggesting that HMF attenuates hepatic damage and steatosis caused by HFDs, with concurrent reductions in oxidative stress. A recent transcriptome analysis demonstrated that HMF supplementation markedly down-regulated hepatic genes related to adipogenesis and inflammatory responses, while increasing fatty acid oxidation and energy expenditure (Feng et al, 2019), and we hypothesize that this can contribute to the observed effect of HMF on the steatosis mitigation. that biological actions of the PMFs are largely due to their various metabolites.…”
Section: Discussionmentioning
confidence: 63%
“…(Kim et al, 2012) TAN ingestion mediated activities of enzymes important for carbohydrate metabolism and reduced glycosylated hemoglobin in diabetic rats (Sundaram et al, 2014). HMF has been also reported to regulate body weight, lipid profiles, and blood serum lipid levels in rats continuously fed a high-fat diet (HFD; Feng et al, 2019). Nobiletin (3′,4′,5,6,7,8-hex amethoxyflavone), a structurally related polymethoxylated flavone (PMF), improves adiposity, dyslipidemia, hyperglycemia, and insulin resistance in obese mice and also regulates glucose transport in muscles and white adipose tissue (Lee et al, 2010(Lee et al, , 2013.…”
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.
“…Recently, various natural bioactive compounds considered safe and effective, such as curcumin, propyl gallate, and resveratrol, have been explored for the treatment of obesity (WHO 2018; Feng et al. 2019).…”
Context: Ephedrae Herba (EH), the dried stems and leaves of Ephedra sinica Stapf., E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge. (Ephedraceae [Ephedra]) is used to treat respiratory diseases. Recently, especially in the Republic of Korea, EH has also been used for weight reduction. Objective: We evaluated the effects and molecular targets of methanol EH extract (EHM) on high-fat diet (HFD)-induced hyperlipidemic ICR mice. Materials and methods: EHM was orally administered (100 mg/kg body weight/day) for 3 weeks. We observed changes in body weight (BW), total cholesterol (TC), high-density lipoprotein-cholesterol, and triglycerides to evaluate the physiological changes induced by HFD or EHM administration. To evaluate lipid peroxidation and liver toxicity, malondialdehyde and blood alanine aminotransferase levels were measured. In addition to analyzing liver gene expression profiles, EHM target proteins were identified using a protein interaction database. Results: EHM administration for 3 weeks significantly (p < 0.05) decreased TC and triglyceride levels without altering BW in mice, and gene expression levels in the livers of EHM-treated mice were restored at 34.0% and 48.4% of those up-or down-regulated by hyperlipidaemia, respectively. Proteins related to DNA repair and energy metabolism were identified via protein interaction network analysis as molecular targets of EHM that play key roles in ameliorating hyperlipidaemia. Discussion and conclusions: EHM regulated hyperlipidaemia by decreasing total blood lipid and triglyceride levels in hyperlipidaemic mice. EHM showed preventive effects against hyperlipidaemia in mice, possibly via the regulation of DNA repair and the expression of energy metabolism-related genes and proteins.
“…Three of the 4 active compounds (IC 50 <5 μM); curcumin (IC 50 = 2.2 μM), α-mangostin (IC 50 = 1.2 μM), and nobiletin (IC 50 = 0.9 μM), are reported to have SIRT1-activating effects (7,17,28,29,41,43,55). Another compound, HMF showing IC 50 = 1.0 μM, is reported to ameliorate brain and bone injuries (30,31,35,36,45), and recently shown to possess anti-metabolic effects (16). However, HMF-induced SIRT1-related functions are yet to be reported.…”
Caloric restriction (CR) is a major contributor to good health and longevity. CR mimetics (CRMs) are a group of plant-derived compounds capable of inducing the benefits of CR. Since a longevity gene, SIRT1, inhibits T-cell activation and SIRT1 loss results in increased T-cell activation, we hypothesized that compounds capable of activating SIRT1 signaling can inhibit T-cell activation and function as CRMs. Thus we propose, in the present study, the application of a T-cell activation-inhibitory assay to screen candidate CRMs. Well-known CRMs, such as resveratrol, butein, and fisetin, suppressed the anti-CD3/CD28 antibody-induced activation of mouse spleen T-cells. We next randomly assessed 68 plant-derived compounds for screening novel candidate CRMs using this bioassay and found that all four compounds showing IC 50 values <5 μM, such as curcumin, α-mangostin, nobiletin, and heptamethoxyflavone, have beneficial functions for health such as anti-inflammatory effect. These results suggest that the T-cell activation-inhibitory assay can be used to screen candidate CRMs.
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