Displaying publications 1 - 20 of 41 in total

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  1. Adnan A, Allaudin ZN, Hani H, Loh HS, Khoo TJ, Ting KN, et al.
    BMC Complement Altern Med, 2019 Jul 10;19(1):169.
    PMID: 31291936 DOI: 10.1186/s12906-019-2586-5
    BACKGROUND: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known.

    METHODS: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells. The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays.

    RESULTS: The 50% cytotoxicity concentration (CC50) values obtained were 237.5, 555.0, and 

  2. Booi HN, Lee MK, Fung SY, Ng ST, Tan CS, Lim KH, et al.
    Int J Med Mushrooms, 2022;24(10):1-14.
    PMID: 36374826 DOI: 10.1615/IntJMedMushrooms.2022045068
    COVID-19 infection has been a key threat to the public health system globally, with an estimated 248 million cases worldwide. COVID-19 patients are subject to a higher risk of developing chronic respiratory disorders that are closely associated with long-term disability, multi-morbidity, and premature mortality. Although there have been recent advancements in respiratory treatment regimens, there has also been increased interest in the use of medicinal mushrooms in bridging the unaddressed pathways of action within the treatment algorithms. In this review, we provide a collection of medicinal mushrooms that are beneficial in promoting respiratory health and potentially reducing COVID-19 symptoms in patients who are newly diagnosed and those who have recovered. While reviewing the use of immunomodulatory pathways, which have shown promising results in tackling side effects and post-COVID syndromes, we also provide insights into how the antioxidant elements present in medicinal mushrooms help to achieve the same results, especially in the prophylactic and therapeutic management of COVID-19 infection. To date, medicinal mushrooms are regarded as a functional food, which, however, need further quality, safety, and efficacy assessments. These requirements are also highlighted in the present review to promote the future development and application of medicinal mushrooms for better respiratory health.
  3. Chai BK, Lau YS, Loong BJ, Rais MM, Ting KN, Dharmani DM, et al.
    Physiol Res, 2018 Nov 14;67(5):729-740.
    PMID: 29750886
    The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (R(max)=53+/-4.7 %; pEC50=6+/-0.2) compared to endothelium-intact aortas (R(max)=100+/-9.9 %; pEC50=7+/-0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.
  4. Chai BK, Al-Shagga M, Pan Y, Then SM, Ting KN, Loh HS, et al.
    Lipids, 2019 06;54(6-7):369-379.
    PMID: 31124166 DOI: 10.1002/lipd.12154
    Dysregulated hepatic gluconeogenesis is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM). Although existing drugs have been proven to improve gluconeogenesis, achieving this objective with functional food is of interest, especially using conjugated linoleic acid (CLA) found in dairy products. Both cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12) isomers of CLA were tested in human (HepG2) and rat (H4IIE) hepatocytes for their potential effects on gluconeogenesis. The hepatocytes exposed for 24 h with 20 μM of c9,t11-CLA had attenuated the gluconeogenesis in both HepG2 and H4IIE by 62.5% and 80.1%, respectively. In contrast, t10,c12-CLA had no effect. Of note, in HepG2 cells, the exposure of c9,t11-CLA decreased the transcription of gluconeogenic enzymes, cytosolic phosphoenolpyruvate carboxykinase (PCK1) by 87.7%, and glucose-6-phosphatase catalytic subunit (G6PC) by 38.0%, while t10,c12-CLA increased the expression of G6PC, suggesting the isomer-specific effects of CLA on hepatic glucose production. In HepG2, the peroxisome proliferator-activated receptor (PPAR) agonist, rosiglitazone, reduced the glucose production by 72.9%. However, co-administration of c9,t11-CLA and rosiglitazone neither exacerbated nor attenuated the efficacy of rosiglitazone to inhibit glucose production; meanwhile, t10,c12-CLA abrogated the efficacy of rosiglitazone. Paradoxically, PPARγ antagonist GW 9662 also led to 70.2% reduction of glucose production and near undetectable PCK1 expression by abrogating CLA actions. Together, while the precise mechanisms by which CLA isomers modulate hepatic gluconeogenesis directly or via PPAR warrant further investigation, our findings establish that c9,t11-CLA suppresses gluconeogenesis by decreasing PEPCK on hepatocytes.
