A crude methanol extract of Goniothalamus andersonii J. Sinclair strongly inhibited elongation of lettuce (Lactuca sativa L.) radicles. We conducted bioassay-guided purification of G. andersonii bark extract and obtained goniothalamin as the major bioactive compound. Its EC50 values against elongation of lettuce radicles and hypocotyls were 50 and 125 micromol L(-1), respectively. Among the six species tested, timothy was the most sensitive to goniothalamin. Quantification of this compound in other Goniothalamus species suggested that the plant inhibitory activity of this genus is explainable by goniothalamin, with G. calcareus as an exception.
Twelve compounds isolated from Alpinia mutica Roxb., Kaempferia rotunda Linn., Curcuma xanthorhiza Roxb., Curcuma aromatica Valeton and Zingiber zerumbet Smith (Family: Zingiberaceae) and three synthesized derivatives of xanthorrhizol were evaluated for their ability to inhibit arachidonic acid- (AA), collagen- and ADP-induced platelet aggregation in human whole blood. Antiplatelet activity of the compounds was measured in vitro by the Chrono Log whole blood aggregometer using an electrical impedance method. Among the compounds tested, curcumin from C. aromatica, cardamonin, pinocembrine and 5,6-dehydrokawain from A. mutica and 3-deacetylcrotepoxide from K. rotunda showed strong inhibition on platelet aggregation induced by AA with IC(50) values of less than 84 microM. Curcumin was the most effective antiplatelet compound as it inhibited AA-, collagen- and ADP-induced platelet aggregation with IC(50) values of 37.5, 60.9 and 45.7 microM, respectively.
Successful activation of the pyranonigrin biosynthetic gene cluster and gene knockout in Aspergillus niger plus in vivo and in vitro assays led to isolation of six new products, including a spiro cyclobutane-containing dimeric compound, which served as the basis for the proposed comprehensive pyranonigrin biosynthetic pathway. Two redox enzymes are key to forming the characteristic fused γ-pyrone core, and a protease homologue performs the exo-methylene formation.
The nuclear factor-kappaB (NF-kappaB) signaling pathway is constitutively active in many types of cancers and is a potential therapeutic target. Using a cell-based assay for stability of inhibitor of kappa B (IkappaB), a critical regulator of NF-kappaB activity, we found that an organic solvent extract of the plant Cryptocarya rugulosa inhibited constitutive NF-kappaB activity in human lymphoma cell lines. The active components were identified as rugulactone, a new alpha-pyrone (1), and the known cryptocaryone (2). Rugulactone was the more active compound, exhibiting up to 5-fold induction of IkappaB at 25 microg/mL; maximal activity was observed with 10 h exposure of test cells to 1 or 2.
Eleven compounds:goniomicin A (1), goniomicin B (2), goniomicin C (3), goniomicin D (4), tapisoidin (5), goniothalamin (6), 9-deoxygoniopypyrone (7), pterodondiol (8), liriodenine (9), benzamide (10) and cinnamic acid (11), were isolated from the stem bark of Goniothalamus tapisoides. All compounds were identified by spectroscopic analysis and, for known compounds, by comparison with published data. Goniothalamin (6) exhibited mild cytotoxic activity towards a colon cancer cell line (HT-29), with an IC(50)value of 64.17 ± 5.60 µM. Goniomicin B (2) give the highest antioxidant activity in the DPPH assay among all compounds tested, with an IC(50) of 0.207 µM.
Goniothalamus macrophyllus (Blume) Hook. f. & Thoms. is a plant widely distributed in Malaysia. The aim of this study is to identify compounds from the roots of G. macrophyllus. The ground roots were extracted with aqueous methanol and partitioned sequentially with n-hexane, chloroform and butanol. Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene-A (1), -B (2). The absolute configuration of goniolandrene B (2) was established by circular dichrosim. The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0.42 to 160 μM. Goniothalamin (3) exhibited the highest inhibition of 0.42 μM.
Phytochemical investigation on the bark of Goniothalamus tapis Miq. and G. uvaroides King has resulted in the isolation of eight styryl-lactones, (-)-cryptomeridiol, liriodenine, 3-methyl-1H-benz[f]indole-4,9-dione, (-)-stigmasterol and dimethyl terephthalate. The structures of the compounds were elucidated by spectroscopic techniques. The compounds were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using (3) H-PAF as a ligand. Among the compounds tested, (-)-cryptomeridiol, (+)-goniothalamin and (+)-isoaltholactone exhibited a significant and concentration-dependent inhibitory effect on PAF receptor binding, with inhibitory concentration (IC)(50) values of 17.5, 19.7 and 46.5 µm, respectively. The inhibitory effects of the first two compounds were comparable to that obtained from the positive control, cedrol. The results indicated that these compounds were strong PAF receptor binding inhibitors.
(R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-α induced NF-κB activation. GTN concentrations up to 20 μM showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in Jurkat and K562 leukemia cells at concentrations as low as 5 μM as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-κB to its DNA response element and reduced TNF-α-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-α-induced NF-κB activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound.