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1.
Korean J Med Educ ; 35(3): 235-247, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37670520

RESUMO

PURPOSE: The perception of faculty members about an individually tailored, flexible-length, outcomes-based curriculum for undergraduate medical students was studied. Their opinion about the advantages, disadvantages, and challenges was also noted. This study was done to help educational institutions identify academic and social support and resources required to ensure that graduate competencies are not compromised by a flexible education pathway. METHODS: The study was done at the International Medical University, Malaysia, and the University of Lahore, Pakistan. Semi-structured interviews were conducted from 1st August 2021 to 17th March 2022. Demographic information was noted. Themes were identified, and a summary of the information under each theme was created. RESULTS: A total of 24 (14 from Malaysia and 10 from Pakistan) faculty participated. Most agreed that undergraduate medical students can progress (at a differential rate) if they attain the required competencies. Among the major advantages mentioned were that students may graduate faster, learn at a pace comfortable to them, and develop an individualized learning pathway. Several logistical challenges must be overcome. Providing assessments on demand will be difficult. Significant regulatory hurdles were anticipated. Artificial intelligence (AI) can play an important role in creating an individualized learning pathway and supporting time-independent progression. The course may be (slightly) cheaper than a traditional one. CONCLUSION: This study provides a foundation to further develop and strengthen flexible-length competency-based medical education modules. Further studies are required among educators at other medical schools and in other countries. Online learning and AI will play an important role.


Assuntos
Estudantes de Medicina , Humanos , Inteligência Artificial , Currículo , Docentes , Educação Baseada em Competências
2.
BMC Med Educ ; 23(1): 397, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268906

RESUMO

BACKGROUND: Open book examinations have been used to assess students' higher order cognitive skills. These examinations can be conducted online remotely with the advancement of technology. However, there are concerns regarding its validity and reliability particularly if the examinations are not proctored. The objective of this study was to explore the perceptions of faculty and students in health professions programmes about remote online open book examinations (ROOBE). METHODS: Semi-structured interviews were conducted among 22 faculty staff who were involved in ROOBE in health professions programmes. All interviews were audio recorded, transcribed verbatim and analysed using a thematic analysis approach. The perceptions of 249 medical students were obtained using an online questionnaire after they completed ROOBE. RESULTS: The faculty agreed that open book examinations could promote students' higher order cognitive skills and reduce students' stress. However, they were concerned about students' academic integrity during non-invigilated ROOBE which could affect recognition by accreditation and professional bodies. The shift from traditional practice of closed-book examinations to ROOBE required change management with the support of guidelines and faculty training.  Majority of the students claimed that the examinations were challenging as they assessed their ability to apply knowledge in real world problems. Nevertheless, they preferred ROOBE due to less anxiety and memorisation, and more emphasis on problem solving skills. The shortcomings were insufficient time for information searching during examinations and uncertainty in preparedness for future practice as they focused less on memorisation of factual knowledge during examination preparation. Cheating among peers and internet instability during non-invigilated ROOBE were the concerns highlighted by some students. CONCLUSIONS: Faculty and students expressed favourable views about ROOBE in promoting higher order cognitive skills. Adequate technological support was essential during ROOBE. While there was a need to address issues related to academic integrity, ROOBE could be included as an authentic assessment within the systems of assessment.


Assuntos
Docentes , Estudantes de Medicina , Humanos , Reprodutibilidade dos Testes , Estudantes de Medicina/psicologia , Ocupações em Saúde
3.
Med Sci Educ ; 31(6): 1919-1929, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34518785

RESUMO

The achievement of learning goals via laboratory practical depends on both extrinsic and intrinsic factors. They could be limited by laboratory time, incurred cost, safety, self-efficacy, inadequate prior preparation by learners, and different learning styles. Hence, virtual laboratory simulation (vLAB) may be an appropriate e-learning tool to overcome these restrictions. In this study, student's perception of the usefulness of vLAB was determined by using deoxyribonucleic acid (DNA) gel electrophoresis and polymerase chain reaction (PCR) as case examples. The perception of Year 2 and 3 health science undergraduate students' (N = 87) was studied using a questionnaire consisting of 12 items, rated on a 5-point Likert-scale. The attainment of learning outcomes was assessed using pre-and post-tests containing multiple-choice questions (MCQs). In addition, student's experience and learning from the vLAB were further explored using qualitative analysis. Although there was no significant difference between the mean scores of the pre-and post-tests, results showed that all participants perceived vLAB well, with a median score of 4 (Agree) for all items in the questionnaire. It provides a meaningful learning experience and an authentic environment where students feel safe to practice what they have learnt in lectures. Moreover, vLAB facilitates individualised learning and enhances self-efficacy among students. In conclusion, vLAB prepares students for physical laboratory sessions by activating the prehension dimension of Kolb's learning cycle, therefore complementing and strengthening the attainments of health sciences laboratory learning goals and outcomes.

