THESIS
2014
xx, 103 pages : illustrations (some color) ; 30 cm
Abstract
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...[
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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.
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