title: The extract of Rhodiolae Crenulatae Radix et Rhizoma induces the accumulation of HIF-1α via blocking the degradation pathway in cultured kidney fibroblasts.
abstract: Rhodiolae Crenulatae Radix et Rhizoma (Rhodiola), the root and rhizome of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba, has been used as a traditional Chinese medicine (TCM) to increase the body resistance against hypoxia in mountain sickness. The mechanism of this adaptogenic property deriving from Rhodiola, however, has not been revealed. Erythropoietin (EPO) is an erythrocyte-specific hematopoietic hormone that increases the production of red blood cells: this hormone is a crucial factor in regulating the body balance in responding to hypoxia. In cultured kidney fibroblasts (HEK293T), application of water extract deriving from Rhodiola induced the expression of EPO both in mRNA and protein levels. The activation of the Hypoxia Response Element (HRE) located on the promoter region of the EPO gene is one of the mechanisms accounting for transcriptional activation. In addition, the Rhodiola-induced EPO expression was triggered by an increase of hypoxia-inducible factor-1 α (HIF-1 α) protein, via the reduction of HIF-1 α degradation but not the induction of HIF-1 α mRNA. Moreover, the same EPO induction effect by Rhodiola was also observed in cultured liver cells since liver is another vital organ to provide EPO regulation apart from the kidney. These results therefore elucidate one of the molecular mechanisms of this herb in mediating the anti-hypoxia function.
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, Hong Kong, China.
authors.forename: Ken Y
authors.initials: KY
authors.lastname: Zheng
authors.forename: Ava J
authors.initials: AJ
authors.lastname: Guo
authors.forename: Cathy W
authors.initials: CW
authors.lastname: Bi
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Zhu
authors.forename: Gallant K
authors.initials: GK
authors.lastname: Chan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Xu
authors.forename: Janis Y
authors.initials: JY
authors.lastname: Zhan
authors.forename: David T
authors.initials: DT
authors.lastname: Lau
authors.forename: Tina T
authors.initials: TT
authors.lastname: Dong
authors.forename: Roy C
authors.initials: RC
authors.lastname: Choi
authors.forename: Karl W
authors.initials: KW
authors.lastname: Tsim
mesh_terms: D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000276:immunology / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D018517:Plant Roots / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D020218:Response Elements / Q000235:genetics; D027343:Rhizome / Q000737:chemistry; D029771:Rhodiola / Q000737:chemistry*; D017262:Siderophores / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D017262:Siderophores; D004921:Erythropoietin; D006899:Mixed Function Oxygenases; D003676:Deferoxamine