Displaying publications 1 - 20 of 105 in total

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  1. Rehiman SH, Lim SM, Neoh CF, Majeed ABA, Chin AV, Tan MP, et al.
    Ageing Res Rev, 2020 07;60:101066.
    PMID: 32294542 DOI: 10.1016/j.arr.2020.101066
    In order to gauge the impact of proteomics in discovery of Alzheimer's disease (AD) blood-based biomarkers, this study had systematically reviewed articles published between 1984-2019. Articles that fulfilled the inclusion criteria were assessed for risk of bias. A meta-analysis was performed for replicable candidate biomarkers (CB). Of the 1651 articles that were identified, 17 case-control and two cohort studies, as well as three combined case-control and longitudinal designs were shortlisted. A total of 207 AD and mild cognitive impairment (MCI) CB were discovered, with 48 reported in >2 studies. This review highlights six CB, namely alpha-2-macroglobulin (α2M)ps, pancreatic polypeptide (PP)ps, apolipoprotein A-1 (ApoA-1)ps, afaminp, insulin growth factor binding protein-2 (IGFBP-2)ps and fibrinogen-γ-chainp, all of which exhibited consistent pattern of regulation in >three independent cohorts. They are involved in AD pathogenesis via amyloid-beta (Aβ), neurofibrillary tangles, diabetes and cardiovascular diseases (CVD). Meta-analysis indicated that ApoA-1ps was significantly downregulated in AD (SMD = -1.52, 95% CI: -1.89, -1.16, p 
  2. Rashidah NH, Lim SM, Neoh CF, Majeed ABA, Tan MP, Khor HM, et al.
    Ageing Res Rev, 2022 Dec;82:101744.
    PMID: 36202312 DOI: 10.1016/j.arr.2022.101744
    This systematic review appraised previous findings on differential gut microbiota composition and intestinal permeability markers between frail and healthy older adults. A literature search was performed using PubMed, Scopus, ScienceDirect and the Cochrane Library. Relevant studies were shortlisted based on inclusion and exclusion criteria as well as assessed for risk of bias. The primary outcome was the differential composition of gut microbiota and/ or intestinal permeability markers between frail and healthy older adults. A total of 10 case-control studies and one cohort study were shortlisted. Based on consistent findings reported by more than one shortlisted study, the microbiota of frail older adults was characterised by decreased phylum Firmicutes, with Dialister, Lactobacillus and Ruminococcus being the prominent genera. Healthy controls, on the other hand, exhibited higher Eubacterium at the genera level. In terms of intestinal permeability, frail older adults were presented with increased serum zonulin, pro-inflammatory cytokines (TNF-α, HMGB-1, IL-6, IL1-ra, MIP-1β) and amino acids (aspartic acid and phosphoethanolamine) when compared to healthy controls. Altogether, frail elderlies had lower gut microbiota diversity and lower abundance of SCFA producers, which may have led to leaky guts, upregulated pro-inflammatory cytokines, frailty and sarcopenia.
  3. Syakila RN, Lim SM, Agatonovic-Kustrin S, Lim FT, Ramasamy K
    Anal Bioanal Chem, 2019 Feb;411(6):1181-1192.
    PMID: 30680424 DOI: 10.1007/s00216-018-1544-2
    The cholesterol-lowering properties of 12 lactic acid bacteria (LAB) in the absence or presence of 0.3% bile salts were assessed and compared quantitatively and qualitatively in vitro. A new, more sensitive and cost-effective high-performance thin-layer chromatography method combined with digital image evaluation of derivatised chromatographic plates was developed and validated to quantify cholesterol in LAB culture media. The performance of the method was compared with that of the o-phthalaldehyde method. For qualitative assessment, assimilated fluorescently tagged cholesterol was visualised by confocal microscopy. All LAB strains exhibited a cholesterol-lowering effect of various degrees (19-59% in the absence and 14-69% in the presence of bile salts). Lactobacillus plantarum LAB12 and Pentosaceus pentosaceus LAB6 were the two best strains of lactobacilli and pediococci. They lowered cholesterol levels by 59% and 54%, respectively, in the absence and by 69% and 58%, respectively, in the presence of bile salts. Confocal microscopy showed that cholesterol was localised at the outermost cell membranes of LAB12 and LAB6. The present findings warrant in-depth in vivo study. Graphical abstract (A) 3D plots based on scan at 525 nm of (B) derivatized HPTLC plate of separated cholesterol and (C) confocal microscopic image showing the localisation of NBD-cholesterol assimilated by LAB.
