Displaying publications 1 - 20 of 77 in total

Abstract:
Sort:
  1. Fulltext 9-Benzyl-6-benzyl-sulfanyl-9H-purin-2-amine
    Hariono M, Wahab HA, Tan ML, Rosli MM, Razak IA
    Acta Crystallogr Sect E Struct Rep Online, 2014 Mar 1;70(Pt 3):o288.
    PMID: 24764997 DOI: 10.1107/S1600536814001986
    In the title compound, C19H17N5S, the dihedral angles between the purine ring system (r.m.s. deviation = 0.009 Å) and the S-bound and methyl-ene-bound phenyl rings are 74.67 (8) and 71.28 (7)°, respectively. In the crystal, inversion dimers linked by pairs of N-H⋯N hydrogen bonds generate R 2 (2)(8) loops. C-H⋯N inter-actions link the dimers into (100) sheets.
  2. The 'Pink herring'
    Foong SC, Tan ML, Foong WC, Ho JJ
    Arch Dis Child Educ Pract Ed, 2020 12;105(6):372-373.
    PMID: 31073039 DOI: 10.1136/archdischild-2018-316682
  3. The mTOR signalling pathway in cancer and the potential mTOR inhibitory activities of natural phytochemicals
    Tan HK, Moad AI, Tan ML
    Asian Pac J Cancer Prev, 2014;15(16):6463-75.
    PMID: 25169472
    The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.
  4. Lack of increased P15INK4B protein expression in basal cell carcinomas
    Moad AI, Tan ML, Kaur G, Mabruk M
    Asian Pac J Cancer Prev, 2012;13(12):6239-44.
    PMID: 23464438
    BACKGROUND: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. P15INK4b is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of p15INK4b protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate p15INK4b protein expression in BCCs.

    MATERIALS AND METHOD: Protein expression of p15INK4b in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach.

    RESULTS: The expression of p15INK4b was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and p15INK4b protein expression.

    CONCLUSIONS: Our finding may indicate that p15INK4b protein expression does not play a role in the genesis of BCC.

  5. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
    Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  6. Fulltext Advanced Nanoparticle-Based Drug Delivery Systems and Their Cellular Evaluation for Non-Small Cell Lung Cancer Treatment
    Mohtar N, Parumasivam T, Gazzali AM, Tan CS, Tan ML, Othman R, et al.
    Cancers (Basel), 2021 Jul 15;13(14).
    PMID: 34298753 DOI: 10.3390/cancers13143539
    Lung cancers, the number one cancer killer, can be broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC being the most commonly diagnosed type. Anticancer agents for NSCLC suffer from various limitations that can be partly overcome by the application of nanomedicines. Nanoparticles is a branch within nanomedicine that can improve the delivery of anticancer drugs, whilst ensuring the stability and sufficient bioavailability following administration. There are many publications available in the literature exploring different types of nanoparticles from different materials. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. This includes the developed nanoparticles, to prove their safety and efficacy. Many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. However, in cellular works, the physiological dynamics that is available in the body could not be mimicked entirely, and hence, there is still possible development of false positive or false negative results from the in vitro models. This article provides an overview of NSCLC, the different nanoparticles available to date, and in vitro evaluation of the nanoparticles. Different types of cells suitable for in vitro study and the important precautions to limit the development of false results are also extensively discussed.
  7. Fulltext Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1
    Lai SL, Tan ML, Hollows RJ, Robinson M, Ibrahim M, Margielewska S, et al.
    Cancers (Basel), 2019 Nov 09;11(11).
    PMID: 31717573 DOI: 10.3390/cancers11111766
    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.
  8. Rapamycin induces apoptosis when autophagy is inhibited in T-47D mammary cells and both processes are regulated by Phlda1
    Moad AI, Muhammad TS, Oon CE, Tan ML
    Cell Biochem Biophys, 2013 Jul;66(3):567-87.
