Intravenous infusion of dihydroginsenoside Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL.
Red ginseng root (Panax Ginseng CA Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of Red ginseng root is ginsenoside Rb(1) (gRb1). Previously, we showed that intravenous infusion of gRb1 ameliorated ischemic brain damage through upregulation of an anti-apoptotic factor, Bcl-x(L) and that topical application of gRb1 to burn wound lesion facilitated wound healing through upregulation of vascular endothelial growth factor (VEGF). In the present study, we produced dihydroginsenoside Rb1 (dgRb1), a stable chemical derivative of gRb1, and showed that intravenous infusion of dgRb1 improved spinal cord injury (SCI) as well as ischemic brain damage. As we expected, the effective dose of dgRb1 was ten times lower than that of gRb1. Intravenous infusion of dgRb1 at this effective dose did not affect brain temperature, blood pressure or cerebral blood flow, suggesting that dgRb1 rescued damaged neurons without affecting systemic parameters. In subsequent in vitro studies that focused on dgRb1-induced expression of gene products responsible for neuronal death or survival, we showed that dgRb1 could upregulate the expression of not only Bcl-x(L), but also a potent angiogenic and neurotrophic factor, VEGF. We also showed that dgRb1-induced expression of bcl-x(L) and VEGF mRNA was HRE (hypoxia response element) and STRE (signal transducers and activators of transcription 5 (Stat5) response element) dependent, respectively.
Sakanaka
Masahiro
M
Department of Functional Histology, Ehime University Graduate School of Medicine, Shitukawa, Toon, Ehime, Japan.
Zhu
Pengxiang
P
Zhang
Bo
B
Wen
Tong-Chun
TC
Cao
Fang
F
Ma
Yong-Jie
YJ
Samukawa
Keiichi
K
Mitsuda
Noriaki
N
Tanaka
Junya
J
Kuramoto
Makoto
M
Uno
Hidemitsu
H
Hata
Ryuji
R
D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D051020:bcl-X Protein / Q000235:genetics*
C494813:Bcl2l1 protein, rat; D036145:Ginsenosides; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D051020:bcl-X Protein; C522353:dihydroginsenoside Rb1; C442759:ginsenoside Rb1