Flavonoids with prolyl oligopeptidase inhibitory activity isolated from Scutellaria racemosa Pers

Abstract

Prolyl oligopeptidase (POP) is a serine protease highly expressed in the brain that hydrolyses peptide bonds at the carboxyl terminal of prolyl residues. There is evidence that this enzyme participates in several functions of the central nervous system. Scutellaria racemosa Pers demonstrated significant and selective POP inhibition. Fractionation of the hydroalcoholic extract resulted in the isolation of four main constituents identified for the first time from S. racemosa Pers, the triterpenoid lupeol (1) and the flavonoids oroxylin A (5,7-dihydroxy-6-methoxyflavone, 2), hispidulin (4',5,7-trihydroxy-6-methoxyflavone, 3), and oroxyloside (oroxylin A 7-O-glucuronide, 4). Inhibitory assays indicated that 3 and 4 at a concentration of 100 microM inhibit 43 and 34% of total POP activity, respectively.

Medicinal importance, pharmacological activities, and analytical aspects of hispidulin: A concise report

“…Hispidulin and other phytochemical were isolated from the leaves of C. chinense 58 . Fractionation of hydroalcoholic extract of S. racemosa Pers resulted in the isolation of four main constituents including hispidulin 59 . Phytochemical study of leaves of Leuzea carthamoides was performed and the result showed the presence of seven natural compounds including hispidulin 60 .…”

Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1

“…The residue was purified by silica gel chromatography (EtOAc−n-hexane, 1:1) to give hispidulin (89 mg, 80%) as a yellow microcrystalline powder; mp 275−277°C (lit. 32 Expression and Purification of Pim-1. The production and purification of the recombinant His 6 -tagged Pim-1 for crystallography have been described previously.…”

Isoquinoline alkaloids as prolyl oligopeptidase inhibitors

“…Some natural products are known POP inhibitors in the micromolar range such as the flavonoids baicalin [7] and oroxylin [8], the alkaloid berberine [9], and 6-(8´Z-pentadecenyl)salicylic acid [10].…”