4.
Med Teach ; 43(sup1): S6-S11, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31408404

RESUMO

BACKGROUND: Lifelong learning (LL) is an important outcome of medical training. The objective of this study is to measure the orientation of medical students toward LL and to determine the types of self-directed learning (SDL) activities that contribute toward LL skills. METHODS: The Jefferson Scale of Physician Lifelong Learning for medical student (JeffSPLL-MS) questionnaire was used. Factor analysis was performed, Cronbach's alpha and effect size were calculated. The types of learning activities that contribute to LL skills were identified. RESULTS: Three-factor structure emerged from the factor analysis and were identified as learning beliefs and motivation, skills in seeking information and attention to learning opportunities. A significant increase (p < .05; ES = 0.27) in orientation toward LL with academic progression was observed. Clinical students improved significantly in the domains of 'skills in seeking information' (p < .001; ES = 0.48) and 'attention to learning opportunities' (p < .001; ES = 0.55). Problem-based learning, flipped classroom, guided reading, projects and experiential learning activities are perceived to be effective for promoting LL. CONCLUSIONS: Medical students' LL skills develop progressively from preclinical to clinical years. Self-directed learning activities are perceived to be effective in promoting LL skills.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Currículo , Avaliação Educacional , Humanos , Aprendizagem
5.
Med Teach ; 43(sup1): S25-S32, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31491355

RESUMO

BACKGROUND: Student evaluation of the learning environment is important to enhance learning experiences. Programs such as Pharmacy use feedback from the evaluation to identify teaching-learning issues and use it to improve the quality of the learning experiences. The article aims to explore the general observations from the evaluation; to identify how the feedback is used to improve the learning environment and to identify lessons for educators in managing and using the feedback. METHODS: A cross-sectional data analysis of Pharmacy students' learning environment from 2011-2015 based on data from module, faculty, IMU-REEM and Student Barometer Survey was applied. Feedback obtained from the data was triangulated to establish commonalities/differences of the issues. RESULTS: Based on the analysis, issues affecting Pharmacy student learning experiences were identified. The identified issues included teaching by subject matter experts, pedagogical delivery and physical learning environment. Seven lessons were presented for educators to assess the practicality of the feedback. CONCLUSIONS: The feedback serves as a means to improve the Pharmacy program. Nonetheless, the challenges lie between the ideal and realistic expectations of students in optimizing the learning experiences. Lessons acquired from the evaluation of the learning environment are essential for educators in managing and using the information.


Assuntos
Educação em Farmácia , Farmácia , Estudantes de Farmácia , Estudos Transversais , Humanos , Aprendizagem
6.
Med Teach ; 43(sup1): S12-S17, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31522577

RESUMO

Outcome-based education (OBE) has brought along a significant development in health professions education in the past decade. The shift from a process-driven to product-driven model of education is valuable for ensuring graduate quality and facilitating global movement of healthcare workers. Such a model can align the expectations of key stakeholders in an era of rapid knowledge expansion and technological advancement. Nevertheless, the experienced benefits of OBE depend on the effectiveness of its implementation. This article therefore provides practical tips and strategies for implementing OBE in order to maximize its potential.