  5. Chan ZY, Krishnan P, Modaresi SM, Hii LW, Mai CW, Lim WM, et al.
    J Nat Prod, 2021 08 27;84(8):2272-2281.
    PMID: 34342431 DOI: 10.1021/acs.jnatprod.1c00374
    Seven new tropane alkaloids, including five monomeric (1-5), one dimeric (6), and one trimeric (7) 3α-nortropane ester, along with two known monomeric nortropane alkaloids (8 and 9), were isolated from the leaves and bark of Pellacalyx saccardianus. Their structures, including the absolute configuration of the enantiomeric pair of (±)-6, were elucidated by comprehensive spectroscopic analyses. Alkaloids 6 and 7 showed cytotoxicity toward human pancreatic cancer cell lines (AsPC-1, BxPC3, PANC-1, and SW1990). Alkaloids 1, 4, and 9 induced a smooth muscle relaxation effect comparable to that of atropine (Emax 106.1 ± 7.5%, 97.0 ± 5.2%, 100.9 ± 1.4%, 111.7 ± 1.7%, respectively) on isolated rat tracheal rings.
  6. Chen HL, Gibbins CN, Selvam SB, Ting KN
    Environ Pollut, 2021 Nov 15;289:117895.
    PMID: 34364115 DOI: 10.1016/j.envpol.2021.117895
    Microplastic pollution is widely recognised as a global issue, posing risks to natural ecosystems and human health. The combination of rapid industrial and urban development and relatively limited environmental regulation in many tropical countries may increase the amount of microplastic entering rivers, but basic data on contamination levels are lacking. This is especially the case in tropical South East Asian countries. In this paper, the abundance, composition and spatio-temporal variation of microplastic in the Langat River, Malaysia, were assessed, and the relationship between microplastic concentration and river discharge was investigated. Water samples were collected over a 12-month period from 8 sampling sites on the Langat, extending from forested to heavily urbanised and industrial areas. All 508 water samples collected over this period contained microplastic; mean concentration across all sites and times was 4.39 particles/L but extended up to 90.00 particles/L in some urban tributaries. Most microplastics were secondary in origin, and dominated by fibres. Microplastic counts correlated directly with river discharge, and counts increased and decreased in response to changes in flow. A time-integrated assessment of the microplastic load conveyed by the Langat suggested that the river is typically (50 % of the time) delivering around 5 billion particles per day to the ocean. The positive correlation between the concentration of microplastics and suspended sediments in the Langat suggested that continuously logging turbidity sensors could be used to provide better estimates of microplastic loads and improve assessment of human and ecological health risks.
  7. Chen HL, Selvam SB, Ting KN, Gibbins CN
    Environ Monit Assess, 2023 Jan 18;195(2):307.
    PMID: 36652034 DOI: 10.1007/s10661-022-10856-5
    Recent increase in awareness of the extent of microplastic contamination in marine and freshwater systems has heightened concerns over the ecological and human health risks of this ubiquitous material. Assessing risks posed by microplastic in freshwater systems requires sampling to establish contamination levels, but standard sampling protocols have yet to be established. An important question is whether sampling and assessment should focus on microplastic concentrations in the water or the amount deposited on the bed. On three dates, five replicated water and bed sediment samples were collected from each of the eight sites along the upper reach of the Semenyih River, Malaysia. Microplastics were found