Displaying publications 21 - 37 of 37 in total

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  1. Antituberculosis potential of some ethnobotanically selected Malaysian plants
    Mohamad S, Zin NM, Wahab HA, Ibrahim P, Sulaiman SF, Zahariluddin AS, et al.
    J Ethnopharmacol, 2011 Feb 16;133(3):1021-6.
    PMID: 21094237 DOI: 10.1016/j.jep.2010.11.037
    Many local plants are used in Malaysian traditional medicine to treat respiratory diseases including symptoms of tuberculosis. The aim of the study was to screen 78 plant extracts from 70 Malaysian plant species used in traditional medicine to treat respiratory diseases including symptoms of tuberculosis for activity against Mycobacterium tuberculosis H37Rv using a colorimetric microplate-based assay.
  2. Andrographolide and 14-deoxy-11, 12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells
    Ooi JP, Kuroyanagi M, Sulaiman SF, Muhammad TS, Tan ML
    Life Sci, 2011 Feb 28;88(9-10):447-54.
    PMID: 21219911 DOI: 10.1016/j.lfs.2010.12.019
    Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells.
  3. Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line
    Tan ML, Sulaiman SF, Najimuddin N, Samian MR, Muhammad TS
    J Ethnopharmacol, 2005 Jan 4;96(1-2):287-94.
    PMID: 15588681
    Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Here, we report the cytotoxicity activity and the mechanism of cell death exhibited by the methanol extract prepared from Pereskia bleo (Kunth) DC. (Cactaceae) plant against human breast carcinoma cell line, T-47D. In vitro cytotoxicity screening of methanol extract of Pereskia bleo plant indicated the presence of cytotoxicity activity of the extract against T-47D cells with EC50 of 2.0 microg/ml. T-47D cell death elicited by the extract was found to be apoptotic in nature based a clear indication of DNA fragmentation which is a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics (the presence of chromatin margination and apoptotic bodies) in the extract-treated cells. RT-PCR analysis showed the mRNA expression levels of c-myc, and caspase 3 were markedly increased in the cells treated with the plant extract. However, p53 expression was only slightly increased as compared to caspase 3 and c-myc. Thus, the results from this study strongly suggest that the methanol extract of Pereskia bleo may contain bioactive compound(s) that caused breast carcinoma, T-47D cell death by apoptosis mechanism via the activation of caspase-3 and c-myc pathways.
  4. The inhibitory effects of mitragynine on P-glycoprotein in vitro
    Rusli N, Amanah A, Kaur G, Adenan MI, Sulaiman SF, Wahab HA, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2019 04;392(4):481-496.
    PMID: 30604191 DOI: 10.1007/s00210-018-01605-y
    Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 μM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.
  5. The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression
    Teah YF, Abduraman MA, Amanah A, Adenan MI, Sulaiman SF, Tan ML
    Food Chem Toxicol, 2017 Sep;107(Pt A):293-301.
    PMID: 28689918 DOI: 10.1016/j.fct.2017.07.011
    Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr blocker.
  6. In Vitro Efficacy of Aqueous and Methanol Extract of Cassia siamea Against the Motility of Caenorhabditis elegans
    Gagman HA, Him NAIIN, Ahmad H, Sulaiman SF, Zakaria R, Termizi FHM
    Trop Life Sci Res, 2020 Oct;31(3):145-159.
    PMID: 33214861 DOI: 10.21315/tlsr2020.31.3.10
    Gastrointestinal nematode infections can cause great losses in revenue due to decrease livestock production and animal death. The use of anthelmintic to control gastrointestinal nematode put a selection pressure on nematode populations which led to emergence of anthelmintic resistance. Because of that, this study was carried out to investigate the efficacy of aqueous and methanol extract of Cassia siamea against the motility of C. elegans Bristol N2 and C. elegans DA1316. Caenorhabditis elegans Bristol N2 is a susceptible strain and C. elegans DA1316 is an ivermectin resistant strain. In vitro bioassay of various concentrations of (0.2, 0.6, 0.8, 1.0 and 2.0 mg mL-1) aqueous and methanol extracts of C. siamea was conducted against the motility of L4 larvae of C. elegans Bristol N2 and C. elegans DA1316. The L4 larvae were treated with 0.02 μg mL-1 of ivermectin served as positive control