    PMID: 23300026 DOI: 10.1007/s12013-012-9504-5
    Autophagy is an evolutionarily conserved lysosomal degradation pathway and plays a critical role in the homeostatic process of recycling proteins and organelles. Functional relationships have been described between apoptosis and autophagy. Perturbations in the apoptotic machinery have been reported to induce autophagic cell deaths. Inhibition of autophagy in cancer cells has resulted in cell deaths that manifested hallmarks of apoptosis. However, the molecular relationships and the circumstances of which molecular pathways dictate the choice between apoptosis and autophagy are currently unknown. This study aims to identify specific gene expression of rapamycin-induced autophagy and the effects of rapamycin when the autophagy process is inhibited. In this study, we have demonstrated that rapamycin is capable of inducing autophagy in T-47D breast carcinoma cells. However, when the autophagy process was inhibited by 3-MA, the effects of rapamycin became apoptotic. The Phlda1 gene was found to be up-regulated in both autophagy and apoptosis and silencing this gene was found to reduce both activities, strongly suggests that Phlda1 mediates and positively regulates both autophagy and apoptosis pathways.
  9. Fulltext Cytotoxic data of 14-deoxy-11, 12-didehydroandrographolide (14-DDA), double transfection and DDIT3 silencing data in T-47D breast carcinoma cells
    Tan HK, Tengku Muhammad TS, Tan ML
    Data Brief, 2016 Jun;7:1506-10.
    PMID: 27182548 DOI: 10.1016/j.dib.2016.04.046
    The data presented in this article are related to the research article entitled "14-deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells", which the mechanistic toxicology properties of 14-deoxy-11,12-didehydroandrographolide (14-DDA) were investigated (Tan et al., 2016 [1]). This article describes the derivation of cytotoxic parameters of 14-DDA, cell viability data after double transfection and DDIT3 silencing in T-47D cells.
  10. Fulltext Data on the construction of a recombinant HEK293 cell line overexpressing hERG potassium channel and examining the presence of hERG mRNA and protein expression
    Teah YF, Abduraman MA, Amanah A, Adenan MI, Fariza Sulaiman S, Tan ML
    Data Brief, 2017 Oct;14:584-591.
    PMID: 28879216 DOI: 10.1016/j.dib.2017.08.008
    The data presented in this article are related to the research article entitled "The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression" (Y.F. Teah, M.A. Abduraman, A. Amanah, M.I. Adenan, S.F. Sulaiman, M.L. Tan) [1], which the possible hERG blocking properties of deoxyelephantopin were investigated. This article describes the construction of human embryonic kidney 293 (HEK293) cells overexpressing HERG potassium channel and verification of the presence of hERG mRNA and protein expression in this recombinant cell line.
  11. The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms' activities, a review of possible herb-drug interaction risks
    Tan ML, Lim LE
    Drug Chem Toxicol, 2015;38(3):241-53.
    PMID: 25156015 DOI: 10.3109/01480545.2014.947504
    Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.
  12. Fulltext Trace metals contamination in groundwater and implications on human health: comprehensive assessment using hydrogeochemical and geostatistical methods
    Brindha K, Paul R, Walter J, Tan ML, Singh MK
    Environ Geochem Health, 2020 Nov;42(11):3819-3839.
    PMID: 32601907 DOI: 10.1007/s10653-020-00637-9
    Monitoring the groundwater chemical composition and identifying the presence of pollutants is an integral part of any comprehensive groundwater management strategy. The present study was conducted in a part of West Tripura, northeast India, to investigate the presence and sources of trace metals in groundwater and the risk to human health due to direct ingestion of groundwater. Samples were collected from 68 locations twice a year from 2016 to 2018. Mixed Ca-Mg-HCO3, Ca-Cl and Ca-Mg-Cl were the main groundwater types. Hydrogeochemical methods showed groundwater mineralization due to (1) carbonate dissolution, (2) silicate weathering, (3) cation exchange processes and (4) anthropogenic sources. Occurrence of faecal coliforms increased in groundwater after monsoons. Nitrate and microbial contamination from wastewater infiltration were apparent. Iron, manganese, lead, cadmium and arsenic were above the drinking water limits prescribed by the Bureau of Indian Standards. Water quality index indicated 1.5% had poor, 8.7% had marginal, 16.2% had fair, 66.2% had good and 7.4% had excellent water quality. Correlation and principal component analysis reiterated the sources of major ions and trace metals identified from hydrogeochemical methods. Human exposure assessment suggests health risk due to high iron in groundwater. The presence of unsafe levels of trace metals in groundwater requires proper treatment measures before domestic use.
