Displaying publications 1 - 20 of 30 in total

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  1. Ng CH, Tan TH, Tioh NH, Seng HL, Ahmad M, Ng SW, et al.
    J Inorg Biochem, 2021 07;220:111453.
    PMID: 33895694 DOI: 10.1016/j.jinorgbio.2021.111453
    The cobalt(II), copper(II) and zinc(II) complexes of 1,10-phenanthroline (phen) and maltol (mal) (complexes 1, 2, 3 respectively) were prepared from their respective metal(II) chlorides and were characterized by FT-IR, elemental analysis, UV spectroscopy, molar conductivity, p-nitrosodimethylaniline assay and mass spectrometry. The X-ray structure of a single crystal of the zinc(II) analogue reveals a square pyramidal structure with distinctly shorter apical chloride bond. All complexes were evaluated for their anticancer property on breast cancer cell lines MCF-7 and MDA-MB-231, and normal cell line MCF-10A, using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and morphological studies. Complex 2 was most potent for 24, 48 and 72 h treatment of cancer cells but it was not selective towards cancer over normal cells. The mechanistic studies of the cobalt(II) complex 1 involved apoptosis assay, cell cycle analysis, dichloro-dihydro-fluorescein diacetate assay, intracellular reactive oxygen species assay and proteasome inhibition assay. Complex 1 induced low apoptosis, generated low level of ROS and did not inhibit proteasome in normal cells. The study of the DNA binding and nucleolytic properties of complexes 1-3 in the absence or presence of H2O2 or sodium ascorbate revealed that only complex 1 was not nucleolytic.
    Matched MeSH terms: Pyrones/pharmacology*
  2. Mohd Ridzuan MA, Ruenruetai U, Noor Rain A, Khozirah S, Zakiah I
    Trop Biomed, 2006 Dec;23(2):140-6.
    PMID: 17322815 MyJurnal
    Malaria is a disease which is still endemic and has become a disastrous scourge because of the emergence of antimalarial drug resistant Plasmodium falciparum. A new approach in addressing this is in developing a combination drug. This study is to show the enhancement of antimalarial properties, when single compound, goniothalamin combine with standard drug, chloroquine. Based on 4 Day Test, percentage of parasite growth on treated infected mice were determined. Oral treatment with 1 mg/kg BW of chloroquine on experimental mice suppressed 70% and 76.7% of both Plasmodium yoelii and Plasmodium berghei, respectively. The infection of P. berghei in mice was inhibited less than 50% by goniothalamin individual treatment at all doses in this study. About 27.8% and 18.5% inhibition of infection were observed in P. yoelii infected mice treated with 30 mg/kg and 60 mg/kg of goniothalamin respectively and the suppression exceed more than 50% at higher doses (90 and 120 mg/kg). Combination of 1 mg/kg chloroquine with either 30 mg/kg or 60 mg/kg of goniothalamin decreased the parasitemia of P. yoelii infected mice more than 90% and prolong the survival up to 100% after treatment. Similar treatment to P. berghei infected mice only shows about 60% reduction of parasitemia. The study findings showed that antimalarial property of goniothalamin was enhanced by combination with chloroquine at lower dose of each drug.
    Matched MeSH terms: Pyrones/pharmacology*
  3. Lew SY, Lim SH, Lim LW, Wong KH
    BMC Complement Med Ther, 2020 Nov 11;20(1):340.
    PMID: 33176761 DOI: 10.1186/s12906-020-03132-x
    BACKGROUND: Hericium erinaceus is a culinary and medicinal mushroom in Traditional Chinese Medicines. It has numerous pharmacological effects including immunomodulatory, anti-tumour, anti-microbial, anti-aging and stimulation of nerve growth factor (NGF) synthesis, but little is known about its potential role in negating the detrimental effects of oxidative stress in depression. The present study investigated the neuroprotective effects of H. erinaceus standardised aqueous extract (HESAE) against high-dose corticosterone-induced oxidative stress in rat pheochromocytoma (PC-12) cells, a cellular model mimicking depression.

