Displaying publications 21 - 40 of 46 in total

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  1. Zakaria ZA, Mohamad AS, Ahmad MS, Mokhtar AF, Israf DA, Lajis NH, et al.
    Biol Res Nurs, 2011 Oct;13(4):425-32.
    PMID: 21112917 DOI: 10.1177/1099800410386590
    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of inflammation. However, despite their effectiveness, most NSAIDs cause various side effects that negatively affect the management of inflammation and, in part, pain. Thus, there is a need to search for new anti-inflammatory agents with few, or no, side effects. Natural products of plant, animal, or microorganism origin have been good sources of new bioactive compounds. The present study was carried out to evaluate the acute and chronic anti-inflammatory activities of the essential oil of the rhizomes of Zingiber zerumbet (Zingiberaceae) using the carrageenan-induced paw edema and cotton pellet-induced granuloma tests, respectively. The effect of the essential oil on inflammatory- and noninflammatory-mediated pain was also assessed using the formalin test. Essential oil of Z. zerumbet, at doses of 30, 100, and 300 mg/kg, was administered intraperitoneally to rats. The substance exhibited significant anti-inflammatory activity both in acute and chronic animal models. The essential oil also inhibited inflammatory- and noninflammatory-mediated pain when assessed using the formalin test. In conclusion, the essential oil of Z. zerumbet possessed anti-inflammatory activity, in addition to its antinociceptive activity, which may explain its traditional uses to treat inflammatory-related ailments.
  2. Israf DA, Tham CL, Syahida A, Lajis NH, Sulaiman MR, Mohamad AS, et al.
    Phytomedicine, 2010 Aug;17(10):732-9.
    PMID: 20378317 DOI: 10.1016/j.phymed.2010.02.006
    In a previous communication we showed that atrovirinone, a 1,4-benzoquinone isolated from the roots of Garcinia atroviridis, was able to inhibit several major proinflammatory mediators of inflammation. In this report we show that atrovirinone inhibits NO and PGE(2) synthesis through inhibition of iNOS and COX-2 expression. We also show that atrovirinone inhibits the secretion of IL-1beta and IL-6 in a dose dependent fashion whereas the secretion of IL-10, the anti-inflammatory cytokine, was enhanced. Subsequently we determined that the inhibition of proinflammatory cytokine synthesis and inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation of p38 and ERK1/2. We also showed that atrovirinone prevented phosphorylation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation as demonstrated by expression analysis. We conclude that atrovirinone is a potential anti-inflammatory drug lead that targets both the MAPK and NF-kappaB pathway.
  3. Sulaiman MR, Perimal EK, Zakaria ZA, Mokhtar F, Akhtar MN, Lajis NH, et al.
    Fitoterapia, 2009 Jun;80(4):230-2.
    PMID: 19535012 DOI: 10.1016/j.fitote.2009.02.002
    We have investigated the antinociceptive activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, in acetic acid-induced abdominal writhing test and hot plate test in mice. 1 given by intraperitoneal route produced significant dose-dependent antinociceptive effect in all the test models used. In addition, the antinociceptive effect of 1 in the hot plate test was reversed by the non-selective opioid receptor antagonist naloxone, suggesting that the opioid system is involved in its analgesic mechanism of action.
  4. Mediani A, Abas F, Khatib A, Tan CP, Ismail IS, Shaari K, et al.
    Plant Foods Hum Nutr, 2015 Jun;70(2):184-92.
    PMID: 25800644 DOI: 10.1007/s11130-015-0478-5
