Flavonoids from Radix Astragali Induce the Expression of Erythropoietin in Cultured Cells: A Signaling Mediated via the Accumulation of Hypoxia-Inducible Factor-1α

Abstract

Radix Astragali (RA) is commonly used as a health food supplement to reinforce the body vital energy. Flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-d-glucoside, are considered to be the major active ingredients within RA. Here, we provided different lines of evidence that the RA flavonoids stimulated the expression of erythropoietin (EPO), the central regulator of red blood cell mass, in cultured human embryonic kidney fibroblasts (HEK293T). A plasmid containing hypoxia response element (HRE), a critical regulator for EPO transcription, was tagged upstream of a firefly luciferase gene, namely, pHRE-Luc, which was being transfected into fibroblasts. The application of RA flavonoids onto the transfected cells induced the transcriptional activity of HRE. To account for the transcriptional activation after the treatment of flavonoids, the expression of hypoxia-inducible factor-1α (HIF-1α) was markedly increased: The increase was in both mRNA and protein levels. In addition, the degradation of HIF-1α was reduced under the effect of flavonoids. The regulation of HIF-1α therefore could account for the activation of EPO expression mediated by the RA flavonoids. The current results therefore reveal the function of this herb in enhancing hematopoietic functions.

Fruit of Ziziphus jujuba (Jujube) at Two Stages of Maturity: Distinction by Metabolic Profiling and Biological Assessment

“…12 This suggests that the pHRE-Luc activity of jujube does not relate to the content of flavonoids. In parallel to this notion, flavonoids derived from herbal medicines have been reported to be able to induce the expression of EPO, 29 suggesting that flavonoids may be one of the active ingredients for this action.…”

A High Throughput Screening Platform for Skin Tuning Properties from Natural Products: Identification of Skin Tanning Compounds

“…For the past decades, our group has studied several decoctions with Astragalius Radix, such as Danggui Buxue Tang [16] [17] [18]; Fo Shou San and Yu Ping Feng San [19] [20] [21]. Astragalius Radix was able to abolish the ubiquity in degradation system and resulted the accumulation of hypoxia inducible factor 1 alpha (HIF-1α) [22] [23]. Thus, a pseudo-hypoxic environment could be generated at cellular level.…”

Effect of the Jianpi Bushen Prescription on the expression of SHP-1, Wnt3a, and AP-1 proteins in chemically damaged mice

“…Radix astragalus has a comprehensive and sustained effect in elevating whole blood cells, recovering red blood cell, while blood cell, and platelet levels to normal. In addition, it promotes the secretion of hematopoietic cytokine, stimulating the function of the hematopoietic system, and counteracting bone marrow suppression caused by chemotherapy and radiotherapy (Gao et al, 2006;Zheng et al, 2011). In summary, modern medicine has demonstrated that the spleen and kidney have the dual role of promoting the regulation of hematopoietic cell proliferation and immune function.…”