Displaying publications 1 - 20 of 146 in total

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  1. Lim KH, Lim YC, Liam CK, Wong CM
    Chest, 2001 Mar;119(3):955-7.
    PMID: 11243981
  2. Al-Khdhairawi AAQ, Krishnan P, Mai CW, Chung FF, Leong CO, Yong KT, et al.
    J Nat Prod, 2017 10 27;80(10):2734-2740.
    PMID: 28926237 DOI: 10.1021/acs.jnatprod.7b00500
    Tengerensine (1), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (2), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of Ficus fistulosa var. tengerensis, along with three other known alkaloids. The structures of 1 and 2 were determined by spectroscopic data interpretation and X-ray diffraction analysis. The enantiomers of 1 were separated by chiral-phase HPLC, and the absolute configurations of (+)-1 and (-)-1 were established via experimental and calculated ECD data. Compound 1 is notable in being a rare unsymmetrical cyclobutane adduct and is the first example of a dimeric benzopyrroloisoquinoline alkaloid, while compound 2 represents the first naturally occurring halogenated phenanthroindolizidine alkaloid. Compound (+)-1 displayed a selective in vitro cytotoxic effect against MDA-MB-468 cells (IC50 7.4 μM), while compound 2 showed pronounced in vitro cytotoxic activity against all three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC50 values of 0.038-0.91 μM).
  3. Chu JN, Krishnan P, Lim KH
    Nat Prod Bioprospect, 2023 Nov 27;13(1):53.
    PMID: 38010490 DOI: 10.1007/s13659-023-00418-8
    Sarcandra glabra (Thunb.) Nakai is a perennial evergreen herb categorised within the Sarcandra Gardner genus under the Chloranthaceae family. Indigenous to tropical and subtropical regions of East Asia and India, this species is extensively distributed across China, particularly in the southern regions (Sichuan, Yunnan, and Jiangxi). In addition to its high ornamental value, S. glabra has a rich history of use in traditional Chinese medicine, evident through its empirical prescriptions for various ailments like pneumonia, dysentery, fractures, bruises, numbness, amenorrhea, rheumatism, and other diseases. Besides, modern pharmacological studies have revealed various biological activities, such as antitumour, anti-bacterial, anti-viral anti-inflammatory and immunomodulatory effects. The diverse chemical constituents of S. glabra have fascinated natural product researchers since the 1900s. To date, over 400 compounds including terpenoids, coumarins, lignans, flavonoids, sterols, anthraquinones, organic acids, and organic esters have been isolated and characterised, some featuring unprecedented structures. This review comprehensively examines the current understanding of S. glabra's phytochemistry and pharmacology, with emphasis on the chemistry and biosynthesis of its unique chemotaxonomic marker, the lindenane-type sesquiterpenoids.
  4. Lim KH, Liam CK, Wong CM
    Postgrad Med J, 2000 Aug;76(898):512, 518-9.
    PMID: 10908387
  5. Lim SW, Ting KN, Bradshaw TD, Zeenathul NA, Wiart C, Khoo TJ, et al.
    J Ethnopharmacol, 2011 Nov 18;138(2):616-23.
    PMID: 22008878 DOI: 10.1016/j.jep.2011.10.005
    The seeds of Acalypha wilkesiana have been used empirically by traditional healers in Southwest Nigeria together with other plants as a powder mixture to treat patients with breast tumours and inflammation.
  6. Liam CK, Lim KH, Wong CM
    Asian Pac J Allergy Immunol, 2000 Sep;18(3):135-40.
    PMID: 11270467
    This study aimed to evaluate dry powder inhaler naive asthmatic patients' perception and preference of the Accuhaler, a multidose dry powder inhaler and the pressurized metered dose inhaler (pMDI). After the first instruction, 66.7% of 48 patients enrolled in the study could demonstrate the correct use of the Accuhaler. When the patients were asked to compare the pMDI and the Accuhaler after using the Accuhaler to administer salmeterol for 4 weeks, the Accuhaler scored significantly better than the pMDI for the following features: knowing how many doses are left, presence of an attached cover, taste, instruction for use, attractiveness, ease of use, ease of holding, shape, and comfortable mouthpiece. The pMDI scored better to the Accuhaler in terms of size. More patients preferred the Accuhaler than the pMDI; the presence of a dose counter and perceived ease of use were the main reasons cited for their preference for the Accuhaler.
    Study site: Asthma Clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  7. Teh CH, Rampal S, Lim KH, Azahadi O, Tahir A
    Nicotine Tob Res, 2023 Jun 09;25(7):1340-1347.
    PMID: 36879440 DOI: 10.1093/ntr/ntad035
    INTRODUCTION: Tobacco use is one of the major preventable risk factors for premature death and disability worldwide. Understanding the trend of tobacco use over time is important for informed policy making.

