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  1. Fulltext An inhibited dopamine synthesizing cell model of AADC deficiency
    Melati Khalid, Mohamad Aris Mohd Moklas
    Life Sciences, Medicine and Biomedicine, 2019;3(2):1-7.
    MyJurnal
    Aromatic L-amino acid decarboxylase deficiency (AADC) is a rare autosomal recessive pediatric neurotransmitter disease. To date it remains poorly understood mainly due to an absence of a disease model. The dopaminergic neuroblastoma cell SH-SY5Y was chosen to develop our AADC deficiency model. These cells are not native dopamine synthesizers. Objective: To develop a dopamine-producing cellular model of AADC deficiency using SH-SY5Y neuroblastoma cells. Methods: Dopamine pathway proteins were identified with Western Blotting. Dopaminergic differentiation was attempted using all-trans retinoic acid (ATRA) with dopamine detection via HPLC-ECD post alumina extraction. Treatment with L-DOPA provided SH-SY5Y with excess precursor. RT-PCR was used to determine the expression of markers of mature neurons. Results: Western Blot screening identified AADC, dopamine β-hydroxylase and tyrosine hyrdoxylase proteins, indicative of a dopaminergic pathway. ATRA was unsuccessful in producing dopamine from the cells. L-DOPA treatment however, generated dopamine first visible as a HPLC-ECD peak 30 minutes post-incubation. Prior to this, SH-SY5Y dopamine synthesis from L-DOPA has never been documented. This de novo synthesis is then inhibited using benserazide to form our AADC deficiency cell model. RT-PCR showed that SH-SY5Y cells express markers of mature neurons in its ‘native’ state and is not affected by L-DOPA and benserazide treatment. This cell model will potentially benefit many areas of AADC deficiency research. Conclusion: SH-SY5Y cells produced HPLC-ECD measureable amounts of dopamine with the addition of L-DOPA. Our model of AADC deficiency is generated by quelling the dopamine production with Benserazide.
  2. Fulltext Anatomical variations of thenar muscle of hand, among Cadavers In Universiti Putra Malaysia (UPM)
    Che Norma Mat Taib, Jegathis Prushothuman, Muhammad Adib Farhan Abdullah, Mohamad Aris, Mohd Moklas
    Malaysian Journal of Medicine and Health Sciences, 2019;15(107):86-86.
    MyJurnal
    Introduction: Detailed information of structural and functional anatomy of thenar muscle is very significant in order to improve diagnostic and various conditions of hand surgeries so that the function of hand movement can be re-stored and to prevent further iatrogenic injuries. Methods: In this study, fifty hands were dissected to determine the variation in each of the thenar muscle. Results: Only the abductor pollicis brevis showed significant findings. Normal formation of one belly in abductor pollicis brevis represented 72.0% (18) and 84.0% (21) for the left and right hands, respectively. Variations according to the number of belly of the abductor pollicis brevis were also observed. One of the variations is the absence of the abductor pollicis brevis, 4.0% (1) in the right hand. Two belly formations of abductor pollicis brevis were observed, 28.0% (7) and 12.0% (3) for left and right sides of hand respectively. Thus, more variations were observed to occur on the left hand (7) compared to the right hand (4). Many studies describe about the variations of each thenar muscle, but few literatures were found discussing on the association of thenar muscle variation with the sides of hand. Using the Fisher Exact Test, it showed that there was no significant associa-tion of variations in the thenar muscle in relation to the sides of hand. Conclusion: This study conclude that there is no consistency between variations of the thenar muscle in relation to the sides of hand. However, clinical awareness of these variations is important in the context of compartment syndrome, use of the aberrant structures as grafting material in reconstructive surgery and proper interpretation of imaging modalities.
  3. Fulltext Morphological Changes and Cellular Uptake of Functionalized Graphene Oxide Loaded with Protocatechuic Acid and Folic Acid in Hepatocellular Carcinoma Cancer Cell
    Buskaran K, Hussein MZ, Mohd Moklas MA, Fakurazi S
    Int J Mol Sci, 2020 Aug 16;21(16).