    The study investigated the changes in the metabolite, antioxidant and α-glucosidase inhibitory activities of Phyllanthus niruri after three drying treatments: air, freeze and oven dryings. Water extracts and extracts obtained using different solvent ratios of ethanol and methanol (50, 70, 80 and 100%) were compared. The relationships among the antioxidant, α-glucosidase inhibitory activity and metabolite levels of the extracts were evaluated using partial least-square analysis (PLS). The solvent selectivity was assessed based on the phytochemical constituents present in the extract and their concentrations quantitatively analyzed using high performance liquid chromatography. The freeze-dried P. niruri samples that were extracted with the mixture of ethanol or methanol with low ratio of water showed higher biological activity values compared with the other extracts. The PLS results for the ethanolic with different ratio and water extracts demonstrated that phenolic acids (chlorogenic acid and ellagic acid) and flavonoids were highly linked to strong α-glucosidase inhibitory and antioxidant activities.
  5. Permana D, Lajis NH, Mackeen MM, Ali AM, Aimi N, Kitajima M, et al.
    J Nat Prod, 2001 Jul;64(7):976-9.
    PMID: 11473441
    Two new prenylated compounds, the benzoquinone atrovirinone (1) and the depsidone atrovirisidone (2), were isolated from the roots of Garcinia atroviridis. Their structures were determined on the basis of the analysis of spectroscopic data. While compound 2 showed some cytotoxicity against HeLa cells, both compounds 1 and 2 were only mildly inhibitory toward Bacillus cereus and Staphylococcus aureus.
  6. Habsah M, Amran M, Mackeen MM, Lajis NH, Kikuzaki H, Nakatani N, et al.
    J Ethnopharmacol, 2000 Oct;72(3):403-10.
    PMID: 10996279
    Dichloromethane and methanol extracts of 13 Zingiberaceae species from the Alpinia, Costus and Zingiber genera were screened for antimicrobial and antioxidant activities. The antimicrobial activity of most of the extracts was antibacterial with only the methanol extract of Costus discolor showing very potent antifungal activity against only Aspergillus ochraceous (MID, 15.6 microg per disc). All the extracts showed strong antioxidant activity comparable with or higher that of alpha-tocopherol.
  7. Mackeen MM, Ali AM, Lajis NH, Kawazu K, Hassan Z, Amran M, et al.
    J Ethnopharmacol, 2000 Oct;72(3):395-402.
    PMID: 10996278
    Crude extracts (methanol) of various parts, viz. the leaves, fruits, roots, stem and trunk bark, of Garcinia atroviridis were screened for antimicrobial, cytotoxic, brine shrimp toxic, antitumour-promoting and antioxidant activities. The crude extracts exhibited predominantly antibacterial activity with the root extract showing the strongest inhibition against the test bacteria at a minimum inhibitory dose (MID) of 15.6 microg/disc. Although all the extracts failed to inhibit the growth of most of the test fungi, significant antifungal activity against Cladosporium herbarum was exhibited by most notably the fruit (MID: 100 microg), and the leaf (MID: 400 microg) extracts. None of the extracts were significantly cytotoxic, and lethal towards brine shrimps. The root, leaf, trunk and stem bark extracts (except for the fruits) showed strong antioxidant activity exceeding that of the standard antioxidant, alpha-tocopherol. Antitumour-promoting activity (>95% inhibition) was shown by the fruit, leaf, stem and trunk bark extracts.
  8. Lajis NH, Abdullah AS, Salim SJ, Bremner JB, Khan MN
    Steroids, 1993 Aug;58(8):387-9.
    PMID: 8212090
    Spectroscopic examination of purified extracts of the rumen content of sheep intoxicated by Brachiaria decumbens revealed the presence of two spirostanes, identified as epi-sarsasapogenin and epi-smilagenin. Sarsasapogenone was obtained by the oxidation of sarsasapogenin. The reduction of sarsasapogenone using lithium aluminum hydride yielded isomeric products, sarsasapogenin (20%) and epi-sarsasapogenin (80%).
