Jacareubin

Jacareubin inhibits FcepsilonRI-induced extracellular calcium entry and production of reactive oxygen species required for anaphylactic degranulation of mast cells.[Pubmed:29802828]

Biochem Pharmacol. 2018 Aug;154:344-356.

Mast cells (MCs) are important effectors in allergic reactions since they produce a number of pre-formed and de novo synthesized pro-inflammatory compounds in response to the high affinity IgE receptor (FcepsilonRI) crosslinking. IgE/Antigen-dependent degranulation and cytokine synthesis in MCs have been recognized as relevant pharmacological targets for the control of deleterious inflammatory reactions. Despite the relevance of allergic diseases worldwide, efficient pharmacological control of mast cell degranulation has been elusive. In this work, the xanthone Jacareubin was isolated from the heartwood of the tropical tree Callophyllum brasilense, and its tridimensional structure was determined for the first time by X-ray diffraction. Also, its effects on the main activation parameters of bone marrow-derived mast cells (BMMCs) were evaluated. Jacareubin inhibited IgE/Ag-induced degranulation in a dose-response manner with an IC50=46nM. It also blocked extracellular calcium influx triggered by IgE/Ag complexes and by the SERCA ATPase inhibitor thapsigargin (Thap). Inhibition of calcium entry correlated with a blockage on the reactive oxygen species (ROS) accumulation. Antioxidant capacity of Jacareubin was higher than the showed by alpha-tocopherol and caffeic acid, but similar to trolox. Jacareubin shown inhibitory actions on xanthine oxidase, but not on NADPH oxidase (NOX) activities. In vivo, Jacareubin inhibited passive anaphylactic reactions and TPA-induced edema in mice. Our data demonstrate that Jacareubin is a potent natural compound able to inhibit anaphylactic degranualtion in mast cells by blunting FcepsilonRI-induced calcium flux needed for secretion of granule content, and suggest that xanthones could be efficient anti-oxidant, antiallergic, and antiinflammatory molecules.

Cytogenetic effects of Jacareubin from Calophyllum brasiliense on human peripheral blood mononucleated cells in vitro and on mouse polychromatic erythrocytes in vivo.[Pubmed:28943391]

Toxicol Appl Pharmacol. 2017 Nov 15;335:6-15.

Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000muM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC50 at 72h by MTT: 85.9muM) than on G0 phase-PBMCs (IC50 315.6muM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1muM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5muM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G0/G1 phase of the cell cycle (from 5muM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5muM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5muM) and frequency of hypodiploid cells (from 10muM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD50; 0.548g/kg. Approximately to 300muM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.

Antioxidative compounds from Garcinia buchananii stem bark.[Pubmed:25625705]

J Nat Prod. 2015 Feb 27;78(2):234-40.

An aqueous ethanolic extract of the stem bark of Garcinia buchananii showed strong antioxidative activity using H2O2 scavenging, oxygen radical absorbance capacity (ORAC), and Trolox equivalent antioxidant capacity (TEAC) assays. Activity-guided fractionation afforded three new compounds, isomanniflavanone (1), an ent-eriodictyol-(3alpha-->6)-dihydroquercetin-linked biflavanone, 1,5-dimethoxyaJacareubin (2), and the depsidone garcinisidone-G (3), and six known compounds, (2''R,3''R)-preussianon, euxanthone, 2-isoprenyl-1,3,5,6-tetrahydroxyxanthone, Jacareubin, isogarcinol, and garcinol. All compounds were described for the first time in Garcinia buchananii. The absolute configurations were determined by a combination of NMR, ECD spectroscopy, and polarimetry. These natural products showed high in vitro antioxidative power, especially isomanniflavanone, with an EC50 value of 8.5 muM (H2O2 scavenging), 3.50/4.95 mmol TE/mmol (H/L-TEAC), and 7.54/14.56 mmol TE/mmol (H/L-ORAC).

Antioxidant properties of xanthones from Calophyllum brasiliense: prevention of oxidative damage induced by FeSO(4).[Pubmed:24119308]

BMC Complement Altern Med. 2013 Oct 11;13:262.