    PMID: 32824281 DOI: 10.3390/ijms21165874
    The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to ensure successful utilisation of the nanocomposites. Studies have suggested that the nanocomposites' ability to permeate into biological cells is attributable to their well-defined physicochemical properties with nanoscale size, which is relevant to the nanoscale components of biology and cellular organelles. The functionalized graphene oxide coated with polyethylene glycol, loaded with protocatechuic acid and folic acid (GOP-PCA-FA) nanocomposite intracellular uptake was analysed using transmission electron microscope. The accumulation of fluorescent-labelled nanocomposites in the HepG2 cell was also analysed using a fluorescent microscope. In vitro cellular uptake showed that there was uptake of the drug from 24 h into the cells and the release study using fluorescently tagged nanocomposite demonstrated that release and accumulation were observed at 24 h and 48 h. Moreover, the migration ability of tumor cells is a key step in tumor progression which was observed 48 h after treatment. The GOP serves as a potential nanocarrier system which is capable of improving the therapeutic efficacy of drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated drugs. Nonetheless, it is essential to analyse the translocation of our newly developed GOP-PCA-FA, and its efficiency for drug delivery, effective cellular uptake, and abundant intracellular accumulation would be compromised by possible untoward side effects.
  4. Fulltext Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats
    Suliman NA, Taib CNM, Moklas MAM, Basir R
    Neurotox Res, 2018 02;33(2):402-411.
    PMID: 28933048 DOI: 10.1007/s12640-017-9806-x
    Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis. Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured. Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective. Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.
  5. Fulltext Inhibitory Activity of Ficus deltoidea var. trengganuensis Aqueous Extract on Lipopolysaccharide-Induced TNF-α Production from Microglia
    Wang H, Vidyadaran S, Mohd Moklas MA, Baharuldin MTH
    Evid Based Complement Alternat Med, 2017;2017:2623163.
    PMID: 29358962 DOI: 10.1155/2017/2623163
    Objective: To explore the effect of Ficus deltoidea (FD) aqueous extracts on the release of tumor necrosis factor-α (TNF-α), the expression of CD40, and the morphology of microglial cells in lipopolysaccharide- (LPS-) activated BV2 cells.

    Methods: The cytotoxicity of FD extract was assessed by MTS solution. BV2 cells were divided into 5 experimental groups, intervened, respectively, by FD (4 mg/mL) and LPS + FD (0, 1, 2, and 4 mg/mL). Besides, a blank control group was set up without any intervention. TNF-α release was assessed by enzyme linked immunosorbent assay (ELISA). The expression of CD40 was examined by flow cytometry. Immunocytochemical staining was used to show the morphology of BV2 cells.

    Results: FD extract of different concentrations (1, 2, and 4 mg/mL) had no significant toxic effects on the BV2 cells. FD suppressed the activation of microglia in morphology and reduced TNF-α production and expression of CD40 induced by LPS.

    Conclusion: FD extract has a therapeutic potential against neuroinflammatory diseases.

  6. Fulltext Arthroscopic mumford procedure utilizing the anteromedial and neviaser portals – a pilot cadaveric study on neurovascular structures at risk
    Nasir Mohd Nizlan, Azfar Rizal Ahmad, Hisham Abdul Rashid, Paisal Hussin, Che Hamzah Fahrudin, Abdullah Arifaizad, et al.
    Malaysian Journal of Medicine and Health Sciences, 2016;12(2):16-20.
    MyJurnal
    Introduction: Degenerative disorder involving the acromioclavicular
    joint (ACJ) is quite common especially in the elderly.
    One of the surgical modalities of treatment of this disorder is the
    Mumford Procedure. Arthroscopic approach is preferred due to
    its reduced morbidity and faster post-operative recovery. One
    method utilizes the anteromedial and Neviaser portals, which
    allow direct and better visualization of the ACJ from the
    subacromial space. However, the dangers that may arise from
    incision and insertion of instruments through these portals are
    not fully understood. This cadaveric study was carried out to
    investigate the dangers that can arise from utilization of these
    portals and which structures are at risk during this procedure.
    Methods: Arthroscopic Mumford procedures were performed
    on 5 cadaver shoulders by a single surgeon utilizing the
    anteromedial and Neviaser portals. After marking each portals
    with methylene blue, dissection of nearby structures were
    carried out immediately after each procedure was completed.
    Important structures (subclavian artery as well as brachial plexus
    and its branches) were identified and the nearest measurements
    were made from each portal edges to these structures. Results:
    The anteromedial portal was noted to be closest to the
    suprascapular nerve (SSN) at 2.91 cm, while the Neviaser portal
    was noted to be closest also to the SSN at 1.60 cm. The
    suprascapular nerve was the structure most at risk during the
    Mumford procedure. The anteromedial portal was noted to be
    the most risky portal to utilize compared to the Neviaser portal.