  4. Zakaria N, Ramli MZ, Ramasamy K, Meng LS, Yean CY, Banga Singh KK, et al.
    Anal Biochem, 2018 08 15;555:12-21.
    PMID: 29879415 DOI: 10.1016/j.ab.2018.05.031
    A miniaturized biosensing platform, based on monoclonal amyloid-beta antibodies (mAβab) that were immobilized on a disc-shaped platinum/iridium (Pt/Ir) microelectrode surface coupled with an impedimetric signal transducer, was developed for the label-free and sensitive detection of amyloid-beta peptide fragment 1-40 (Aβ40); a reliable biomarker for early diagnosis of Alzheimer's disease (AD). A Pt/Ir microelectrode was electropolymerized with poly (ortho-phenylenediamine), a conducting free amine-containing aromatic polymer; followed by crosslinking with glutaraldehyde for subsequent coupling of mAβab on the microelectrode surface. This modification strategy efficiently improved the impedimetric detection performance of Aβ40 in terms of charge transfer resistance (∼400-fold difference) and normalized impedance magnitude percentage change (∼40% increase) compared with a passive adsorption-based immobilization method. The sensitivity of the micro-immunosensing assay was found to be 1056 kΩ/(pg/mL)/cm2 and the limit of detection was found to be 4.81 pg/mL with a dynamic range of 1-104 pg/mL (R2 = 0.9932). The overall precision of the assay, as measured by relative standard deviation, ranged from 0.84 to 5.15%, demonstrating its reliability and accuracy; while in respect to assay durability and stability, the immobilized mAβab were able to maintain 80% of their binding activity to Aβ40 after incubation for 48 h at ambient temperature (25 °C). To validate the practical applicability, the assay was tested using brain tissue lysates prepared from AD-induced rats. Results indicate that the proposed impedimetric micro-immunosensing platform is highly versatile and adaptable for the quantitative detection of other disease-related biomarkers.
  5. Khoramnia A, Abdullah N, Liew SL, Sieo CC, Ramasamy K, Ho YW
    Anim Sci J, 2011 Feb;82(1):127-35.
    PMID: 21269371 DOI: 10.1111/j.1740-0929.2010.00804.x
    A rotatable central composite design (CCD) was used to study the effect of cryoprotectants (skim milk, sucrose and lactose) on the survival rate of a probiotic Lactobacillus strain, L. reuteri C10, for poultry, during freeze-drying and storage. Using response surface methodology, a quadratic polynomial equation was obtained for response value by multiple regression analyses: Y = 8.59546-0.01038 X(1)-0.09382 X(2)-0.07771 X(3)-0.054861 X(1)(2)-0.04603 X(3)(2)-0.10938 X(1)X(2). Based on the model predicted, sucrose exerted the strongest effect on the survival rate. At various combinations of cryoprotectants, the viability loss of the cells after freeze-drying was reduced from 1.65 log colony forming units (CFU)/mL to 0.26-0.66 log CFU/mL. The estimated optimum combination for enhancing the survival rate of L. reuteri C10 was 19.5% skim milk, 1% sucrose and 9% lactose. Verification experiments confirmed the validity of the predicted model. The storage life of freeze-dried L. reuteri C10 was markedly improved when cryoprotectants were used. At optimum combination of the cryoprotectants, the survival rates of freeze-dried L. reuteri C10 stored at 4°C and 30°C for 6 months were 96.4% and 73.8%, respectively. Total viability loss of cells which were not protected by cryoprotectants occurred after 12 and 8 weeks of storage at 4°C and 30°C, respectively.
  6. Hazalin NA, Lim SM, Cole AL, Majeed AB, Ramasamy K
    Anticancer Drugs, 2013 Sep;24(8):852-61.
    PMID: 23764760 DOI: 10.1097/CAD.0b013e3283635a47
    There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.
  7. Mohd-Zubri NS, Ramasamy K, Abdul-Rahman NZ
    Arch Oral Biol, 2022 Nov;143:105515.
    PMID: 36084351 DOI: 10.1016/j.archoralbio.2022.105515
    OBJECTIVE: This study aims to characterise the lactic acid bacteria (LAB) isolated from local Malaysian fermented foods with oral probiotics properties.