    METHODS: PC-12 cells was pre-treated with HESAE for 48 h followed by 400 μM corticosterone for 24 h to induce oxidative stress. Cells in complete medium without any treatment or pre-treated with 3.125 μg/mL desipramine served as the negative and positive controls, respectively. The cell viability, lactate dehydrogenase (LDH) release, endogenous antioxidant enzyme activities, aconitase activity, mitochondrial membrane potentials (MMPs), intracellular reactive oxygen species (ROS) levels and number of apoptotic nuclei were quantified. In addition, HESAE ethanol extract was separated into fractions by chromatographic methods prior to spectroscopic analysis.

    RESULTS: We observed that PC-12 cells treated with high-dose corticosterone at 400 μM had decreased cell viability, reduced endogenous antioxidant enzyme activities, disrupted mitochondrial function, and increased oxidative stress and apoptosis. However, pre-treatment with HESAE ranging from 0.25 to 1 mg/mL had increased cell viability, decreased LDH release, enhanced endogenous antioxidant enzyme activities, restored MMP, attenuated intracellular ROS and protected from ROS-mediated apoptosis. The neuroprotective effects could be attributed to significant amounts of adenosine and herierin III isolated from HESAE.

    CONCLUSIONS: HESAE demonstrated neuroprotective effects against high-dose corticosterone-induced oxidative stress in an in vitro model mimicking depression. HESAE could be a potential dietary supplement to treat depression.

    Matched MeSH terms: Pyrones/pharmacology
  4. El Hassane A, Shah SA, Hassan NB, El Moussaoui N, Ahmad R, Zulkefeli M, et al.
    Molecules, 2014;19(3):3489-507.
    PMID: 24662069 DOI: 10.3390/molecules19033489
    Hispidin oligomers are styrylpyrone pigments isolated from the medicinal fungi Inonotus xeranticus and Phellinus linteus. They exhibit diverse biological activities and strong free radical scavenging activity. To rationalize the antioxidant activity of a series of four hispidin oligomers and determine the favored mechanism involved in free radical scavenging, DFT calculations were carried out at the B3P86/6-31+G (d, p) level of theory in gas and solvent. The results showed that bond dissociation enthalpies of OH groups of hispidin oligomers (ArOH) and spin density delocalization of related radicals (ArO•) are the appropriate parameters to clarify the differences between the observed antioxidant activities for the four oligomers. The effect of the number of hydroxyl groups and presence of a catechol moiety conjugated to a double bond on the antioxidant activity were determined. Thermodynamic and kinetic studies showed that the PC-ET mechanism is the main mechanism involved in free radical scavenging. The spin density distribution over phenoxyl radicals allows a better understanding of the hispidin oligomers formation.
    Matched MeSH terms: Pyrones/pharmacology
  5. Yamamoto T, Tsunematsu Y, Noguchi H, Hotta K, Watanabe K
    Org. Lett., 2015 Oct 16;17(20):4992-5.
    PMID: 26414728 DOI: 10.1021/acs.orglett.5b02435
    Successful activation of the pyranonigrin biosynthetic gene cluster and gene knockout in Aspergillus niger plus in vivo and in vitro assays led to isolation of six new products, including a spiro cyclobutane-containing dimeric compound, which served as the basis for the proposed comprehensive pyranonigrin biosynthetic pathway. Two redox enzymes are key to forming the characteristic fused γ-pyrone core, and a protease homologue performs the exo-methylene formation.
    Matched MeSH terms: Pyrones/pharmacology
  6. Inayat-Hussain SH, Osman AB, Din LB, Taniguchi N
    Toxicol Lett, 2002 May 28;131(3):153-9.
    PMID: 11992734
    Plant styryl-lactone derivatives isolated from Goniothalamus sp. are potential compounds for cancer chemotherapy. In this study, we have examined the mechanisms of apoptosis induced by altholactone, a stryl-lactone isolated from the Malaysian plant G. malayanus on human HL-60 promyelocytic leukemia cells. Flow cytometric analysis of the externalization of phosphatidylserine (PS) using the annexin V/PI method on altholactone treated HL-60 cells showed a concentration-dependent increase of apoptosis from concentrations ranging from 10.8 (2.5 microg/ml) to 172.4 microM (40 microg/ml). Pre-treatment with the antioxidant N-acetylcysteine (1 mM) completely abrogated apoptosis induced by altholactone, suggesting for the involvement of oxidative stress. Further flow cytometric assessment of the level of intracellular peroxides using the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) confirmed that altholactone induced an increase in cellular oxidative stress in HL-60 cells which was suppressed by N-acetylcysteine. In summary, our results demonstrate for the first time that altholactone induced apoptosis in HL-60 cells occurs via oxidative stress.
