Displaying publications 1 - 20 of 48 in total

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  1. Fulltext The efficacy of xylocaine topical anaesthetic in reducing injection pain
    Yaacob HB, M Nor G, Malek SN, Mahfuz MA
    Med J Malaysia, 1983 Mar;38(1):59-61.
    PMID: 6633339
    The efficacy of xylocaine topical anaesthetic and a placebo in reducing intraoral injection pain were tested in 72 patients. The topical agent was found to be very effective in reducing such pain and the authors recommend its use prior to intraoral injections for the benefit of the patient.
  2. Fulltext Cytotoxic components of Pereskia bleo (Kunth) DC. (Cactaceae) leaves
    Malek SN, Shin SK, Wahab NA, Yaacob H
    Molecules, 2009;14(5):1713-24.
    PMID: 19471192 DOI: 10.3390/molecules14051713
    Dihydroactinidiolide (1) and a mixture of sterols [campesterol (2), stigmasterol (3) and beta-sitosterol (4)], together with the previously isolated individual compounds beta-sitosterol (4), 2,4-di-tert-butylphenol (5), alpha-tocopherol (6), phytol (7) were isolated from the active ethyl acetate fraction of Pereskia bleo (Kunth) DC. (Cactaceae) leaves. Cytotoxic activities of the above mentioned compounds against five human carcinoma cell lines, namely the human nasopharyngeal epidermoid carcinoma cell line (KB), human cervical carcinoma cell line (CasKi), human colon carcinoma cell line (HCT 116), human hormone-dependent breast carcinoma cell line (MCF7) and human lung carcinoma cell line (A549); and non-cancer human fibroblast cell line (MRC-5) were investigated. Compound 5 possessed very remarkable cytotoxic activity against KB cells, with an IC(50 )value of 0.81microg/mL. This is the first report on the cytotoxic activities of the compounds isolated from Pereskia bleo.
  3. Fulltext Phytochemical and cytotoxic investigations of Alpinia mutica rhizomes
    Malek SN, Phang CW, Ibrahim H, Norhanom AW, Sim KS
    Molecules, 2011 Jan 14;16(1):583-9.
    PMID: 21240148 DOI: 10.3390/molecules16010583
    The methanol and fractionated extracts (hexane, ethyl acetate and water) of Alpinia mutica (Zingiberaceae) rhizomes were investigated for their cytotoxic effect against six human carcinoma cell lines, namely KB, MCF7, A549, Caski, HCT116, HT29 and non-human fibroblast cell line (MRC 5) using an in vitro cytotoxicity assay. The ethyl acetate extract possessed high inhibitory effect against KB, MCF7 and Caski cells (IC₅₀ values of 9.4, 19.7 and 19.8 µg/mL, respectively). Flavokawin B (1), 5,6-dehydrokawain (2), pinostrobin chalcone (3) and alpinetin (4), isolated from the active ethyl acetate extract were also evaluated for their cytotoxic activity. Of these, pinostrobin chalcone (3) and alpinetin (4) were isolated from this plant for the first time. Pinostrobin chalcone (3) displayed very remarkable cytotoxic activity against the tested human cancer cells, such as KB, MCF7 and Caski cells (IC₅₀ values of 6.2, 7.3 and 7.7 µg/mL, respectively). This is the first report of the cytotoxic activity of Alpinia mutica.
  4. Chemical composition and antioxidant properties of extracts of fresh fruiting bodies of Pleurotus sajor-caju (Fr.) Singer
    Kanagasabapathy G, Malek SN, Kuppusamy UR, Vikineswary S
    J Agric Food Chem, 2011 Mar 23;59(6):2618-26.
    PMID: 21348494 DOI: 10.1021/jf104133g
    The chemical composition and in vitro antioxidant activity of aqueous butanol and ethyl acetate extracts of Pleurotus sajor-caju were investigated in this study. Twenty-two compounds comprising methyl esters, hydrocarbon fatty acids, ethyl esters, and sterols were identified in ethyl acetate extracts, while cinnamic acid, nicotinamide, benzeneacetamide, and 4-hydroxybenzaldyhde were identified in butanol extracts by gas chromatography-mass spectrometry and NMR analysis. The antioxidant activity was determined by a β-carotene bleaching method, ferric reducing antioxidant power, trolox equivalent antioxidant capacity, and lipid peroxidation assays, while the total phenolic content in P. sajor-caju was assessed by Folin-Ciocalteau's method. The aqueous and butanol extracts exhibited the highest antioxidant activity, corresponding to the total phenolic content. The subfractions from the ethyl acetate extract (EP1, EP2, EP3, and EP4), however, showed moderate antioxidant activity. The regular consumption of P. sajor-caju as a part of our diet may render nutritional and nutraceuticals benefits for good health.
