Platelet-activating factor (PAF) antagonistic activity of a new biflavonoid from Garcinia nervosa var. pubescens King.

The methanol extract of the leaves of Garcinia nervosa var. pubescens King, which showed strong inhibitory effects on platelet-activating factor (PAF) receptor binding, was subjected to bioassay-guided isolation to obtain a new biflavonoid, II-3,I-5, II-5,II-7,I-4',II-4'-hexahydroxy-(I-3,II-8)-flavonylflavanonol together with two known flavonoids, 6-methyl-4'-methoxyflavone and acacetin. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit PAF receptor binding to rabbit platelets using ³H-PAF as a ligand. The biflavonoid and acacetin showed strong inhibition with IC50 values of 28.0 and 20.4 µM, respectively. The results suggest that these compounds could be responsible for the strong PAF antagonistic activity of the plant.

Platelet-activating factor (PAF) receptor binding activity of the roots of Enicosanthellum pulchrum.

CONTEXT: Enicosanthellum pulchrum (King) Heusden (Annonaceae) is a coniferous tree that is confined to mountain forests. The chemical constituents of this species have been studied previously; however, its biological activity has never been investigated before and is reported here for the first time. OBJECTIVE: The extracts, fractions and compounds from the roots of E. pulchrum were investigated for their inhibitory effects on platelet-activating factor (PAF) receptor binding to rabbit platelets using (3)H-PAF as a ligand. MATERIALS AND METHODS: The PAF receptor binding inhibitory effect using rabbit platelets was determined in vitro by measuring the difference between total amount of bound (3)H-PAF in the presence and the absence of excess unlabelled PAF. The compounds were isolated by bioassay-guided fractionation and their structures were elucidated by spectroscopic techniques. RESULTS AND DISCUSSION: Among the extracts tested, the ethyl acetate extract was the most active with 85.6% inhibition, while hexane and methanol extracts showed 40.2 and 42.5% inhibition, respectively. Fractionation of the ethyl acetate extract using vacuum liquid chromatography (VLC) yielded six fractions AEA(I--VI). Chromatography fraction AEA(VI) yielded a new compound, 1-(2',3',4'-trimethoxyphenyl)hexan-1-ol, while fraction AEA(III) afforded three compounds, namely liriodenine, cleistopholine and dehydroanonaine. 1-(2',3',4'-Trimethoxyphenyl)hexan-1-ol, cleistopholine and dehydroanonaine showed relatively strong inhibition with IC(50) values of 26.6, 50.2 and 45.4 µM, respectively. CONCLUSION: The results suggest that these compounds could be responsible for the PAF antagonistic activity of the ethyl acetate extract of this plant.

Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants.

The methanol extracts of 20 selected medicinal plants were investigated for their effects on the respiratory burst of human whole blood, isolated human polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the extracts on chemotactic migration of PMNs using the Boyden chamber technique. The extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C. xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to 0.7 µg/ml. For macrophage cells, the extracts which showed strong suppressive activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9 to 1.5 µg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.) Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic migration of cells, with IC(50) values comparable to that of ibuprofen (1.5 µg/ml). The results suggest that some of these plants were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.

Isolation and immunomodulatory properties of a flavonoid, casticin from Vitex agnus-castus.

Casticin (1), a flavonoid isolated from the aerial parts of Vitex agnus-castus, was found to be a potent immunomodulatory and cytotoxic compound. The activity was tested in vitro for chemiluminescence, chemotaxis, T-cell proliferation and cytotoxicity. Casticin (1) exhibited a significant inhibitory effect on monocyte oxidative burst in a dose dependent manner. It was found to have a significant suppressive effect on the chemotaxic action at higher concentrations on fMLP (10(-8) m) stimulated neutrophils. It also showed a potent suppressive effect on PHA stimulated T-cell (PMBC).

Antiplatelet activity of aporphine and phenanthrenoid alkaloids from Aromadendron elegans Blume.

Six aporphine and one phenanthrenoid alkaloids isolated from Aromadendron elegans Blume were investigated for their ability to inhibit arachidonic acid (AA), collagen and ADP induced platelet aggregation in human whole blood. The antiplatelet activity of the compounds was measured in vitro by the Chrono Log whole blood aggregometer using an electrical impedance method. Of the compounds tested, (-)-N-acetylnornuciferine, (-)-N-acetylanonaine and 1-(N-acetyl-N-methylamino)ethyl-3,4,6-trimethoxy-7-hydroxyphenanthrene showed strong inhibition on platelet aggregation caused by all three inducers. (-)-N-acetylanonaine was the most effective antiplatelet compound as it inhibited both arachidonic acid, collagen and ADP-induced platelet aggregation with IC(50) values of 66.1, 95.1 and 80.6 microm, respectively.