    DESIGN: The LAB strains isolated from Malaysian fermented foods, Lactobacillus brevis FT 6 and Lactobacillus plantarum FT 12, were assessed for their antimicrobial properties against Porphyromonas gingivalis ATCC 33277 via disc diffusion assay. Anti-biofilm properties were determined by treating the overnight P. gingivalis ATCC 33277 biofilm with different concentrations of LAB cell-free supernatant (LAB CFS). Quantification of biofilm was carried out by measuring the optical density of stained biofilm. The ability of L. brevis FT 6 and L. plantarum FT 12 to tolerate salivary amylase was also investigated. Acid production with different sugars was carried out by pH measurement and screening for potential antimicrobial organic acid by disc diffusion assay of neutralised probiotics CFS samples. In this study, L. rhamnosus ATCC 7469, a commercial strain was used to compare the efficacy of the isolated strain with the commercial strain.

    RESULTS: Lactobacillus brevis FT 6 and L. plantarum FT 12 possess antimicrobial activity against P. gingivalis with inhibition diameters of more than 10 mm, and the results were comparable with L. rhamnosus ATCC 7469. The MIC and MBC assay results for all tested strains were recorded to be 25 µl/µl concentration. All LAB CFS reduced biofilm formation proportionally to the CFS concentration and tolerated salivary amylase with more than 50% viability. Overnight cultures of all lactic acid bacteria strains showed a pH reduction and neutralised CFS of all lactic acid bacteria strains did not show any inhibition towards P. gingivalis.

    CONCLUSIONS: These results indicate that the isolated probiotics have the potential as probiotics to be used as a supportive oral health treatment, especially against a periodontal pathogen, P. gingivalis.

  8. Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):60.
    PMID: 31384808 DOI: 10.1186/s13065-019-0575-x
    In order to overcome the challenges of microbial resistance as well as to improve the effectiveness and selectivity of chemotherapeutic agents against cancer, a novel series of 4-(4-bromophenyl)-thiazol-2-amine derivatives was synthesized and its molecular structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were further evaluated for their in vitro antimicrobial activity using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. The antimicrobial activity results revealed that compound p2, p3, p4 and p6 exhibited promising antimicrobial activity that are comparable to standard norfloxacin (antibacterial) and fluconazole (antifungal). Anticancer screening results demonstrated that compound p2 was found to be the most active one against cancer cell line when compared to the rest of the compounds and comparable to the standard drug (5-fluorouracil). The molecular docking study demonstrated that compounds, p2, p3, p4 and p6 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and showed promising ADME properties.
  9. Tahlan S, Kumar S, Ramasamy K, Lim SM, Shah SAA, Mani V, et al.
    BMC Chem, 2019 Dec;13(1):50.
    PMID: 31384798 DOI: 10.1186/s13065-019-0567-x
    Background: Nitrogen containing heterocycles are widely used and investigated by pharmaceutical industry, as they are important in discovery and designing of new drug molecules. Drugs with a benzimidazole nucleus possess exclusive structural features and electron-rich atmosphere, which enable them to bind to a number of biologically important targets and result in a wide range of activities. This has served as the basis of the present study whereby new scaffolds with benzimidazole moiety were designed and synthesized.

    Methods: The structures of synthesized compounds were confirmed by physicochemical and spectral means. The synthesized compounds were screened for their antimicrobial and antiproliferative activities by tube dilution and Sulforhodamine B (SRB) assays, respectively.

    Results and conclusion: The in vitro biological screening results revealed that compound Z24 exhibited promising antimicrobial and anticancer activities which are comparable to standards.

  10. Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):46.
    PMID: 31384794 DOI: 10.1186/s13065-019-0564-0
    To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.
  11. Tahlan S, Ramasamy K, Lim SM, Shah SAA, Mani V, Narasimhan B
    BMC Chem, 2019 Dec;13(1):12.
    PMID: 31384761 DOI: 10.1186/s13065-019-0533-7
    Background: Dihydrofolate reductase (DHFR) is an important target for antimetabolite class of antimicrobials because it participates in purine synthesis. 2-mercaptobenzimidazole (2MBI) has similar structural features as purine nucleotides. Given that benzimidazole and similar heteroaromatics have been broadly examined for their anticancer potential, so, we hereby report the design, synthesis and biological studies (i.e. antimicrobial and anticancer studies) of 2MBI derivatives.

    Methodology: The antimicrobial activity of synthesized 2MBI derivatives were evaluated against Gram positive and Gram negative bacterial species as well as fungal species by tube dilution technique whereas their anticancer activity was assessed against human colorectal carcinoma cell line (HCT116) by Sulforhodamine B (SRB) assay. They were also structurally characterized by IR, NMR, MS and elemental analyses.

    Results discussion and conclusion: The antimicrobial activity findings revealed that compound N1 (MIC
    bs,st,
    ca
     = 1.27, 2.54, 1.27 µM), N8 (MIC
    ec
    = 1.43 µM), N22 (MIC
    kp,an
    = 2.60 µM), N23 and N25 (MIC
    sa
    = 2.65 µM) exhibited significant antimicrobial effects against tested strains, i.e. Gram-positive, Gram-negative (bacterial) and fungal strains. The anticancer screening results demonstrated that compounds N9, N18 (IC50 = 5.85, 4.53 µM) were the most potent compounds against cancer cell line (HCT116) even more than 5-FU, the standard drug (IC50 = 9.99 µM).

