In vitro BACE-1 Inhibitory Phenolic Components from the Seeds of Psoralea corylifolia

Abstract

A new isoflavone, neocorylin (1) was isolated from the seeds extract of Psoralea corylifolia L. (Fabaceae), together with eight known constituents (2 – 9), i. e., bakuchiol (2), psoralen (3), bavachromene (4), isobavachromene (5), bavachalcone (6), isobavachalcone (7), 7,8-dihydro-8-(4-hydrophenyl)-2,2-dimethyl-2H,6H-[1,2-b:5,4-b′]dipyran-6-one (8), and bavachinin (9). The structure of the new isoflavone 1 was elucidated as 7-hydroxy-3-[2-methyl-2-(4-methylpenten-3-yl)-2H-chromen-6-yl]-4H-chromen-4-one by spectroscopic analyses. Neocorylin (1) as well as related compounds 2, 4 – 6, 8 and 9 exhibited a significant inhibitory effect on baculovirus-expressed BACE-1 in vitro.

Key words

Psoralea corylifolia L - Fabaceae - BACE-1 - isoflavones - neocorylin

References

• 1 Guo J, Weng X, Wu H, Li Q, Bi K. Antioxidants from a Chinese medicinal herb – Psoralea corylifolia L.  Food Chem. 2005;  91 287-92
• 2 Lee M H, Kim J Y, Ryu J H. Prenylfalvones from Psoralea corylifolia inhibit nitric oxide synthase expression through the inhibition of I-κB-α degradation in activated microglial cells.  Biol Pharm Bull. 2005;  28 2253-7
• 3 Latha P G, Evans D A, Panikkar K R, Jayavardhanan K K. Immunomodulatory and antitumour properties of Psoralea corylifolia seeds.  Fitoterapia. 2000;  71 223-31
• 4 Yin S, Fan C Q, Wang Y, Dong L, Yue J M. Antibacterial prenylflavone derivatives from Psoralea corylifolia, and their structure-activity relationship study.  Bioorg Med Chem. 2004;  212 4387-92
• 5 Ryu S Y, Chio S U, Lee C O, Zee O P. Antitumor activity of Psoralea corylifolia.  Arch Pharm Res. 1992;  15 356-9
• 6 Sun N J, Woo S H, Cassady J M, Snapka R M. DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia.  J Nat Prod. 1998;  61 362-6
• 7 Tsai W J, Hsin W C, Chen C C. Antiplatelet flavonoids from seeds of Psoralea corylifolia.  J Nat Prod. 1996;  59 671-2
• 8 Prasad R N, Anandi C, Balasubramanian S, Pugalend K V. Antidermatophytic activity of extracts from Psoralea corylifolia (Fabaceae) correlated with the presence of a flavonoid compound.  J Ethnopharmacol. 2004;  91 21-4
• 9 Selkoe D J. Alzheimer′s disease: genotypes, phenotypes, and treatments.  Science. 1997;  275 630-1
• 10 Vassar R, Bennett B D, Babu-Khan S, Kahn S, Mendiaz E A, Denis P. et al . Beta-secretase cleavage of Alzheimer′s amyloid precursor protein by the transmembrane aspartic protease BACE.  Science. 1999;  286 735-41
• 11 Zhao L, Huang C, Shan Z, Xiang B, Mei L. Fingprint analysis of Psoralea corylifolia L. by HPLC and LC-MS.  J Chromatogr B. 2005;  821 67-74
• 12 Nkengfack A E, Kouam J, Vouffo T W, Meyer M, Tempesta M S, Fomum Z T. An isoflavanone and a coumestan from Erythrina sigmoidea.  Phytochemistry. 1994;  35 521-6
• 13 Pistelli L, Spera K, Flamini G, Mele S, Moelli I. Isoflavonoids and chalcones from Anthyllis hermanniae.  Phytochemistry. 1996;  42 1455-8
• 14 Iserloh U, Wu Y, Cumming J N, Pan J, Wang L Y, Stamford A W. et al . Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.  Bioorg Med Chem Lett. 2008;  18 414-7
• 15 Sinha S, Anderson J P, Barbour R, Basi G S, Caccavello R, Davis D. et al . Purification and cloning of amyloid precursor protein beta-secretase from human brain.  Nature. 1999;  402 537-40