Complement-Inhibiting Constituents of Bridelia ferruginea Stem Bark

Abstract

A bioassay-guided fractionation of an 80% acetone extract from Bridelia ferruginea stem bark showing a dose-dependent inhibitory effect towards both the classical and the alternative pathways of the complement system resulted in the isolation of a biflavanol (gallocatechin-(4′-O-7)-epigallocatechin) (1), 3,5-dicaffeoylquinic acid (2), 1,3,4,5-tetracaffeoylquinic acid (3), and a series of 3-methoxyflavone derivatives, including quercetin 3-methyl ether (4), quercetin 3,7,3′,4′-tetramethyl ether (5), myricetin 3′,4′,5′-trimethyl ether (6; new compound) named ferrugin, myricetin 3,3′,4′,5′-tetramethyl ether (7), myricetin (8), and quercetin 3-O-glucoside (9) as the active constituents. Especially the biflavanol 1 and the caffeoyl esters of quinic acid 2 and 3 showed a strong inhibitory effect (IC₅₀ < 10 µM) on the classical pathway, compared to rosmarinic acid. Also on the alternative pathway, the biflavanol 1, the quinic acid derivatives 2 and 3, and some of the 3-methoxyflavones 5, 7 and 8 were more active than rosmarinic acid. The quinic acid derivatives were shown to be inhibitors of the C1 component and the terminal route of the complement system.

Key words

Bridelia ferruginea - Euphorbiaceae - anticomplementary activity - biflavonoid - quinic acid derivatives - 3-methoxyflavone derivatives - myricetin 3′,4′,5′-tetramethyl ether