    Matched MeSH terms: Pyrones/pharmacology
  7. Hawariah A, Stanslas J
    In Vivo, 1998 Jul-Aug;12(4):403-10.
    PMID: 9706492
    Early studies reported that a styrylpyrone derivative (SPD) purified from the Goniothalamus sp. acts as a non-competitive antiestrogen in early pregnant mice (1). In the immature rat uterine wet weight test, we found that SPD markedly reduced uterine weight at doses 1 and 100 mg/kg, thus reflecting negative antiestrogenicity, probably attributed to low binding affinities towards ER. Tamoxifen (Tam) on the other hand exhibited partial antiestrogenicity at all doses (0.01-10 mg/kg BW) and dose-dependent estrogenicity. However, the estrogen antagonism: agonism ratio for SPD is much higher than Tam, which is indicative of the breast cancer antitumor activity as seen in compounds such as MER-25. Pretreatment assessment on 1 mg/kg BW SPD and Tam showed that SPD is not a very good, estrogen antagonist compared to Tam, as it was unable to revert the estrogenicity effect of estradiol benzoate (EB) on immature rat uterine weight. Antitumor activity assessment for SPD exhibited significant tumor growth retardation in 7,12-dimethyl benzanthracene (DMBA) induced rat mammary tumors at all doses employed (2, 10 and 50 mg/kg) compared to the controls (p < 0.01). This compound was found to be more potent than Tam (2 and 10 mg/kg) and displayed greater potency at a dose of 10 mg/kg. It caused complete remission of 33.3% of tumors but failed to prevent onset of new tumors. However, SPD administration at 2 mg/kg caused 16.7% complete remission and partial remission. It also prevented the onset of new tumors throughout the experiment.
    Matched MeSH terms: Pyrones/pharmacology*
  8. Meragelman TL, Scudiero DA, Davis RE, Staudt LM, McCloud TG, Cardellina JH, et al.
    J Nat Prod, 2009 Mar 27;72(3):336-9.
    PMID: 19093800 DOI: 10.1021/np800350x
    The nuclear factor-kappaB (NF-kappaB) signaling pathway is constitutively active in many types of cancers and is a potential therapeutic target. Using a cell-based assay for stability of inhibitor of kappa B (IkappaB), a critical regulator of NF-kappaB activity, we found that an organic solvent extract of the plant Cryptocarya rugulosa inhibited constitutive NF-kappaB activity in human lymphoma cell lines. The active components were identified as rugulactone, a new alpha-pyrone (1), and the known cryptocaryone (2). Rugulactone was the more active compound, exhibiting up to 5-fold induction of IkappaB at 25 microg/mL; maximal activity was observed with 10 h exposure of test cells to 1 or 2.
    Matched MeSH terms: Pyrones/pharmacology*
  9. Tanaka S, Yoichi S, Ao L, Matumoto M, Morimoto K, Akimoto N, et al.
    Phytother Res, 2001 Dec;15(8):681-6.
    PMID: 11746860
    In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances.
    Matched MeSH terms: Pyrones/pharmacology
  10. Inayat-Hussain SH, Annuar BO, Din LB, Ali AM, Ross D
    Toxicol In Vitro, 2003 Aug;17(4):433-9.
    PMID: 12849726
    Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.
    Matched MeSH terms: Pyrones/pharmacology*
  11. Yen HK, Fauzi AR, Din LB, McKelvey-Martin VJ, Meng CK, Inayat-Hussain SH, et al.
    PMID: 25107315 DOI: 10.1186/1472-6882-14-295
    Selective Alzheimer Disease Indicator-1 (or Seladin-1) is a multifunctional protein first discovered by downregulation of its expression in Alzheimer's disease. Interestingly, the expression of this protein is upregulated in several cancers, including primary bladder cancer. However, its role in cancer formation has yet to be discovered. Goniothalamin is a natural product that has been demonstrated to induce apoptosis in various cancer cell lines. In this study, we have elucidated the role of Seladin-1 in goniothalamin-induced cytotoxicity towards human urinary bladder cancer cell line RT4.
