Displaying publications 161 - 180 of 257 in total

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  1. Tan MM, Jamil ASA, Ismail R, Donnelly M, Su TT
    BMC Public Health, 2023 Jul 10;23(1):1319.
    PMID: 37430228 DOI: 10.1186/s12889-023-16227-0
    BACKGROUND: Many upper-middle-income countries (UMICs), including Malaysia, continue to face low breast cancer (BC) screening rates and patients with delayed presentation of BC. This study investigated the role of beliefs about BC and use of screening (e.g. beliefs about whether or not screening reduced the possibility of dying from BC).

    METHODS: A nationwide cross-sectional study was conducted in which a total of 813 women (aged ≥ 40 years old) were randomly selected and surveyed using the validated Awareness and Beliefs about Cancer (ABC) measure. The association between BC screening use, sociodemographic characteristics, and negative beliefs about BC screening were analysed using stepwise Poisson regressions.

    RESULTS: Seven out of ten Malaysian women believed that BC screening was necessary only when experiencing cancer symptoms. Women > 50 years and from households with more than one car or motorcycle were 1.6 times more likely to attend a mammogram or a clinical breast examination (mammogram: Prevalence Ratio (PR) = 1.60, 95% Confidence Interval (CI) = 1.19-2.14, Clinical Breast Examination (CBE): PR = 1.61, 95% CI = 1.29-1.99). About 23% of women expected to feel anxious about attending BC screening, leading them to avoid the procedure. Women who held negative beliefs about BC screening were 37% less likely to attend a mammogram (PR = 0.63, 95% CI = 0.42-0.94) and 24% less likely to seek a CBE (PR = 0.75, 95% CI = 0.60-0.95).

    CONCLUSIONS: Public health strategies or behaviour interventions targeting negative beliefs about BC screening among Malaysian women may increase uptake and reduce late presentation and advanced-stage cancer. Insights from the study suggest that women under 50 years, in the lower income group without a car or motorcycle ownership, and of Malay or Indian ethnicity (compared to Chinese-Malay) are more likely to hold beliefs inhibiting BC screening.

