Two new xanthones, characterized as 4-(1,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxyxanthone (1) and penangianaxanthone (2), with three known xanthones, cudratricusxanthone H (3), macluraxanthone C (4) and gerontoxanthone C (5), as well as friedelin and stigmasterol were isolated from the leaves of Garcinia penangiana. Their structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with the literature ones. Significant cytotoxicity against DU-145, MCF-7 and NCI-H460 cancer cell lines was demonstrated by compounds 1-5, with IC50 values ranging from 3.5 to 72.8 microM.
Trypanosoma evansi, the causative agent of "surra", infects many species of wild and domestic animals worldwide. In the current study, the aqueous and ethanolic extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and Strobilanthes crispus were screened in vitro for activity against T. evansi. The cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero) cells using MTT-cell proliferation assay. The median inhibitory concentrations (IC50) of the extracts ranged between 2.30 and 800.97 μg/ml and the median cytotoxic concentrations (CC50) ranged between 29.10 μg/ml and 14.53 mg/ml. The aqueous extract of G. hombroniana exhibited the highest selectivity index (SI) value of 616.36, followed by A. malaccensis aqueous extract (47.38). Phytochemical screening of the G. hombroniana aqueous extract revealed the presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here that the aqueous extract of G. hombroniana has potential antitrypanosomal activity with a high SI, and may be considered as a potential source for the development of new antitrypanosomal compounds.
Trypanothione reductase is a key enzyme that upholds the redox balance in hemoflagellate protozoan parasites such as T. congolense. This study aims at unraveling the potency of Kolaviron against trypanothione reductase in T. congolense infection using Chrysin as standard. The experiment was performed using three different approaches; in silico, in vitro and in vivo. Kolaviron and Chrysin were docked against trypanothione reductase, revealing binding energies (-9.3 and -9.0 kcal/mol) and Ki of 0.211μM and 0.151μM at the active site of trypanothione reductase as evident from the observed strong hydrophobic/hydrogen bond interactions. Parasitized blood was used for parasite isolation and trypanothione reductase activity assay using standard protocol. Real-time PCR (qPCR) assay was implored to monitor expression of trypanothione reductase using primers targeting the 177-bp repeat satellite DNA in T. congolense with SYBR Green to monitor product accumulation. Kolaviron showed IC50 values of 2.64μg/ml with % inhibition of 66.78 compared with Chrysin with IC50 values of 1.86μg/ml and % inhibition of 53.80. In vivo studies following the administration of these compounds orally after 7 days post inoculation resulted in % inhibition of Chrysin (57.67) and Kolaviron (46.90). Equally, Kolaviron relative to Chrysin down regulated the expression trypanothione reductase gene by 1.352 as compared to 3.530 of the infected group, in clear agreement with the earlier inhibition observed at the fine type level. Overall, the findings may have unraveled the Kolaviron potency against Trypanosoma congolense infection in rats.
The anti-Trypanosoma evansi activity of Garcinia hombroniana (seashore mangosteen) leaves aqueous extract was tested on experimentally infected Sprague-Dawley rats. Treatment of infected rats with G. hombroniana extract resulted in a significantly extended post-infection longevity (p
The methanol extract of the twigs of Garcinia hombroniana, which showed strong LDL antioxidation and antiplatelet aggregation activities, was subjected to column chromatography to obtain 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone, 1,7-dihydroxyxanthone and eight triterpenoids, garcihombronane B, D, E and F, friedelin, glutin-5-en-3β-ol, stigmasterol and lupeol. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit copper-mediated LDL oxidation and arachidonic acid (AA)-, adenosine diphosphate (ADP)-, collagen-induced platelet aggregation in vitro. Among the compounds tested, 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone and 1,7-dihydroxyxanthone showed strong inhibitory activity on LDL oxidation with half-maximal inhibitory concentration (IC(50)) values of 6.6 and 1.7 µM, respectively. 3,5,3',5'-Tetrahydroxy-4-methoxybenzophenone exhibited strong activity on AA-, ADP- and collagen-induced platelet aggregation with IC(50) values of 53.6, 125.7 and 178.6 µM, respectively, while 1,7 dihydroxyxanthone showed significant and selective inhibitory activity against ADP-induced aggregation with IC(50) value of 5.7 µM. Of the triterpenoids tested, garcihombronane B showed moderate activity against LDL oxidation and garcihombronane D and F showed selective inhibition on ADP-induced platelet aggregation.