while those in M9 solution served as negative control. The activity of the extracts was observed after 24 h and 48 h. A significant difference was recorded in the extract performance compared to control at (P < 0.001) after 48 h against the motility of the larvae of both strains. The methanol extracts inhibited the motility of C. elegans Bristol N2 by 86.7% as well as DA1316 up to 84.9% at 2.0 mg mL-1 after 48 h. The methanol extract was more efficient than aqueous extract (P < 0.05) against the motility of both strains of C. elegans. Cassia siamea may be used as a natural source of lead compounds for the development of alternative anthelmintic against parasitic nematodes as well ivermectin resistant strains of nematodes.
  7. Insight into potential mechanisms of hypobaric hypoxia-induced learning and memory deficit - Lessons from rat studies
    Qaid E, Zakaria R, Sulaiman SF, Yusof NM, Shafin N, Othman Z, et al.
    Hum Exp Toxicol, 2017 Dec;36(12):1315-1325.
    PMID: 28111974 DOI: 10.1177/0960327116689714
    Impairment of memory is one of the most frequently reported symptoms during sudden hypoxia exposure in human. Cortical atrophy has been linked to the impaired memory function and is suggested to occur with chronic high-altitude exposure. However, the precise molecular mechanism(s) of hypoxia-induced memory impairment remains an enigma. In this work, we review hypoxia-induced learning and memory deficit in human and rat studies. Based on data from rat studies using different protocols of continuous hypoxia, we try to elicit potential mechanisms of hypobaric hypoxia-induced memory deficit.
  8. Chemopreventive effects of standardized papaya leaf fraction on oxidatively stressed human liver cells
    Tan SA, Goya L, Ramanathan S, Sulaiman SF, Alam M, Navaratnam V
    Food Res Int, 2014 Oct;64:387-395.
    PMID: 30011665 DOI: 10.1016/j.foodres.2014.06.040
    Extract from papaya leaves, a waste material from fruit farms in Malaysia was previously reported to possess remarkable antioxidative activities. In this study, papaya leaf extract was separated into fractions of different polarities [petroleum ether (PE), ethyl acetate (EA), n-butanol (NB) and water (W) fractions]. The aim of this research was to determine the most active fraction in terms of its chemopreventive effects towards oxidative stress and the chemical constituents involved. The cytoprotective nature of the papaya fractions was observed against t-BOOH-induced oxidative stress on HepG2 liver cell line. ROS assay indicated that only PE and EA effectively reduced the increment of radical due to the pro-oxidant, t-BOOH. Nevertheless, PE was a stronger ROS scavenger by demonstrating ROS reducing activity in a dose-dependent manner to the basal level. This fraction was also found to inhibit cell death caused by t-BOOH toxicity, attenuating lactate dehydrogenase enzyme leakage by more than 90% (p<0.05). In addition, gene expression of phase II antioxidant enzymes (hmox-1 and nqo-1) and their transcription factor (nrf-2) were shown to be upregulated upon PE treatment during a time-course study. A GC-MS fingerprint of the active fraction was subsequently obtained with standardization using the marker compound; α-tocopherol, a well known antioxidant. However, this pure compound was not as effective as its corresponding PE concentrations in ROS reduction. Hence, PE of papaya leaf extract was a strong antioxidant and cytoprotectant with tremendous potential to be harnessed into the next therapeutic remedy against oxidative stress of the liver.
  9. The regulatory effects of mitragynine on P-glycoprotein transporter
    Abduraman MA, Amanah A, Hamid SBS, Abdullah MFIL, Sulaiman SF, Tan ML
    J Pharm Pharmacol, 2024 Nov 14.
    PMID: 39541262 DOI: 10.1093/jpp/rgae131
    OBJECTIVES: Kratom preparation containing Mitragyna speciosa Korth plant is frequently used as a recreational drug. Mitragynine, a major alkaloid isolated from M. speciosa, is often detected concurrently with other drugs during forensic analysis, indicating a safety concern. P-glycoprotein (P-gp) is a multidrug transporter. Modulation of P-gp transport activity by drugs or herbal compounds in the brain may lead to drug-herb interactions, resulting in neurotoxicity. We aim to determine the effects of mitragynine on the P-gp regulation and possible neurotoxicity.

