Antihyperlipidemic Effect of Fisetin, a Bioflavonoid of Strawberries, Studied in Streptozotocin‐Induced Diabetic Rats

Prasath, Gopalan Sriram; Subramanian, S.

doi:10.1002/jbt.21583

Cited by 39 publications

(19 citation statements)

References 41 publications

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“…Fisetin has a plasma terminal half-life of just over 3 hours in mice, with its metabolites being excreted in feces and urine. It alleviates dysfunction in animal models of chronic disease, including diabetic kidney disease and acute kidney injury [19, 20, 27-29], attributes consistent with those expected from a senolytic agent [9]. Here we demonstrate that fisetin is indeed senolytic in senescent HUVECs, but not in senescent IMR-90 cells or human preadipocytes.…”

Section: Discussionsupporting

confidence: 78%

New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463

Zhu

Doornebal

Pirtskhalava

et al. 2017

Aging

551

385

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Senescent cells accumulate with aging and at sites of pathology in multiple chronic diseases. Senolytics are drugs that selectively promote apoptosis of senescent cells by temporarily disabling the pro-survival pathways that enable senescent cells to resist the pro-apoptotic, pro-inflammatory factors that they themselves secrete. Reducing senescent cell burden by genetic approaches or by administering senolytics delays or alleviates multiple age- and disease-related adverse phenotypes in preclinical models. Reported senolytics include dasatinib, quercetin, navitoclax (ABT263), and piperlongumine. Here we report that fisetin, a naturally-occurring flavone with low toxicity, and A1331852 and A1155463, selective BCL-XL inhibitors that may have less hematological toxicity than the less specific BCL-2 family inhibitor navitoclax, are senolytic. Fisetin selectively induces apoptosis in senescent but not proliferating human umbilical vein endothelial cells (HUVECs). It is not senolytic in senescent IMR90 cells, a human lung fibroblast strain, or primary human preadipocytes. A1331852 and A1155463 are senolytic in HUVECs and IMR90 cells, but not preadipocytes. These agents may be better candidates for eventual translation into clinical interventions than some existing senolytics, such as navitoclax, which is associated with hematological toxicity.

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Section: Discussionsupporting

confidence: 78%

New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463

Zhu

Doornebal

Pirtskhalava

et al. 2017

Aging

551

385

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“…Glucose homeostasis is related to endogenous production and utilization of glucose by target tissues (Wilding 2014 ). Insulin regulates the activities of various enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and fructose 1,6-bisphosphatase which are involved in carbohydrate metabolism (Prasath & Subramanian 2014 ). Hexokinase is one of the key enzymes, in glycolysis, which catalyzes the conversion of glucose to glucose 6‐phosphate in liver and plays a pivotal role in the maintenance of blood glucose homeostasis (Matschinsky 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Babukumar

Vinothkumar

Sankaranarayanan

et al. 2017

Pharmaceutical Biology

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Context: Geraniol, an acyclic monoterpene alcohol is found in medicinal plants, is used traditionally for several medical purposes including diabetes.Objectives: The present study evaluates the antihyperglycemic potential of geraniol on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats.Materials and methods: Diabetes was induced in experimental rats, by a single intraperitoneal (i.p) injection of STZ [40 mg/kg body weight (b.w.)]. Different doses of geraniol (100, 200 and 400 mg/kg b.w.) and glyclazide (5 mg/kg b.w.) were administrated orally to diabetic rats for 45 days. Body weight, food intake, plasma glucose, insulin, blood haemoglobin (Hb), glycosylated haemoglobin (HbA1c), hepatic glucose metabolic enzymes and glycogen were examined.Results: The LD50 value of geraniol is 3600 mg/kg b.w. at oral administration in rats. Administration of geraniol in a dose-dependent manner (100, 200, 400 mg/kg b.w.) and glyclazide (5 mg/kg b.w.) for 45 days significantly improved the levels of insulin, Hb and decreased plasma glucose, HbA1C in diabetic-treated rats. Geraniol at its effective dose (200 mg/kg b.w.) ameliorated the altered activities of carbohydrate metabolic enzymes near normal effects compared with two other doses (100 and 400 mg/kg b.w.). Geraniol treatment to diabetic rats improved hepatic glycogen content suggesting its anti-hyperglycemic potential. Geraniol supplement was found to preserve the normal histological appearance of hepatic cells and pancreatic β-cells in diabetic rats.Discussion and conclusions: The present findings suggest that geraniol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes even though clinical studies used to evaluate this possibility are warranted.

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“…Nikte (66.5 mg/100 g DW), showing mean levels almost 3-fold higher than in the other cultivars. Although some flavonols such as fisetin are minor phenolics found in some cases only in traces, they have remarkable health benefits, and hence nutritional importance (Prasath & Subramanian, 2014).…”

Section: Phenolic Composition Of Strawberry Cultivarsmentioning

confidence: 99%

Assessment of the differences in the phenolic composition and color characteristics of new strawberry ( Fragaria x ananassa Duch.) cultivars by HPLC–MS and Imaging Tristimulus Colorimetry

Fernández-Lara

Gordillo

Rodríguez-Pulido

et al. 2015

Food Research International

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a b s t r a c t a r t i c l e i n f oThe phenolic composition (by HPLC-DAD-MS) and color characteristics (by Imaging Tristimulus Colorimetry) of four strawberry cultivars that have shown good climate adaptation to subtropical area (Nikte, Zamorana, Jacona and Pakal) have been assessed. 24 monomeric phenolics were identified, including 15 anthocyanins, 5 phenolic acids, 1 flavanol and 4 flavonols. Nikte and Zamorana showed the highest phenolic potential mainly due to their higher content of anthocyanins, while Pakal was richer in phenolic acids. Regarding color, Nikte and Zamorana were the more similar cultivars having the lowest values of lightness and hue. On the contrary, the color of Pakal was quite different from all the rest, due to the specific distribution between pelargonidin and cyanidin. The inclusion of both phenolic and colorimetric information in the Linear Discriminant Analysis allowed reaching very good discriminations among cultivars.

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Antihyperlipidemic Effect of Fisetin, a Bioflavonoid of Strawberries, Studied in Streptozotocin‐Induced Diabetic Rats

Cited by 39 publications

References 41 publications

New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463

New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463

Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Assessment of the differences in the phenolic composition and color characteristics of new strawberry ( Fragaria x ananassa Duch.) cultivars by HPLC–MS and Imaging Tristimulus Colorimetry

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