Displaying publications 1 - 20 of 65 in total

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  1. Umar MI, Asmawi MZ, Sadikun A, Abdul Majid AM, Atangwho IJ, Khadeer Ahamed MB, et al.
    Pharm Biol, 2014 Nov;52(11):1411-22.
    PMID: 25026347 DOI: 10.3109/13880209.2014.895017
    Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures.
  2. Umar MI, Asmawi MZ, Sadikun A, Majid AM, Al-Suede FS, Hassan LE, et al.
    Clinics (Sao Paulo), 2014 Feb;69(2):134-44.
    PMID: 24519205 DOI: 10.6061/clinics/2014(02)10
    The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga.
  3. Tabana YM, Hassan LE, Ahamed MB, Dahham SS, Iqbal MA, Saeed MA, et al.
    Microvasc Res, 2016 09;107:17-33.
    PMID: 27133199 DOI: 10.1016/j.mvr.2016.04.009
    We recently reported the antineovascularization effect of scopoletin on rat aorta and identified its potential anti-angiogenic activity. Scopoletin could be useful as a systemic chemotherapeutic agent against angiogenesis-dependent malignancies if its antitumorigenic activity is investigated and scientifically proven using a suitable human tumor xenograft model. In the present study, bioassay-guided (anti-angiogenesis) phytochemical investigation was conducted on Nicotiana glauca extract which led to the isolation of scopoletin. Further, anti-angiogenic activity of scopoletin was characterized using ex vivo, in vivo and in silico angiogenesis models. Finally, the antitumorigenic efficacy of scopoletin was studied in human colorectal tumor xenograft model using athymic nude mice. For the first time, an in vivo anticancer activity of scopoletin was reported and characterized using xenograft models. Scopoletin caused significant suppression of sprouting of microvessels in rat aortic explants with IC50 (median inhibitory concentration) 0.06μM. Scopoletin (100 and 200mg/kg) strongly inhibited (59.72 and 89.4%, respectively) vascularization in matrigel plugs implanted in nude mice. In the tumor xenograft model, scopoletin showed remarkable inhibition on tumor growth (34.2 and 94.7% at 100 and 200mg/kg, respectively). Tumor histology revealed drastic reduction of the extent of vascularization. Further, immunostaining of CD31 and NG2 receptors in the histological sections confirmed the antivascular effect of scopoletin in tumor vasculature. In computer modeling, scopoletin showed strong ligand affinity and binding energies toward the following angiogenic factors: protein kinase (ERK1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). These results suggest that the antitumor activity of scopoletin may be due to its strong anti-angiogenic effect, which may be mediated by its effective inhibition of ERK1, VEGF-A, and FGF-2.
  4. Shafaei A, Esmailli K, Farsi E, Aisha AF, Abul Majid AM, Ismail Z
    PMID: 26467526 DOI: 10.1186/s12906-015-0885-z
    Orthosiphon stamineus (OS) Benth is a medicinal plant and native in Southeast Asia. Pharmacological effects of OS are attributed to the presence of lipophilic flavones. However; lipophilic compounds suffer from poor aqueous solubility which limits the OS oral bioavailability and therapeutic applications. Therefore, OS was prepared in nano formulation form using liposomes from soybean phospholipids. The aim of the present study is to evaluate the in vitro genotoxicity and in vivo oral toxicity of nano liposomes of OS ethanolic extract (OS-EL).
  5. Shafaei A, Sultan Khan MS, F A Aisha A, Abdul Majid AM, Hamdan MR, Mordi MN, et al.
    Molecules, 2016 Nov 09;21(11).
    PMID: 27834876
    This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure-activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX: BioSolveIT's LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC50 value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.
  6. Seow LJ, Beh HK, Majid AM, Murugaiyah V, Ismail N, Asmawi MZ
    J Ethnopharmacol, 2011 Mar 24;134(2):221-7.
    PMID: 21167271 DOI: 10.1016/j.jep.2010.12.007
    Gynura segetum is a popular medicinal plant in Indonesia and Malaysia, known to possess various medicinal properties especially for treatment of cancer, diabetes and hypertension.
  7. Saidan NH, Aisha AF, Hamil MS, Majid AM, Ismail Z
    Pharmacognosy Res, 2015 Jan-Mar;7(1):23-31.
    PMID: 25598631 DOI: 10.4103/0974-8490.147195
    Orthosiphon stamineus Benth. (Lamiaceae) is a traditional medicinal plant which has been used in treating various ailments such as kidney diseases, bladder inflammation, arthritis and diabetes. The leaves contain high concentration of phenolic compounds, thus, rosmarinic acid (RA), 3'-hydroxy-5, 6, 7, 4'-tetramethoxyflavone (TMF), sinensetin (SIN) and eupatorin (EUP) were chosen as a marker compounds for standardization of various O. stamineus leaf extracts.
  8. Saidan NH, Hamil MS, Memon AH, Abdelbari MM, Hamdan MR, Mohd KS, et al.
    PMID: 26446501 DOI: 10.1186/s12906-015-0884-0
    Studies on selected metabolites profiling of Orthosiphon stamineus extracts using chromatographic and spectroscopic techniques combined with chemometric tools have not been fully elucidated. Thus present study was performed to profile selected metabolites in O. stamineus leaves extracts using HPLC and FTIR combined with chemometric tools and correlated with biological activities.
  9. Saghir SA, Sadikun A, Al-Suede FS, Majid AM, Murugaiyah V
    Curr Pharm Biotechnol, 2016 6 6;17(10):915-25.
    PMID: 27262321 DOI: 10.2174/1389201017666160603013434
    BACKGROUND: Star fruit (Averrhoa carambola) is a well-known plant in Malaysia which bears a great significance in traditional medicine.