    METHODS: The effects of mitragynine on the P-gp regulation were investigated in human brain capillary endothelial cells (hCMEC/D3) using molecular docking and dynamic simulation and an optimized bidirectional transport assay, respectively. Repeated-dose treatment and neurotoxicity assessment were carried out using a blood-brain barrier model and polimerase chain reaction (PCR) array.

    KEY FINDINGS: Mitragynine inhibits the P-gp transport activity via binding onto the nucleotide-binding domain site and forms a stable interaction with the P-gp protein complex. Nontoxic concentrations of mitragynine (<4 μM) and substrate drugs (0.001 μM) in the cells significantly enhanced endothelial cell permeability and elicited signs of neurotoxicity in PC-12 cells.

    CONCLUSIONS: Mitragynine is likely a P-gp inhibitor, hence concurrent administration of kratom products with P-gp substrates may lead to clinically significant interactions and neurotoxicity.

  10. Bioassay-Guided Fractionation of Acetone and Methanol Extracts of Quercus infectoria Galls with Antimalarial Properties
    Hamidon NH, Dona ACT, Zin NNINM, Nordin NI, Sulaiman SF, Abu-Bakar N
    Trop Life Sci Res, 2024 Jul;35(2):167-185.
    PMID: 39234468 DOI: 10.21315/tlsr2024.35.2.8
    The antimalarial properties of crude extracts from Quercus infectoria galls were investigated through bioassay-guided fractionation. Acetone (QIA) and methanol (QIM) crude extracts have been reported to have promising antimalarial activity against Plasmodium falciparum (3D7 strain). These extracts were subjected to fractionation using automated preparative high-performance liquid chromatography (prep-HPLC) to identify the most active fractions. Nine fractions were isolated from each extract, of which the fractions QIA11 and QIM16 showed antimalarial activity, with IC50 values of 17.65 ± 1.82 μg/mL and 24.21 ± 1.88 μg/mL, respectively. In comparison, the standard antimalarial drug artemisinin has an IC50 value of 0.004 ± 0.001 μg/mL). Through high-resolution liquid chromatography coupled with mass spectrometry (HR-LCMS) analysis of the fractions, four known compounds were successfully identified: gallic acid, ellagic acid, 1,3,6-tris-o-(3,4,5-trihydroxybenzoyl)-beta-d-glucose and 1-O,6-O-digalloyl-beta-D-glucose.
  11. A new chalcone structure of (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl)prop-2-en-1-one: Synthesis, structural characterizations, quantum chemical investigations and biological evaluations
    Thanigaimani K, Arshad S, Khalib NC, Razak IA, Arunagiri C, Subashini A, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Oct 5;149:90-102.
    PMID: 25942090 DOI: 10.1016/j.saa.2015.04.028
    The structure of (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl)prop-2-en-1-one (C19H13BrO) crystallized in the triclinic system of P-1 space group. The unit cell dimensions are: a=5.8944 (9)Å, b=7.8190 (12)Å, c=16.320 (2)Å, α=102.4364 (19)°, β=95.943 (2)°, γ=96.274 (2)° and Z=2. The physical properties of this compound was determined by the spectroscopic methods (FTIR and (1)H and (13)C NMR). Quantum chemical investigations have been employed to investigate the structural and spectral properties. The molecular structure, vibrational assignments, (1)H and (13)C NMR chemical shift values, non-linear optical (NLO) effect, HOMO-LUMO analysis and natural bonding orbital (NBO) analysis were calculated using HF and DFT/B3LYP methods with 6-311++G(d,p) basis set in the ground state. The results show that the theoretical calculation of the geometrical parameters, vibrational frequencies and chemical shifts are comparable with the experimental data. The crystal structure is influenced and stabilized by weak C-H⋯π interactions connecting the molecules into infinite supramolecular one dimensional ladder-like arrangement. Additionally, this compound is evaluated for their antibacterial activities against gram positive and gram negative strains using a micro dilution procedure and shows activities against a panel of microorganisms.
  12. Fulltext Tualang Honey Ameliorates Hypoxia-induced Memory Deficits by Reducing Neuronal Damage in the Hippocampus of Adult Male Sprague Dawley Rats
    Qaid EYA, Zakaria R, Mohd Yusof NA, Sulaiman SF, Shafin N, Othman Z, et al.
    Turk J Pharm Sci, 2020 Oct;17(5):555-564.
    PMID: 33177938 DOI: 10.4274/tjps.galenos.2019.32704
    Objectives: A growing body of evidence indicates that hypoxia exposure causes learning and memory deficits. An effective natural therapeutic approach has, however, not been explored widely. Our previous studies found that Tualang honey administration protected learning and memory functions in ovariectomized rats. Therefore, the present study investigated its efficacy in ameliorating hypoxia-induced memory deficits in adult male Sprague Dawley rats.