  13. Spatial-temporal pattern of change in production-living-ecological space of Nanchong City from 2000 to 2020 and underlying factors
    Xu H, Zhang F, Li W, Shi J, Johnson BA, Tan ML
    Environ Monit Assess, 2023 Dec 27;196(1):94.
    PMID: 38150164 DOI: 10.1007/s10661-023-12249-8
    This study analyzed the spatial-temporal change pattern and underlying factors in production-living-ecological space (PLES) of Nanchong City, China, over the past 20 years using historical land use data (2000, 2010, 2020). A land use transfer matrix was calculated from the historical land use maps, and spatial analysis was conducted to analyze changes in the land use dynamics degree, standard deviation ellipse, and center of gravity. The results showed that there was a rapid spatial evolution of the PLES in Nanchong from 2000 to 2010, followed by a stabilization in the second decade. The transfer of ecological-production space occurred mainly in the Jialing and Yilong River basins, while the reduction of production space and the increase of living space were most prominent in the intersection of three districts (Shunqing, Jialing, and Gaoping districts). The return of production-ecological space was observed in the south and northeast of Yingshan, and there was little notable transfer of other types. The distribution of production space in Nanchong evolved in a north-south to east-west trend, with the center of gravity moving from Yilong to Peng'an County. The living space and production space expanded in a north-south direction, and the center of gravity position was in Nanbu, indicating a more balanced growth or decrease in the last 20 years. The changes in the spatial-temporal pattern of PLES in Nanchong were attributed to the intertwined factors of national policies, economic development, population growth, and the natural environment. This study introduced a novel approach towards rational planning of land resources in Nanchong, which may facilitate more sustainable urban planning and development.
  14. Pollutant source, ecological and human health risks assessment of heavy metals in soils from coal mining areas in Xinjiang, China
    Zhang H, Zhang F, Song J, Tan ML, Kung HT, Johnson VC
    Environ Res, 2021 11;202:111702.
    PMID: 34284019 DOI: 10.1016/j.envres.2021.111702
    This study aims to analyze the pollution characteristics and sources of heavy metal elements for the first time in the Zhundong mining area in Xinjiang using the linear regression model. Additionaly, the health risks with their probability and infleuencing factors on different groups of people's were also evaluated using Monte Carlo (MC) simulation approach. The results shows that 89.28% of Hg was from coal combustion, 40.28% of Pb was from transportation, and 19.54% of As was from atmospheric dust. The main source of Cu and Cr was coal dust, Hg has the greatest impact on potential ecological risks. which accounted for 60.2% and 81.46% of the Cu and Cr content in soil, respectively. The all samples taken from Pb have been Extremely polluted (100%). 93.3% samples taken from As have been Extremely polluted. The overall potential ecological risk was moderate. Adults experienced higher non-carcinogenic risks of heavy metals from their diets than children. Interestingly, body weight was the main factor affecting the adult's health risks. This research provides more comprehensive information for better soil management, soil remediation, and soil pollution control in the Xinjiang mining areas.
  15. Megacities' environmental assessment for Iraq region using satellite image and geo-spatial tools
    Tao H, Hashim BM, Heddam S, Goliatt L, Tan ML, Sa'adi Z, et al.
    Environ Sci Pollut Res Int, 2023 Mar;30(11):30984-31034.
    PMID: 36441299 DOI: 10.1007/s11356-022-24153-8
    Urban areas are quickly established, and the overwhelming population pressure is triggering heat stress in the metropolitan cities. Climate change impact is the key aspect for maintaining the urban areas and building proper urban planning because spreading of the urban area destroyed the vegetated land and increased heat variation. Remote sensing-based on Landsat images are used for investigating the vegetation circumstances, thermal variation, urban expansion, and surface urban heat island or SUHI in the three megacities of Iraq like Baghdad, Erbil, and Basrah. Four satellite imageries are used aimed at land use and land cover (LULC) study from 1990 to 2020, which indicate the land transformation of those three major cities in Iraq. The average annually temperature is increased during  30 years like Baghdad (0.16 °C), Basrah (0.44 °C), and Erbil (0.32 °C). The built-up area is increased 147.1 km2 (Erbil), 217.86 km2 (Baghdad), and 294.43 km2 (Erbil), which indicated the SUHI affects the entire area of the three cities. The bare land is increased in Baghdad city, which indicated the local climatic condition and affected the livelihood. Basrah City is affected by anthropogenic activities and most areas of Basrah were converted into built-up land in the last 30 years. In Erbil, agricultural land (295.81 km2) is increased. The SUHI study results indicated the climate change effect in those three cities in Iraq. This study's results are more useful for planning, management, and sustainable development of urban areas.