    OBJECTIVES: This study aimed to evaluate the antihyperlipidemic effect, antioxidant potential and cytotoxicity of aqueous and methanolic extracts of ripe and unripe fruits, leaves and stem of A. carambola.

    METHODS: Antihyperlipidemic activity was assessed in poloxamer-407 (P-407) induced acute hyperlipidemic rat's model. The antioxidant activity was assessed in vitro using 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging, 1-diphenyl-2-dipicrylhydrazyl radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP) assays. In addition, cytotoxicity of A. carambola extracts was assessed using MTS assay on four leukemic cell lines (human colon cancer, human promyeloid leukemia, erythroid leukemia, acute myeloid leukemia) and one normal cell (human umbilical vein endothelial cells).

    RESULTS: Methanolic extract of leaves had the most potent antihyperlipidemic activity in P-407 model, whereby it significantly reduced serum levels of total cholesterol (P<0.01), triglycerides (P<0.01), low-density lipoprotein (P<0.05), verylow- density lipoprotein (P<0.01) and atherogenic index (P<0.01). On the other hand, methanolic extracts of A. carambola stem and leaves showed the strongest antioxidant activity. Total phenolic and flavonoid contents of the extracts exhibited significant correlations with antioxidant but not with antihyperlipidemic activities. All plant parts showed no cytotoxic effect on the selected cancer or normal cell lines.

    CONCLUSION: Antihyperlipidemic activity of different parts of A. carambola is greatly affected by extraction solvents used. Methanolic extract of A. carambola leaves exhibited higher antihyperlipidemic and antioxidant potentials compared to other parts of the plant.
  10. Piaru SP, Mahmud R, Abdul Majid AM, Mahmoud Nassar ZD
    Asian Pac J Trop Med, 2012 Apr;5(4):294-8.
    PMID: 22449521 DOI: 10.1016/S1995-7645(12)60042-X
    OBJECTIVE: Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans (M. fragrans) (nutmeg) and Morinda citrifolia (M. citrifolia)(mengkudu) oils.

    METHODS: The nutmeg and megkudu essential oils were obtained by steam distillation. The antioxidant activities of both essential oils were determined by beta-carotene/linoleic acid bleaching assay and reducing power while the anti-angiogenic activity was investigated using rat aortic ring assay using various concentrations.