    Materials and Methods: The rats were divided into four groups: i) Normoxia treated with sucrose (n=12), ii) Normoxia treated with Tualang honey (n=12), iii) Hypoxia treated with sucrose (n=12), and iv) Hypoxia treated with Tualang honey (n=12). Tualang honey (0.2 g/kg/BW) and sucrose (1 mL of 7.9%) supplementations were administered orally to the rats daily for 14 days. Then the hypoxia groups were exposed to hypoxia (~11%) for 7 days, while the normoxia groups were kept in normal conditions. Following exposure to hypoxia, the rats' memories were analyzed using a novel object recognition task and T-maze test.

    Results: The data revealed that rats exposed to hypoxia showed significant impairment in short-term memory (STM), spatial memory (p<0.01), and long-term memory (LTM) when compared to the normoxia group. Hypoxia rats treated with Tualang honey showed significant improvement in STM, LTM, and spatial memory (p<0.05) compared with those treated with sucrose (p<0.05). Tualang honey also reduced neuronal damage in the hippocampus of adult male Sprague Dawley rats exposed to hypoxia.

    Conclusion: It is suggested that Tualang honey pretreatment has protective effects against hypoxia-induced memory deficits, possibly through its antioxidant contents.

  13. Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity
    Lee WT, Tan BK, Eng SA, Yuen GC, Chan KL, Sim YK, et al.
    Food Funct, 2019 Sep 01;10(9):5759-5767.
    PMID: 31453615 DOI: 10.1039/c9fo01357a
    A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity. Black sea cucumber (Holothuria atra) is a tropical sea cucumber species traditionally consumed as a remedy for many ailments. There is a paucity of knowledge on the anti-infective capacity of H. atra and the underlying mechanisms involved. The objective of this study is to utilize the Caenorhabditis elegans-P. aeruginosa infection model to elucidate the anti-infective properties of H. atra. A bioactive H. atra extract and subsequently its fraction were shown to have the capability of promoting the survival of C. elegans during a customarily lethal P. aeruginosa infection. The same entities also attenuate the production of elastase, protease, pyocyanin and biofilm in P. aeruginosa. The treatment of infected transgenic lys-7::GFP worms with this H. atra fraction restores the repressed expression of the defense enzyme lys-7, indicating an improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid, and inosine in this fraction. Collectively, our findings show that H. atra possesses anti-infective properties against P. aeruginosa infection, by inhibiting pathogen virulence and, eventually, reinstating host lys-7 expression.
  14. Evaluation of in vitro cytochrome P450 induction and inhibition activity of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber L
    Koe XF, Lim EL, Seah TC, Amanah A, Wahab HA, Adenan MI, et al.
    Food Chem Toxicol, 2013 Oct;60:98-108.
    PMID: 23876819 DOI: 10.1016/j.fct.2013.07.030
