guttiferone-k and garcinol

Topics: Benzophenones; Garcinia; Models, Molecular; Molecular Docking Simulation; Prenylation; Terpenes; Topoisomerase II Inhibitors

Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1-3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in KD values in the micromolar range. Consistent with the observed high affinity toward the STAT-1 protein, garcinol and guttiferones K and M were able to modulate cytokine signaling in different cultured cell lines, mainly by inhibiting STAT-1 nuclear transfer and DNA binding, as assessed by an electrophorectic mobility shift assay.

Topics: Benzophenones; Blotting, Northern; Female; Fruit; Garcinia cambogia; Humans; Lipopolysaccharides; Macrophages; Methicillin-Resistant Staphylococcus aureus; Molecular Conformation; Molecular Structure; NF-kappa B; Signal Transduction; Sri Lanka; STAT1 Transcription Factor; Terpenes

The effects of garcinol and guttiferone K, two polyisoprenylated benzophenones occurring a food plant called Garcinia cambogia, on oxidative/nitrative protein damage (determined by parameters such as levels of protein carbonyl groups and nitrotyrosine residues) in human blood platelets and plasma after treatment with peroxynitrite (ONOO(-)) were studied in vitro. We also investigated the effects of garcinol and guttiferone K on lipid peroxidation in blood platelets and plasma induced by ONOO(-) (100 microM). Exposure of blood platelets or plasma to peroxynitrite (100 microM) resulted in an increased level of carbonyl groups and nitrotyrosine residues in proteins, and an increase of lipid peroxidation measured by the level of thiobarbituric acid reactive species (TBARS). In the presence of garcinol and guttiferone K (0.1-25 microg/ml), a distinct reduction in the formation of carbonyl groups in plasma and platelet proteins together with the decrease of TBARS caused by 100 microM peroxynitrite, was observed. However, garcinol and guttiferone K did not inhibit plasma and platelet protein nitration induced by peroxynitrite. Polyisoprenylated benzophenones present in human diet such as garcinol or guttiferone K in vitro have protective effects against lipid and protein oxidation and may have some promising effects in vivo because they are good antioxidants in the tested models in vitro. Garcinol and guttiferone K can be also useful as protecting factors against diseases associated with oxidative stress.

Topics: Adult; Benzophenones; Blood Platelets; Blood Proteins; Garcinia cambogia; Humans; Lipid Peroxidation; Male; Oxidation-Reduction; Oxidative Stress; Peroxynitrous Acid; Terpenes; Young Adult

In light of the wide range of biological activities of garcinol and with the aim of exploring some of them, we carried out its isolation from the fruits of Garcinia cambogia L. (Guttiferae). Surprisingly, the fruits were also found to contain guttiferones I, J, and K, compounds never reported in G. cambogia, along with three new compounds, namely, guttiferone M (1), guttiferone N (2), and the oxidized derivative of guttiferone K (6). Oxy-guttiferone K (6) is the first example of tetracyclic xanthone derived from the oxidation of a polyisoprenylated benzophenone from natural source. The natural formation of oxy-guttiferone K is in agreement with the previously described cyclization of garcinol by DPPH.

Topics: Benzophenones; Fruit; Garcinia cambogia; Oxidation-Reduction; Plant Extracts; Terpenes