  16. Assessing the factors influencing water quality using environment water quality index and partial least squares structural equation model in the Ebinur Lake Watershed, Xinjiang, China
    Liu C, Zhang F, Wang X, Chan NW, Rahman HA, Yang S, et al.
    Environ Sci Pollut Res Int, 2022 Jan 07.
    PMID: 34993791 DOI: 10.1007/s11356-021-17886-5
    Surface water quality deterioration is commonly associated with environmental changes and human activities. Although some research has been carried out to evaluate the relationship between various influencing factors and water quality, there is still very little scientific understanding on how to accurately define the key factors of water quality deterioration. This study aims to quantify the impact of environmental factors and land use land cover (LULC) changes on water quality in the Ebinur Lake Watershed, Xinjiang, China. A total of 20 water parameters were used to calculate the Environment Water Quality Index (CWQI). Meanwhile, the partial least squares-structural equation model (PLS-SEM) was used to quantify the impact of eleven factors influencing water quality in the watershed. About 33.3% of the monitoring points that located mostly in the downstream region with dominant anthropogenic activities were detected as poor quality. There were no obvious temporal changes in water quality from 2016 to 2019. The PLS-SEM simulation shows that the latent variable "land use/cover types" (path coefficient =  - 0.600) and "Environmental factor" (path coefficient =  - 0.313) are two major factors affected water quality in the Ebinur Lake Watershed, with a strong explanatory power to water quality change (R2 = 0.727). In the latent variable "Environmental factors", the "NDVI" and "night light brightness value" have a great influence on water quality, with the weights of 0.451 and 0.427, respectively. Correspondingly, the "farmland" and "forest land" within the latent variable of "Land use/cover type" have a considerable impact water quality, with the weights of 0.361 and - 0.340, respectively. In conclusion, the influence of anthropogenic activities on surface water quality of the Ebinur Lake Watershed is greater than that of environmental factors. Compared with the traditional multivariate statistical method, PLS-SEM provides a new insight for quantifying the complex relationship between different influencing factors and water quality.
  17. Spatio-temporal changes in fractional vegetation cover and the driving forces during 2001-2020 in the northern slopes of the Tianshan Mountains, China
    He X, Zhang F, Cai Y, Tan ML, Chan NW
    Environ Sci Pollut Res Int, 2023 Jun;30(30):75511-75531.
    PMID: 37222898 DOI: 10.1007/s11356-023-27702-x
    This study aims to understand the factors and mechanisms influencing the spatio-temporal changes of fractional vegetation cover (FVC) in the northern slopes of the Tianshan Mountains. The MOD13Q1 product data between June and September (peak of plants growing) during the 2001-2020 period was incorporated into the pixel dichotomy model to calculate the vegetation cover changes. Then, the principal component analysis method was used to identify the primary driving factors affecting the change in vegetation cover from the natural, human, and economic perspectives. Finally, the partial correlation coefficients of FVC with temperature and precipitation were further calculated based on the pixel scale. The findings indicate that (1) FVC in the northern slopes of the Tianshan Mountains ranged from 0.37 to 0.47 during the 2001-2020 period, with an obvious inter-annual variation and an overall upward trend of about 0.4484/10 a. Although the vegetation cover had some changes over time, it was generally stable, and the area of strong variation only accounted for 0.58% of the total. (2) The five grades of vegetation cover were distributed spatially similarly, but the area-weighted gravity center for each vegetation class shifted significantly. The FVC under different land use/land cover types and elevations was obviously different, and as elevation increased, vegetation coverage presented a trend of a "∩"-shape change. (3) According to the results of principal component analysis, human activities, economic growth, and natural climate were the main driving factors that caused the changes in vegetation cover, and the cumulative contribution of the three reached 89.278%. In addition, when it came to climatic factors, precipitation had a greater driving force on the vegetation cover change, followed by temperature and sunshine hours. (4) Overall, precipitation and temperature were correlated positively with FVC, with the average correlation coefficient values of 0.089 and 0.135, respectively. Locally, the correlations vary greatly under different LULC and altitudes. This research can provide some scientific basis and reference for the vegetation evolution pattern and ecological civilization construction in the region.