    Drug metabolism involving cytochrome P450 (CYP) enzymes is a key determinant of significant drug interactions. Deoxyelephantopin was evaluated for its effects on the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4, and protein expression and resultant enzymatic activity. The mRNA and protein expression of cytochrome isoforms were carried out using an optimized multiplex qRT-PCR assay and Western blot analysis, respectively. Human CYP3A4 protein expression was determined using an optimized hCYP3A4-HepG2 cell-based assay and the enzymatic activity was evaluated using P450-Glo™ CYP3A4 assay. The molecular interaction and possible inhibition of deoxyelephantopin of the CYP3A4 enzyme was determined in silico and further validated using substrate-specific CYP3A4 inhibition assays. Deoxyelephantopin produced no significant effect on the CYP1A2 and CYP2D6 mRNA and protein expression. However, it has a weak induction effect on CYP3A4 at the transcriptional level. In silico docking simulation showed that deoxyelephantopin has a weak interaction with CYP3A4 enzyme and it minimally affects the metabolism of CYP3A4 substrates. Deoxyelephantopin is not an in vitro CYP1A2 and CYP2D6 inducer. It is both a weak in vitro CYP3A4 inducer and inhibitor and is unlikely to elicit a clinically significant effect in human.
  15. Spectaflavoside A, a new potent iron chelating dimeric flavonol glycoside from the rhizomes of Zingiber spectabile Griff
    Sivasothy Y, Hadi AH, Mohamad K, Leong KH, Ibrahim H, Sulaiman SF, et al.
    Bioorg Med Chem Lett, 2012 Jun 1;22(11):3831-6.
    PMID: 22546674 DOI: 10.1016/j.bmcl.2012.02.064
    The rhizomes of Zingiber spectabile yielded a new dimeric flavonol glycoside for which the name kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside-(I-6,II-8)-kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside; spectaflavoside A (1) was proposed, along with kaempferol and its four acetylrhamnosides (2-6), demethoxycurcumin (7) and curcumin (8). The structure of spectaflavoside A was elucidated by spectroscopic methods including, 1D and 2D NMR techniques. This is the first report on the occurrence of a dimeric flavonol glycoside in the Zingiberaceae and the second in nature. Spectaflavoside A was found to be a potent iron chelating agent.
  16. Fulltext Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities
    Kumar CS, Then LY, Chia TS, Chandraju S, Win YF, Sulaiman SF, et al.
    Molecules, 2015 Sep 11;20(9):16566-81.
    PMID: 26378514 DOI: 10.3390/molecules200916566
    A series of five new 2-(1-benzofuran-2-yl)-2-oxoethyl 4-(un/substituted)benzoates 4(a-e), with the general formula of C₈H₅O(C=O)CH₂O(C=O)C₆H₄X, X = H, Cl, CH₃, OCH₃ or NO₂, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a-e) were characterized by FTIR, ¹H-, (13)C- and ¹H-(13)C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% ± 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% ± 1.06%) in metal chelating (MC) activity.
  17. Swietenia macrophylla extract promotes the ability of Caenorhabditis elegans to survive Pseudomonas aeruginosa infection
    Dharmalingam K, Tan BK, Mahmud MZ, Sedek SA, Majid MI, Kuah MK, et al.
    J Ethnopharmacol, 2012 Jan 31;139(2):657-63.
    PMID: 22193176 DOI: 10.1016/j.jep.2011.12.016
    Swietenia macrophylla or commonly known as big leaf mahogany, has been traditionally used as an antibacterial and antifungal agent.
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