Three benzophenones, 2,6,3',5'-tetrahydroxybenzophenone (1), 3,4,5,3',5'-pentahydroxybenzophenone (3) and 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone (4), as well as a xanthone, 1,3,6-trihydroxy-5-methoxy-7-(3'-methyl-2'-oxo-but-3'-enyl)xanthone (9), were isolated from the twigs of Garcinia cantleyana var. cantleyana. Eight known compounds, 3,4,5,3'-tetrahydroxy benzophenone (2), 1,3,5-trihydroxyxanthone (5), 1,3,8-trihydroxyxanthone (6), 2,4,7-trihydroxyxanthone (7), 1,3,5,7-tetrahydroxyxanthone (8), quercetin, glutin-5-en-3β-ol and friedelin were also isolated. The structures of the compounds were elucidated by spectroscopic methods. The compounds were investigated for their ability to inhibit low-density lipoprotein (LDL) oxidation and platelet aggregation in human whole blood in vitro. Most of the compounds showed strong antioxidant activity with compound 8 showing the highest inhibition with an IC₅₀ value of 0.5 μM, comparable to that of probucol. Among the compounds tested, only compound 4 exhibited strong inhibitory activity against platelet aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen. Compounds 3, 5 and 8 showed selective inhibitory activity on platelet aggregation induced by ADP.
Phytochemical studies on the leaves and trunk bark of Garcinia cantleyana yielded five caged-xanthonoids including one tetra- and four tri-prenylated xanthones, cantleyanone A (1), 7-hydroxyforbesione (2) and cantleyanones B-D (4-6), as well as a simple xanthone, 4-(1,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxyxanthone (3). Eight other known compounds, deoxygaudichaudione A, gaudichaudione H, friedelin, garbogiol, macranthol, glutin-5-en-3beta-ol, and a mixture of sitosterol and stigmasterol were also isolated. Their structures were elucidated by means of spectroscopic data and comparison of their NMR data with literature values. Significant cytotoxicity against MDA-MB-231, CaOV-3, MCF-7 and HeLa cancer cell-lines was demonstrated by cantleyanones B-D, 7-hydroxyforbesione, deoxygaudichaudione A and macranthol, with IC(50) values ranging from 0.22 to 17.17 microg/ml.
Garcinia species are reported to possess antimicrobial, anti-inflammatory, anticancer, anti-HIV and anti-Alzheimer's activities. This study aimed to investigate the in vitro cholinesterase enzyme inhibitory activities of garcihombronane C (1), garcihombronane F (2), garcihombronane I (3), garcihombronane N (4), friedelin (5), clerosterol (6), spinasterol glucoside (7) and 3β-hydroxy lup-12,20(29)-diene (8) isolated from Garcinia hombroniana, and to perform molecular docking simulation to get insight into the binding interactions of the ligands and enzymes. The cholinesterase inhibitory activities were evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. In this study, compound 4 displayed the highest concentration-dependent inhibition of both AChE and BChE. Docking studies exhibited that compound 4 binds through hydrogen bonds to amino acid residues of AChE and BChE. The calculated docking and binding energies also supported the in vitro inhibitory profiles of IC50. In conclusion, garcihombronanes C, F, I and N (1-4) exhibited dual and moderate inhibitory activities against AChE and BChE.
Friedelin and lanosterol have been isolated from twigs of Garcinia prainiana. Their structures were elucidated by spectroscopic methods. The compounds were examined for their effects on 3T3-L1 adipocytes. In the MTT assay, it was found that the compounds had no cytotoxic effects up to 25 µM. Adipocyte differentiation analysis was carried out by Oil Red O staining method. In the presence of adipogenic cocktail (MDI), it was found that friedelin and lanosterol enhanced intracellular fat accumulation by 2.02 and 2.18-fold, respectively, compared with the vehicle-treated cells. Deoxyglucose uptake assay was used to examine the insulin sensitivity of adipocytes in the presence of the compounds. It was found that friedelin was able to stimulate glucose uptake up to 1.8-fold compared with insulin-treated cells. It was suggested that friedelin and lanosterol may be beneficial to mimic insulin action that would be useful in the treatment of diabetes type 2 patients.
A detailed chemical study on the stem bark of Garcinia nitida has led to the isolation of five xanthones. They are 1,6-dihydroxy-5-methoxy-6,6-dimethylpyrano[2',3':2,3]-xanthone (1), inophyllin B (2), osajaxanthone (3), 3-isomangostin (4) and rubraxanthone (5). The structures of these compounds were established using mainly 1-D and 2-D NMR spectroscopy ((1)H, (13)C, DEPT, COSY, HMBC and HMQC) while molecular masses were determined via MS techniques; 1 is a new compound.
Studies on the stem of Garcinia mangostana have led to the isolation of one new xanthone mangosharin (1) (2,6-dihydroxy-8-methoxy-5-(3-methylbut-2-enyl)-xanthone) and six other prenylated xanthones, alpha-mangostin (2), beta-mangostin (3), garcinone D (4), 1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)-xanthone (5), mangostanol (6) and 5,9-dihydroxy-8- methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-2H,6H-pyrano-[3,2-b]-xanthene-6-one (7). The structures of these compounds were determined by spectroscopic methods such as 1H NMR, 13C NMR, mass spectrometry (MS) and by comparison with previous studies. All the crude extracts when screened for their larvicidal activities indicated very good toxicity against the larvae of Aedes aegypti. This article reports the isolation and identification of the above compounds as well as bioassay data for the crude extracts. These bioassay data have not been reported before.