    Conclusion: Extra precaution needs to be given to the
    anteromedial portal while performing an arthroscopic distal
    clavicle resection in view of the risk of injuring the
    suprascapular nerve of the affected limb.
  7. Fulltext Crystallographic analysis of ground and space thermostable T1 lipase crystal obtained via counter diffusion method approach
    Mohamad Aris SN, Thean Chor AL, Mohamad Ali MS, Basri M, Salleh AB, Raja Abd Rahman RN
    Biomed Res Int, 2014;2014:904381.
    PMID: 24516857 DOI: 10.1155/2014/904381
    Three-dimensional structure of thermostable lipase is much sought after nowadays as it is important for industrial application mainly found in the food, detergent, and pharmaceutical sectors. Crystallization utilizing the counter diffusion method in space was performed with the aim to obtain high resolution diffracting crystals with better internal order to improve the accuracy of the structure. Thermostable T1 lipase enzyme has been crystallized in laboratory on earth and also under microgravity condition aboard Progress spacecraft to the ISS in collaboration with JAXA (Japanese Aerospace Exploration Agency). This study is conducted with the aims of improving crystal packing and structure resolution. The diffraction data set for ground grown crystal was collected to 1.3 Å resolution and belonged to monoclinic C2 space group with unit cell parameters a = 117.40 Å, b = 80.95 Å, and c = 99.81 Å, whereas the diffraction data set for space grown crystal was collected to 1.1 Å resolution and belonged to monoclinic C2 space group with unit cell parameters a = 117.31 Å, b = 80.85 Å, and c = 99.81 Å. The major difference between the two crystal growth systems is the lack of convection and sedimentation in microgravity environment resulted in the growth of much higher quality crystals of T1 lipase.
  8. Fulltext Exploring potential neuroprotective properties of Aqueous Centella Asiatica extract in chronic stress-induced rats
    Muhamad Zulhusni Abdul Wahab, Muhammad Zaim Zainal Abidin, Fatin Nadzirah Zakaria, Mohamad Aris Mohd Moklas, Zulkhairi Amom, Nina Keterina Hashim, et al.
    Pertanika Journal of Science & Technology, 2019;27(4):1561-1574.
    MyJurnal
    Centella asiatica is one of the traditional herbs consumed by many communities due to its wide range of applications such as treating Parkinsonism, promoting memory enhancement, and preventing oxidative stress. This study was conducted to investigate the neuroprotective potential of aqueous C. asiatica extract (CAE) against neurodegeneration induced by chronic stress. Administration of CAE at three different dosages (200 mg/kg/day, 400 mg/ kg/day and 800 mg/kg/day) was conducted for a period of 21 days along with exposure to chronic stress using restrainer and forced swimming regimes. The administration of CAE significantly improved the thickness of dentate gyrus and reduced the amount of neuronal cell death at dentate gyrus and CA3 (p
  9. Fulltext Antidepressant-like effects of omega-3 fatty acids in postpartum model of depression in rats
    Arbabi L, Baharuldin MT, Moklas MA, Fakurazi S, Muhammad SI
    Behav Brain Res, 2014 Sep 1;271:65-71.
    PMID: 24867329 DOI: 10.1016/j.bbr.2014.05.036
    Postpartum depression (PPD) is a psychiatric disorder that occurs in 10-15% of childbearing women. It is hypothesized that omega-3 fatty acids, which are components of fish oil, may attenuate depression symptoms. In order to examine this hypothesis, the animal model of postpartum depression was established in the present study. Ovariectomized female rats underwent hormone-simulated pregnancy (HSP) regimen and received progesterone and estradiol benzoate or vehicle for 23 days, mimicking the actual rat's pregnancy. The days after hormone termination were considered as the postpartum period. Forced feeding of menhaden fish oil, as a source of omega-3, with three doses of 1, 3, and 9g/kg/d, fluoxetine 15mg/kg/d, and distilled water 2ml/d per rat started in five postpartum-induced and one vehicle group on postpartum day 1 and continued for 15 consecutive days. On postpartum day 15, all groups were tested in the forced swimming test (FST) and open field test (OFT), followed by a biochemical assay. Results showed that the postpartum-induced rats not treated with menhaden fish oil, exhibited an increase in immobility time seen in FST, hippocampal concentration of corticosterone and plasmatic level of corticosterone, and pro-inflammatory cytokines. These depression-related effects were attenuated by supplementation of menhaden fish oil with doses of 3 and 9g/kg. Moreover, results of rats supplemented with menhaden fish oil were comparable to rats treated with the clinically effective antidepressant, fluoxetine. Taken together, these results suggest that menhaden fish oil, rich in omega-3, exerts beneficial effect on postpartum depression and decreases the biomarkers related to depression such as corticosterone and pro-inflammatory cytokines.
