Tetrandrine ameliorates dextran-sulfate-sodium-induced colitis in mice through inhibition of nuclear factor -kappaB activation.
BACKGROUND
Activation of nuclear factor (NF)-kappaB has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC), and tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to be a potent inhibitor of NF-kappaB activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of UC.


METHODS
Tetrandrine was administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. NF-kappaB DNA binding activity was assessed by electrophoretic mobility shift assay. The expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.


RESULTS
A significant improvement was observed in DAI and histological score in mice with tetrandrine, and the increase in NF-kappaB DNA binding activity, myeloperoxidase activity, IL-1beta, and TNF-alpha in mice with DSS-induced colitis was significantly reduced following administration of tetrandrine.


CONCLUSIONS
The administration of tetrandrine leads to an amelioration of DSS-induced colitis, suggesting administration of tetrandrine may provide a therapeutic approach for UC.
Zhang
Dei Kui
DK
Department of Geriatric Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
Cheng
Li Na
LN
Huang
Xiao Li
XL
Shi
Wei
W
Xiang
Jun Ying
JY
Gan
Hua Tian
HT
D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D044182:Benzylisoquinolines; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C009438:tetrandrine; D016264:Dextran Sulfate; D009195:Peroxidase