Assuntos
Educação Médica , Ocupações em Saúde , Escolaridade , Pessoal de Saúde/educação , Humanos , Conhecimento
7.
J Med Educ Curric Dev ; 7: 2382120520970894, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33283046

RESUMO

A preparatory framework called EASI (Evaluate, Align, Student-centred, Implement and Improve) was developed with the aim of creating awareness about interim options and implementation opportunities for online Clinical and Communication Skills (CCS) learning. The framework, when applied requires faculty to evaluate current resources, align sessions to learning outcomes with student-centred approaches and to continuously improve based on implementation experiences. Using the framework, we were able to generate various types of online CCS learning sessions for implementation in a short period of time due to the recent Covid-19 pandemic. Importantly we learnt a few lessons post-implementation from both students and faculty perspective that will be used for planning and delivery of future sessions. In summary, the framework was useful for creating or redesigning CCS sessions which were disrupted during the pandemic, however post-implementation experience suggests the framework can also be used for future solutions in online CCS learning as healthcare systems and delivery are increasingly decentralised and widely distributed.

8.
Korean J Med Educ ; 32(3): 185-195, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32723985

RESUMO

PURPOSE: Direct student involvement in quality processes in education has been suggested to encourage shared responsibilities among faculty and students. The objectives of this study were to explore undergraduate health professions students' understanding of quality assurance (QA) in education, and identify the challenges and enablers for student involvement in an Asian context. METHODS: Twenty semi-structured interviews were conducted among medical, dentistry, and pharmacy students in a Malaysian University. The interviews were audio-recorded, transcribed verbatim, and thematically analyzed to understand the students' perspectives of QA in education. RESULTS: The participants recognized the importance of QA towards ensuring the quality of their training, which will consequently impact their work readiness, employability, and quality of healthcare services. Academic governance, curriculum structure, content and delivery, faculty and student quality, teaching facilities, and learning resources were indicated as the QA areas. The challenges for students' involvement included students' attitude, maturity, and cultural barrier. To enhance their buy-in, clear objectives and impact, efficient QA mechanism, and recognition of students' contribution had been suggested. CONCLUSION: The findings of this study support student-faculty partnership in QA processes and decision making.


Assuntos
Atitude , Educação Profissionalizante/normas , Ocupações em Saúde/educação , Melhoria de Qualidade , Estudantes de Odontologia , Estudantes de Medicina , Estudantes de Farmácia , Adulto , Animais , Compreensão , Currículo , Tomada de Decisão Compartilhada , Educação de Graduação em Medicina/normas , Docentes , Feminino , Humanos , Malásia , Masculino , Pesquisa Qualitativa , Estudantes de Ciências da Saúde , Inquéritos e Questionários , Universidades , Adulto Jovem
10.
MedEdPublish (2016) ; 9: 153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-38073814

RESUMO

This article was migrated. The article was marked as recommended. The COVID-19 outbreak has led to lockdown of cities and restricted access to university campuses, and hence face-to-face delivery of education has been disrupted worldwide. In order to continue teaching, learning and assessment activities, academic institutions have embarked on online delivery and assessments using technology. Online open book examination is one of the tools considered during the crisis period to ensure that students' progression in the academic programmes and graduation are not delayed. Its use is supported by literature evidences that show promotion of critical thinking and problem solving skills amongst students. The positive findings from our previous study on the impact of open book examinations on student performance and learning approach have encouraged us to implement online open book examinations in various health professional programmes in our institution during the COVID-19 pandemic. While some successful progress has been made, there are areas that need further exploration to provide detailed insights on the practice and effectiveness of remote online open book examinations. The objective of this paper is to share the practical tips for implementing online open book examinations remotely, in order to ensure the validity, reliability and fairness of the examinations.

11.
Am J Pharm Educ ; 83(6): 6851, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31507283

RESUMO

Objective. To evaluate pharmacy students' perceptions of the educational value of reflective portfolio and to gain an understanding of the factors that might influence these perceptions. Methods. Bachelor of Pharmacy (BPharm) students' perceptions of using reflective portfolios were evaluated by administering the same questionnaire at the beginning of years 2, 3 and 4 of the curriculum. Statistical analysis was carried out to determine the differences among the perception scores of different academic years. Semi-structured interviews were completed with fourth-year students to further explore their experiences with the reflective portfolio. Students' deep information processing (DIP) skills were compared with those of students from another pharmacy cohort whose curriculum did not include a reflective portfolio. Results. The students' perceptions of the reflective portfolio improved significantly as they progressed from year 2 to year 4 of the curriculum. The factors that contributed to a positive experience were a clear understanding of objectives and guidelines for the reflective portfolio, useful mentor feedback, a positive learning attitude and motivation, and having a user-friendly technology platform for submission of the portfolio. The students' DIP skills after completing the reflective portfolio were higher than those of students who did not have a reflective portfolio assignment in their curriculum. Conclusion. Pharmacy students' appreciation of the educational value of a reflective portfolio increased as they progressed to their final year, and their DIP skills improved. These findings support the use of a reflective portfolio as a learning tool for BPharm students' personal and professional development.