  5. Fulltext Phytochemical and cytotoxic investigations of Curcuma mangga rhizomes
    Malek SN, Lee GS, Hong SL, Yaacob H, Wahab NA, Faizal Weber JF, et al.
    Molecules, 2011 May 31;16(6):4539-48.
    PMID: 21629182 DOI: 10.3390/molecules16064539
    Investigations on the cytotoxic effects of the crude methanol and fractionated extracts (hexane, ethyl acetate) C. mangga against six human cancer cell lines, namely the hormone-dependent breast cell line (MCF-7), nasopharyngeal epidermoid cell line (KB), lung cell line (A549), cervical cell line (Ca Ski), colon cell lines (HCT 116 and HT-29), and one non-cancer human fibroblast cell line (MRC-5) were conducted using an in-vitro neutral red cytotoxicity assay. The crude methanol and fractionated extracts (hexane and ethyl acetate) displayed good cytotoxic effects against MCF-7, KB, A549, Ca Ski and HT-29 cell lines, but exerted no damage on the MRC-5 line. Chemical investigation from the hexane and ethyl acetate fractions resulted in the isolation of seven pure compounds, namely (E)-labda-8(17),12-dien-15,16-dial (1), (E)-15,16-bisnor-labda-8(17),11-dien-13-on (2), zerumin A (3), β-sitosterol, curcumin, demethoxycurcumin and bis-demethoxycurcumin. Compounds 1 and 3 exhibited high cytotoxic effects against all six selected cancer cell lines, while compounds 2 showed no anti-proliferative activity on the tested cell lines. Compound 1 also demonstrated strong cytotoxicity against the normal cell line MRC-5. This paper reports for the first time the cytotoxic activities of C. mangga extracts on KB, A549, Ca Ski, HT-29 and MRC-5, and the occurrence of compound 2 and 3 in C. mangga.
  6. Multispectroscopic and molecular modeling approach to investigate the interaction of flavokawain B with human serum albumin
    Feroz SR, Mohamad SB, Bujang N, Malek SN, Tayyab S
    J Agric Food Chem, 2012 Jun 13;60(23):5899-908.
    PMID: 22624666 DOI: 10.1021/jf301139h
    Interaction of flavokawain B (FB), a multitherapeutic flavonoid from Alpinia mutica with the major transport protein, human serum albumin (HSA), was investigated using different spectroscopic probes, i.e., intrinsic, synchronous, and three-dimensional (3-D) fluorescence, circular dichroism (CD), and molecular modeling studies. Values of binding parameters for FB-HSA interaction in terms of binding constant and stoichiometry of binding were determined from the fluorescence quench titration and were found to be 6.88 × 10(4) M(-1) and 1.0 mol of FB bound per mole of protein, respectively, at 25 °C. Thermodynamic analysis of the binding data obtained at different temperatures showed that the binding process was primarily mediated by hydrophobic interactions and hydrogen bonding, as the values of the enthalpy change (ΔH) and the entropy change (ΔS) were found to be -6.87 kJ mol(-1) and 69.50 J mol(-1) K(-1), respectively. FB binding to HSA led to both secondary and tertiary structural alterations in the protein as revealed by intrinsic, synchronous, and 3-D fluorescence results. Increased thermal stability of HSA in the presence of FB was also evident from the far-UV CD spectral results. The distance between the bound ligand and Trp-214 of HSA was determined as 3.03 nm based on the Förster resonance energy transfer mechanism. Displacement experiments using bilirubin and warfarin coupled with molecular modeling studies assigned the binding site of FB on HSA at domain IIA, i.e., Sudlow's site I.
  7. Fulltext Glucan-rich polysaccharides from Pleurotus sajor-caju (Fr.) Singer prevents glucose intolerance, insulin resistance and inflammation in C57BL/6J mice fed a high-fat diet
    Kanagasabapathy G, Kuppusamy UR, Abd Malek SN, Abdulla MA, Chua KH, Sabaratnam V
    BMC Complement Altern Med, 2012;12:261.
