In Vitro BACE-1 Inhibitory Activity of Resveratrol Oligomers from the Seed Extract of Paeonia lactiflora

Abstract

A new resveratrol oligomer (1) together with eight related components (2–9) were isolated from the seed extract of Paeonia lactiflora (Paeoniaceae) as active principles responsible for the inhibition of beta-site APP-cleaving enzyme 1 (BACE-1) in vitro. The chemical structure of 1 was established as (−)-7a,8a-cis-ε-viniferin with the aid of spectroscopic analyses including NOESY experiments. All isolated resveratrol oligomers (1–9) demonstrated significant inhibition on baculovirus-expressed BACE-1 in a dose-dependent manner, which was assessed by the FRET assay using Rh-EVNLDAEFK as a substrate in vitro.

Key words

Paeonia lactiflora - Paeoniaceae - BACE‐1 inhibitors - resveratrol oligomer

References

• 1 Tanaka T, Kataoka M, Tsuboi N, Kouno I. New monoterpene glycoside esters and phenolic constituents of Paeoniae Radix, and increase of water solubility of proanthocyanidins in the presence of paeoniflorin.  Chem Pharm Bull. 2000;  48 201-207
• 2 Ikuta A, Kamiya K, Satake T, Saiki Y. Triterpenoids from callus tissue cultures of Paeonia species.  Phytochemistry. 1995;  38 1203-1207
• 3 Kim H J, Chang E J, Bae S J, Chim S M, Park H D, Rhee C H, Park J H, Choi S W. Cytotoxic and antimutagenic stilbenes from seeds of Paeonia lactiflora.  Arch Pharm Res. 2002;  25 293-299
• 4 Kim H J, Chang E J, Cho S H, Chung S K, Park H D, Choi S W. Antioxidative activity of resveratrol and its derivatives isolated from seeds of Paeonia lactiflora.  Biosci Biotechnol Biochem. 2002;  66 1990-1993
• 5 Lee B M, Shin Y W, Bae E A. Antiallergic effect of the root of Paeonia lactiflora and its constituents paeoniflorin and paeonol.  Arch Pharm Res. 2008;  31 445-450
• 6 Choi C W, Choi Y H, Cha M R, Park J H, Kim Y S, Kim Y K, Choi S U, Yon G H, Hong K S, Kim Y H, Ryu S Y. α-Glucosidase inhibitors from seeds extract of Paeonia lactiflora.  J Korean Soc Appl Biol Chem. 2009;  52 638-642
• 7 Vassar R, Bennett B D, Babu-Khan S, Kahn S, Mendiaz E A, Denis P, Teplow D B, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski M A, Biere A L, Curran E, Burgess T, Louis J C, Collins F, Treanor J, Rogers G, Citron M. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.  Science. 1999;  286 735-741
• 8 Huang K S, Lin M, Yu L N, Kong M. Four novel oligostilbenes from the roots of Vitis amurensis.  Tetrahedron. 2000;  56 1321-1329
• 9 Huang Y L, Tsai W J, Shen C C, Chen C C. Resveratrol derivatives from the roots of Vitis thunbergii.  J Nat Prod. 2005;  68 217-220
• 10 Choi Y H, Yoo M Y, Choi C W, Cha M R, Yon G H, Kwon D Y, Kim Y S, Park W K, Ryu S Y. A new specific BACE-1 inhibitor from the Stembark Extract of Vitis vinifera.  Planta Med. 2009;  75 537-540
• 11 Iserloh U, Wu Y, Cumming J N, Pan J, Wang L Y, Stamford A W, Kennedy M E, Kuvelkar R, Chen X, Parker E M, Strickland C, Voigt J. Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.  Bioorg Med Chem Lett. 2008;  18 414-417
• 12 Jeon S Y, Kwon S H, Seong Y H, Bae K, Hur J M, Lee Y Y, Suh D Y, Song K S. Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax Rhizoma.  Phytomedicine. 2007;  14 403-408
• 13 Jang M H, Piao X L, Kim H Y, Cho E J, Baek S H, Kwon S W, Park J H. Resveratrol oligomers from Vitis amurensis attenuate β-amyloid-induced oxidative stress in PC12 cells.  Biol Pharm Bull. 2007;  30 1130-1134
• 14 Sinha S, Anderson J P, Barbour R, Basi G S, Caccavello R, Davis D, Doan M, Dovey H F, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, Seubert P, Suomensaari S M, Wang S, Walker D, Zhao J, McConlogue L, John V. Purification and cloning of amyloid precursor protein beta-secretase from human brain.  Nature. 1999;  402 537-540