    AIMS AND METHODS: The present study aimed to examine the changes in mean daily cigarette consumption among random samples of the Malaysian current smoker population over 20 years using an age-period-cohort (APC) approach. We conducted APC analysis using a multilevel hierarchical age-period-cohort model and data from four nationally representative, repeated cross-sectional surveys (National Health and Morbidity Survey) conducted in 1996, 2006, 2011, and 2015 among individuals aged 18 to 80 years. Analyses were also stratified by gender and ethnicity.

    RESULTS: Overall, mean daily cigarette consumption (smoking intensity) among current smokers increased with age until 60, after which a drop was observed. There were increases in daily cigarette consumption across birth cohorts. Age and cohort trends did not vary by gender but by ethnicity. The decreasing cigarette consumption after age 60 among the current smoker population was consistent with those observed among the Chinese and Indians, a trend that was not observed in Malays and other aborigines. In contrast, the increasing cohort trend was consistent with those observed among the Malays and other bumiputras.

    CONCLUSIONS: The present study highlighted important ethnic-specific trends for mean daily cigarette consumption among the current smoker population in Malaysia. These findings are essential in guiding the formulation of interventional strategies or implementation of national tobacco control policies and help achieve the Ministry of Health Malaysia's 2025 and 2045 targets for smoking prevalence.

    IMPLICATIONS: This is the first APC study on smoking intensity among current smokers in a multiracial, middle-income nation. Very few studies had performed gender- and ethnic-stratified APC analyses. The ethnic-stratified APC analyses provide useful insights into the overall age and cohort trends observed among the current smoker population in Malaysia. Therefore, the present study could add evidence to the existing literature on the APC trends of smoking intensity. The APC trends are also important in guiding the government to develop, implement, and evaluate antismoking strategies.

  8. Lim KH, Cheong YL, Sulaiman N, Yah XY, Mahadzir ME, Lim JH, et al.
    Tob Induc Dis, 2022;20:105.
    PMID: 36474605 DOI: 10.18332/tid/155376
    INTRODUCTION: Measuring the level of nicotine addiction among smokers is an integral part of enhancing smoking cessation as nicotine dependence is one of the barriers to smoking cessation. In this study, we compared the level of agreement between FTND and HSI in detecting high nicotine dependence among daily smokers.

    METHODS: We collected data from participants of a public smoking cessation clinic in Selangor. A trained pharmacist conducted face-to-face interviews with 152 daily smokers using a structured validated questionnaire. Respondents were classified as having high nicotine dependence using both the HSI (score ≥4) and the FTND (score ≥6), and concordance between the two measures, kappa statistics and sensitivity, specificity of the HSI were then determined with the FTND classification as the reference standard.

    RESULTS: The HSI had a substantial agreement with the FTND (Cohen's kappa=0.72) in measuring high levels of nicotine addiction, with good sensitivity (83.3%) and specificity (89.4%).

    CONCLUSIONS: The findings suggest that the HSI can be used instead of the FTND in clinical-based investigations to screen for high nicotine dependence among daily smokers in the clinical setting.