  10. Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats
    Sharifudin SA, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P
    Pharm Biol, 2013 Mar;51(3):279-88.
    PMID: 23043505 DOI: 10.3109/13880209.2012.720993
    Moringa oleifera Lam. (Moringaceae) is a rich source of essential minerals and antioxidants; it has been used in human and animal nutrition. The leaves and flowers are being used by the population with great dietary importance.
  11. Fulltext Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system
    Shamima AR, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P
    Int J Mol Sci, 2012;13(9):11427-42.
    PMID: 23109863 DOI: 10.3390/ijms130911427
    Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1) and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt). In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist), naloxone (non-selective opioid antagonist), naltrindole (δ-opioid antagonist) naloxonazine (μ(1)-receptor antagonist) and norbinaltorpimine (κ-opioid antagonist) respectively, prior to administration of MG (35 mg/kg). The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.
  12. Barrier protective effect of asiatic acid in TNF-α-induced activation of human aortic endothelial cells
    Fong LY, Ng CT, Cheok ZL, Mohd Moklas MA, Hakim MN, Ahmad Z
    Phytomedicine, 2016 Feb 15;23(2):191-9.
    PMID: 26926181 DOI: 10.1016/j.phymed.2015.11.019
    Endothelial cell activation is characterized by increased endothelial permeability and increased expression of cell adhesion molecules (CAMs). This allows monocyte adherence and migration across the endothelium to occur and thereby initiates atherogenesis process. Asiatic acid is a major triterpene isolated from Centella asiatica (L.) Urban and has been shown to possess anti-oxidant, anti-hyperlipidemia and anti-inflammatory activities.
  13. Fulltext Antidepressant-Like Properties of Fish Oil on Postpartum Depression-Like Rats Model: Involvement of Serotonergic System
    Abdul Aziz NU, Chiroma SM, Mohd Moklas MA, Adenan MI, Ismail A, Hidayat Baharuldin MT
    Brain Sci, 2020 Oct 13;10(10).
    PMID: 33066310 DOI: 10.3390/brainsci10100733
    Pathophysiology of postpartum depression (PPD) has been associated with many factors, such as neuroendocrine, neuroinflammation and neurotransmitter changes. Fish oil (FO) improves PPD both in humans and animals. However, little is known with regards to its pharmacology on a PPD-like rat model. Hence, the current study aimed at investigating the effects of FO on a PPD-like rat model. Female rats were induced with PPD-like symptoms and then randomly divided into six groups (n = 6) for two experimental protocols. Protocol 1 consisted of PPD-like rats (2 mL distilled water), PPD-like + FO (9 g/kg/d) and PPD-like + Fluoxetine (FLX) (15 mg/kg/d) groups of rats, whereas Protocol 2 consisted of PPD-like rats (2 mL distilled water) + PCPA (p-chlorophenylalanine) 150 mg/kg, PPD-like + FO (9 g/kg/d) + PCPA 150 mg/kg and PPD-like + FLX (15 mg/d) + PCPA 150 mg/kg groups of rats, respectively. All treatments were administered orally for 10 days postpartum, except PCPA, which was given intraperitoneally. Prior to euthanasia, the antidepressant-like effect of the FO was evaluated using the forced swimming test (FST) and open field test (OFT) on day 10 postpartum. Biochemical analysis of serotonin, serotonin metabolite and serotonin turnover from their prefrontal cortex and hippocampus were also measured. The results showed that FO decreased immobility time and increased swimming time significantly, but not climbing time in FST. Further, it also decreased serotonin metabolite and turnover significantly in the hippocampus of the PPD-like rats. In contrast, administration with PCPA reversed all the outcomes. The antidepressant-like effects of FO were found to be similar with that of FLX. Thus, it can be concluded that FO exerts its antidepressant-like effects in PPD-like rats through modulation of serotonergic system.
