Research

My research interest is in metabolic drug-drug interactions focusing on herb-drug interactions. The most common types of these interactions are inhibition and induction of the drug metabolizing enzymes. Induction of these enzymes may reduce drug efficacy whereas inhibition of these enzymes may result in drug toxicity. I am particularly interested in assessing the inhibitory potential of herbal components on phase II drug metabolizing enzymes including glutathione S-transferase (GST) and uridine diphospho glucuronosyltransferase (UGT) enzymes. The inhibitory potential of herbal extracts or their constituents (Areca catechu, Andrographis paniculata, Cinnamomum iners, Curcuma xanthorrhiza, Eurycoma longifolia, Ficus deltoidea, Gynura procumbens, Mitragyna speciosa, Morinda citrifolia, Phyllanthus niruri and Orthosiphon stamineus) on drug metabolizing enzymes had been assessed in vitro and in vivo in rats. Recent study is on the effects of these herbs on human recombinant UGT isoforms using a high throughput approach. UGTs are the most important phase II drug metabolizing enzymes as they are responsible for the removal of endogenous compounds like bilirubin and steroids and foreign compounds which include drugs and phytochemicals. Understanding the mechanisms of herbal inhibition on UGT enzyme activities provide data which is essential for assessing and minimizing herb-drug interaction clinical risks.

Current Research Projects:

• Investigation of metabolism and toxicity of oil palm empty fruit bunch lignin for pharmaceutical application
• In vivo study on the effects of herbal extracts on drug metabolizing enzymes
• High-throughput, cost effective LC-MS/MS based drug metabolizing enzymes inhibition method for herbal product safety evaluation

People

Current MSc students (as main supervisor)

• Qamarulizzat Syazwan Kamarulazua
• Nurul Huda Abdullah

Publications

SELECTED PUBLICATIONS (FROM 2010)