  2. Mohamad N, Ismail R, Ibrahim MF, Abdul Shukor IH, Mohamad MZ, Mahmud MF, et al.
    Healthcare (Basel), 2023 Aug 18;11(16).
    PMID: 37628536 DOI: 10.3390/healthcare11162339
    During the COVID-19 pandemic, persons under surveillance (PUS) were isolated in quarantine centres instead of at home. However, there is limited knowledge regarding the mental health issues experienced by these persons. This study aimed to assess mental health outcomes and associated factors among PUS and frontline workers at quarantine centres. This study conducted an analysis of secondary data from a cross-sectional survey carried out by the Mental Health and Psychosocial Support Services (MHPSS). The MHPSS employed the Depression, Anxiety, and Stress Scale (DASS-21) to evaluate mental health outcomes across 49 quarantine centres in Malaysia. The study included a total of 4577 respondents. The prevalence of stress, anxiety, and depression was found to be 0.9%, 11.4%, and 10.2%, respectively. Frontline workers and being part of the younger age group were found to be associated with depression, anxiety, and stress. Other factors associated with mental health issues were being female, staying at an institution-type centre, and a longer duration of the stay or work at the centre. In conclusion, assessing the mental health status and its associated factors among quarantine centre occupants is crucial for developing future strategies to safeguard their mental well-being.
  3. Hanafi MM, Azizi P, Akinbola ST, Ismail R, Sahibin AR, Wan Mohd Razi I, et al.
    Sci Rep, 2021 Jul 27;11(1):15234.
    PMID: 34315931 DOI: 10.1038/s41598-021-93704-9
    Sandy texture soil, a major problem for agriculture requires structure and capacity improvements. However, utilization of soil conditioner may arrest this problem. This research was carried out to investigate the accumulated levels of metal ions and radionuclides in water, soil and plants following phosphogypsum organic (PG organic) added to a sandy soil for 23-month in 3 cropping seasons. The condition in the field was simulated in the laboratory using an open leaching column for 30-day under constant but different pH of leachant. More ions were released at pH  5.6. The metal ions measured in the surface and borehole water, and soils were below the target values for respective standard raw drinking water. The metal ions did not accumulate in soil, plant and grain, and water as indicated by biological accumulation coefficients, contamination factors, I-geo index and pollution load index in a sandy soil that received the PG organic. Naturally occurring radionuclide concentrations, such as 226Ra, 228Ra, and 40K, in soil and plant tissue were found to be lower than the average value reported by several earlier studies. Under field condition the pH of water (i.e., rainfall) was greater than pH 5.6, thus renders PG organic became less soluble. There was no leaching of natural occurring radionuclides to the groundwater. Therefore, the application of PG organic to the studied soil had no impact on the soil, plants, and water and suitable as a soil conditioner in sandy texture soils.
  4. Mohd Yusoff H, Ismail KI, Ismail R, Khamis NK, Muhamad Robat R, Bryce JM
    Heliyon, 2024 Jan 15;10(1):e23735.
    PMID: 38226263 DOI: 10.1016/j.heliyon.2023.e23735
    Driving is the most prevalent form of commuting for most workers but is also perhaps the most hazardous mode of travel with unsafe driving contributing significantly to road traffic accidents. Despite nurses having been reported as being at higher risk of commuter-related accidents over the last three decades, little is known about unsafe driving behaviours among nurses while commuting, which is unique from other driving routines. Additionally, the lack of appropriate tools to measure such behaviours is apparent. This study aims i) to identify unsafe driving behaviours among nurses while commuting and ii) to develop a scale to assess nurses' unsafe commuting driving behaviours. The study employed a multiphase and multimethod approach to develop the scale, which was subject to stringent validation and evaluation. Themes were specified via the Nominal Group Technique (NGT). Six themes were identified namely: i) violations and reckless driving, ii) negative emotions, iii) drowsy driving iv) mind wandering, v) error and vi) carelessness. Content and face validity were sought through expert review. A total of 442 nurses' data were collected across multisite hospitals for evaluation. Exploratory factor analysis (EFA) resulted in recovered structure and was confirmed through Confirmatory Factor Analysis (CFA) with structural equation analyses being conducted to test predictive validity. All constructs met adequate validity and reliability. Nurses' unsafe driving behaviours while commuting were identified with a novel scale to assess them being both developed and validated. The resulting MyUDWC scale is a suitable tool for measuring nurses' unsafe driving behaviours while commuting.
  5. Rahmani M, Ghafoorifard H, Afrang S, Ahmadi MT, Rahmani K, Ismail R
    IET Nanobiotechnol, 2019 Aug;13(6):584-592.
    PMID: 31432790 DOI: 10.1049/iet-nbt.2018.5288
    The response of trilayer graphene nanoribbon (TGN)-based ion-sensitive field-effect transistor (ISFET) to different pH solutions and adsorption effect on the sensing parameters are analytically studied in this research. The authors propose a TGN-based sensor to electrochemically detect pH. To this end, absorption effect on the sensing area in the form of carrier concentration, carrier velocity, and conductance variations are investigated. Also, the caused electrical response on TGN as a detection element is analytically proposed, in which significant current decrease of the sensor is observed after exposure to high pH values. In order to verify the accuracy of the model, it is compared with recent reports on pH sensors. The TGN-based pH sensor exposes higher current compared to that of carbon nanotube (CNT) counterpart for analogous ambient conditions. While, the comparative results demonstrate that the conductance of proposed model is lower than that of monolayer graphene-counterpart for equivalent pH values. The results confirm that the conductance of the sensor is decreased and Vg-min is obviously right-shifted by increasing value of pH. The authors demonstrate that although there is not the experimental evidence reported in the part of literature for TGN sensor, but the model can assist in comprehending experiments involving nanoscale pH sensors.
  6. Soo CI, Mak WW, Nasaruddin MZ, Ismail R, Ban AY, Abdul Rahaman JA
    Singapore Med J, 2024 Feb 01;65(2):119-122.
    PMID: 34617697 DOI: 10.11622/smedj.2021144
  7. Nouri M, Meshginqalam B, Sahihazar MM, Sheydaie Pour Dizaji R, Ahmadi MT, Ismail R
    IET Nanobiotechnol, 2018 Dec;12(8):1125-1129.
    PMID: 30964025 DOI: 10.1049/iet-nbt.2018.5068
    Nowadays, sensitive biosensors with high selectivity, lower costs and short response time are required for detection of DNA. The most preferred materials in DNA sensor designing are nanomaterials such as carbon and Au nanoparticles, because of their very high surface area and biocompatibility which lead to performance and sensitivity improvements in DNA sensors. Carbon nanomaterials such as carbon nanotubes (CNTs) can be considered as a suitable DNA sensor platform due to their high surface-to-volume ratio, favourable electronic properties and fast electron transfer rate. Therefore, in this study, the CNTs which are synthesised by pulsed AC arc discharge method on a high-density polyethylene substrate are used as conducting channels in a chemiresistor for the electrochemical detection of double stranded DNA. Moreover, the response of the proposed sensor is investigated experimentally and analytically in different temperatures, which confirm good agreement between the presented model and experimental data.
  8. George R, Donald PM, Nagraj SK, Idiculla JJ, Hj Ismail R
    Malays J Med Sci, 2013 Jan;20(1):76-80.
    PMID: 23785258 MyJurnal
    Sex determination is the most important step in personal identification in forensic investigations. DNA-based sex determination analysis is comparatively more reliable than the other conventional methods of sex determination analysis. Advanced technology like real-time polymerase chain reaction (PCR) offers accurate and reproducible results and is at the level of legal acceptance. But still there are situations like chimerism where an individual possess both male and female specific factors together in their body. Sex determination analysis in such cases can give erroneous results. This paper discusses the phenomenon of chimerism and its impact on sex determination analysis in forensic investigations.
  9. Zahari Z, Salleh MR, Zahri Johari MK, Musa N, Ismail R
    Malays J Med Sci, 2011 Oct;18(4):44-57.
    PMID: 22589672 MyJurnal
    The dopamine D2 receptor gene (DRD2) plays a role in many diseases such as schizophrenia, Parkinson's disease, and addictive behaviour. Methods currently available for the detection of DRD2 polymorphisms are costly and cannot detect all 8 polymorphisms of our research interest simultaneously (Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, A-241G, and -141C Ins/Del). Therefore, we developed a nested multiplex polymerase chain reaction (PCR) for simultaneous detection of these polymorphisms.
  10. Al Sulayyim H, Ismail R, Al Hamid A, Mohammed B, Abdul Ghafar N
    J Infect Dev Ctries, 2024 Mar 31;18(3):371-382.
    PMID: 38635620 DOI: 10.3855/jidc.19071
    INTRODUCTION: Prevalence of antibiotic resistance (AR) during the coronavirus 2019 (COVID-19) pandemic was higher than pre-pandemic times. This study determined the prevalence and patterns of AR among Gram-positive and negative bacteria before, during and after COVID-19 in Saudi Arabia and identified the associated factors.