  9. Abdullah AS, Lajis NH, Bremner JB, Davies NW, Mustapha W, Rajion MA
    Vet Hum Toxicol, 1992 Apr;34(2):154-5.
    PMID: 1509678
    Spectroscopic examinations of purified extracts of the rumen content of sheep intoxicated by Brachiaria decumbens revealed the presence of a mixture of sapogenins, identified as 3-spirostanols. These isomeric steroid sapogenins (C27H44O3) are believed the toxic principles in causing toxicity in sheep after feeding on B. decumbens.
  10. Ali AM, Mackeen MM, Intan-Safinar I, Hamid M, Lajis NH, el-Sharkawy SH, et al.
    J Ethnopharmacol, 1996 Sep;53(3):165-9.
    PMID: 8887024
  11. Saha K, Lajis NH, Israf DA, Hamzah AS, Khozirah S, Khamis S, et al.
    J Ethnopharmacol, 2004 Jun;92(2-3):263-7.
    PMID: 15138010
    Methanol extracts of seven Malaysian medicinal plants were screened for antioxidant and nitric oxide inhibitory activities. Antioxidant activity was measured by using FTC, TBA and DPPH free radical scavenging methods and Griess assay was used for the measurement of nitric oxide inhibition in lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-treated RAW 264.7 cells. All the extracts showed strong antioxidant activity comparable to or higher than that of alpha-tocopherol, BHT and quercetin in FTC and TBA methods. The extracts from Leea indica and Spermacoce articularis showed strong DPPH free radical scavenging activity comparable with quercetin, BHT and Vit C. Spermacoce exilis showed only moderate activity but other species were weak as compared to the standards. In the Griess assay Lasianthus oblongus, Chasalia chartacea, Hedyotis verticillata, Spermacoce articularis and Leea indica showed strong inhibitory activity on nitric oxide production in LPS and IFN-gamma-induced RAW 264.7 cells. Extracts from Psychotria rostrata and Spermacoce exilis also inhibited NO production but this was due to their cytotoxic effects upon cells during culture.
  12. Chong TM, Abdullah MA, Fadzillah NM, Lai OM, Lajis NH
    Plant Cell Rep, 2004 Jul;22(12):951-8.
    PMID: 15067428
    The effects of medium strategies [maintenance (M), intermediary (G), and production (P) medium] on cell growth, anthraquinone (AQ) production, hydrogen peroxide (H2O2) level, lipid peroxidation, and antioxidant vitamins in Morinda elliptica cell suspension cultures were investigated. These were compared with third-stage leaf and 1-month-old callus culture. With P medium strategy, cell growth at 49 g l(-1), intracellular AQ content at 42 mg g(-1) DW, and H2O2 level at 9 micromol g(-1) FW medium were the highest as compared to the others. However, the extent of lipid peroxidation at 40.4 nmol g(-1) FW and total carotenoids at 13.3 mg g(-1) FW for cultures in P medium were comparable to that in the leaf, which had registered sevenfold lower AQ and 2.2-fold lower H2O2 levels. Vitamin C content at 30-120 microg g(-1) FW in all culture systems was almost half the leaf content. On the other hand, vitamin E content was around 400-500 microg g(-1) FW in 7-day-old cultures from all medium strategies and reduced to 50-150 microg g(-1) FW on day 14 and 21; as compared to 60 microg g(-1) FW in callus and 200 microg g(-1) FW in the leaf. This study suggests that medium strategies and cell growth phase in cell culture could influence the competition between primary and secondary metabolism, oxidative stresses and antioxidative measures. When compared with the leaf metabolism, these activities are dynamic depending on the types and availability of antioxidants.
  13. Abu Bakar NA, Sulaiman MR, Lajis N, Akhtar MN, Mohamad AS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S711-S717.
    PMID: 33828366 DOI: 10.4103/jpbs.JPBS_344_19
    Introduction: Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties.

    Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivo.

    Materials and Methods: The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets.

    Results: It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test.

    Conclusion: Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.

  14. Latifah SY, Gopalsamy B, Abdul Rahim R, Manaf Ali A, Haji Lajis N
    Molecules, 2021 Mar 12;26(6).
    PMID: 33808969 DOI: 10.3390/molecules26061554
    BACKGROUND: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of Morinda elliptica on T-lymphoblastic leukaemia (CEM-SS) cell lines.

    METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.

    RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.

    CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.

  15. Jada SR, Matthews C, Saad MS, Hamzah AS, Lajis NH, Stevens MF, et al.
    Br J Pharmacol, 2008 Nov;155(5):641-54.
    PMID: 18806812 DOI: 10.1038/bjp.2008.368
    BACKGROUND AND PURPOSE: Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.
    EXPERIMENTAL APPROACH: Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry.
    KEY RESULTS: Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G(1) arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis.
    CONCLUSION AND IMPLICATIONS: The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G(1) phase cell cycle arrest, coupled with induction of apoptosis.
  16. Maulidiani, Abas F, Khatib A, Perumal V, Suppaiah V, Ismail A, et al.
    J Ethnopharmacol, 2016 Mar 2;180:60-9.
    PMID: 26775274 DOI: 10.1016/j.jep.2016.01.001
    'Pegaga' is a traditional Malay remedy for a wide range of complaints. Among the 'pegaga', Centella asiatica has been used as a remedy for diabetes mellitus. Thus, we decided to validate this claim by evaluating the in vivo antidiabetic property of C. asiatica (CA) on T2DM rat model using the holistic (1)H NMR-based metabolomics approach.
  17. Abdullah MA, Ariff AB, Marziah M, Ali AM, Lajis NH
    J Agric Food Chem, 2000 Sep;48(9):4432-8.
    PMID: 10995375
    The effects of medium strategy, number of impellers, aeration mode, and mode of operation on Morinda elliptica cell suspension cultures in a stirred-tank bioreactor are described. A lower number of impellers and continuous aeration contributed toward high cell growth rate, whereas a higher number of impellers reduced cell growth rate, although not anthraquinone yield. The semicontinuous mode could indirectly imitate the larger scale version of production medium strategy and improved anthraquinone production even with 0. 012% (v/v) antifoam addition. Production medium promoted both growth (maximum dry cell weight of 24.6 g/L) and anthraquinone formation (maximum content of 19.5 mg/g of dry cell weight), without any necessity for antifoam addition. Cultures in production medium or with higher growth rate and anthraquinone production were less acidic than cultures in growth medium or with lower growth rate and anthraquinone production. Using the best operating variables, growth of M. elliptica cells (24.6 g/L) and anthraquinone yield (0.25 g/L) were 45% and 140%, respectively, lower than those using a shake flask culture after 12 days of cultivation.
  18. Israf DA, Lajis NH, Somchit MN, Sulaiman MR
    Life Sci, 2004 Jun 11;75(4):397-406.
    PMID: 15147827
    An experiment was conducted with the objective to enhance mucosal immunity against ovalbumin (OVA) by co-administration of OVA with an aqueous extract from the fruit of Solanum torvum (STE). Five groups of female ICR mice aged approximately 8 weeks at the commencement of the experiment were caged in groups of eight and received various treatments. The treatments included OVA alone, OVA with cholera toxin (CT), and OVA with various doses of STE. Mice were primed intraperitoneally with 500 microg of OVA alone or co-administered with 0.1 microg CT, or with 1 microg STE. All mice were boosted orally via gastric intubation 14 days after priming with 10 mg OVA alone, or co-administered with 10 microg CT or with 10 mg, 1 mg or 0.1 mg STE. One week later all mice were killed and organs obtained for analysis of the immune response. Intestinal, faecal and pulmonary OVA-specific sIgA concentration was significantly increased (p<0.05) in mice that received booster combinations of OVA/CT and OVA with all extract doses (p<0.05). Specific serum IgG titres did not differ significantly between groups. It is concluded that STE can significantly enhance secretory immunity in the intestine to OVA with mucosal homing to the lungs. The adjuvant effect of STE is comparable to that of CT.
  19. Ismail NI, Othman I, Abas F, H Lajis N, Naidu R
    Molecules, 2020 Aug 20;25(17).
    PMID: 32825505 DOI: 10.3390/molecules25173798
    The cytotoxic and apoptotic effects of turmeric (Curcuma longa) on colon cancer have been well documented but specific structural modifications of curcumin have been shown to possess greater growth-suppressive potential on colon cancer than curcumin. Therefore, the aim of this study is to identify the anti-cancer properties of curcumin analogue-MS13, a diarylpentanoid on the cytotoxicity, anti-proliferative and apoptotic activity of primary (SW480) and metastatic (SW620) human colon cancer cells. A cell viability assay showed that MS13 has greater cytotoxicity effect on SW480 (EC50: 7.5 ± 2.8 µM) and SW620 (EC50: 5.7 ± 2.4 µM) compared to curcumin (SW480, EC50: 30.6 ± 1.4 µM) and SW620, EC50: 26.8 ± 2.1 µM). Treatment with MS13 at two different doses 1X EC50 and 2X EC50 suppressed the colon cancer cells growth with lower cytotoxicity against normal cells. A greater anti-proliferative effect was also observed in MS13 treated colon cancer cells compared to curcumin at 48 and 72 h. Subsequent analysis on the induction of apoptosis showed that MS13 treated cells exhibited morphological features associated with apoptosis. The findings are also consistent with cellular apoptotic activities shown by increased caspase-3 activity and decreased Bcl-2 protein level in both colon cancer cell lines. In conclusion, MS13 able to suppress colon cancer cell growth by inhibiting cell proliferation and induce apoptosis in primary and metastatic human colon cancer cells.
  20. Israf DA, Khaizurin TA, Syahida A, Lajis NH, Khozirah S
    Mol Immunol, 2007 Feb;44(5):673-9.
    PMID: 16777230
    Cardamonin, a chalcone isolated from the fruits of a local plant Alpinia rafflesiana, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we evaluated the ability of cardamonin to suppress both NO and PGE2 synthesis, iNOS and COX-2 expression and enzymatic activity, and key molecules in the NF-kappaB pathway in order to determine its molecular target. Cardamonin suppressed the production of NO and PGE2 in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells. This inhibition was demonstrated to be caused by a dose-dependent down-regulation of both inducible enzymes, iNOS and COX-2, without direct effect upon iNOS or COX-2 enzyme activity. Subsequently we determined that the inhibition of inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation and degradation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation. We conclude that cardamonin is a potential anti-inflammatory drug lead that targets the NF-kappaB pathway.
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