Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice

Sim, Mi-Ok; Ham, Ju Ri; Lee, Hae-In; Seo, Kwon‐Il

doi:10.1016/j.cbi.2014.03.003

Cited by 44 publications

(16 citation statements)

References 51 publications

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“…4-MU has also been shown to have protective effects on non-infectious inflammation, including renal ischemia and reperfusion ( 130 ), and airway inflammation secondary to cigarette smoke ( 131 ). 4-MU was shown to restore normoglycemia and promote insulin sensitivity in obese, diabetic mice via increased production of adiponectin ( 132 ).…”

Section: -Methylumbelliferonementioning

confidence: 99%

4-Methylumbelliferone Treatment and Hyaluronan Inhibition as a Therapeutic Strategy in Inflammation, Autoimmunity, and Cancer

et al. 2015

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Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug in Europe and Asia called “hymecromone” where it is used to treat biliary spasm. However, there is uncertainty regarding how 4-MU treatment provides benefit in these animal models and the potential long-term consequences of HA inhibition. Here, we review what is known about how HA contributes to immune dysregulation and tumor progression. Then, we review what is known about 4-MU and hymecromone in terms of mechanism of action, pharmacokinetics, and safety. Finally, we review recent studies detailing the use of 4-MU to treat animal models of cancer and autoimmunity.

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Section: -Methylumbelliferonementioning

confidence: 99%

4-Methylumbelliferone Treatment and Hyaluronan Inhibition as a Therapeutic Strategy in Inflammation, Autoimmunity, and Cancer

et al. 2015

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“…The insulin resistance in liver is strongly related with hyperglycemia and decreased glycogen synthesis in T2DM (Samuel and Shulman, ). In our study, we found that the UMB significantly decreased blood glucose level, which corresponds to the reports of antihyperglycemic effect of UMB in HFD‐fed mice (Sim et al, ) and in type 1 diabetic rats (Ramesh and Pugalendi, ). Interestingly, our results showed that the treatment of T2DM with UMB causes the increases in serum insulin level and insulin action that is evident by the significant decrease in HOMA‐IR.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that UMB can stimulate adipogenesis in 3 T3‐L1 cells (Naowaboot et al, ). A recent study found that UMB and 4‐methylumbelliferone reduced the hypertriglyceridemia and hyperglycemia in HFD‐induced obese mice (Sim et al, ). However, the mechanism of these actions of UMB was not clearly demonstrated.…”

Section: Introductionmentioning

confidence: 99%

“…Coumarin plays a major role as an antioxidant (Hoult and Paya, 1996). There are many coumarin derivatives, which have an effect in the management of metabolic diseases, such as osthole, 4-methylumbelliferone, and 7-hydroxycourmarin [umbelliferone (UMB)] (Liang et al, 2009;Lee et al, 2011;Sim et al, 2014). Umbelliferone (UMB) is a common natural product of the coumarin family.…”

Section: Introductionmentioning

confidence: 99%

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Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in High-Fat Diet/Streptozotocin-Induced Type 2 Diabetic Rats

et al. 2015

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Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high-fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non-esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα-protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.

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“…An accelerated lipid peroxidation within the kidney tissue is probably concerned in the onset of kidney lesions within the rodent models of obesity [32]. Elevated ranges of TBARS and LHP inside the kidney of HFD precipitated diabetic mice is regular with a preceding record that HFD induces oxidative damage [33]. The antioxidant enzymes along with SOD, CAT and GPX are themselves liable to reactive oxygen species (ROS) assault [34].…”

Section: Discussionmentioning

confidence: 99%

Effect of Bergenin on the Kidney of C57BL/6J Mice with High Fat-Diet Induced Oxidative Stress

Sagadevan

Ramalingam

2016

ILNS

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ABSTRACT. The present study evaluated the protective effect of bergenin on high fat diet (HFD) induced diabetic mice. C57BL/6J mice were segregated in two groups, one fed standard diet (NC) and the other fed HFD for 16 weeks. Mice were fed continuously with high fat diet for 16 weeks and subjected to intragastric administration of bergenin (10, 20 and 40 mg/kg body weight (BW)), metformin (25 mg/kg BW) 9 to 16 weeks. At the end of the treatment nephritic markers, lipid peroxidation product, antioxidant and histopathological examination were carried out to assess the efficacy of the treatment. HFD fed mice showed increased plasma glucose, insulin, altered nephritic markers, antioxidant and histopathological abnormalities. Oral Treatment with bergenin (40 mg/kg BW) showed near normalized levels of plasma glucose, lipid peroxidation product, antioxidants, improved insulin and reduced kidney damage. The effects of bergenin were comparable with standard drug, metformin. These data suggest that bergenin protect kidney from deleterious effect of glucose.

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Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice

Cited by 44 publications

References 51 publications

4-Methylumbelliferone Treatment and Hyaluronan Inhibition as a Therapeutic Strategy in Inflammation, Autoimmunity, and Cancer

4-Methylumbelliferone Treatment and Hyaluronan Inhibition as a Therapeutic Strategy in Inflammation, Autoimmunity, and Cancer

Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in High-Fat Diet/Streptozotocin-Induced Type 2 Diabetic Rats

Effect of Bergenin on the Kidney of C57BL/6J Mice with High Fat-Diet Induced Oxidative Stress

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