BACKGROUND: Reactive oxygen species (ROS) are important mediators in a number of degenerative diseases. Oxidative stress refers to the imbalance between the production of ROS and the ability to scavenge these species through endogenous antioxidant systems. Since antioxidants can inhibit oxidative processes, it becomes relevant to describe natural compounds with antioxidant properties which may be designed as therapies to decrease oxidative damage and stimulate endogenous cytoprotective systems. The present study tested the protective effect of two xanthones isolated from the heartwood of Calophyllum brasilienses against FeSO(4)-induced toxicity. METHODS: Through combinatory chemistry assays, we evaluated the superoxide (O(2).(-)), hydroxyl radical (OH.), hydrogen peroxide (H(2)O(2)) and peroxynitrite (ONO(-)) scavenging capacity of Jacareubin (xanthone III) and 2-(3,3-dimethylallyl)-1,3,5,6-tetrahydroxyxanthone (xanthone V). The effect of these xanthones on murine DNA and bovine serum albumin degradation induced by an OH. generator system was also evaluated. Additionally, we investigated the effect of these xanthones on ROS production, lipid peroxidation and glutathione reductase (GR) activity in FeSO(4)-exposed brain, liver and lung rat homogenates. RESULTS: Xanthone V exhibited a better scavenging capacity for O(2).(-), ONOO(-) and OH. than xanthone III, although both xanthones were unable to trap H(2)O(2). Additionally, xanthones III and V prevented the albumin and DNA degradation induced by the OH. generator system. Lipid peroxidation and ROS production evoked by FeSO(4) were decreased by both xanthones in all tissues tested. Xanthones III and V also prevented the GR activity depletion induced by pro-oxidant activity only in the brain. CONCLUSIONS: Altogether, the collected evidence suggests that xanthones can play a role as potential agents to attenuate the oxidative damage produced by different pro-oxidants.

A new prenylated xanthone from the branches of Calophyllum inophyllum.[Pubmed:21409690]

J Asian Nat Prod Res. 2011 Mar;13(3):265-9.

The investigation of chemical constituents from the branches of Calophyllum inophyllum Linn led to the isolation of a new prenylated xanthone, named caloxanthone Q (1), together with three known compounds, 2-deprenylrheediaxanthone B (2), Jacareubin (3), and 6-deoxyJacareubin (4). Their structures were completely elucidated on the basis of spectroscopic methods (UV, IR, HR-ESI-MS, 1D NMR, and 2D NMR).

[Xanthones from leaves of Calophyllum inophyllum Linn].[Pubmed:19408685]

Yao Xue Xue Bao. 2009 Feb;44(2):154-7.

To study the xanthones from the leaves of Calophyllum inophyllum Linn., several chromatography methods were employed to isolate the constituents. Investigation on the CHCl3 extract led to the isolation of a new xanthone named inophyxanthone A (1) and four known compounds, which were pancixanthone A (2), gerontoxanthone B (3), Jacareubin (4) and pyranoJacareubin (5). Among them, compound 2 was obtained from this plant firstly, and compound 3 was obtained for the first time from this genus. The structure of inophyxanthone A (1) was identified as 1, 3, 5-trihydroxy-2-(1, 1-dimethylallyl)xanthone by spectral analysis.

Antibacterial activity of crude extracts from Mexican medicinal plants and purified coumarins and xanthones.[Pubmed:15707768]

J Ethnopharmacol. 2005 Feb 28;97(2):293-9.

Thirty-two extracts from 22 Mexican medicinal plants of 15 different families were assayed to determine their antibacterial activity against Escherichia coli and Staphylococcus aureus. Seventeen plants showed antibacterial activity, while five plants showed no activity against both bacteria. All of the extracts showed higher activity against Staphylococcus aureus (methicillin-sensitive and methicillin-resistant) than against Escherichia coli, except one. Among the plants examined, Bursera simaruba (L.) Sarg. (Burseraceae), Haematoxylum brasiletto H. Karst. (Fabaceae), Calophyllum brasiliense Cambess. (Clusiaceae), and Mammea americana L. (Clusiaceae) were highly active against Staphylococcus aureus. Coumarins (mammea A/BA and mammea A/AA) and xanthones, namely Jacareubin and 1,3,5,6-tetrahydroxy-2-(3,3-dimethylallyl) xanthone, were isolated as the principle compounds from the last two plants.

Trypanocidal constituents in plants 3. Leaves of Garcinia intermedia and heartwood of Calophyllum brasiliense.[Pubmed:14709920]

Biol Pharm Bull. 2004 Jan;27(1):141-3.

The constituents of the leaves of Garcinia intermedia and heartwood of Calophyllum brasiliense were investigated based on their trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent of Chagas' disease. As the active components, the polyisoprenylated benzophenone derivative guttiferone A and the xanthone 8-desoxygartanin were isolated along with the biflavonoids podocarpusflavone A and amentoflavone, and friedelin from the former. Three xanthones, Jacareubin, 6-deoxyJacareubin, and 1,3,5,6-tetrahydroxy-2-(3-methyl-2-butenyl)xanthone from the latter showed activity. The trypanocidal activity of these compounds against trypomastigotes, an infectious form of T. cruzi, was examined as well as gossypol, berberine chloride, and harmine for comparison.