  12. Kumar S, Sharma D, Narasimhan B, Ramasamy K, Shah SAA, Lim SM, et al.
    BMC Chem, 2019 Dec;13(1):96.
    PMID: 31355369 DOI: 10.1186/s13065-019-0613-8
    Heterocyclic 1,3-diazine nucleus is a valuable pharmacophore in the field of medicinal chemistry and exhibit a wide spectrum of biological activities. PharmMapper, a robust online tool used for establishing the target proteins based on reverse pharmacophore mapping. PharmMapper study is carried out to explore the pharmacological activity of 1,3-diazine derivatives using reverse docking program. PharmMapper, an open web server was used to recognize for all the feasible target proteins for the developed compounds through reverse pharmacophore mapping. The results were analyzed via molecular docking with maestro v11.5 (Schrodinger 2018-1) using GTPase HRas as possible target. The molecular docking studies displayed the binding behavior of 1,3-diazine within GTP binding pocket. From the docking study compounds s3 and s14 showed better docked score with anticancer potency against cancer cell line (HCT116). Hence, the GTPase HRas may be the possible target of 1,3-diazine derivatives for their anticancer activity where the retrieved information may be quite useful for developing rational drug designing. Furthermore the selected 1,3-diazine compounds were evaluated for their in vitro anticancer activity against murine macrophages cell line. 1,3-Diazine compounds exhibited good selectivity of the compounds towards the human colorectal carcinoma cell line instead of the murine macrophages. The toxicity study of the most active compounds was also performed on non cancerous HEK-293 cell line.
  13. Kumar S, Kaushik A, Narasimhan B, Shah SAA, Lim SM, Ramasamy K, et al.
    BMC Chem, 2019 Dec;13(1):85.
    PMID: 31384832 DOI: 10.1186/s13065-019-0601-z
    Pyrimidine nucleus is a significant pharmacophore that exhibited excellent pharmacological activities. A series of pyrimidine scaffolds was synthesized and its chemical structures were confirmed by physicochemical and spectral analysis. The synthesized compounds were evaluated for their antimicrobial potential towards Gram positive and negative bacteria as well as fungal species. They were also assessed for their anticancer activity toward a human colorectal carcinoma cell line (HCT116). Whilst results of antimicrobial potential revealed that compounds Ax2, Ax3, Ax8 and Ax14 exhibited better activity against tested microorganisms, the results of antiproliferative activity indicated that compounds Ax7 and Ax10 showed excellent activity against HCT116. Further, the molecular docking of pyrimidine derivatives Ax1, Ax9 and Ax10 with CDK8 (PDB id: 5FGK) protein indicated that moderate to better docking results within the binding pocket. Compounds Ax8 and Ax10 having significant antimicrobial and anticancer activities may be selected as lead compounds for the development of novel antimicrobial and anticancer agent, respectively.
  14. Kumari M, Tahlan S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2021 Jan 21;15(1):5.
    PMID: 33478538 DOI: 10.1186/s13065-020-00717-y
    BACKGROUND: Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

    METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

    RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).

