4.7 Article

The flavonoids induce the transcription of mRNA encoding erythropoietin in cultured embryonic stem cells via the accumulation of hypoxia-inducible factor-1a

Journal

CHEMICO-BIOLOGICAL INTERACTIONS
Volume 382, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2023.110609

Keywords

Erythropoietin; Flavonoid screening; Hypoxia response element; Hypoxia-inducible factor

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Some flavonoids have been found to enhance the production of EPO (erythropoietin) by increasing the activity of hypoxia response element (HRE). This suggests that flavonoids may have potential as important components of food supplements for brain health.
Flavonoids are the most common phytochemicals in vegetables and herbal products. The beneficial functions of flavonoids in the brain and erythropoietic system have been proposed. Erythropoietin (EPO) is a potent protective agent in the brain; but which has difficulty to cross the blood brain barrier (BBB). Here, about 60 flavonoids were screened for their potential activation on the transcription of EPO mRNA in the neuronal embryonic stem cell lines, NT2/D1 and PC12. Amongst the screened flavonoids, formononetin, calycosin, ononin, chrysin, baicalein and apigenin showed robust up regulation of EPO production via enhancement of hypoxia response element (HRE) activity in cultured embryonic stem cells. In addition, the flavonoids showed activation of HRE activity by having increased accumulation of HIF-1 & alpha;, but not on level of HIF-1 & beta;, in the cultures. The accumulation of HIF-1 & alpha; was attributed to up regulation of HIF-1 & alpha; mRNA and blockade of HIF-1 & alpha; degradation upon treatment of the flavonoids. These results suggested a promising trend of developing commercial products of flavonoids as food supplements tailored for brain health.

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