  18. Surface water quality index forecasting using multivariate complementing approach reinforced with locally weighted linear regression model
    Hai T, Ahmadianfar I, Halder B, Heddam S, Al-Areeq AM, Demir V, et al.
    Environ Sci Pollut Res Int, 2024 Apr 23.
    PMID: 38653893 DOI: 10.1007/s11356-024-33027-0
    River water quality management and monitoring are essential responsibilities for communities near rivers. Government decision-makers should monitor important quality factors like temperature, dissolved oxygen (DO), pH, and biochemical oxygen demand (BOD). Among water quality parameters, the BOD throughout 5 days is an important index that must be detected by devoting a significant amount of time and effort, which is a source of significant concern in both academic and commercial settings. The traditional experimental and statistical methods cannot give enough accuracy or solve the problem for a long time to detect something. This study used a unique hybrid model called MVMD-LWLR, which introduced an innovative method for forecasting BOD in the Klang River, Malaysia. The hybrid model combines a locally weighted linear regression (LWLR) model with a wavelet-based kernel function, along with multivariate variational mode decomposition (MVMD) for the decomposition of input variables. In addition, categorical boosting (Catboost) feature selection was used to discover and extract significant input variables. This combination of MVMD-LWLR and Catboost is the first use of such a complete model for predicting BOD levels in the given river environment. In addition, an optimization process was used to improve the performance of the model. This process utilized the gradient-based optimization (GBO) approach to fine-tune the parameters and better the overall accuracy of predicting BOD levels. To assess the robustness of the proposed method, we compared it to other popular models such as kernel ridge (KRidge) regression, LASSO, elastic net, and gaussian process regression (GPR). Several metrics, comprising root-mean-square error (RMSE), R (correlation coefficient), U95% (uncertainty coefficient at 95% level), and NSE (Nash-Sutcliffe efficiency), as well as visual interpretation, were used to evaluate the predictive efficacy of hybrid models. Extensive testing revealed that, in forecasting the BOD parameter, the MVMD-LWLR model outperformed its competitors. Consequently, for BOD forecasting, the suggested MVMD-LWLR optimized with the GBO algorithm yields encouraging and reliable results, with increased forecasting accuracy and minimal error.
  19. The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression
    Teah YF, Abduraman MA, Amanah A, Adenan MI, Sulaiman SF, Tan ML
    Food Chem Toxicol, 2017 Sep;107(Pt A):293-301.
    PMID: 28689918 DOI: 10.1016/j.fct.2017.07.011
    Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr blocker.
  20. Evaluation of in vitro cytochrome P450 induction and inhibition activity of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber L
    Koe XF, Lim EL, Seah TC, Amanah A, Wahab HA, Adenan MI, et al.
    Food Chem Toxicol, 2013 Oct;60:98-108.
    PMID: 23876819 DOI: 10.1016/j.fct.2013.07.030
    Drug metabolism involving cytochrome P450 (CYP) enzymes is a key determinant of significant drug interactions. Deoxyelephantopin was evaluated for its effects on the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4, and protein expression and resultant enzymatic activity. The mRNA and protein expression of cytochrome isoforms were carried out using an optimized multiplex qRT-PCR assay and Western blot analysis, respectively. Human CYP3A4 protein expression was determined using an optimized hCYP3A4-HepG2 cell-based assay and the enzymatic activity was evaluated using P450-Glo™ CYP3A4 assay. The molecular interaction and possible inhibition of deoxyelephantopin of the CYP3A4 enzyme was determined in silico and further validated using substrate-specific CYP3A4 inhibition assays. Deoxyelephantopin produced no significant effect on the CYP1A2 and CYP2D6 mRNA and protein expression. However, it has a weak induction effect on CYP3A4 at the transcriptional level. In silico docking simulation showed that deoxyelephantopin has a weak interaction with CYP3A4 enzyme and it minimally affects the metabolism of CYP3A4 substrates. Deoxyelephantopin is not an in vitro CYP1A2 and CYP2D6 inducer. It is both a weak in vitro CYP3A4 inducer and inhibitor and is unlikely to elicit a clinically significant effect in human.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links