    PMID: 23259700 DOI: 10.1186/1472-6882-12-261
    BACKGROUND: Pleurotus sajor-caju (P. sajor-caju) has been extremely useful in the prevention of diabetes mellitus due to its low fat and high soluble fiber content for thousands of years. Insulin resistance is a key component in the development of diabetes mellitus which is caused by inflammation. In this study, we aimed to investigate the in vivo efficacy of glucan-rich polysaccharide of P. sajor-caju (GE) against diabetes mellitus and inflammation in C57BL/6J mice fed a high-fat diet.
    METHODS: Diabetes was induced in C57BL/6J mice by feeding a high-fat diet. The mice were randomly assigned to 7 groups (n=6 per group). The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120 and HFD240 (for high-fat), where the mice were administrated with three dosages of GE (60, 120, 240 mg GE/kg b.w respectively). Metformin (2 mg/kg b.w) served as positive control. The glucose tolerance test, glucose and insulin levels were measured at the end of 16 weeks. Expressions of genes for inflammatory markers, GLUT-4 and adiponectin in the adipose tissue of the mice were assessed. One-way ANOVA and Duncan's multiple range tests (DMRT) were used to determine the significant differences between groups.
    RESULTS: GE treated groups improved the glucose tolerance, attenuated hyperglycemia and hyperinsulinemia in the mice by up-regulating the adiponectin and GLUT-4 gene expressions. The mice in GE treated groups did not develop insulin resistance. GE also down-regulated the expression of inflammatory markers (IL-6, TNF-α, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-κB).
    CONCLUSION: Glucan-rich polysaccharide of P. sajor-caju can serve as a potential agent for prevention of glucose intolerance, insulin resistance and inflammation.
  8. Fulltext Antioxidant potential, cytotoxic activity and total phenolic content of Alpinia pahangensis rhizomes
    Phang CW, Malek SN, Ibrahim H
    BMC Complement Altern Med, 2013 Oct 01;13:243.
    PMID: 24083445 DOI: 10.1186/1472-6882-13-243
    BACKGROUND: Alpinia pahangensis, a wild ginger distributed in the lowlands of Pahang, Malaysia, is used by the locals to treat flatulence. In this study, the antioxidant and cytotoxic activities of the crude aqueous methanol and fractionated extracts of Alpinia pahangensis against five different cancer and one normal cell lines were investigated. The total phenolic content of each extract and its fractions were also quantified. This is the first report on the antioxidant and cytotoxic activities of Alpinia pahangensis extract.

    METHODS: In the current study, the crude methanol and fractionated extract of the rhizomes of Alpinia pahangensis were investigated for their antioxidant activity using four different assays namely, the DPPH scavenging activity, superoxide anion scavenging, β-carotene bleaching and reducing power assays whilst their phenolic contents were measured by the Folin-Ciocalteu's method.In vitro neutral red cytotoxicity assay was employed to evaluate the cytotoxic activity against five different cancer cell lines, colon cancer (HCT 116 and HT-29), cervical cancer (Ca Ski), breast cancer (MCF7) and lung cancer (A549) cell lines, and one normal cell line (MRC-5). The extract that showed high cytotoxic activity was further investigated for its chemical constituents by GC-MS (gas chromatography-mass spectrometry) analysis.

    RESULTS: The ethyl acetate fraction showed the strongest DPPH radical scavenging (0.35 ± 0.094 mg/ml) and SOD activities (51.77 ± 4.9%) whilst the methanol extract showed the highest reducing power and also the strongest antioxidant activity in the β-carotene bleaching assays in comparison to other fractions. The highest phenolic content was found in the ethyl acetate fraction, followed by the crude methanol extract, hexane and water fractions. The results showed a positive correlation between total phenolic content with DPPH radical scavenging capacities and SOD activities. The hexane fraction showed potent cytotoxic effect against KB, Ca Ski and HCT 116 cell lines with IC₅₀ of 5.8 ± 0.1 and 9.1 ± 2.0 ug/ml, respectively. The major components of hexane fraction analysed by GC-MS analysis were mostly methyl esters.

    CONCLUSIONS: The current study suggests that the methanol extract and ethyl acetate fraction of A. pahangensis is a potential source of natural antioxidant for protective as well as prevention of life-threatening diseases. The hexane fraction of A. pahangensis may have the potential to be developed into therapeutic option for treating cancer.

  9. Fulltext Cytotoxic effect of Alpinia scabra (Blume) Náves extracts on human breast and ovarian cancer cells
    Reddy AS, Abd Malek SN, Ibrahim H, Sim KS
    BMC Complement Altern Med, 2013 Nov 12;13:314.