in all 160 samples, with mean concentrations of 3.12 ± 2.49 particles/L in river water and 6027.39 ± 16,585.87 particles/m2 deposited on the surface of riverbed sediments. Fibres were the dominant type of microplastic in all samples, but fragments made up a greater proportion of the material on the bed than in the water. Within-site variability in microplastic abundance was high for both water and bed sediments, and very often greater than between-site variability. Patterns suggest that microplastic accumulation on the bed is spatially variable, and single samples are therefore inadequate for assessing bed contamination levels at a site. Sites with the highest mean concentrations in samples of water were not those with the highest concentrations on the bed, indicating that monitoring based only on water samples may not provide a good picture of either relative or absolute bed contamination levels, nor the risks posed to benthic organisms.
  8. Chen HL, Selvam SB, Ting KN, Gibbins CN
    Environ Sci Pollut Res Int, 2021 Oct;28(39):54222-54237.
    PMID: 34386926 DOI: 10.1007/s11356-021-15826-x
    Plastics are synthetic polymers known for their outstanding durability and versatility, and have replaced traditional materials in many applications. Unfortunately, their unique traits ensure that they pose a major threat to the environment. While literature on freshwater microplastic contamination has grown over the recent years, research undertaken in rapidly developing countries, where plastic production and use are increasing dramatically, has lagged behind that in other parts of the world. In the South East Asia (SEA) region, basic information on levels of contamination is very limited and, as a consequence, the risk to human and ecological health remains hard to assess. This review synthesises what is currently known about microplastic contamination of freshwater ecosystems in SEA, with a particular focus on Malaysia. The review 1) summarises published studies that have assessed levels of contamination in freshwater systems in SEA, 2) discusses key sources and transport pathways of microplastic in freshwaters, 3) outlines what is known of the impacts of microplastic on freshwater organisms, and 4) identifies key knowledge gaps related to our understanding of the transport, fate and effects of microplastic.
  9. Clarke G, Ting KN, Wiart C, Fry J
    Antioxidants (Basel), 2013;2(1):1-10.
    PMID: 26787618 DOI: 10.3390/antiox2010001
    Extracts of plants from the Malaysian rainforest and other fragile habitats are being researched intensively for identification of beneficial biological actions, with assessment of antioxidant behavior being a common component of such assessments. A number of tests for antioxidant behavior are used, with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reduction activity potential (FRAP) assays often being used in parallel, and also with measurement of total phenolics content (TPC) as a surrogate marker for antioxidant capacity. The present study investigated the possible redundancy in using all three assays to determine antioxidant capacity in 92 extracts obtained from 27 plants from the Malaysian rainforest. The results demonstrated that the assays displayed a high (R ≥ 0.82) and significant (P < 0.0001) correlation with one another, indicating a high level of redundancy if all three assays are used in parallel. This appears to be a waste of potentially valuable plant extracts. Because of problems with the FRAP assay relating to color interference and variable rates of reaction point, the DPPH assay is the preferred assay in preliminary screening of extracts of plants from the Malaysian rainforest.
  10. Gnanasan S, Ting KN, Wong KT, Mohd Ali S, Muttalif AR, Anderson C
    Int J Clin Pharm, 2011 Feb;33(1):44-52.
    PMID: 21365392 DOI: 10.1007/s11096-010-9452-3
    OBJECTIVE: To assess the feasibility of providing a pharmacist-led pharmaceutical care service to patients with tuberculosis and diabetes mellitus.