    Matched MeSH terms: Pyrones/pharmacology*
  12. Mohideen M, Zulkepli S, Nik-Salleh NS, Zulkefeli M, Weber JF, Weber JF, et al.
    Arch Pharm Res, 2013 Jul;36(7):812-31.
    PMID: 23543632 DOI: 10.1007/s12272-013-0099-1
    A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from commercially available (3,4-dihydro-2H-pyran-2-yl)methanol/5-(hydroxymethyl)dihydrofuran-2(3H)-one in three steps with good to moderate overall yields and their cytotoxicity against lymphoblastic leukemic T cell line (Jurkat E6.1) have been evaluated. Among the synthesized analogs, (Z)-Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 μM). Structure-activity relationship study indicates that introducing substituent in phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the ring size of lactones (from six to five member) do not increase the cytotoxicity.
    Matched MeSH terms: Pyrones/pharmacology*
  13. Chien AL, Pihie AH
    J. Biochem. Mol. Biol., 2003 May 31;36(3):269-74.
    PMID: 12787481
    In the fight against cancer, novel chemotherapeutic agents are constantly being sought to complement existing drugs. Various studies have presented evidence that the apoptosis that is induced by these anticancer agents is implicated in tumor regression, and Bcl-2 family genes play a part in apoptosis following treatment with various stimuli. Here, we present data that a styrylpyrone derivative (SPD) that is extracted from the plant Goniothalamus sp. showed cytotoxic effects on the human breast cancer cell line MCF-7. SPD significantly increased apoptosis in MCF-7 cells, as visualized by phase contrast microscopy and evaluated by the Tdt-mediated dUTP nick end-labeling assay and nuclear morphology. Western blotting and immunostaining revealed up-regulation of the proapoptotic Bax protein expression. SPD, however, did not affect the expression of the anti-apoptotic protein, Bcl-2. These results, therefore, suggest SPD as a potent cytotoxic agent on MCF-7 cells by inducing apoptosis through the modulation of Bax levels.
    Matched MeSH terms: Pyrones/pharmacology*
  14. Soo JS, Ng CH, Tan SH, Malik RA, Teh YC, Tan BS, et al.
    Apoptosis, 2015 Oct;20(10):1373-87.
    PMID: 26276035 DOI: 10.1007/s10495-015-1158-5
    Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers.
    Matched MeSH terms: Pyrones/pharmacology
  15. Ali AM, Mackeen MM, Hamid M, Aun QB, Zauyah Y, Azimahtol HL, et al.
    Planta Med, 1997 Feb;63(1):81-3.
    PMID: 9063100
    The cytotoxicity of goniothalamin was found to be strong towards both cancerous (HGC-27, MCF-7, PANC-1, HeLa), and non-cancerous (3T3) cell lines, especially in cases of dividing cells. Drug exposure studies indicated that the cytotoxic action of goniothalamin was time- and dose-dependent. At the ultrastructural level, goniothalamin-induced cytotoxicity revealed a necrotic mode of cell death towards MCF-7 cells.
    Matched MeSH terms: Pyrones/pharmacology*
  16. Jantan I, Raweh SM, Sirat HM, Jamil S, Mohd Yasin YH, Jalil J, et al.
    Phytomedicine, 2008 Apr;15(4):306-9.
    PMID: 17913483
    Twelve compounds isolated from Alpinia mutica Roxb., Kaempferia rotunda Linn., Curcuma xanthorhiza Roxb., Curcuma aromatica Valeton and Zingiber zerumbet Smith (Family: Zingiberaceae) and three synthesized derivatives of xanthorrhizol were evaluated for their ability to inhibit arachidonic acid- (AA), collagen- and ADP-induced platelet aggregation in human whole blood. Antiplatelet activity of the compounds was measured in vitro by the Chrono Log whole blood aggregometer using an electrical impedance method. Among the compounds tested, curcumin from C. aromatica, cardamonin, pinocembrine and 5,6-dehydrokawain from A. mutica and 3-deacetylcrotepoxide from K. rotunda showed strong inhibition on platelet aggregation induced by AA with IC(50) values of less than 84 microM. Curcumin was the most effective antiplatelet compound as it inhibited AA-, collagen- and ADP-induced platelet aggregation with IC(50) values of 37.5, 60.9 and 45.7 microM, respectively.
