Salidroside stimulates the accumulation of HIF-1α protein resulted in the induction of EPO expression: a signaling via blocking the degradation pathway in kidney and liver cells.
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 to mountain sickness in preventing hypoxia; however, the functional ingredient responsible for this adaptogenic effect has not been revealed. Here, we have identified salidroside, a glycoside predominantly found in Rhodiola, is the chemical in providing such anti-hypoxia effect. Cultured human embryonic kidney fibroblast (HEK293T) and human hepatocellular carcinoma (HepG2) were used to reveal the mechanism of this hematopoietic function mediated by salidroside. The application of salidroside in cultures induced the expression of erythropoietin (EPO) mRNA from its transcription regulatory element hypoxia response element (HRE), located on EPO gene. The application of salidroside stimulated the accumulation of hypoxia-inducible factor-1α (HIF-1α) protein, but not HIF-2α protein: the salidroside-induced HIF-1α protein was via the reduction of HIF-1α degradation but not the mRNA induction. The increased HIF-1α could account for the activation of EPO gene. These results supported the notion that hematopoietic function of Rhodiola was triggered, at least partially, by salidroside.
Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
Ken Yu-Zhong
KY
Zheng
Zhen-Xia
ZX
Zhang
Ava Jiang-Yang
AJ
Guo
Cathy Wen-Chuang
CW
Bi
Kevin Yue
KY
Zhu
Sherry Li
SL
Xu
Janis Ya-Xian
JY
Zhan
David Tai-Wei
DT
Lau
Tina Ting-Xia
TT
Dong
Roy Chi-Yan
RC
Choi
Karl Wah-Keung
KW
Tsim
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D057809:HEK293 Cells; D006397:Hematinics / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D004921:Erythropoietin; D005960:Glucosides; D006397:Hematinics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010636:Phenols; D000099162:Endothelial PAS Domain-Containing Protein 1; C009172:rhodioloside