    METHODOLOGY: A retrospective cross-sectional study was employed to identify patients with positive AR bacteria between March 2019 and March 2022. The bacterial isolates and patients' data were identified from laboratory and medical records departments retrospectively. Binary logistic regression analysis was performed to identify the factors associated with AR and deaths. Multinominal logistic regression was applied to confirm the factors associated with AR classification.

    RESULTS: AR Gram-negative bacteria decreased during and after the pandemic. However, S. aureus showed a negligible increase in resistance rate after pandemic, while E. faecium, recorded a higher-than-average resistance rate during the pandemic. The prevalence of pan drug resistance (PDR) during the pandemic (85.7%) was higher than before (0%) and after (14.3%), p = 0.001. The length of stay and time were significant predictors for AR classification. The odds of multi drug resistance (MDR) development to PDR during the pandemic were 6 times higher than before and after (OR = 6.133, CI =, p = 0.020). Age, nationality, COVID-19 infection, smoking, liver disease, and type and number of bacteria were associated with death of patients with positive AR.

    CONCLUSIONS: Further studies are recommended to explore the prevalence of PDR and to justify the increased rates of E. faecium AR during the COVID-19 pandemic.

  11. Chong CY, Bustam A, Noor Azhar M, Abdul Latif AK, Ismail R, Poh K
    Am J Emerg Med, 2024 May;79:19-24.
    PMID: 38330879 DOI: 10.1016/j.ajem.2024.01.044
    BACKGROUND AND IMPORTANCE: Acute cardiogenic pulmonary oedema (ACPO) is a common indication for non-invasive ventilation (NIV) in the emergency department (ED). HACOR score of >5 is used to predict NIV failure. The predictive ability of HACOR may be affected by altered physiological parameters in ACPO patients due to medications or comorbidities.