1. Perumal, S., Mahmud, R., Ismail, S. (2017) Mechanism of action of isolated caffeic acid and epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa. Pharmacogn Mag., 13(Suppl 2), S311.
2. Husni, Z., Ismail, S., Zulkiffli, M.H., Afandi, A., Haron, M. (2017) In vitro inhibitory effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea, and Curcuma xanthorrhiza extracts and constituents on human liver glucuronidation activity. Pharmacogn Mag., 13(Suppl 2), S236.
3. Salleh, N.M., Ismail, S., Ibrahim, M.N.M. (2017) The inhibition of hepatic and renal glucuronidation of p-nitrophenol and 4-methylumbelliferone by oil palm empty fruit bunch lignin and its main oxidation compounds. Pharmacogn Mag., 13 (Suppl 1), S102-S114.
4. Salleh, N.A., Ismail, S., Ab Halim, M.R. (2016) Effects of Curcuma xanthorrhiza extracts and their constituents on phase ii drug-metabolizing enzymes activity. Pharmacognosy Res., 8 (4), 309-315.
5. Moath Kahtan Bashir, Sabariah Ismail, Ma HQ, Nurul Huda Abdullah, Abas Haji Hussin (2015) The in vitro and ex vivo effect of Phyllanthus niruri methanol extract on hepatic glutathione s-transferase activity in STZ-induced diabetic Sprague Dawley rats. Asian Journal of Pharmaceutical and Clinical Research, 8 (5), 157-160.
6. Bashir, M.K., Ismail, S., Chan, K.L. Chua, J.K., Hussin, A.H. (2015) The in vitro and ex vivo effect of Phyllanthus niruri methanol extract on hepatic UDP-glucuronyltransferase enzyme activity in STZ-induced diabetic Sprague Dawley rats. International Journal of Pharmacy and Pharmaceutical Sciences, 7 (11), 105-109.
7. Haron, M., Ismail, S. (2015) Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5'-diphospho-glucuronosyltransferase isoforms. Pharmacognosy Res., 7 (4), 341-349.
8. Norliyana Mohd Salleh, Sabariah Ismail, Mohamad Nasir Mohamad Ibrahim (2015) Radical scavenging activity of lignin extracted from oil palm empty fruit bunch and its effect on glutathione-s-transferase enzymes activity. Asian Journal of Pharmaceutical and Clinical Research, 8 (3), 81-87.
9. Zainal Abidin, S., Liew, W.L.., Ismail, S., Chan, K.L., Mahmud, R. (2014) Inhibitory effects of active constituents and extracts of Andrographis paniculata on UGT1A1, UGT1A4, and UGT2B7 enzyme activities. International Journal of Pharmacy and Pharmaceutical Sciences, 6 (6), 58-66.
10. Lee, W.C., Mahmud, R., Noordin, R., Piaru, S.P., Perumal, S., Ismail, S. (2013) Free radicals scavenging activity, cytotoxicity and anti-parasitic activity of essential oil of Psidium guajava L. leaves against Toxoplasma gondii. Journal of Essential Oil Bearing Plants, 16 (1), 32-38.
11. Hanapi, N.A., Ismail, S., Mansor, S.M. (2013). Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities. Pharmacognosy Res., 5 (4), 241-246.
12. Devaraj, S., Ismail, S., Ramanathan, S., Yam, M.F. (2013) In vivo toxicological investigations of standardized ethanolic extract of Curcuma xanthorrhiza Roxb. rhizome. Journal Natural Product Plant Resources, 3 (1), 67-73.
13. Azizi, J., Ismail, S., Mansor, S.M. (2013) Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers. Drug Metabol Drug Interact., 28 (2), 95-105.
14. Lee, W.C., Mahmud, R., Pillai, S., Perumal, S., Ismail, S. (2012) Antioxidant activities of essential oil of Psidium guajava L. leaves. APCBEE Procedia, 2, 86-91.
15. Lee, W.C., Mahmud, R., Noordin, R., Piaru, S.P., Perumal, S., Ismail, S. (2012) Alkaloids content, cytotoxicity and anti-Toxoplasma gondii activity of Psidium guajava L. and Tinospora crispa. Bangladesh Journal of Pharmacology, 7 (4), 272-276.
16. Piaru, S.P., Perumal, S., Lee, W.C., Mahmud, R., Abdul Majid, A.M., Ismail, S., Man, C.N. (2012) Chemical composition, anti-angiogenic and cytotoxicity activities of the essential oils of Cymbopogan citratus (lemon grass) against colorectal and breast carcinoma cell lines. Journal of Essential Oil Research, 24 (5), 453-459.
17. Piaru, S.P., Mahmud, R., Abdul Majid, A.M., Ismail, S., Man, C.N. (2012) Chemical composition, antioxidant and cytotoxicity activities of the essential oils of Myristica fragrans and Morinda citrifolia. J Sci Food Agric., 92 (3), 593-597.
18. Piaru, S.P., Mahmud, R., Ismail, S. (2012) Studies on the phytochemical properties and brine shrimp toxicity of essential oil extracted from Myristica fragrans Houtt. (Nutmeg). Journal of Essential Oil-Bearing Plants, 15 (1), 53-57.
19. Anwar, R., Ismail, S., Mansor, S.M. (2012). In vitro effect of mitragynine on the activity of drug metabolizing enzymes, N-demethylase and glutathione-S-transferase in streptozotocin-induced diabetic rats. PharmacologyOnline, 1, 68-75.