  9. Abubakar IB, Lim KH, Loh HS
    Nat Prod Res, 2015;29(22):2137-40.
    PMID: 25515603 DOI: 10.1080/14786419.2014.991927
    Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2-34.7 fold of reduction in IC50 values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.
  10. Kam TS, Lim KH
    Alkaloids Chem Biol, 2008;66:1-111.
    PMID: 19025097
  11. 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.
  12. Lim KH, Tan LH, Liam CK, Wong CM
    Chest, 2001 Nov;120(5):1728-31.
    PMID: 11713160
  13. Abuzaid H, Abdelrazig S, Ferreira L, Collins HM, Kim DH, Lim KH, et al.
    ACS Omega, 2022 Jun 28;7(25):21473-21482.
    PMID: 35785302 DOI: 10.1021/acsomega.2c00997
    The O-acetyl (or acetate) derivative of the Aspidosperma alkaloid Jerantinine A (JAa) elicits anti-tumor activity against cancer cell lines including mammary carcinoma cell lines irrespective of receptor status (0.14 < GI50 < 0.38 μM), targeting microtubule dynamics. By exploiting breast cancer cells' upregulated transferrin receptor 1 (TfR1) expression and apoferritin (AFt) recognition, we sought to develop an AFt JAa-delivery vehicle to enhance tumor-targeting and reduce systemic toxicity. Optimizing pH-mediated reassembly, ∼120 JAa molecules were entrapped within AFt. Western blot and flow cytometry demonstrate TfR1 expression in cancer cells. Enhanced internalization of 5-carboxyfluorescein-conjugated human AFt in SKBR3 and MDA-MB-231 cancer cells is observed compared to MRC5 fibroblasts. Accordingly, AFt-JAa delivers significantly greater intracellular JAa levels to SKBR3 and MDA-MB-231 cells than naked JAa (0.2 μM) treatment alone. Compared to naked JAa (0.2 μM), AFt-JAa achieves enhanced growth inhibition (2.5-14-fold; <0.02 μM < GI50 < 0.15 μM) in breast cancer cells; AFt-JAa treatment results in significantly reduced clonal survival, more profound cell cycle perturbation including G2/M arrest, greater reduction in cell numbers, and increased apoptosis compared to the naked agent (p < 0.01). Decreased PLK1 and Mcl-1 expression, together with the appearance of cleaved poly (ADP-ribose)-polymerase, corroborate the augmented potency of AFt-JAa. Hence, we demonstrate that AFt represents a biocompatible vehicle for targeted delivery of JAa, offering potential to minimize toxicity and enhance JAa activity in TfR1-expressing tumors.
  14. Lim KH, Kam TS
    Org. Lett., 2006 Apr 13;8(8):1733-5.
    PMID: 16597153
    [structure: see text] A new indole alkaloid, arboflorine, possessing a novel pentacyclic carbon skeleton and incorporating a third nitrogen atom was obtained from the Malayan Kopsia arborea. The structure was established by spectroscopic analysis, and a possible biogenetic pathway from a preakuammicine-type precursor is presented.
  15. Wong SP, Gan CY, Lim KH, Ting KN, Low YY, Kam TS
    Org. Lett., 2015 Jul 17;17(14):3628-31.
    PMID: 26183592 DOI: 10.1021/acs.orglett.5b01757
    A new monoterpene indole alkaloid characterized by an unprecedented pentacyclic cage skeleton, arboridinine (1), was isolated from a Malaysian Kopsia species. The structure and absolute configuration of the alkaloid were determined based on NMR, MS, and X-ray diffraction analysis. A possible biogenetic pathway from a pericine precursor is presented.
  16. Wong SP, Chong KW, Lim KH, Lim SH, Low YY, Kam TS
    Org. Lett., 2016 Apr 1;18(7):1618-21.
    PMID: 27033525 DOI: 10.1021/acs.orglett.6b00478
    Two new monoterpene indole alkaloids, characterized by previously unencountered natural product skeletons, viz., arborisidine (1), incorporating indolizidine and cyclohexanone moieties fused to an indole unit, and arbornamine (2), incorporating an unprecedented 6/5/6/5/6 "arbornane" skeleton (distinct from the eburnan or tacaman skeleton), were isolated from a Malayan Kopsia arborea. The structures of the alkaloids were determined based on analysis of the NMR and MS data. Possible biogenetic pathways to these alkaloids from a common pericine precursor (3) are presented.
  17. Wong CMM, Lim KH, Liam CK
    Med J Malaysia, 2002 Dec;57(4):515-23; quiz 524-5.
    PMID: 12733182
  18. Kee CC, Sumarni MG, Lim KH, Selvarajah S, Haniff J, Tee GHH, et al.
    Public Health Nutr, 2017 May;20(7):1226-1234.
    PMID: 28077198 DOI: 10.1017/S136898001600344X
    OBJECTIVE: To determine the relationship between BMI and risk of CVD mortality and all-cause mortality among Malaysian adults.