    SETTING: The study was conducted at a tertiary hospital in the northern region of Peninsular Malaysia. Methods Action research methodology was used.

    MAIN OUTCOME MEASURE: Pharmaceutical care issues.

    RESULTS: The prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 15% (53/352). Out of 53 patients identified, 35 participated in the study. Patients' ages ranged between 29 and 73 years (mean of 52 ± 10 years). The male: female ratio was 1.7:1. Pharmaceutical care issues identified by pharmacists were nonadherence, uncontrolled diabetes mellitus, adverse drug reactions and individual patient's medication related problems. Pharmacists were able to intervene and resolve some of the pharmaceutical care issues.

    CONCLUSION: Pharmacists played an important role in integrating the provision of care for tuberculosis and diabetes mellitus by providing individualised pharmaceutical care management. There still remains a need to address logistic barriers that impinged on the ability to conduct the pharmaceutical care service to its full potential.

  11. Islahudin F, Pleass RJ, Avery SV, Ting KN
    J Antimicrob Chemother, 2012 Oct;67(10):2501-5.
    PMID: 22763566 DOI: 10.1093/jac/dks253
    OBJECTIVES: Recent work with the yeast model revealed that the antiprotozoal drug quinine competes with tryptophan for uptake via a common transport protein, causing cellular tryptophan starvation. In the present work, it was hypothesized that similar interactions may occur in malaria patients receiving quinine therapy.

    PATIENTS AND METHODS: A direct observational study was conducted in which plasma levels of drug and amino acids (tryptophan, tyrosine and phenylalanine) were monitored during quinine treatment of malaria patients with Plasmodium falciparum infections.

    RESULTS: Consistent with competition for uptake from plasma into cells, plasma tryptophan and tyrosine levels increased ≥2-fold during quinine therapy. Plasma quinine levels in individual plasma samples were significantly and positively correlated with tryptophan and tyrosine in the same samples. Control studies indicated no effect on phenylalanine. Chloroquine treatment of Plasmodium vivax-infected patients did not affect plasma tryptophan or tyrosine. During quinine treatment, plasma tryptophan was significantly lower (and quinine significantly higher) in patients experiencing adverse drug reactions.

    CONCLUSIONS: Plasma quinine levels during therapy are related to patient tryptophan and tyrosine levels, and these interactions can determine patient responses to quinine. The study also highlights the potential for extrapolating insights directly from the yeast model to human malaria patients.

  12. Islahudin F, Tindall SM, Mellor IR, Swift K, Christensen HE, Fone KC, et al.
    Sci Rep, 2014 Jan 09;4:3618.
    PMID: 24402577 DOI: 10.1038/srep03618
    The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.
  13. Krishnan P, Lee FK, Chong KW, Mai CW, Muhamad A, Lim SH, et al.
    Org. Lett., 2018 12 21;20(24):8014-8018.
    PMID: 30543301 DOI: 10.1021/acs.orglett.8b03592
    Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.
  14. Krishnan P, Lee FK, Yap VA, Low YY, Kam TS, Yong KT, et al.
    J Nat Prod, 2020 01 24;83(1):152-158.
    PMID: 31935094 DOI: 10.1021/acs.jnatprod.9b01160
    Schwarzinicines A-G (1-7), representing the first examples of 1,4-diarylbutanoid-phenethylamine conjugates, were isolated from the leaves of Ficus schwarzii. The structures of these compounds were determined by detailed analysis of their MS, 1D and 2D NMR data. Compounds 1-4 exhibited pronounced vasorelaxant effects in the rat isolated aorta (Emax 106-120%; EC50 0.96-2.10 μM). However, compounds 1 and 2 showed no cytotoxic effects against A549, MCF-7, and HCT 116 human cancer cells (IC50 > 10 μM).
  15. Lee FK, Krishnan P, Muhamad A, Low YY, Kam TS, Ting KN, et al.
    Nat Prod Res, 2021 Mar 22.
    PMID: 33749454 DOI: 10.1080/14786419.2021.1903005
    A concise synthesis of the 1,4-diarylbutanoid-phenethylamine alkaloids, schwarzinicines A (1) and B (2), recently isolated from Ficus schwarzii, is reported. Key steps include a Claisen condensation to assemble the 1,4-diaryl-2-butanone intermediate, followed by a reductive amination to furnish the core skeleton of the target compounds. The overall synthetic yields of 1 and 2 were 9.1% and 3.5%, respectively. Synthetic (-)-1, (+)-1 and (±)-1 exhibited comparable vasorelaxation as natural schwarzinicine A on rat isolated aortic rings, suggesting that the observed vasorelaxant effects were not influenced by the chirality at C-2.
  16. Lee FK, Chan NJ, Krishnan P, Datu Abdul Salam DS, Chee XW, Muhamad A, et al.
    J Nat Prod, 2024 Apr 26;87(4):675-691.
    PMID: 38442031 DOI: 10.1021/acs.jnatprod.3c00707
    Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (Emax) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.
  17. Lee MK, Lim KH, Millns P, Mohankumar SK, Ng ST, Tan CS, et al.
    Phytomedicine, 2018 Mar 15;42:172-179.
    PMID: 29655683 DOI: 10.1016/j.phymed.2018.03.025
    BACKGROUND: Lignosus rhinocerotis (Cooke) Ryvarden is a popular medicinal mushroom used for centuries in Southeast Asia to treat asthma and chronic cough. The present study aimed to investigate the effect of this mushroom on airways patency.