    OBJECTIVES: To validate the HACOR scale in predicting NIV failure among acute cardiogenic pulmonary oedema (ACPO) patients.

    DESIGN, SETTINGS AND PARTICIPANTS: This is a prospective, observational study of consecutive ACPO patients requiring NIV admitted to the ED.

    OUTCOME MEASURE AND ANALYSIS: Primary outcome was the ability of the HACOR score to predict NIV failure. Clinical, physiological, and HACOR score at baseline and at 1 h, 12 h and 24 h were analysed. Other potential predictors were assessed as secondary outcomes.

    MAIN RESULTS: A total of 221 patients were included in the analysis. Fifty-four (24.4%) had NIV failure. Optimal HACOR score was >5 at 1 h after NIV initiation in predicting NIV failure (AUC 0.73, sensitivity 53.7%, specificity 83.2%). As part of the HACOR score, respiratory rate and heart rate were not found to be significant predictors. Other significant predictors of NIV failure in ACPO patients were acute coronary syndrome, acute kidney injury, presence of congestive heart failure as a comorbid, and the ROX index.

    CONCLUSIONS: The HACOR scale measured at 1 h after NIV initiation predicts NIV failure among ACPO patients with acceptable accuracy. The cut-off level > 5 could be a useful clinical decision support tool in ACPO patient. However, clinicians should consider other factors such as the acute coronary and acute kidney diagnosis at presentation, presence of underlying congestive heart failure and the ROX index when clinically deciding on timely invasive mechanical ventilation.

  12. Ibrahim N, Teo SS, Che Din N, Abdul Gafor AH, Ismail R
    PLoS One, 2015;10(7):e0129015.
    PMID: 26131714 DOI: 10.1371/journal.pone.0129015
    BACKGROUND: Chronic kidney disease (CKD) is commonly associated with various negative health outcomes. The aim of this study was to examine the influence of personality and social support on health-related quality of life in patients with chronic kidney disease. Health-related quality of life (HRQoL) is the quality of life studied in relation to health, and it provides important information of patients' coping with their health issues.

    METHOD: Participants comprised of 200 patients experiencing various stages of chronic kidney disease. All participants completed the Short-Form 36 (SF-36), Big Five Inventory (BFI) and the Medical Outcomes Study (MOS) Social Support questionnaires.

    RESULTS: Participants consisted of 108 males (54.0%) and 92 females (46.0%) with the mean age of 59.3 years (SD 14.5). Results showed that higher levels of extraversion and lower perceived affectionate social support were associated with higher physical HRQoL, whereas higher levels of neuroticism were associated with poorer mental HRQoL.

    CONCLUSION: The current study found that certain personality traits, namely extraversion and neuroticism, were found to be associated with HRQoL. In addition, affectionate social support was also associated with higher HRQoL. Therefore, special attention should be paid to the personality of CKD patients, as well as the type of social support that they have, in planning interventions to improve their health outcomes.