    RESULTS: The results showed that nutmeg oil has higher antioxidant activity than mengkudu oil. The nutmeg oil effectively inhibited the oxidation of linoleic acid with (88.68±0.1)% while the inhibition percentage of oxidation of linoleic acid of the mengkudu oil is (69.44±0.4)%. The nutmeg oil and mengkudu oil showed reducing power with an EC(50) value of 181.4 μg/mL and 3 043.0 μg/mL, respectively. The antiangiogenic activity of nutmeg oil showed significant antiangiogenic activity with IC(50) of 77.64 μg/mL comparing to mengkudu oil which exhibits IC(50) of 109.30 μg/mL.

    CONCLUSIONS: Bioactive compound(s) will be isolated from the nutmeg essential oil to be developed as antiangiogenic drugs.

  11. Piaru SP, Mahmud R, Abdul Majid AM, Ismail S, Man CN
    J Sci Food Agric, 2012 Feb;92(3):593-7.
    PMID: 25520982
    In this study the chemical composition, antioxidant activities and cytotoxic effect of the essential oils of Myristica fragrans (nutmeg) and Morinda citrifolia (mengkudu) were determined.
  12. Ng KW, Salhimi SM, Majid AM, Chan KL
    Planta Med, 2010 Jun;76(9):935-40.
    PMID: 20112179 DOI: 10.1055/s-0029-1240813
    Angiogenesis plays an important role in tumor formation and proliferation. The development of anti-angiogenic agents to block new blood vessel growth will inhibit metastasis and induce apoptosis of the cancer cells. Nine medicinal plants, Strobilanthes crispus, Phyllanthus niruri, Phyllanthus pulcher, Phyllanthus urinaria, Ailanthus malabarica, Irvingia malayana, Smilax myosotiflora, Tinospora crispa and blumea balsamifera were screened for anti-angiogenic properties using the rat aortic ring assay. Of these, the methanol extracts of Phyllanthus species and Irvingia malayana exhibited the highest activity. At 100 microg/mL, P. pulcher, P. niruri, P. urinaria and I. malayana recorded an inhibition of 78.8 %, 59.5 %, 56.7 % and 46.4 %, respectively, against rat aortic vascular growth. Their activities were further investigated by the tube formation assay involving human umbilical vein endothelial cells (HUVEC) on Matrigel. I. malayana, P. niruri and P. urinaria showed a significant decrease of 45.5, 37.9 and 35.6 %, respectively, whilst P. pulcher showed a much lower decrease of 15.5 % when compared with that of the rat aortic ring assay. All the plant extracts were evaluated for cytotoxicity on a panel of human cancer cell lines using the MTT assay. None of them displayed acute cytotoxicity. The HPLC of P. niruri, P. urinaria and P. pulcher indicated the extracts contained some identical chromatographic peaks of lignans. Further fractionation of I. malayana yielded betulinic acid reported in this plant for the first time and at 100 microg/mL it exhibited a 67.3 % inhibition of vessel outgrowth and 46.5 % inhibition of tube formation.
  13. Nassar ZD, Aisha AF, Idris N, Khadeer Ahamed MB, Ismail Z, Abu-Salah KM, et al.
    Oncol Rep, 2012 Mar;27(3):727-33.
    PMID: 22134768 DOI: 10.3892/or.2011.1569
    Deregulated cell signaling pathways result in cancer development. More than one signal transduction pathway is involved in colorectal cancer pathogenesis and progression. Koetjapic acid (KA) is a naturally occurring seco-A-ring oleanene triterpene isolated from the Sandoricum koetjape stem bark. We report the cellular and molecular mechanisms of anticancer activity of KA towards human colorectal cancer. The results showed that KA induces apoptosis in HCT 116 colorectal carcinoma cells by inducing the activation of extrinsic and intrinsic caspases. We confirmed that KA-induced apoptosis was mediated by DNA fragmentation, nuclear condensation and disruption in the mitochondrial membrane potential. Further studies on the effect of KA on cancer pathways show that the compound causes down-regulation of Wnt, HIF-1α, MAP/ERK/JNK and Myc/Max signaling pathways and up-regulates the NF-κB signaling pathway. The result of this study highlights the anticancer potential of KA against colorectal cancer.
  14. Nassar ZD, Aisha AF, Al Suede FS, Abdul Majid AS, Abdul Majid AM
    Biol Pharm Bull, 2012;35(4):503-8.
    PMID: 22466553
