Modulation of VEGF signaling in a mouse model of diabetes by xanthohumol and 8‐prenylnaringenin: Unveiling the angiogenic paradox and metabolism interplay

Costa, Raquel; Rodrigues, Ilda; Guardão, Luísa; Lima, Joana; Sousa, Emı́lia; Soares, Raquel; Negrão, Rita

doi:10.1002/mnfr.201600488

Cited by 17 publications

(20 citation statements)

References 62 publications

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“…In recent years, XN ( 1 ), IX ( 2 ) and 8-PN ( 4 ) have been extensively tested for their anti-diabetic properties [ 96 , 134 , 135 ]. Costa et al tested XN ( 1 ) and 8-PN ( 4 ) in a mouse model and found that both compounds have the potential for therapeutic intervention in diabetics type 2 [ 134 ].…”

Section: Phytoestrogensmentioning

confidence: 99%

Flavonoids as Phytoestrogenic Components of Hops and Beer

2020

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The value of hops (Humulus lupulus L.) in beer production has been undisputed for centuries. Hops is rich in humulones and lupulones which gives the characteristic aroma and bitter taste, and preserves this golden drink against growing bacteria and molds. Besides α- and β-acids, the lupulin glands of hop cones excrete prenylated flavonoids, which exhibit a broad spectrum of biological activities and therefore has therapeutic potential in humans. Recently, interest in hops was raised due to hop prenylated flavanones which show extraordinary estrogen activities. The strongest known phytoestrogen so far is 8-prenylnaringenin (8-PN), which along with 6-prenylanaringenin (6-PN), 6,8-diprenylnaringenin (6,8-DPN) and 8-geranylnaringenin (8-GN) are fundamental for the potent estrogen activity of hops. This review provides insight into the unusual hop phytoestrogens and shows numerous health benefits associated with their wide spectrum of biological activities including estrogenic, anticancer, neuropreventive, antinflamatory, and antimicrobial properties, which were intensively studied, and potential applications of these compounds such as, as an alternative to hormone replacement therapy (HRT).

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Section: Phytoestrogensmentioning

confidence: 99%

Flavonoids as Phytoestrogenic Components of Hops and Beer

2020

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“…In vivo studies: Costa et al, reported that XN consumption 10 mg/l reduced angiogenesis, vascular endothelial growthfactor receptor (VEGFR)-2 expression and activity, and also reduced levels of VEGF-B and its receptors (i.e. VEGFR1 and neuropilin-1), VEGF-A as well as endothelial markers in T2DM mice [39]. Altogether, these findings suggest that XN may have a preventative effect on neovascularisation and the associated pathways seen as complications in T2DM.…”

Section: Xanthohumol and Type 2 Diabetes Mellitusmentioning

confidence: 99%

Benefits of Xanthohumol in Hyperlipidaemia, Obesity and Type 2 Diabetes Mellitus: A Review

Rossi¹,

Whyand²,

Caplin³

2019

J Obes Chronic Dis

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Diabetes, obesity, hyperlipidaemia, as well as cardiovascular diseases in general, have become an increasing social and economic problem in developed countries. Hops contain Xanthohumol (XN), a chalcone within a group of prenylated phenols. Used alone, it has recently shown promising results in the management of these individual conditions and we have therefore undertaken a review and assessed the evidence for XN as a food supplement in this setting. Materials and Methods: A PubMed and Cochrane search was performed for the terms: xanthohumol; hyperlipidaemia; obesity; type 2 diabetes mellitus. All relevant articles published over the last 15 years were considered for this review. Results: A total of 39 papers were considered and 18 papers met the criteria for review and these included both in vitro and in vivo (including animal) studies. The studies suggest that XN improves high density lipoprotein (HDL) levels and optimise cholesterol transport, thus having a protective effect against atherosclerosis. Furthermore, XN might exert an anti-obesity effect by decreasing adipogenesis and inducing lipolysis. Finally, XN might also prevent insulin resistance and modulate glucose metabolic pathways. Conclusion: In vitro and in vivo studies (predominantly animal studies) showed promising results for XN in the prevention and treatment of hyperlipidaemia, obesity and T2DM. However, further studies in humans are required to draw more robust conclusions.

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“…Adipose tissue is highly vascularized in which the adipocytes are nourished by an extensive capillary network [5][6][7]. Expansion of adipogenesis requires angiogenesis [5], whereas, inadequate angiogenesis or vascular dysfunction is closely associated with many metabolic disorders [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

A MetAP2 inhibitor blocks adipogenesis, yet improves glucose uptake in cells

et al. 2019

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Adipose tissue expansion involves angiogenesis to remodel its capillary network. The enzymemethionine aminopeptidase 2(MetAP2) promotes angiogenesis.MetAP2 inhibitors suppress angiogenesis and have potential anti-obesity effect. However, impairment in adipose tissue expansion is also linked with impaired glycemic control.This study investigated the effect of BL6, a MetAP2 inhibitor, on adipogenesis and glucose disposal.To test effect on angiogenesis, Human Umbilical Vein Endothelial Cells(HUVECs) were treated with BL6 for 24h to determine tube formation. Further, to test effect on adipogenesis and glucose disposal,3T3-L1 pre-adipocytes were treated with BL6(0 µM, 20µM, 50 µM or 100µM) during differentiation. Differentiated cells were stained with Oil Red O for determining lipid accumulation, and glucose uptake assay. Protein levels and RNA expression for key genes involved in the adipogenic cascade were determined.BL6 treatment of HUVECs dose dependently blocked angiogenesis. During differentiation of pre-adipocytes, 50μM and 100µM BL6 significantly reduced lipid accumulation. Treatment with 100µM BL6 significantly decreased expression of adipogenic genes. Interestingly, BL6 treatment dose dependently increased glucose uptake by 3T3-L1 cells.MetAP2 inhibitor blocks angiogenesis, attenuates adipogenesis, yet increases cellular glucose uptake. Collectively this proof of concept study supports a possible role for MetAP2 inhibitor BL6, as a putative anti-obesity therapeutic agent.

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Modulation of VEGF signaling in a mouse model of diabetes by xanthohumol and 8‐prenylnaringenin: Unveiling the angiogenic paradox and metabolism interplay

Cited by 17 publications

References 62 publications

Flavonoids as Phytoestrogenic Components of Hops and Beer

Flavonoids as Phytoestrogenic Components of Hops and Beer

Benefits of Xanthohumol in Hyperlipidaemia, Obesity and Type 2 Diabetes Mellitus: A Review

A MetAP2 inhibitor blocks adipogenesis, yet improves glucose uptake in cells

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