  15. Tahlan S, Kumar S, Ramasamy K, Lim SM, Shah SAA, Mani V, et al.
    BMC Chem, 2019 Dec;13(1):90.
    PMID: 31384837 DOI: 10.1186/s13065-019-0608-5
    Benzimidazole is a valuable pharmacophore in the field of medicinal chemistry and exhibit wide spectrum of biological activity. Molecular docking technique is routinely used in modern drug discovery for understanding the drug-receptor interaction. The selected data set of synthesized benzimidazole compounds was evaluated for its in vitro anticancer activity against cancer cell lines (HCT116 and MCF7) by sulforhodamine B (SRB) assay. Further, molecular docking study of data set was carried out by Schrodinger-Maestro v11.5 using CDK-8 (PDB code: 5FGK) and ER-alpha (PDB code: 3ERT) as possible target for anticancer activity. Molecular docking results demonstrated that compounds 12, 16, N9, W20 and Z24 displayed good docking score with better interaction within crucial amino acids and corelate to their anticancer results. ADME results indicated that compounds 16, N9 and W20 have significant results within the close agreement of the Lipinski's rule of five and Qikprop rule within the range and these compounds may be taken as lead molecules for the discovery of new anticancer agents.
  16. Mehta S, Kumar S, Marwaha RK, Narasimhan B, Ramasamy K, Lim SM, et al.
    BMC Chem, 2019 Dec;13(1):113.
    PMID: 31517312 DOI: 10.1186/s13065-019-0629-0
    In the present study, a series of 2-(4-(2-chloroacetyl)piperazin-1-yl)-N-(2-(4-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetamide derivatives was synthesized and its chemical structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were evaluated for their in vitro antimicrobial (tube dilution technique) and anticancer (MTT assay) activities along with molecular docking study by Schrodinger 2018-1, maestro v11.5. The antimicrobial results indicated that compounds 3, 8, 11 and 12 displayed the significant antimicrobial activity and comparable to the standards drugs (ciprofloxacin and fluconazole). The anticancer activity results indicated that compound 5 have good anticancer activity among the synthesized compounds but lower active than the standard drugs (5-fluorouracil and tomudex). Molecular docking study demonstrated that compounds 5 and 7 displayed the good docking score with better anticancer potency within the binding pocket and these compounds may be used as a lead for rational drug designing for the anticancer molecules.
  17. Hazalin NA, Ramasamy K, Lim SM, Wahab IA, Cole AL, Abdul Majeed AB
    PMID: 19930582 DOI: 10.1186/1472-6882-9-46
    Endophytes, microorganisms which reside in plant tissues, have potential in producing novel metabolites for exploitation in medicine. Cytotoxic and antibacterial activities of a total of 300 endophytic fungi were investigated.
  18. Sejari N, Kamaruddin K, Ramasamy K, Lim SM, Neoh CF, Ming LC
    BMC Complement Altern Med, 2016 Jan 15;16:16.
    PMID: 26767971 DOI: 10.1186/s12906-016-0988-1
    BACKGROUND: The treatment of low back pain is very challenging due to the recurrent nature of the problem. It is believed that traditional Malay massage helps to relieve such back pain but there is a lack of scientific evidence to support both the practice of traditional Malay massage and the mechanism by which it exerts its effect. The aim of this study is to investigate the immediate effect of traditional Malay massage on the pain scale, substance P, inflammatory mediators, and functional outcomes among low back pain patients.

    METHODS: A non-blinded, randomised controlled trial will be conducted. A total of sixty-six patients who fulfil the inclusion criteria will be recruited. The participants will be randomly allocated into intervention (traditional Malay massage) and control (relaxation position) groups. Blood and saliva samples will be collected before and immediately after intervention. All collected samples will be analysed. The primary outcomes are the changes in the level of substance P in both saliva and blood samples between both groups. The secondary outcomes include the levels of inflammatory mediators [i.e. TNF-α, IL-1β, IL-8, monocyte chemotactic protein-1, IL-6 and IL-10, and the soluble form of the intercellular adhesion molecule], the pain intensity as measured by a visual analogous scale and functional outcomes using the Roland-Morris Disability Questionnaire.

    DISCUSSION: Massage is a type of physical therapy that has been proven to be potentially capable of reducing unpleasant pain sensations by a complex sensory response and chemical mediators such as substance P and various inflammatory mediators. Previous studies conducted using Thai, Swedish, or other forms of massage therapies, have showed inconsistent findings on substance P levels pre and post the interventions. Each massage genre varies in terms of massage and joint mobilization points, as well as the lumbar spinous process. Traditional Malay massage, known locally as "Urut Melayu", involves soft-tissue manipulation of the whole body applied using the hands and fingers. This massage technique combines both deep muscular tissue massage and spiritual rituals. This trial is expected to give rise to new knowledge underlying the mechanisms for pain and inflammation relief that are activated by traditional Malay massage.

    TRIAL REGISTRATION: Australian New Zealand Clinical Trials ACTRN12615000537550 .

  19. Harun A, Vidyadaran S, Lim SM, Cole AL, Ramasamy K
    PMID: 26047814 DOI: 10.1186/s12906-015-0685-5
    Excessive production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines like tumour necrosis factor-alpha (TNF-α) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. This study investigated the protective role of five endophytic extracts (HAB16R12, HAB16R13, HAB16R14, HAB16R18 and HAB8R24) against LPS-induced inflammatory events in vitro. These endophytic extracts were previously found to exhibit potent neuroprotective effect against LPS-challenged microglial cells.
  20. Harun A, James RM, Lim SM, Abdul Majeed AB, Cole AL, Ramasamy K
    BMC Complement Altern Med, 2011 Sep 24;11:79.
    PMID: 21943123 DOI: 10.1186/1472-6882-11-79
    BACKGROUND: BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.

    METHODS: Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.

    RESULTS: Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).

    CONCLUSIONS: This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.

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