    Breast cancer is the most common cancer in women, and it can metastasize very rapidly. Tumor metastasis is the primary cause of cancer deaths. In the present study, we investigated the capability of koetjapic acid, a natural triterpene, in the induction of apoptosis and the inhibition of metastasis in the breast cancer cell line (MCF 7). The effects of koetjapic acid against 4 steps of metastasis have been assessed, including cell survival, clonogenicity, migration and invasion. Koetjapic acid exhibited cytotoxic activity against MCF 7 cells with an IC(50) of 68.88±6.075 μg/mL. The mechanism of cell death was confirmed due to the induction of apoptosis machineries; early and late apoptosis-related changes were detected, including the stimulation of caspase 3/7 activities, apoptosis-related morphological changes such as membrane blebbing, chromatin condensation and DNA fragmentation. A mitochondrial apoptosis pathway was found to be involved in koetjapic acid-induced cell death induction. Moreover, at a sub-toxic dose (15 μg/mL), Koetjapic acid inhibited cell migration and invasion significantly. Finally, koetjapic acid inhibited the colony formation properties of MCF 7 significantly. These results indicate that koetjapic acid possesses significant antitumor and antimetastatic effects, and warrants further investigation.
  15. Nassar ZD, Aisha AF, Ahamed MB, Ismail Z, Abu-Salah KM, Alrokayan SA, et al.
    Cancer Cell Int, 2011;11(1):12.
    PMID: 21524294 DOI: 10.1186/1475-2867-11-12
    Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.
  16. Muslim NS, Nassar ZD, Aisha AF, Shafaei A, Idris N, Majid AM, et al.
    PMID: 23126282 DOI: 10.1186/1472-6882-12-210
    Angiogenesis plays a critical role in embryonic development and various physiological processes. However, excessive angiogenesis is associated with several pathological conditions including cancer. Pithecellobium jiringa (Jack) Prain is a traditional medicinal plant from the family Leguminosae. It is native to the Southeast Asia, where it has been used traditionally for treatment of various ailments such as hypertension and diabetes. The present work is aimed to study antioxidant and antiangiogenesis activities of P. jiringa ethanol extracts.
  17. Memon AH, Ismail Z, Al-Suede FS, Aisha AF, Hamil MS, Saeed MA, et al.
    Molecules, 2015;20(8):14212-33.
    PMID: 26248073 DOI: 10.3390/molecules200814212
    Two flavanones named (2S)-7-Hydroxy-5-methoxy-6,8-dimethyl flavanone (1), (S)-5,7-dihydroxy-6,8-dimethyl-flavanone (2), along with known chalcone, namely, (E)-2',4'- dihydroxy-6'-methoxy-3',5'-dimethylchalcone (3) and two triterpenoids, namely, betulinic and ursolic acids (4 and 5), were isolated from the leaves of Syzygium campanulatum Korth (Myrtaceae). The structures of compounds (1 and 2) were determined on the basis of UV-visible, FTIR, NMR spectroscopies and LC-EIMS analytical techniques. Furthermore, new, simple, precise, selective, accurate, highly sensitive, efficient and reproducible RP-HPLC method was developed and validated for the quantitative analysis of the compounds (1-5) from S. campanulatum plants of five different age. RP-HPLC method was validated in terms of specificity, linearity (r2 ≤ 0.999), precision (2.0% RSD), and recoveries (94.4%-105%). The LOD and LOQ of these compounds ranged from 0.13-0.38 and 0.10-2.23 μg·mL-1, OPEN ACCESS respectively. Anti-proliferative activity of isolated flavanones (1 and 2) and standardized extract of S. campanulatum was evaluated on human colon cancer (HCT 116) cell line. Compounds (1 and 2) and extract revealed potent and dose-dependent activity with IC50 67.6, 132.9 and 93.4 μg·mL-1, respectively. To the best of our knowledge, this is the first study on isolation, characterization, X-ray crystallographic analysis of compounds (1 and 2) and simultaneous RP-HPLC determination of five major compounds (1-5) from different age of S. campanulatum plants.
  18. Memon AH, Hamil MS, Laghari M, Rithwan F, Zhari S, Saeed MA, et al.
    J Zhejiang Univ Sci B, 2016 Sep;17(9):683-982.
    PMID: 27604860 DOI: 10.1631/jzus.B1600019