    Matched MeSH terms: Pyrones/pharmacology
  17. Chan KM, Rajab NF, Ishak MH, Ali AM, Yusoff K, Din LB, et al.
    Chem Biol Interact, 2006 Feb 1;159(2):129-40.
    PMID: 16297902
    Restenosis represents a major impediment to the success of coronary angioplasty. Abnormal proliferation of vascular smooth muscle cells (VSMCs) has been shown to be an important process in the pathogenesis of restenosis. A number of agents, particularly rapamycin and paclitaxel, have been shown to impact on this process. This study was carried out to determine the mechanisms of cytotoxicity of goniothalamin (GN) on VSMCs. Results from MTT cytotoxicity assay showed that the IC(50) for GN was 4.4 microg/ml (22 microM), which was lower compared to the clinically used rapamycin (IC(50) of 25 microg/ml [27.346 microM]). This was achieved primarily via apoptosis where up to 25.83 +/- 0.44% of apoptotic cells were detected after 72 h treatment with GN. In addition, GN demonstrated similar effects as rapamycin in inhibiting VSMCs proliferation using bromodeoxyuridine (BrdU) cell proliferation assay after 72 h treatment at IC(50) concentration (p > 0.05). In order to understand the mechanisms of GN, DNA damage detection using comet assay was determined at 2h post-treatment with GN. Our results showed that there was a concentration-dependent increase in DNA damage in VSMCs prior to cytotoxicity. Moreover, GN effects were comparable to rapamycin. In conclusion, our data show that GN initially induces DNA damage which subsequently leads to cytotoxicity primarily via apoptosis in VSMCs.
    Matched MeSH terms: Pyrones/pharmacology*
  18. Chan KL, Sugiyama H, Saito I, Hara M
    Phytochemistry, 1995 Nov;40(5):1373-4.
    PMID: 8534399
    The kapurimycin A3-guanine adduct was formed by alkylation of the antitumour antibiotic with d(CGCG)2. The site of alkylation of the guanine was confirmed by comparative NMR studies with N-7-methyl-guanine in DMSO-d6.
    Matched MeSH terms: Pyrones/pharmacology
  19. Wasano N, Takemura T, Ismil R, Bakar B, Fujii Y
    Nat Prod Commun, 2015 May;10(5):725-7.
    PMID: 26058144
    Goniothalamin produced by the Malaysian medicinal plant, Goniothalamus andersonii J. Sinclair, strongly inhibits plant growth. However, its mode of action has not been characterized at the gene expression level. We conducted DNA microarray assay to analyze the changes in early gene responses of Arabidopsis thaliana seedlings. After a 6-h exposure to goniothalamin, we observed an upregulation of genes highly associated with heat response, and 22 heat shock protein (AtHSP) genes were upregulated more than 50 fold. Together with these genes, we observed upregulation of the genes related to oxidative stress and protein folding. Also, the genes related to cell wall modification and cell growth, expansin (AtEXPA) genes, were significantly downregulated. The results suggested that goniothalamin induces oxidative stresses and inhibits the expression of cell wall-associated proteins resulting in growth inhibition of Arabidopsis seedlings.
    Matched MeSH terms: Pyrones/pharmacology*
  20. Takemura T, Kamo T, Ismil R, Bakar B, Wasano N, Hiradate S, et al.
    Nat Prod Commun, 2012 Sep;7(9):1197-8.
    PMID: 23074907
    A crude methanol extract of Goniothalamus andersonii J. Sinclair strongly inhibited elongation of lettuce (Lactuca sativa L.) radicles. We conducted bioassay-guided purification of G. andersonii bark extract and obtained goniothalamin as the major bioactive compound. Its EC50 values against elongation of lettuce radicles and hypocotyls were 50 and 125 micromol L(-1), respectively. Among the six species tested, timothy was the most sensitive to goniothalamin. Quantification of this compound in other Goniothalamus species suggested that the plant inhibitory activity of this genus is explainable by goniothalamin, with G. calcareus as an exception.
    Matched MeSH terms: Pyrones/pharmacology*
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