Tenuifolin, an extract derived from tenuigenin, inhibits amyloid-beta secretion in vitro.
OBJECTIVE
Previous studies have shown that tenuigenin, a crude extract of Polygala tenuifolia Willd. that is commonly used in traditional Chinese herbal medicine for memory loss, can reduce the secretion of Abeta from cultured cells. However, the mechanism underlying this effect and the active compound derived from tenuigenin is unknown. In this study, a purified component of tenuigenin, tenuifolin, was examined and revealed to be an effective compound in vitro.


METHODS
Abeta secretion from three sets of COS-7 cells, each carrying a plasmid expressing a different form of APP was examined following the treatment with tenuifolin. Initially, tenuifolin was determined to have no inherent toxicity to either the transfected or wild type cells at the effective concentrations. Cells were then treated with 0.5-2.0 microg mL(-1) tenuifolin for 12 h and their media were examined via an ELISA for Abeta1-40 and Abeta-42.


RESULTS
We found that treatment with 2.0 microg mL(-1) tenuifolin significantly decreased Abeta secretion from COS-7 cells without altering the ratio of Abeta1-40 and Abeta-42. This effect is most probably due to inhibition of the beta-site APP cleaving enzyme as Abeta secretion was not inhibited from cells expressing the C99 fragment.


CONCLUSIONS
Tenuifolin is an effective compound from tenuigenin. We believe that this finding should lead the way for future experiments to determine the exact mechanism for tenuifolin's effect on Abeta secretion.
Lv
J
J
Institute of Mental Health, Peking University, 100083 Beijing, China.
Jia
H
H
Jiang
Y
Y
Ruan
Y
Y
Liu
Z
Z
Yue
W
W
Beyreuther
K
K
Tu
P
P
Zhang
D
D
D000818:Animals; D006801:Humans; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D002522:Chlorocebus aethiops; D019556:COS Cells; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D008517:Phytotherapy; D031801:Polygala; D013997:Time Factors; D012503:Saponins
D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases; D045786:Diterpenes, Kaurane; D004365:Drugs, Chinese Herbal; C532370:tenuifolin diterpene; C493220:tenuigenin; C407311:tenuifolic saponin; D012503:Saponins