Timosaponin-BII inhibits the up-regulation of BACE1 induced by ferric chloride in rat retina.
BACKGROUND
Our previous studies indicated that oxidative stress up-regulated the expression of β-amyloid precursor protein cleavage enzyme-1 (BACE1) in rat retina. Pharmacological reports have shown Timosaponin-BII, a purified extract originating from Chinese medical herb Rhizoma Anemarrhenae, is characterized as an antioxidant. Our present study aimed to determine whether Timosaponin-BII affected the expression of BACE1, β-amyloid precursor protein cleavage production of Aβ1-40 and β-C-terminal fragment (β-CTF) in rat retina, which were pre-treated with the oxidizing agent (solution of FeCl₃).


RESULTS
Few distinctions of BACE1 distribution were observed among all groups (normal control group, model group, Timosaponin-BII treated and vehicle control groups). Rat retinas in model group and vehicle control group manifested an apparent up-regulation of BACE1 expression. Meanwhile, the level of malonaldehyde (MDA), Aβ1-40 and β-CTF were increased. However, when comparing with the vehicle control group, the retinas in Timosaponin-BII treated group showed significantly less BACE1 (p<0.05) and accumulated less Aβ1-40 or β-CTF (p<0.05). It also showed significantly decreased level of MDA (p<0.05) and prolonged partial thromboplastin time (p<0.05).


CONCLUSIONS
Our data suggested that Timosaponin-BII remarkably inhibited the up-regulation of BACE1 and reduced the over-production of β-CTF and Aβ in rat retina, which was induced by FeCl₃. The mechanism of Timosaponin-BII on BACE1 expression may be related to its antioxidant property.
Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan 410013, China.
Ju-Fang
JF
Huang
Lei
L
Shang
Pei
P
Liu
Meng-Qi
MQ
Zhang
Shuang
S
Chen
Dan
D
Chen
Chun-Ling
CL
Fan
Hui
H
Wang
Kun
K
Xiong
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D031403:Anemarrhena / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002712:Chlorides; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005290:Ferric Compounds; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010314:Partial Thromboplastin Time; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D027343:Rhizome; D012503:Saponins / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology*; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002712:Chlorides; D004365:Drugs, Chinese Herbal; D005290:Ferric Compounds; D012503:Saponins; D013256:Steroids; C523027:timosaponin B-II; D008315:Malondialdehyde; D053829:Amyloid Precursor Protein Secretases; C024555:ferric chloride