title: 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.
authors.affiliation: Section of Marine Ecology and Biotechnology, Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
authors.forename: Ken Y Z
authors.initials: KY
authors.lastname: Zheng
authors.forename: Roy C Y
authors.initials: RC
authors.lastname: Choi
authors.forename: Anna W H
authors.initials: AW
authors.lastname: Cheung
authors.forename: Ava J Y
authors.initials: AJ
authors.lastname: Guo
authors.forename: Cathy W C
authors.initials: CW
authors.lastname: Bi
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Zhu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Yingqing
authors.initials: Y
authors.lastname: Du
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Zhang
authors.forename: Janis Y X
authors.initials: JY
authors.lastname: Zhan
authors.forename: R
authors.initials: R
authors.lastname: Duan
authors.forename: David T W
authors.initials: DT
authors.lastname: Lau
authors.forename: Tina T X
authors.initials: TT
authors.lastname: Dong
authors.forename: Karl W K
authors.initials: KW
authors.lastname: Tsim
mesh_terms: D027883:Astragalus Plant / Q000737:chemistry; D027885:Astragalus propinquus; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004921:Erythropoietin / Q000235:genetics*; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D004921:Erythropoietin; C027492:Huang Qi