    PMID: 24215354 DOI: 10.1186/1472-6882-13-314
    BACKGROUND: Alpinia scabra, locally known as 'Lengkuas raya', is an aromatic, perennial and rhizomatous herb from the family Zingiberaceae. It is a wild species which grows largely on mountains at moderate elevations in Peninsular Malaysia, but it can also survive in the lowlands like in the states of Terengganu and Northern Johor. The present study reports the cytotoxic potential of A. scabra extracts from different parts of the plant.

    METHODS: The experimental approach in the present study was based on a bioassay-guided fractionation. The crude methanol and fractionated extracts (hexane, chloroform and water) from different parts of A. scabra (leaves, rhizomes, roots and pseudo stems) were prepared prior to the cytotoxicity evaluation against human ovarian (SKOV-3) and hormone-dependent breast (MCF7) carcinoma cells. The identified cytotoxic extracts were then subjected to chemical investigations in order to identify the active ingredients. A normal human lung fibroblast cell line (MRC-5) was used to determine the specificity for cancerous cells. The cytotoxic extracts and fractions were also subjected to morphological assessment, DNA fragmentation analysis and DAPI nuclear staining.

    RESULTS: The leaf (hexane and chloroform) and rhizome (chloroform) extracts showed high inhibitory effect against the tested cells. Ten fractions (LC1-LC10) were yielded after purification of the leaf chloroform extract. Fraction LC4 which showed excellent cytotoxic activity was further purified and resulted in 17 sub-fractions (VLC1-VLC17). Sub-fraction VLC9 showed excellent cytotoxicity against MCF7 and SKOV-3 cells but not toxic against normal MRC-5 cells. Meanwhile, eighteen fractions (RC1-RC18) were obtained after purification of the rhizome chloroform extract, of which fraction RC5 showed cytotoxicity against SKOV-3 cells with high selectivity index. There were marked morphological changes when observed using phase-contrast inverted microscope, DAPI nuclear staining and also DNA fragmentations in MCF7 and SKOV-3 cells after treatment with the cytotoxic extracts and fractions which were indicative of cell apoptosis. Methyl palmitate and methyl stearate were identified in the hexane leaf extract by GC-MS analysis.

    CONCLUSIONS: The data obtained from the current study demonstrated that the cell death induced by cytotoxic extracts and fractions of A. scabra may be due to apoptosis induction which was characterized by apoptotic morphological changes and DNA fragmentation. The active ingredients in the leaf sub-fraction VLC9 and rhizome fraction RC5 may lead to valuable compounds that have the ability to kill cancer cells but not normal cells.

  10. Lipid constituents of the edible mushroom, Pleurotus giganteus demonstrate anti-Candida activity
    Phan CW, Lee GS, Macreadie IG, Malek SN, Pamela D, Sabaratnam V
    Nat Prod Commun, 2013 Dec;8(12):1763-5.
    PMID: 24555294
    Different solvent extracts of Pleurotus giganteus fruiting bodies were tested for antifungal activities against Candida species responsible for human infections. The lipids extracted from the ethyl acetate fraction significantly inhibited the growth of all the Candida species tested. Analysis by GC/MS revealed lipid components such as fatty acids, fatty acid methyl esters, ergosterol, and ergosterol derivatives. The sample with high amounts of fatty acid methyl esters was the most effective antifungal agent. The samples were not cytotoxic to a mammalian cell line, mouse embryonic fibroblasts BALB/c 3T3 clone A31. To our knowledge, this is the first report of antifungal activity of the lipid components of Pleurotus giganteus against Candida species.
  11. Neurotrophic properties of the Lion's mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia
    Lai PL, Naidu M, Sabaratnam V, Wong KH, David RP, Kuppusamy UR, et al.
    Int J Med Mushrooms, 2013;15(6):539-54.
    PMID: 24266378
    Neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.
  12. Fulltext Probing the interaction of a therapeutic flavonoid, pinostrobin with human serum albumin: multiple spectroscopic and molecular modeling investigations
    Feroz SR, Mohamad SB, Bakri ZS, Malek SN, Tayyab S
    PLoS One, 2013;8(10):e76067.