20. Anwar, R., Hussin, A.H., Ismail, S., Mansor, S.M. (2012). In vitro effect of mitragynine (a major alkaloid of Mitragyna speciosa Korth) on aminopyrine metabolism in rat hepatocytes. Int J Pharm Sci Res., 3 (7), 2238-2242.
21. Ab Halim, R., Zabri Tan, M.S., Ismail, S., Mahmud, R. (2012) Standardization and phytochemical analysis of Curcuma xanthorrhiza Roxb. International Journal of Pharmacy and Pharmaceutical Sciences, 4 (3), 606-610.
22. Mustaffa, F., Indurkar, J., Shah, M., Ismail, S., Mansor, S.M. (2012) Review on pharmacological activities of Cinnamomum iners Reinw. ex Blume. Nat Prod Res., 27 (10), 888-895.
23. Hamsar, M.N., Ismail, S., Mordi, M.N., Ramanathan, S., Mansor, S.M. (2011) Antioxidant activity and the effect of different parts of Areca catechu extracts on glutathione-S-transferase activity in vitro. Free Radicals and Antioxidants, 1 (1), 28-33.
24. Mustaffa, F., Indurkar, J., Ismail, S., Mansor, S.M. (2011) An antimicrobial compound isolated from Cinnamomum iners leaves with activity against methicillin-resistant Staphylococcus aureus. Molecules, 16 (4), 3037-3047.
25. Sahgal, G., Ramanathan, S., Sasidharan, S., Mordi, M.N., Ismail, S., Mansor, S.M. (2011) In vitro and in vivo anticandidal activity of Swietenia mahogani methanolic seed extract. Trop Biomed., 28 (1), 132-137.
26. Zabri Tan, M.S.M., Ab Halim, M.R., Ismail, S., Mustaffa, F., Mohd Ali, N.I., Mahmud, R. (2011) Inhibitory effect of selected Malaysian herbal plants on glutathione S-transferase activity. International Journal of Pharmacology, 7(3), 349-355.
27. Devaraj, S., Ismail, S., Ramanathan, S., Marimuthu, S. (2010) Evaluation of the hepatoprotective activity of standardized ethanolic extract of Curcuma xanthorrhiza (Roxb). Journal of Medicinal Plant Research, 4 (23), 2512-2517.
28. Mustaffa, F., Indurkar, J., Ismail, S., Mordi, M.N., Ramanathan, S., Mansor, S.M. (2010) Antioxidant capacity and toxicity screening of Cinnomomum iners standardized leaves methanolic extract. International Journal of Pharmacology, 6 (6), 888-895.
29. Mustaffa, F., Indurkar, J., Ismail, S., Mordi, M.N., Ramanathan, S., Mansor, S.M. (2010). Analgesic activity, toxicity studies and preliminary phytochemical screening of standardized Cinnamomum iners leaves methanolic extract. Pharmacognosy Res., 2 (2), 76 -81.
30. Sahgal, G., Ramanathan, S., Sasidharan, S., Mordi, M.N., Ismail, S., Mansor, S.M. (2010) Brine shrimp lethality and acute oral toxicity studies on Swietenia mahagoni (Linn.) Jacq. seed methanolic extract. Pharmacognosy Res., 2 (4), 215-220.
31. Hanapi, N.A., Azizi, J., Ismail, S., Mansor, S.M. (2010) Evaluation of selected Malaysian medicinal plants on phase I drug metabolizing enzymes, CYP2C9, CYP2D6 and CYP3A4 activities in vitro. International Journal of Pharmacology, 6 (4), 494-499.
32. Parthasarathy, S., Ramanathan, S., Ismail, S., Adenan, M.I., Mansor, S.M., Murugaiyah, V. (2010) Determination of mitragynine in plasma with solid-phase extraction and rapid HPLC-UV analysis, and its application to a pharmacokinetic study in rat. Anal Bioanal Chem., 397 (5), 2023-2030.
33. Ismail, S., Hanapi, N.A., Ab Halim, M.R., Uchaipichat, V., Mackenzie, P.I. (2010) Effects of Andrographis paniculata and Orthosiphon stamineus extracts on the glucuronidation of 4-methylumbelliferone in human UGT isoforms. Molecules, 15 (5), 3578-3592.
34. .Devaraj, S., Esfahani, A.S., Ismail, S., Ramanathan, S., Yam, M.F. (2010). Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizhome of Curcuma xanthorrhiza roxb. Molecules, 15 (4), 2925-2934.
35. Azizi, J., Ismail, S., Mordi, M.N., Ramanathan, S., Mohd Said, M.I., Mansor, S.M. (2010). In vitro and in vivo effects of three different Mitragyna speciosa Korth leaves extracts on phase II drug metabolizing enzymes, glutathione transferases (GSTs). Molecules, 15 (1), 432-441.

Chapter in Book (From 2010)

1. Nurul Afifah Mohd Salleh, Mohd Rohaimi Ab Halim and Sabariah Ismail (2014) In vitro effects of Curcuma xanthorrhiza extracts and constituents on glutathione transferase activity. In: V. K. Gupta (Chief Editor) Medicinal Plants: Phytochemistry, Pharmacology and Therapeutics, Daya Publishing House, New Delhi, 3, 489 - 498.

 Published Abstract

1. Ismail, S., Hanapi, N.A., Azizi, J., Mansor, S.M., Mahmud, R. (2010) Inhibition of human cytochrome P450 isoforms by Mitragyna speciosa extracts. Drug Metabolism Reviews 42, 144. 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX).