Flavonoids are a family of phenolic compounds and widely present in our daily foods and traditional Chinese medicines. In nature, flavonoids serve as the most common plant pigments next to chlorophyll and carotenoids in flower for attracting animal pollinators. In human body, they play a very important role relating to people’s health, e. g. anti-oxidation, anti-tumor, anti-inflammation, as well as beneficial effects in neuron system and bone system. Previous study showed that four flavonoids derived from Astragali Radix could stimulate the expression of erythropoietin (EPO), a glycoprotein hormone that controls red blood cell production, in cultured human embryonic kidney fibroblasts (HEK293T). The possible mechanism of flavonoids in EPO system has been investigated. After the...[ Read more ]

Flavonoids are a family of phenolic compounds and widely present in our daily foods and traditional Chinese medicines. In nature, flavonoids serve as the most common plant pigments next to chlorophyll and carotenoids in flower for attracting animal pollinators. In human body, they play a very important role relating to people’s health, e. g. anti-oxidation, anti-tumor, anti-inflammation, as well as beneficial effects in neuron system and bone system. Previous study showed that four flavonoids derived from Astragali Radix could stimulate the expression of erythropoietin (EPO), a glycoprotein hormone that controls red blood cell production, in cultured human embryonic kidney fibroblasts (HEK293T). The possible mechanism of flavonoids in EPO system has been investigated. After the treatment of flavonoids, the expression of hypoxia-inducible factor 1-α (HIF-1α) protein, the transcriptional activity of hypoxia response element (HRE) and the expression of EPO in mRNA level were all upregulated.

In this project, we aim to extend our effort in searching the functions of other flavonoids in stimulating EPO production. After the screening of 54 flavonoids evaluated by HRE transcriptional activity in cultured HEK293T cells, five of them, i.e., apigenin, chrysin, quercetin, genistein and genistin, were selected for further analysis. To account for the effect of screened flavonoids on EPO production, the expressions of EPO mRNA, HIF-1α, and HIF-2α proteins were tested. All of these flavonoids could upregulate the EPO mRNA expression in a dose-dependent manner. Quercetin increased the level of HIF-1α protein at the dosage of 30 μM. Apigenin, chrysin, and genistin did not make any influence of HIF-1α at 1 μM, 3 μM and 10 μM, while they could down regulate HIF-1α at about 25% at 30 μM. Genistein reduced the amount of HIF-1α protein at all dosages in a dose-dependent manner. All of these flavonoids did not show any significant influence on the amounts of HIF-2α.

To reveal the possible synergistic activity of screened flavonoids, combinations of apigenin, chrysin, quercetin, genistein and genistin were tested in cultured HEK293T cell and human hepatocellular carcinoma cell (Hep3B). Both of the HRE transcriptional activity and the EPO mRNA expression demonstrated that the combination of apigenin and genistin possessed synergistic effect than that of the single drug. The combination of genistein and quercetin suggested synergistic effect in a rather weak level, while the other combinations suggested additive or antagonistic effects.