Assuntos
Documentação/estatística & dados numéricos , Educação em Farmácia/estatística & dados numéricos , Avaliação Educacional/estatística & dados numéricos , Estudantes de Farmácia/estatística & dados numéricos , Adulto , Atitude do Pessoal de Saúde , Currículo/estatística & dados numéricos , Retroalimentação , Feminino , Humanos , Aprendizagem , Masculino , Mentores/estatística & dados numéricos , Motivação , Inquéritos e Questionários , Adulto Jovem
12.
Med Sci Educ ; 29(4): 1103-1108, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34457589

RESUMO

Challenges in assessment implementation include assessment blueprinting, accuracy and timeliness of result processing, item analysis and personalised feedback. These challenges were addressed by an online assessment system (OAS) that translates the educational framework of outcome-based education (OBE) into an integrated platform applicable across academic programmes. OBE principles of transparency, measurability, relevance, and individualisation was feasibly addressed using technology. The system development required continuous stakeholder engagement and feedback. Its implementation involved change management at institutional level with shifts in procedures, responsibilities, staff competencies and resource allocation. This article describes approaches taken and the lessons learned in developing and implementing OAS to enhance assessment practice for medical science programmes.

14.
Nanomedicine (Lond) ; 12(20): 2487-2502, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28972460

RESUMO

AIM: To develop 6-O-palmitoyl-ascorbic acid-based niosomes targeted to transferrin receptor for intravenous administration of tocotrienols (T3) in breast cancer. MATERIALS & METHODS: Niosomes were prepared using film hydration and ultrasonication methods. Transferrin was coupled to the surface of niosomes via chemical linker. Nanovesicles were characterized for size, zeta potential, morphology, stability and biological efficacy. RESULTS: When evaluated in MDA-MB-231 cells, entrapment of T3 in niosomes caused 1.5-fold reduction in IC50 value compared with nonformulated T3. In vivo, the average tumor volume of mice treated with tumor-targeted niosomes was 12-fold lower than that of untreated group, accompanied by marked downregulation of three genes involved in metastasis. CONCLUSION: Findings suggested that tumor-targeted niosomes served as promising delivery system for T3 in cancer therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Lipossomos/química , Tocotrienóis/química , Transferrina/química , Transferrina/farmacologia , Administração Intravenosa/métodos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular , Química Farmacêutica/métodos , Reagentes de Ligações Cruzadas , Sistemas de Liberação de Medicamentos/métodos , Feminino , Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular/métodos , Tamanho da Partícula , Receptores da Transferrina/metabolismo , Propriedades de Superfície , Transferrina/administração & dosagem
15.
Biomed J ; 38(4): 301-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25673170

RESUMO

BACKGROUND: Euphorbia hirta has been reported to possess anti-inflammatory activity. This study was carried out to determine the prostaglandin E 2 (PGE 2 ) inhibition activity of the fractions of the E. hirta aqueous extract on rabbit synovial fibroblast cells (HIG-82). METHODS: E. hirta aqueous extract was fractionated into five fractions (fractions A, B, C, D, and E) by reversed phase flash chromatography. Rabbit synovial fibroblast cells (HIG-82) were activated with phorbol myristate acetate and treated with the fractions. The amount of PGE 2 released into the medium was measured by enzyme-linked immunosorbent assay. RESULTS: Fraction A (0.1, 1, and 10 µg/ml) had the greatest PGE 2 inhibitory effect among the five fractions, and showed a greater extent of PGE 2 inhibition compared to the aqueous extract. In contrast, Fraction E had the greatest stimulatory effect on PGE 2 release. CONCLUSIONS: Fraction A of the aqueous extract inhibited the production of PGE 2 from activated HIG-82 cells to a greater extent than the crude aqueous extract. Bioactive compounds with anti-inflammatory activity are likely to be concentrated in Fraction A of E. hirta aqueous extract.