  13. Mutang JA, Chua BS, Hon KY, Siau CS, Wider W, Ismail R
    Int J Environ Res Public Health, 2022 Sep 07;19(18).
    PMID: 36141527 DOI: 10.3390/ijerph191811258
    The COVID-19 pandemic has had a huge impact not only on healthcare systems and economic threats but also on relationships. Due to the massive measures of the Movement Control Order, such as social distancing, strictly limited physical activities, and making adjustments to working from home-merged with the pandemic's fear-romantic partners may face challenges that affect the quality of their relationships. The purpose of this study was to (i) identify stressors experienced by participants during the COVID-19 lockdown, (ii) evaluate participants'psychological well-being before and during the lockdown, and (iii) see if participants' perceived relationship quality differed before and during the lockdown. An online self-report questionnaire was used to recruit 334 adults (58.1 percent female, 41.9 percent male) with partners (married = 304, engaged = 12, and in committed relationships = 17). Participants were asked about stressors they encountered as a result of COVID-19 using an open-ended question. The Depression Anxiety Stress Scales (DASS-21) were used to assess mental health, and the Perceived Relationship Quality Component (PRQC) Inventory was used to assess relationship quality. According to the findings, the top three common stressors reported by participants were financial problems, restricted movement, and fear of COVID-19 infection. Participants reported significantly higher levels of stress, anxiety, and depression during the lockdown than before. The findings also revealed that participants' relationship quality improved during the lockdown compared to before the lockdown. The current study contributes by providing information on the impact of the COVID-19 pandemic on mental health and the quality of couples' relationships during the pandemic.
  14. Ngow H, Teh LK, Langmia IM, Lee WL, Harun R, Ismail R, et al.
    Xenobiotica, 2008 Jun;38(6):641-51.
    PMID: 18570163 DOI: 10.1080/00498250801999087
    1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of 1, 2, 3 and 4 CYP2C9 alleles, using a nested-allele-specific-multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9 1/1 and 6.8% were CYP2C9 1/3. Warfarin doses were higher in patients with CYP2C91/1. Patients with the 1/3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.
  15. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Am J Drug Alcohol Abuse, 2016 09;42(5):587-596.
    PMID: 27284701 DOI: 10.3109/00952990.2016.1172078
    BACKGROUND: Methadone is a substrate of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Large interindividual variability in serum methadone levels for therapeutic response has been reported. Genetic variations in ABCB1 gene may be responsible for the variability in observed methadone concentrations.
    OBJECTIVE: This study investigated the associations of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval in opioid-dependent patients on methadone maintenance therapy (MMT).
    METHODS: One hundred and forty-eight male opioid-dependent patients receiving MMT were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from whole blood and genotyped for ABCB1 polymorphisms [i.e. 1236C>T (dbSNP rs1128503), 2677G>T/A (dbSNP rs2032582), and 3435C>T (dbSNP rs1045642)] using the allelic discrimination real-time polymerase chain reaction (PCR). Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the dose. Serum methadone concentrations were measured using the Methadone ELISA Kit.
    RESULTS: Our results revealed an association of CGC/TTT diplotype (1236C>T, 2677G>T/A, and 3435C>T) with dose-adjusted serum methadone concentration over the 24-hour dosing interval. Patients with CGC/TTT diplotype had 32.9% higher dose-adjusted serum methadone concentration over the 24-hour dosing interval when compared with those without the diplotype [mean (SD) = 8.12 (0.84) and 6.11 (0.41) ng ml-1mg-1, respectively; p = 0.033].
    CONCLUSION: There was an association between the CGC/TTT diplotype of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval among patients on MMT. Genotyping of ABCB1 among opioid-dependent patients on MMT may help individualize and optimize methadone substitution treatment.
    Study site: Psychiatric Clinic, Hospital Universiti Sains Malaysia (HUSM), and other MMT clinics in Kelantan,
    Malaysia
  16. Keng Yoon Y, Ashraf Ali M, Choon TS, Ismail R, Chee Wei A, Suresh Kumar R, et al.
    Biomed Res Int, 2013;2013:926309.
    PMID: 24381946 DOI: 10.1155/2013/926309
    A total of seven novel benzimidazoles were synthesized by a 4-step reaction starting from 4-fluoro-3-nitrobenzoic acid under relatively mild reaction conditions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H₃₇Rv (MTB-H₃₇Rv) and INH-resistant M. tuberculosis (INHR-MTB) strains using agar dilution method. Three of them displayed good activity with MIC of less than 0.2 μM. Compound ethyl 1-(2-(4-(4-(ethoxycarbonyl)-2-aminophenyl)piperazin-1-yl)ethyl)-2-(4-(5-(4-fluorophenyl)pyridin-3-ylphenyl-1H-benzo[d]imidazole-5-carboxylate (5 g) was found to be the most active with MIC of 0.112 μM against MTB-H₃₇Rv and 6.12 μM against INHR-MTB, respectively.
  17. Mamat R, Kong NC, Ba'in A, Shah SA, Cader R, Wong V, et al.
    J Clin Nurs, 2012 Oct;21(19-20):2879-85.
    PMID: 22646855 DOI: 10.1111/j.1365-2702.2012.04091.x
    The main objective of the study was to correlate the target dry weight in haemodialysis (HD) patients as assessed clinically by nephrologists to those measured by the Body Composition Monitor (BCM - Fresenius) machine. The second objective was to compare pre and postdialysis changes of extracellular fluid and clinical parameters.
  18. Ali MA, Ismail R, Choon TS, Yoon YK, Wei AC, Pandian S, et al.
    Acta Pol Pharm, 2011 May-Jun;68(3):343-8.
    PMID: 21648188
    A series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized by the reaction of 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone with hydroxylamine hydrochloride. The title compounds were tested for their in vitro anti-HIV activity. Among the compounds, (4g) showed a promising anti-HIV activity in the in vitro testing against IIIB and ROD strains. The IC50 of both IIIB and ROD were found to be 9.05 microM and > 125 microM, respectively.
  19. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, et al.
    J Ethnopharmacol, 2010 Jul 20;130(2):275-83.
    PMID: 20457244 DOI: 10.1016/j.jep.2010.05.002
    ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (CA) has been widely cultivated as a vegetable or spice in China, Southeast Asia, India, Sri Lanka, Africa, and Oceanic countries and traditionally used for wound healing and maintaining normal blood pressure.