    MATERIALS AND METHODS: The composition of L. rhinocerotis TM02 cultivar was analyzed. Organ bath experiment was employed to study the bronchodilator effect of Lignosus rhinocerotis cold water extract (CWE) on rat isolated airways. Trachea and bronchus were removed from male Sprague-Dawley rats, cut into rings of 2 mm, pre-contracted with carbachol before adding CWE into the bath in increasing concentrations. To investigate the influence of incubation time, tissues were exposed to intervals of 5, 15 and 30 min between CWE concentrations after pre-contraction with carbachol in subsequent protocol. Next, tissues were pre-incubated with CWE before the addition of different contractile agents, carbachol and 5-hydroxytrptamine (5-HT). The bronchodilator effect of CWE was compared with salmeterol and ipratropium. In order to uncover the mechanism of action of CWE, the role of beta-adrenoceptor, potassium and calcium channels was investigated.

    RESULTS: Composition analysis of TM02 cultivar revealed the presence of β-glucans and derivatives of adenosine. The extract fully relaxed the trachea at 3.75 mg/ml (p 

  18. Lee MK, Li X, Yap ACS, Cheung PCK, Tan CS, Ng ST, et al.
    Front Pharmacol, 2018;9:461.
    PMID: 29867469 DOI: 10.3389/fphar.2018.00461
    Lignosus rhinocerotis has a long history of use by the indigenous community within East Asia to treat a range of health conditions including asthma and chronic cough. To date, there is limited scientific evidence to support its therapeutic effects in relieving these airways conditions. In this study, we examined the effects of the different molecular weight fractions [high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW)] obtained from the cold water sclerotial extract (CWE) of L. rhinocerotis on airways patency using airway segments isolated from Sprague Dawley rat in an organ bath set-up. It is demonstrated that the HMW and MMW fractions exhibited higher efficacy in relaxing the pre-contracted airways when compared to the CWE and LMW fraction. In addition, the HMW fraction markedly supressed carbachol-, 5-hydroxytrptamine-, and calcium-induced airway contractions. CWE demonstrated a lower efficacy than the HMW fraction but it also significantly attenuated carbachol- and calcium-induced airway contractions. Results showed that the bronchorelaxation effect of CWE and fractions is mediated via blockade of extracellular Ca2+ influx. The composition analysis revealed the following parts of carbohydrate and proteins, respectively: HMW fraction: 71 and 4%; MMW fraction: 35 and 1%; and LMW fraction: 22 and 0.3%. Our results strongly suggest that the polysaccharide-protein complex or proteins found in the HMW and MMW fractions is likely to contribute to the bronchorelaxation effect of CWE.
  19. Lee MK, Millns P, Mbaki Y, Ng ST, Tan CS, Lim KH, et al.
    Data Brief, 2018 Jun;18:1322-1326.
    PMID: 29900310 DOI: 10.1016/j.dib.2018.04.033
    The data in this article contain supporting evidence for the research manuscript entitled "Bronchodilator effects of Lignosus rhinocerotis extract on rat isolated airways is linked to the blockage of calcium entry" by Lee et al. (2018) [1]. The data were obtained by calcium imaging technique with fluorescent calcium indicator dyes, Fura 2-AM, to visualize calcium ion movement in the rat dorsal ganglion (DRG) cells. The effects of L. rhinocerotis cold water extract (CWE1) on intracellular calcium levels in the DRG cells were presented.
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