    PMID: 24116089 DOI: 10.1371/journal.pone.0076067
    Interaction of a pharmacologically important flavonoid, pinostrobin (PS) with the major transport protein of human blood circulation, human serum albumin (HSA) has been examined using a multitude of spectroscopic techniques and molecular docking studies. Analysis of the fluorescence quenching data showed a moderate binding affinity (1.03 × 10(5) M(-1) at 25°C) between PS and HSA with a 1∶1 stoichiometry. Thermodynamic analysis of the binding data (ΔS = +44.06 J mol(-1) K(-1) and ΔH = -15.48 kJ mol(-1)) and molecular simulation results suggested the involvement of hydrophobic and van der Waals forces, as well as hydrogen bonding in the complex formation. Both secondary and tertiary structural perturbations in HSA were observed upon PS binding, as revealed by intrinsic, synchronous, and three-dimensional fluorescence results. Far-UV circular dichroism data revealed increased thermal stability of the protein upon complexation with PS. Competitive drug displacement results suggested the binding site of PS on HSA as Sudlow's site I, located at subdomain IIA, and was well supported by the molecular modelling data.
  13. Fulltext In Vitro Morphological Assessment of Apoptosis Induced by Antiproliferative Constituents from the Rhizomes of Curcuma zedoaria
    Syed Abdul Rahman SN, Abdul Wahab N, Abd Malek SN
    Evid Based Complement Alternat Med, 2013;2013:257108.
    PMID: 23762112 DOI: 10.1155/2013/257108
    Bioassay-guided isolation of the active hexane fractions of Curcuma zedoaria led to the identification of five pure compounds, namely, curzerenone (1), neocurdione (2), curdione (3), alismol (4), and zederone (5) and a mixture of sterols, namely, campesterol (6), stigmasterol (7), and β -sitosterol (8). Alismol has never been reported to be present in Curcuma zedoaria. All isolated compounds except (3) were evaluated for their cytotoxic activity against MCF-7, Ca Ski, and HCT-116 cancer cell lines and noncancer human fibroblast cell line (MRC-5) using neutral red cytotoxicity assay. Curzerenone and alismol significantly inhibited cell proliferation in human cancer cell lines MCF-7, Ca Ski, and HCT-116 in a dose-dependent manner. Cytological observations by an inverted phase contrast microscope and Hoechst 33342/PI dual-staining assay showed typical apoptotic morphology of cancer cells upon treatment with curzerenone and alismol. Both compounds induce apoptosis through the activation of caspase-3. It can thus be suggested that curzerenone and alismol are modulated by apoptosis via caspase-3 signalling pathway. The findings of the present study support the use of Curcuma zedoaria rhizomes in traditional medicine for the treatment of cancer-related diseases. Thus, two naturally occurring sesquiterpenoids, curzerenone and alismol, hold great promise for use in chemopreventive and chemotherapeutic strategies.
  14. Fulltext Beta-Glucan-Rich Extract from Pleurotus sajor-caju (Fr.) Singer Prevents Obesity and Oxidative Stress in C57BL/6J Mice Fed on a High-Fat Diet
    Kanagasabapathy G, Malek SN, Mahmood AA, Chua KH, Vikineswary S, Kuppusamy UR
    Evid Based Complement Alternat Med, 2013;2013:185259.
    PMID: 23737819 DOI: 10.1155/2013/185259
    Mushrooms have been used in folk medicine for thousands of years. In this study, the effect of β -glucan-rich extract of P. sajor-caju (GE) on lipid lowering and antioxidant potential was assessed in C57BL/6J mice fed on a high-fat diet. Obesity was induced in C57BL/6J mice by feeding a high-fat diet. The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120, and HFD240 (for high-fat diet), where the mice were administrated with three dosages of GE (60, 120, and 240 mg GE/kg b.w). Metformin (2 mg/kg b.w) served as positive control. GE-treated groups showed significantly reduced body weight, serum lipid, and liver enzymes levels. GE also attenuated protein carbonyl and lipid hydroperoxide levels by increasing the enzymic antioxidants (SOD, CAT, and GPx) activities in the mice. GE-treated groups induced the expression of hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) while downregulated the expression of peroxisome proliferator-activated receptor gamma (PPAR- γ ), sterol regulatory binding protein-1c (SREBP-1c), and lipoprotein lipase (LPL). Hence, GE prevented weight gain in the mice by inducing lipolysis and may be valuable in the formulation of adjuvant therapy for obesity.
  15. Fulltext Induction of apoptosis and cell cycle blockade by helichrysetin in a549 human lung adenocarcinoma cells
    Ho YF, Karsani SA, Yong WK, Abd Malek SN
    Evid Based Complement Alternat Med, 2013;2013:857257.
    PMID: 23533528 DOI: 10.1155/2013/857257
    Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent.
  16. Fulltext Cytotoxic activity of Alpinia murdochii Ridl.: A mountain ginger species from Peninsular Malaysia
    Sim KS, Ibrahim H, Malek SN, Syamsir DR, Awang K
    Pharmacogn Mag, 2014 Jan;10(37):70-2.