Assuntos
Anti-Inflamatórios/farmacologia , Dinoprostona/metabolismo , Euphorbia/metabolismo , Fibroblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Coelhos
16.
J Nat Med ; 65(3-4): 440-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21365364

RESUMO

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 6ß-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.


Assuntos
Andrographis/química , Sistema Enzimático do Citocromo P-450/metabolismo , Diterpenos/farmacologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Extratos Vegetais/farmacologia , Hidrocarboneto de Aril Hidroxilases/metabolismo , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP2C9 , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Humanos , Extratos Vegetais/química
17.
Chem Biol Interact ; 190(1): 1-8, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21276781

RESUMO

Orthosiphon stamineus (OS) has been traditionally used to treat diabetes, kidney and urinary disorders, high blood pressure and bone or muscular pain. To assess the possibility of drug-herb interaction via interference of metabolism, effects of four OS extracts of different polarity and three active constituents (sinensetin, eupatorin and rosmarinic acid) on major human cDNA-expressed cytochrome P450 (CYP) enzymes were investigated. Three substrate-probe based high-performance liquid chromatography (HPLC) assays were established to serve as activity markers for CYP2C9, CYP2D6 and CYP3A4. Our results indicate that OS extracts and constituents exhibited differential modulatory effects on different CYPs. While none of the OS components showed significant inhibition on CYP2C9, eupatorin strongly and uncompetitively inhibited CYP2D6 activity with a K(i) value of 10.2µM. CYP3A4 appeared to be the most susceptible enzyme to OS inhibitory effects. It was moderately inhibited by OS dichloromethane and petroleum ether extract with mixed-type and noncompetitive inhibitions (K(i)=93.7 and 44.9µg/mL), respectively. Correlation study indicated that the inhibition was accounted for by the presence of eupatorin in the extracts. When IC(50) values of these extracts were expressed in volume per dose unit to reflect inhibitory effect at recommended human doses from commercially available products, moderate inhibition was also observed. In addition, CYP3A4 was strongly and noncompetitively inhibited by eupatorin alone, with a K(i) value of 9.3µM. These findings suggest that co-administration of OS products, especially those with high eupatorin content, with conventional drugs may have the potential to cause drug-herb interactions involving inhibition of major CYP enzymes.


Assuntos
Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Inibidores do Citocromo P-450 CYP2D6 , Inibidores do Citocromo P-450 CYP3A , Orthosiphon/química , Extratos Vegetais/farmacologia , Hidrocarboneto de Aril Hidroxilases/metabolismo , Cromatografia Líquida de Alta Pressão , Cinamatos/química , Citocromo P-450 CYP2C9 , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Depsídeos/química , Humanos , Extratos Vegetais/química , Ácido Rosmarínico
18.
J Ethnopharmacol ; 133(2): 881-7, 2011 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-21093571

RESUMO

ETHNO PHARMACOLOGICAL RELEVANCE: Andrographis paniculata (AP), Centella asiatica (CA) and Orthosiphon stamineus (OS) are three popular herbs traditionally used worldwide. AP is known for the treatment of infections and diabetes and CA is good for wound healing and healthy skin while OS is usually consumed as tea to treat kidney and urinary disorders. Interaction of these herbs with human cytochrome P450 2C19 (CYP2C19), a major hepatic CYP isoform involved in metabolism of many clinical drugs has not been investigated to date. AIM OF THE STUDY: In this study, the modulatory effects of various extracts and major active constituents of AP, CA and OS on CYP2C19 activities were evaluated. MATERIALS AND METHODS: S-mephenytoin, the CYP2C19 substrate probe, was incubated in the presence or absence of AP, CA and OS components. The changes in the rate of metabolite (hydroxymephenytoin) formation were subsequently determined by a high-performance liquid chromatography (HPLC)-based enzyme assay to characterize the modulatory effects. RESULTS: Among the herbal extracts studied, AP ethanol extract and CA dichloromethane extract exhibited mixed type inhibition towards CYP2C19 with K(i) values of 67.1 and 16.4 µg/ml respectively; CA ethanol extract and OS petroleum ether extract competitively inhibited CYP2C19 activity (K(i)=39.6 and 41.5 µg/ml respectively). Eupatorin (a major active constituent of OS) was found to significantly inhibit CYP2C19 by mixed type inhibition (K(i)=7.1 µg/ml or 20.6 µM). CONCLUSIONS: It was observed that AP, CA and OS inhibited CYP2C19 activity with varying potency. While weak inhibitory effect was observed with AP, moderate to strong inhibition was observed with CA dichloromethane extract and eupatorin, the major OS constituent. Therefore care should be taken when these CA and OS components are co-administered with CYP2C19 substrates (such as omeprazole, proguanil, barbiturates, citalopram, and diazepam).