    Syzygium campanulatum Korth is a plant, which is a rich source of secondary metabolites (especially flavanones, chalcone, and triterpenoids). In our present study, three conventional solvent extraction (CSE) techniques and supercritical fluid extraction (SFE) techniques were performed to achieve a maximum recovery of two flavanones, chalcone, and two triterpenoids from S. campanulatum leaves. Furthermore, a Box-Behnken design was constructed for the SFE technique using pressure, temperature, and particle size as independent variables, and yields of crude extract, individual and total secondary metabolites as the dependent variables. In the CSE procedure, twenty extracts were produced using ten different solvents and three techniques (maceration, soxhletion, and reflux). An enriched extract of five secondary metabolites was collected using n-hexane:methanol (1:1) soxhletion. Using food-grade ethanol as a modifier, the SFE methods produced a higher recovery (25.5%‒84.9%) of selected secondary metabolites as compared to the CSE techniques (0.92%‒66.00%).
  19. Memon AH, Ismail Z, Aisha AF, Al-Suede FS, Hamil MS, Hashim S, et al.
    PMID: 25530783 DOI: 10.1155/2014/470179
    Syzygium campanulatum Korth is an equatorial, evergreen, aboriginal shrub of Malaysia. Conventionally it has been used as a stomachic. However, in the currently conducted study dimethyl cardamonin or 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) was isolated from S. campanulatum Korth, leaf extract. The structural characterization of DMC was carried out by making use of various techniques including UV, IR, NMR spectral followed by LC-MS, and X-ray crystallographic techniques. For determining the purity of compound, highly effective techniques including TLC, HPLC, and melting point were used. The cytotoxicity of DMC and three different extracts of S. campanulatum was evaluated against human colon cancer cell line (HT-29) by three different assays. DMC and ethanolic extract revealed potent and dose-dependent cytotoxic activity on the cancer cell line with IC50 12.6 and 90.1 µg/mL, respectively. Quite astonishingly to our knowledge, this is the very first report on S. campanulatum as being a rich source (3.5%) of DMC, X-ray crystallography, and anticancer activity on human colon cancer cells.
  20. Majid AM, Smythe G, Denny WA, Wakelin LP
    Mol. Pharmacol., 2007 Apr;71(4):1165-78.
    PMID: 17251328
    Nitrogen mustard alkylating agents are important cancer drugs. Much interest has been focused on redirecting their covalent adducts from the N7 atoms of guanine in the major groove of DNA to the N3 atoms of adenine in the minor groove by attaching mustard groups to AT-selective minor groove binding ligands. Here we describe the use of electrospray ionization and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry to study the structure of the DNA complexes of two minor groove binding polybenzamide mustards, alkamin and alkamini; the former is a bis-half-mustard in which reactive groups are disposed at each end of the ligand, and the latter is its monofunctional analog. Alkamin is potently cytotoxic and active in experimental mouse tumor models, whereas alkamini is not. We have studied their interaction with the DNA dodecamer d(CGCGAATTCGCG)(2), designated A2T2, and we provide a detailed analysis of the observed DNA-ligand adduct ions and their fragmentation products. We find that alkamini alkylates A2T2 at guanine G4 and adenines A5 and A6 in a manner consistent with covalent attack on purine N3 atoms from the minor groove of the AT tract. Alkamin also forms monofunctional adducts at G4 and both adenines in which the second mustard arm is hydrolyzed but, in addition, forms a variety of interstrand cross-links between adenines A5/A6 and A5'/A6', an interstrand cross-link between G4 and A6', and an intrastrand cross-link between G4 and A6. We conclude that the marked cytotoxicity of alkamin and its experimental antitumor activity could be the consequence of its ability to cross-link cellular DNA at AT tract sequences.
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