    DESIGN: Population-based, retrospective cohort study. Participants were followed up for 5 years from 2006 to 2010. Mortality data were obtained via record linkages with the Malaysian National Registration Department. Multiple Cox regression was applied to compare risk of CVD and all-cause mortality between BMI categories adjusting for age, gender and ethnicity. Models were generated for all participants, all participants the first 2 years of follow-up, healthy participants, healthy never smokers, never smokers, current smokers and former smokers.

    SETTING: All fourteen states in Malaysia.

    SUBJECTS: Malaysian adults (n 32 839) aged 18 years or above from the third National Health and Morbidity Survey.

    RESULTS: Total follow-up time was 153 814 person-years with 1035 deaths from all causes and 225 deaths from CVD. Underweight (BMI<18·5 kg/m2) was associated with a significantly increased risk of all-cause mortality, while obesity (BMI ≥30·0 kg/m2) was associated with a heightened risk of CVD mortality. Overweight (BMI=25·0-29·9 kg/m2) was inversely associated with risk of all-cause mortality. Underweight was significantly associated with all-cause mortality in all models except for current smokers. Overweight was inversely associated with all-cause mortality in all participants. Although a positive trend was observed between BMI and CVD mortality in all participants, a significant association was observed only for severe obesity (BMI≥35·0 kg/m2).

    CONCLUSIONS: Underweight was associated with increased risk of all-cause mortality and obesity with increased risk of CVD mortality. Therefore, maintaining a normal BMI through leading an active lifestyle and healthy dietary habits should continue to be promoted.

  19. Chee Cheong K, Lim KH, Ghazali SM, Teh CH, Cheah YK, Baharudin A, et al.
    BMJ Open, 2021 08 18;11(8):e047849.
    PMID: 34408040 DOI: 10.1136/bmjopen-2020-047849
    OBJECTIVES: This study is aimed at determining the association between metabolic syndrome and risk of cardiovascular disease (CVD) mortality and all-cause mortality among Malaysian adults.

    DESIGN: Retrospective cohort study.

    SETTING: The Malaysian Non-Communicable Disease Surveillance (MyNCDS-1) 2005/2006.

    PARTICIPANTS: A total of 2525 adults (1013 men and 1512 women), aged 24-64 years, who participated in the MyNCDS-1 2005/2006.

    METHODS: Participants' anthropometric indices, blood pressure, fasting lipid profile and fasting blood glucose levels were evaluated to determine the prevalence of metabolic syndrome by the Harmonized criteria. Participants' mortality status were followed up for 13 years from 2006 to 2018. Mortality data were obtained via record linkage with the Malaysian National Registration Department. The Cox proportional hazards regression model was applied to determine association between metabolic syndrome (MetS) and risk of CVD mortality and all-cause mortality with adjustment for selected sociodemographic and lifestyle behavioural factors.

    RESULTS: The overall point prevalence of MetS was 30.6% (95% CI: 28.0 to 33.3). Total follow-up time was 31 668 person-years with 213 deaths (111 (11.3%) in MetS subjects and 102 (6.1%) in non-MetS subjects) from all-causes, and 50 deaths (33 (2.9%) in MetS group and 17 (1.2%) in non-MetS group) from CVD. Metabolic syndrome was associated with a significantly increased hazard of CVD mortality (adjusted HR: 2.18 (95% CI: 1.03 to 4.61), p=0.041) and all-cause mortality (adjusted HR: 1.47 (95% CI: 1.00 to 2.14), p=0.048). These associations remained significant after excluding mortalities in the first 2 years.

    CONCLUSIONS: Our study shows that individuals with MetS have a higher hazard of death from all-causes and CVD compared with those without MetS. It is thus imperative to prescribe individuals with MetS, a lifestyle intervention along with pharmacological intervention to improve the individual components of MetS and reduce this risk.

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