Assuntos
Andrographis , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Centella , Inibidores Enzimáticos/farmacologia , Orthosiphon , Andrographis/efeitos adversos , Andrographis/química , Centella/efeitos adversos , Centella/química , Citocromo P-450 CYP2C19 , Inibidores Enzimáticos/efeitos adversos , Etnofarmacologia , Flavonoides/efeitos adversos , Flavonoides/farmacologia , Interações Ervas-Drogas , Humanos , Técnicas In Vitro , Cinética , Orthosiphon/efeitos adversos , Orthosiphon/química , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Plantas Medicinais/efeitos adversos , Plantas Medicinais/química , Proteínas Recombinantes/antagonistas & inibidores , Triterpenos/efeitos adversos , Triterpenos/química , Triterpenos/farmacologia
19.
J Ethnopharmacol ; 130(2): 275-83, 2010 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-20457244

RESUMO

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.


Assuntos
Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Centella , Inibidores do Citocromo P-450 CYP2D6 , Inibidores do Citocromo P-450 CYP3A , Inibidores Enzimáticos/farmacologia , Extratos Vegetais/farmacologia , Hidrocarboneto de Aril Hidroxilases/metabolismo , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP2C9 , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Remoção de Radical Alquila , Dextrometorfano/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/isolamento & purificação , Interações Ervas-Drogas , Humanos , Hidroxilação , Cinética , Metilação , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Testosterona/metabolismo , Tolbutamida/metabolismo , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
20.
J Ethnopharmacol ; 126(3): 406-14, 2009 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-19778596

RESUMO

Euphorbia hirta (E. hirta) is a weed commonly found in tropical countries and has been used traditionally for asthma, bronchitis and conjunctivitis. However, one of the constituents in this plant, quercetin, was previously reported to be mutagenic. This work aimed to determine the level of quercetin in the aqueous and methanol plant extracts and to investigate the mutagenic effects of quercetin and the extracts in the Ames test utilising the mutant Salmonella typhimurium TA98 and TA100 strains. The antimutagenic activity of Euphorbia hirta aqueous and methanol extracts was also studied in Salmonella typhimurium TA98. HPLC analyses showed that quercetin and rutin, a glycosidic form of quercetin, were present in the acid-hydrolysed methanol extract and non-hydrolysed methanol extract respectively. The quercetin concentration was negligible in both non-hydrolysed and acid-hydrolysed aqueous extracts. The total phenolic contents in Euphorbia hirta were determined to be 268 and 93 mg gallic acid equivalent (GAE) per gram of aqueous and methanol extracts, respectively. Quercetin (25 microg/mL) was found to be strongly mutagenic in Salmonella typhimurium TA98 in the absence and presence of S-9 metabolic activation. However, both the aqueous and methanol extracts did not demonstrate any mutagenic properties when tested with Salmonella typhimurium TA98 and TA100 strains at concentrations up to 100 microg/mL in the absence and presence of S-9 metabolic activation. In the absence of S-9 metabolic activation, both the extracts were unable to inhibit the mutagenicity of the known mutagen, 2-nitrofluorene, in Salmonella typhimurium TA98. On the other hand, the aqueous extracts at 100 microg/mL and methanol extracts at 10 and 100 microg/mL exhibited strong antimutagenic activity against the mutagenicity of 2-aminoanthracene, a known mutagen, in the presence of S-9 metabolic activating enzymes. The results indicated that these extracts could modulate the xenobiotic metabolising enzymes in the liver at the higher concentrations.


Assuntos
Antimutagênicos/toxicidade , Euphorbia/química , Metanol/química , Mutagênicos/toxicidade , Extratos Vegetais/farmacologia , Água/química , Cromatografia Líquida de Alta Pressão , Testes de Mutagenicidade , Fenóis/análise , Extratos Vegetais/química , Salmonella typhimurium/genética
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