Gwendoline Ee Cheng Lian

Chemical constituents and antihistamine activity of Bixa orellana leaf extract

BackgroundBixa orellana L. has been traditionally used in Central and South America to treat a number of ailments, including internal inflammation, and in other tropical countries like Malaysia as treatment for gastric ulcers and stomach discomfort. The current study aimed to determine the major chemical constituents of the aqueous extract of B. orellana (AEBO) and to evaluate the antihistamine activity of AEBO during acute inflammation induced in rats.MethodsAcute inflammation was produced by subplantar injection of 0.1 mL of 0.1% histamine into the right hind paw of each rat in the control and treatment groups. The degree of edema was measured before injection and at the time points of 30, 60, 120, 180, 240 and 300 min after injection. Changes of peritoneal vascular permeability were studied using Evans blue dye as a detector. Vascular permeability was evaluated by the amount of dye leakage into the peritoneal cavity in rats. To evaluate the inhibitory effect of AEBO on biochemical mediators of vascular permeability, the levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) were determined in histamine-treated paw tissues. The major constituents of AEBO were determined by gas chromatography–mass spectrometry (GC-MS) analysis.ResultsAEBO produced a significant inhibition of histamine-induced paw edema starting at 60 min time point, with maximal percentage of inhibition (60.25%) achieved with a dose of 150 mg/kg of AEBO at 60 min time point. Up to 99% of increased peritoneal vascular permeability produced by histamine was successfully suppressed by AEBO. The expression of biochemical mediators of vascular permeability, NO and VEGF, was also found to be downregulated in the AEBO treated group. Gas chromatography–mass spectrometry (GC-MS) analysis revealed that the major constituent in AEBO was acetic acid.ConclusionsThe experimental findings demonstrated that the anti-inflammatory activity of AEBO was due to its inhibitory effect on vascular permeability, which was suppressed as a result of the reduced expression of biochemical mediators (NO and VEGF) in tissues. Our results contribute towards the validation of the traditional use of Bixa orellana in the treatment of inflammatory disorders.

Terpenoid, benzenoid and phenylpropanoid compounds in the floral scent of vanda mimi palmer.

Vanda Mimi Palmer is the product of a cross between Vanda Tan Chay Yan and Vanda tessellata. The flower of this hybrid produces a sweet-smelling fragrance during day time at the open-flower stage. This study aimed to investigate the floral scent constituents in Vanda Mimi Palmer. Scent emission analysis of this orchid was carried out at different time points in a 24-h cycle and also at different floral developmental stages. A comparison was also made on the volatiles emitted by Vanda Mimi Palmer and both of its parents. Gas chromatography-mass spectrometry (GC-MS) analysis showed that the scent of Vanda Mimi Palmer was dominated by terpenoid, benzenoid, and phenylpropanoid compounds. The identified terpenoids were ocimene, linalool oxide, linalool, and nerolidol; while the benzenoid and phenylpropanoid compounds were methylbenzoate, benzyl acetate, phenylethanol, and phenylethyl acetate. The emission of terpenoid, benzenoid, and phenylpropanoid compounds was developmentally and temporally regulated. Comparison of the volatiles emitted by both of its parents showed that the scent of Vanda Mimi Palmer is dissimilar to that of its fragrant parent, V. tessellata.

Cytotoxic activity of coumarins from Micromelum minutum

The crude petroleum ether and chloroform extracts of Micromelum minutum (G. Frost.) Wright & Arn (Rutaceae) showed strong cytotoxic activity when tested against a T-lymphoblastic leukemia cell line. Further fractionation of the extracts resulted in the isolation of five new coumarins 3″,4″-dihydrocapnolactone, 2′,3′-epoxyisocapnolactone, 8-hydroxyisocapnolactone-29,39-diol, 8-hydroxy-3″,4″-dihydrocapnolactone-29,39-diol and 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-29,39-diol, and two triterpenes. Some of these compounds were strongly active against T-lymphoblastic leukemia (CEM-SS), promyeolocytic leukemia (HL60), cervical cancer (HeLa) and liver cancer (HepG2) cell lines. 8-Hydroxyisocapnolactone-29,39-diol was found to be the most active with IC50 values of 2.9, 2.5, 6.9, and 5.9 μg/ml, respectively. This was followed by 2′,3′-epoxyisocapnolactone. When evaluated against the normal mouse fibroblast (3T3) cell line, 8-hydroxyisocapnolactone-29,39-diol was found to be inactive, hence it could serve as a valuable lead for further design and synthesis of more active analogues.