    PMID: 24695515 DOI: 10.4103/0973-1296.126666
    Alpinia murdochii (Zingiberaceae) is a wild ginger species restricted to mountain areas of Peninsular Malaysia. Due to rapid development and deforestation activities, this species is becoming rare. This is the first report of the cytotoxic activity of A. murdochii.
  17. Fulltext 1-(2,6-dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone-induced cell cycle arrest in G₁/G₀ in HT-29 cells human colon adenocarcinoma cells
    Lay MM, Karsani SA, Malek SN
    Int J Mol Sci, 2014 Jan 02;15(1):468-83.
    PMID: 24451128 DOI: 10.3390/ijms15010468
    1-(2,6-Dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone (DMHE) was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff.) Boerl fruits and the structure confirmed by GC-MS (gas chromatography-mass spectrometry) and NMR (nuclear magnetic resonance) analysis. This compound was tested on the HT-29 human colon adenocarcinoma cell line using MTT (method of transcriptional and translational) cell proliferation assay. The results of MTT assay showed that DMHE exhibited good cytotoxic effect on HT-29 cells in a dose- and time-dependent manner but no cytotoxic effect on the MRC-5 cell line after 72 h incubation. Morphological features of apoptotic cells upon treatment by DMHE, e.g., cell shrinkage and membrane blebbing, were examined by an inverted and phase microscope. Other features, such as chromatin condension and nuclear fragmentation were studied using acridine orange and propidium iodide staining under the fluorescence microscope. Future evidence of apoptosis/necrosis was provided by result fromannexin V-FITC/PI (fluorescein-isothiocyanate/propidium iodide) staining revealed the percentage of early apoptotic, late apoptotic, necrotic and live cells in a dose- and time-dependent manner using flow cytometry. Cell cycle analysis showed G0/G1 arrest in a time-dependent manner. A western blot analysis indicated that cell death might be associated with the up-regulation of the pro-apoptotic proteins Bax PUMA. However, the anit-apotptic proteins Bcl-2, Bcl-xL, and Mcl-1 were also found to increase in a time-dependent manner. The expression of the pro-apoptotic protein Bak was not observed.
  18. AMP-activated protein kinase mediates insulin-like and lipo-mobilising effects of β-glucan-rich polysaccharides isolated from Pleurotus sajor-caju (Fr.), Singer mushroom, in 3T3-L1 cells
    Kanagasabapathy G, Chua KH, Malek SN, Vikineswary S, Kuppusamy UR
    Food Chem, 2014 Feb 15;145:198-204.
    PMID: 24128468 DOI: 10.1016/j.foodchem.2013.08.051
    Mushrooms have been used to treat various diseases for thousands of years. In the present study, the effects of Pleurotus sajor-caju mushroom on lipogenesis, lipolysis and oxidative stress in 3T3-L1 cells were investigated. The β-glucan-rich polysaccharides (GE) from P. sajor-caju stimulated lipogenesis and lipolysis but attenuated protein carbonyl and lipid hydroperoxide levels in 3T3-L1 cells. This extract caused an increase in the expression of 5'-AMP-activated protein kinase subunit γ-2 (PKRAG2) and 5'-AMP-activated protein kinase subunit γ-3 (PKRAG3) when compared to control (untreated) cells. Moreover, GE induced the expressions of hormone-sensitive lipase, adipose triglyceride lipase enzymes, leptin, adiponectin and glucose transporter-4 in 3T3-L1 cells which may have contributed to the lipolytic and insulin-like activities observed in this study. These findings suggest that GE is a novel AMPK activator that may be valuable in the formulation of nutraceuticals and functional food for the prevention and treatment of diabetes mellitus.
  19. Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways
    Phan CW, Lee GS, Hong SL, Wong YT, Brkljača R, Urban S, et al.
    Food Funct, 2014 Dec;5(12):3160-9.
    PMID: 25288148 DOI: 10.1039/c4fo00452c
    Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways.
  20. Fulltext Essential oil content of the rhizome of Curcuma purpurascens Bl. (Temu Tis) and its antiproliferative effect on selected human carcinoma cell lines
    Hong SL, Lee GS, Syed Abdul Rahman SN, Ahmed Hamdi OA, Awang K, Aznam Nugroho N, et al.
    ScientificWorldJournal, 2014;2014:397430.
    PMID: 25177723 DOI: 10.1155/2014/397430
    Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome's oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death.
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