    AIM OF THE STUDY: The present study was carried out to examine the potential modulatory effects of three commercially available active components (asiaticoside, asiatic acid and madecassic acid) and four extracts (aqueous, ethanol, dichloromethane and hexane) of CA on three major cDNA-expressed human cytochrome P450 (CYP) isoforms.

    MATERIALS AND METHODS: High-performance liquid chromatography (HPLC)-based enzyme assays, namely tolbutamide 4-methyhydroxylase, dextromethorphan O-demethylase and testosterone 6beta-hydroxylase assays were developed to probe activities of CYP2C9, CYP2D6 and CYP3A4, respectively. Probe substrates were incubated with or without each active component and extract for each isoform, followed by examination of the kinetics parameters, IC(50) and K(i), to characterize modulatory effects.

    RESULTS: CYP2C9 was more susceptible to inhibitory effects by CA extracts compared to CYP2D6 and CYP3A4. Moderate degree of inhibition was observed in ethanol (K(i)=39.1 microg/ml) and dichloromethane (K(i)=26.6 microg/ml) extracts implying potential risk of interaction when CYP2C9 substrates are consumed with CA products. The two extracts however showed negligible inhibition towards CYP2D6 and CYP3A4 (IC(50)'s of 123.3 microg/ml and above). Similarly CA aqueous and hexane extracts did not significantly inhibit all three isoforms investigated (IC(50)'s of 117.9 microg/ml and above). Among the active constituents investigated, asiatic acid and madecassic acid appeared to selectively inhibit CYP2C9 and CYP2D6 more than CYP3A4. Of particular interest is the potent inhibitory effect of asiatic acid on CYP2C9 (K(i)=9.1 microg/ml). This signifies potential risk of interaction when substrates for this isoform are taken together with CA products with high asiatic acid content. Inhibitions of asiatic acid with the other isoforms and that of madecassic acid with all isoforms were only moderate (K(i)'s ranged from 17.2 to 84.4 microg/ml). On the other hand, the IC(50) values for asiaticoside were high (1070.2 microg/ml or above) for all three isoforms, indicating negligible or low potential of this compound to modulate CYP enzymatic activity.

    CONCLUSION: Centella asiatica extracts and active constituents inhibited CYP2C9, CYP2D6 and CYP3A4 activities with varying potency with CYP2C9 being the most susceptible isoform to inhibition. Significant inhibition was observed for asiatic acid and CA ethanol and dichloromethane extracts, implying involvement of semipolar constituents from CA in the effect. This study suggested that CA could cause drug-herb interactions through CYP2C9 inhibition.

  20. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, et al.
    J Nat Med, 2011 Jul;65(3-4):440-7.
    PMID: 21365364 DOI: 10.1007/s11418-011-0516-z
    We investigated the effects of Andrographis paniculata (AP) extracts and andrographolide on the catalytic activity of three human cDNA-expressed cytochrome P450 enzymes: CYP2C9, CYP2D6 and CYP3A4. In vitro probe-based high performance liquid chromatography assays were developed to determine CYP2C9-dependent tolbutamide methylhydroxylation, CYP2D6-dependent dextromethorphan O-demethylation and CYP3A4-dependent testosterone 6β-hydroxylation activities in the presence and absence of AP extracts and andrographolide. Our results indicate that AP ethanol and methanol extracts inhibited CYP activities more potently than aqueous and hexane extracts across the three isoforms. Potent inhibitory effects were observed on CYP3A4 and CYP2C9 activities (K (i) values below 20 μg/ml). Andrographolide was found to exclusively but weakly inhibit CYP3A4 activity. In conclusion, data presented in this study suggest that AP extracts have the potential to inhibit CYP isoforms in vitro. There was, however, variation in the potency of inhibition depending on the extracts and the isoforms investigated.
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