  14. Fulltext Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
    Buskaran K, Bullo S, Hussein MZ, Masarudin MJ, Mohd Moklas MA, Fakurazi S
    Materials (Basel), 2021 Feb 09;14(4).
    PMID: 33572054 DOI: 10.3390/ma14040817
    Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites' physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP-PCA-FA) in HepG2 cells. In conclusion, GOP-PCA-FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP-PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system.
  15. Fulltext Antioxidant and anti-inflammatory properties of Erythroxylum cuneatum alkaloid leaf extract
    Li LS, Chiroma SM, Hashim T, Adam SK, Mohd Moklas MA, Yusuf Z, et al.
    Heliyon, 2020 Jun;6(6):e04141.
    PMID: 32637674 DOI: 10.1016/j.heliyon.2020.e04141
    Erythroxylum cuneatum (E. cuneatum) which belongs to Erythroxylaceae family is a tropical flowering plant from the genus of Erythroxylum. It is used in Malaysia and Thailand's traditional medicines, yet there is limited scientific reports on its medicinal value. This study aimed at exploring the antioxidative and anti-inflammatory properties of E. cuneatum alkaloid leaf extract. The alkaloid extract was obtained through Soxhlet heat extraction method, while the antioxidantive properties were assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, ferric reducing antioxidant power (FRAP) and xanthine oxidase inhibition (XOI) assays. Further, anti-inflammatory property of the extract was evaluated on rat's model of carrageenan induced paw model of edema via physical measurements and histology. The extract exhibited antioxidant activity with an EC50 value of 1482 μg/ml in the DPPH radical scavenging assay, an EC1 value of 2191 μg/ml in the FRAP assay and 10.15 ± 6.20% in the XOI assay. Rats pretreated with the extract have shown dose dependent decrease in paw edema when compared to non-treated group of rats. The highest dose (50 mg/kg) of extract exhibited similar effects to aspirin in terms of reducing paw thickness, leucocytes infiltration and disruption of collagen. In conclusion, the E. cuneatum alkaloid leaf extract possesses both antioxidative and anti-inflammatory properties suggesting its potentials for future development of antioxidant and anti-inflammatory drugs.
  16. d-galactose and aluminium chloride induced rat model with cognitive impairments
    Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z
    Biomed Pharmacother, 2018 Jul;103:1602-1608.
    PMID: 29864948 DOI: 10.1016/j.biopha.2018.04.152
    Cognitive impairments and cholinergic dysfunctions have been well reported in old age disorders including Alzheimer's disease (AD). d-galactose (D-gal) has been reported as a senescence agent while aluminium act as a neurotoxic metal, but little is known about their combined effects at different doses. The aim of this study was to establish an animal model with cognitive impairments by comparing the effects of different doses of co-administrated D-gal and aluminium chloride (AlCl3). In this study male albino wistar rats were administered with D-gal 60 mg/kg.bwt intra peritoneally (I.P) injected and AlCl3 (100, 200, or 300 mg/kg.bwt.) was orally administered once daily for 10 consecutive weeks. Performance of the rats were evaluated through behavioural assessments; Morris water maze (MWM) and open field tests (OFT); histopathological examination was performed on the hippocampus; moreover biochemical measurements of acetylcholinesterase (AChE) and hyperphosphorylated tau protein (p-tau) were examined. The results of this experiment on rats treated with D-gal 60 + AlCl3 200 mg/kg.bwt showed near ideal cognitive impairments. The rats exhibited an obvious memory and learning deficits, marked neuronal loss in hippocampus, showed increase in AChE activities and high expression of p-tau within the tissues of the brain. This study concludes that D-gal 60 + AlCl3 200 mg/kg.bwt as the ideal dose for mimicking AD like cognitive impairments in albino wistar rats. It is also crucial to understand the pathogenesis of this neurodegenerative disease and for drug discovery.
  17. Interferon-Gamma Increases Endothelial Permeability by Causing Activation of p38 MAP Kinase and Actin Cytoskeleton Alteration
    Ng CT, Fong LY, Sulaiman MR, Moklas MA, Yong YK, Hakim MN, et al.
    J Interferon Cytokine Res, 2015 Jul;35(7):513-22.
    PMID: 25830506 DOI: 10.1089/jir.2014.0188
    Interferon-gamma (IFN-γ) is known to potentiate the progression of inflammatory diseases, such as inflammatory bowel disease and atherosclerosis. IFN-γ has been found to disrupt the barrier integrity of epithelial and endothelial cell both in vivo and in vitro. However, the mechanisms of IFN-γ underlying increased endothelial cell permeability have not been extensively elucidated. We reported that IFN-γ exhibits a biphasic nature in increasing endothelial permeability. The changes observed in the first phase (4-8 h) involve cell retraction and rounding in addition to condensed peripheral F-actin without a significant change in the F-/G-actin ratio. However, cell elongation, stress fiber formation, and an increased F-/G-actin ratio were noticed in the second phase (16-24 h). Consistent with our finding from the permeability assay, IFN-γ induced the formation of intercellular gaps in both phases. A delayed phase of increased permeability was observed at 12 h, which paralleled the onset of cell elongation, stress fiber formation, and increased F-/G-actin ratio. In addition, IFN-γ stimulated p38 mitogen-activated protein (MAP) kinase phosphorylation over a 24 h period. Inhibition of p38 MAP kinase by SB203580 prevented increases in paracellular permeability, actin rearrangement, and increases in the F-/G-actin ratio caused by IFN-γ. Our results suggest that p38 MAP kinase is activated in response to IFN-γ and causes actin rearrangement and altered cell morphology, which in turn mediates endothelial cell hyperpermeability. The F-/G-actin ratio might be involved in the regulation of actin distribution and cell morphology rather than the increased permeability induced by IFN-γ.
  18. Fulltext The combination of mitragynine and morphine prevents the development of morphine tolerance in mice
    Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P
    Molecules, 2013 Jan 04;18(1):666-81.
    PMID: 23292329 DOI: 10.3390/molecules18010666
    Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.
  19. Fulltext Graphene Oxide Loaded with Protocatechuic Acid and Chlorogenic Acid Dual Drug Nanodelivery System for Human Hepatocellular Carcinoma Therapeutic Application
    Buskaran K, Hussein MZ, Moklas MAM, Masarudin MJ, Fakurazi S
    Int J Mol Sci, 2021 May 28;22(11).
    PMID: 34071389 DOI: 10.3390/ijms22115786
    Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that responsible for 75-90% of all liver cancer in humans. Nanotechnology introduced the dual drug nanodelivery method as one of the initiatives in nanomedicine for cancer therapy. Graphene oxide (GO) loaded with protocatechuic acid (PCA) and chlorogenic acid (CA) have shown some anticancer activities in both passive and active targeting. The physicochemical characterizations for nanocomposites were conducted. Cell cytotoxicity assay and lactate dehydrogenase were conducted to estimate cell cytotoxicity and the severity of cell damage. Next, nanocomposite intracellular drug uptake was analyzed using a transmission electron microscope. The accumulation and localization of fluorescent-labelled nanocomposite in the human hepatocellular carcinoma (HepG2) cells were analyzed using a fluorescent microscope. Subsequently, Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Cell cycle arrest was ascertained at the G2/M phase. There was the depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. In conclusion, HepG2 cells treated with a graphene oxide-polyethylene glycol (GOP)-PCA/CA-FA dual drug nanocomposite exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid, chlorogenic acid and GOP-PCA/CA nanocomposite, may be due to the utilization of a folic acid-targeting nanodrug delivery system.
  20. Fulltext Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic
    Suliman NA, Mat Taib CN, Mohd Moklas MA, Adenan MI, Hidayat Baharuldin MT, Basir R
    Evid Based Complement Alternat Med, 2016;2016:4391375.
    PMID: 27656235 DOI: 10.1155/2016/4391375
    Nootropics or smart drugs are well-known compounds or supplements that enhance the cognitive performance. They work by increasing the mental function such as memory, creativity, motivation, and attention. Recent researches were focused on establishing a new potential nootropic derived from synthetic and natural products. The influence of nootropic in the brain has been studied widely. The nootropic affects the brain performances through number of mechanisms or pathways, for example, dopaminergic pathway. Previous researches have reported the influence of nootropics on treating memory disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Those disorders are observed to impair the same pathways of the nootropics. Thus, recent established nootropics are designed sensitively and effectively towards the pathways. Natural nootropics such as Ginkgo biloba have been widely studied to support the beneficial effects of the compounds. Present review is concentrated on the main pathways, namely, dopaminergic and cholinergic system, and the involvement of amyloid precursor protein and secondary messenger in improving the cognitive performance.
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