The dichloromethane bark extract of Garcinia hombroniana yielded one new cycloartane triterpene; (22Z,24E)-3β-hydroxycycloart-14,22,24-trien-26-oic acid (1) together with five known compounds: garcihombronane G (2), garcihombronane J (3), 3β acetoxy-9α-hydroxy-17,14-friedolanostan-14,24-dien-26-oic acid (4), (22Z, 24E)-3β, 9α-dihydroxy-17,14-friedolanostan-14,22,24-trien-26-oic acid (5) and 3β, 23α-dihydroxy-17,14-friedolanostan-8,14,24-trien-26-oic acid (6). Their structures were established by the spectral techniques of NMR and ESI-MS. These compounds together with some previously isolated compounds; garcihombronane B (7), garcihombronane D (8) 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone (9), volkensiflavone (10), 4''-O-methyll-volkensiflavone (11), volkensiflavone-7-O-glucopyranoside (12), volkensiflavone-7-O-rhamnopyranoside (13), Morelloflavone (14), 3''-O-methyl-morelloflavone (15) and morelloflavone-7-O-glucopyranoside (16) were evaluated for cholinesterase enzymes inhibitory activities using acetylcholinesterase and butyrylcholinesterase. In these activities, compounds 1-9 showed good dual inhibition on both the enzymes while compounds 10-16 did not reasonably contribute to both the cholinesterases inhibitory effects.
Garcinia celebica L., locally known as "manggis hutan" in Malaysia is widely used in folkloric medicine to treat various diseases. The present study was aimed to examine the chemical composition of the essential oil from the leaves of G. celebica L. (EO-GC) and its cytotoxic and antimicrobial potential. EO-GC obtained by hydrodistillation was analysed using capillary GC and GC-MS. Twenty-two compounds were identified, dominated by α-copaene (61.25%), germacrene D (6.72%) and β-caryophyllene (5.85%). In the in vitro MTT assay, EO-GC exhibited significant anti-proliferative effects towards MCF-7 human breast cancer cells with IC50 value of 45.2 μg/mL. Regarding the antimicrobial activity, it showed better inhibitory effects on Gram-positive bacteria than Gram-negative bacteria and none on the fungi and yeasts tested.
Phytochemical studies on the stem bark of Garcinia nervosa has resulted in the discovery of one new pyranoxanthone derivative, garner xanthone (1) and five other compounds, 1,5-dihydroxyxanthone (2), 6-deoxyisojacareubin (3), 12b-hydroxy-des-D-garcigerrin A (4) stigmasterol (5), and β-sitosterol (6). The structures of these compounds were elucidated with the aid of spectroscopic techniques, such as NMR and MS. The crude extracts of the plant were assessed for their antimicrobial activity.
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.
A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5-30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.
Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens-NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.
The genus Garcinia is reported to possess antimicrobial, anti-inflammatory, anticancer, hepatoprotective and anti-HIV activities. Garcinia hombroniana in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to isolate the chemical constituents from the bark of G. hombroniana and explore their possible pharmacological potential. Ethyl acetate extract afforded one new (1) and six (2-7) known 3 → 8 rotameric biflavonoids. Their structures were elucidated by UV, IR and NMR (1D and 2D) spectroscopy together with electron ionization/ESI mass spectrometric techniques and were identified as (2R, 3S) volkensiflavone-7-O-rhamnopyranoside (1), volkensiflavone (2), 4″-O-methyl-volkensiflavone (3), volkensiflavone-7-O-glucopyranoside (4), morelloflavone (5), 3″-O-methyl-morelloflavone (6) and morelloflavone-7-O-glucopyranoside (7). The absolute configuration of compound 1 was assigned by circular dichroism spectroscopy as 2R, 3S. The coexistence of conformers of isolated biflavonoids in solution at 25 °C in different solvents was confirmed by variable temperature NMR studies. At room temperature (25 °C), compounds 1-7 exhibited duplicate NMR signals, while at elevated temperature (90 °C), a single set of signals was obtained. Compound 5 showed significant in vitro antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis-3-ethyl benzthiazoline-6-sulfonic acid radicals. The antibacterial studies showed that compounds 5 and 6 are the most active against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Compounds 3 and 6 also showed moderate antituberculosis activity against H38 Rv. Based on the research findings, G. hombroniana could be concluded as a rich source of flavanone-flavone (3 → 8) biflavonoids that exhibit rotameric behaviour at room temperature and display significant antioxidant and antibacterial activities.
Garcinia atroviridis is a seasonal fruit plant found in many parts of South East Asia. The fruit rind is used in cooking and traditionally consumed for various reasons, including to lower blood cholesterol. A comparative study was undertaken to investigate the influence of extraction solvents and plant parts used on the lipid-lowering and antioxidant activities of Garcinia atroviridis.