Prenylated flavones from Artocarpus altilis

Six prenylated flavones, including one new compound, were isolated and identified from the stem bark extracts of Artocarpus altilis. The new prenylated flavone hydroxyartocarpin (1) was characterized as 3-(γ,γ-dimethylallyl)-6-isopentenyl-5,8,2′,4′-tetrahydroxy-7-methoxyflavone and the known compounds were artocarpin (2), morusin (3), cycloartobiloxanthone (4), cycloartocarpin A (5) and artoindonesianin V (6). The structures of the compounds were determined by spectroscopic methods (IR, MS, 1H-NMR and 13C-NMR) and comparison with published data for the known compounds.

A new coumarin and triterpenes from Malaysian Micromelum minutum

A new coumarin, 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-2′,3′-diol (1) and two known triterpenes, 5(6)-gluten-3-one (2) and 5(6)-gluten-3α-ol (3) were isolated from the leaves of Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia and their structures were characterized by spectroscopic methods.

α-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-κB and Hsp70 protein modulation in vitro, and tumor reduction in vivo.

Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer.

Lignans and Other Constituents from Aerial Parts of Haplophyllum Villosum

During our phytochemical investigation of Haplophyllum villosum (Rutaceae), a perennial herb from Iran, a new 4,8-diaryl-3,7-dioxobicyclo-(3,3,0)-octane type lignan, eudesmin A (1), together with four known compounds–eudesmin (2), haplamine (3), umbelliferone (4) and scopoletin (5)–were isolated from aerial parts of the plant. The structures of the compounds were elucidated using NMR spectral analysis (1H-NMR,13C-NMR, HSQC, COSY and HMBC) as well as UV, IR and MS spectra and comparison with previously reported data.

Furoquinoline alkaloids from Melicope bonwickii (F.Muell.) T.Hartley

Investigation on the leaves of Melicope bonwickii (F.Muell.) T.Hartley (Rutaceae) afforded a new 7-(2′-hydroxy-3′-chloroprenyloxy)-4-methoxyfuroquinoline (1) together with the known 7-(2′,3′-epoxyprenyloxy)-4-methoxyfuroquinoline (2), evellerine (3) kokusaginine (4) and an amide aurantiamide acetate (5). Compounds 1 and 2 showed significant activity against cervical cell lines (Hela).

Anti‐proliferative effects of pandan leaves (Pandanus amarylfolius), kantan flower (Etlingera elatior) and turmeric leaves (Curcuma longa)

Purpose – The purpose of this paper is to screen cytotoxic activities of commonly used culinary plants in Malaysia, Pandanus amaryllifolius (daun pandan), Curcuma longa (turmeric leaves) and Etlingera elatior (kantan flower) against selected cancer cell lines.Design/methodology/approach – Plant samples were extracted exhaustively with ethanol and concentrated under rotary evaporator. Cytotoxic evaluation was carried out with plant extracts (0‐100 μg/ml) using 72‐h MTT assay.Findings – Exposure of plant extracts reduced cell viability of HepG2 (hepatocellular carcinoma), HT‐29 (colon carcinoma), MDA‐MB‐231 (non‐hormone‐dependent breast cancer), MCF‐7 (hormone‐dependent breast cancer) and HeLa (cervical cancer); 50 percent inhibitory values (IC50) were obtained for MDA‐MB‐231, HepG2, HT‐29. Extracts within the concentrations of 10‐100 μg/ml were found not to be effective against proliferation of MCF‐7 and HeLa.Originality/value – The paper shows how culinary plants – daun pandan, turmeric leaves and kantan ...

In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells

Natural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, α-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT assay. Results showed that AM inhibited HeLa cells viability at concentration- and time-dependent manner with IC50 value of 24.53 ± 1.48 µM at 24 h. The apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy analysis. The effect of AM on cell proliferation was also studied through clonogenic assay. ROS production evaluation, flow cytometry (cell cycle) analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were conducted to determine the mechanism of cell apoptosis. This was associated with G2/M phase cell cycle arrest and elevation in ROS production. AM induced mitochondrial apoptosis which was confirmed based on the significant increase in the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP disruption and increased cell permeability, concurrent with cytochrome c release from the mitochondria to the cytosol provided evidence that AM can induce apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor effect and induced characteristic apoptogenic morphological changes on HeLa cells, which indicates the occurrence of cell death. This study reveals that AM could be a potential antitumor compound on cervical cancer in vitro and can be considered for further cervical cancer preclinical and in vivo testing.