The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions

The use of herbs as alternative and/or complementary therapy is increasing worldwide. When herbs are co-administered with modern medicine it may lead to drug-herb interactions that may be clinically significant. Cytochrome P450 (CYP) enzymes have been implicated in a large number of these prevent...

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Main Author: Ooi , Jer Ping
Format: Thesis
Language:English
Published: 2010
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Online Access:http://eprints.usm.my/41697/1/Ooi_Jer_Ping_HJ.pdf
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spelling my-usm-ep.416972019-04-12T05:26:46Z The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions 2010-11 Ooi , Jer Ping R Medicine (General) The use of herbs as alternative and/or complementary therapy is increasing worldwide. When herbs are co-administered with modern medicine it may lead to drug-herb interactions that may be clinically significant. Cytochrome P450 (CYP) enzymes have been implicated in a large number of these preventable drug-herb interactions, especially CYP1A2, CYP2D6, and CYP3A4. Andrographis paniculata Nees is a tropical herb traditionally used for fever, malaria, and diabetes mellitus treatments and has an extensive ethnobotanical history in Asia. Hence, the ability of andrographolide and 14-deoxy-11,12-didehydroandrographolide, the most medicinally active compound isolated from A. paniculata to modulate the CYP1A2, CYP2D6, and CYP3A4 mRNA and protein expressions were examined in HepG2 cells. After treatment of HepG2 cells for 48hr, the qRT-PCR and western blot analysis showed that 20μg/mL andrographolide and 5μg/mL 14-deoxy-11,12- didehydroandrographolide resulted in significant decreased in CYP1A2, CYP2D6, and CYP3A4 mRNA and protein expressions respectively. Interestingly, concurrent treatment of diterpenoid and CYP inducer (β-naphthoflavone and dexamethasone) also resulted in significant decreased in CYP1A2 and CYP3A4 mRNA and protein expressions implicating that both diterpenoids were able to inhibit the induction ability of CYP1A2 and CYP3A4 inducers. As for CYP3A4, both diterpenoids also caused a decrease in CYP3A4 enzymatic activity. 2010-11 Thesis http://eprints.usm.my/41697/ http://eprints.usm.my/41697/1/Ooi_Jer_Ping_HJ.pdf application/pdf en public masters Universiti Sains Malaysia Institut Perubatan & Pergigian Termaju
institution Universiti Sains Malaysia
collection USM Institutional Repository
language English
topic R Medicine (General)
spellingShingle R Medicine (General)
Ooi , Jer Ping
The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions
description The use of herbs as alternative and/or complementary therapy is increasing worldwide. When herbs are co-administered with modern medicine it may lead to drug-herb interactions that may be clinically significant. Cytochrome P450 (CYP) enzymes have been implicated in a large number of these preventable drug-herb interactions, especially CYP1A2, CYP2D6, and CYP3A4. Andrographis paniculata Nees is a tropical herb traditionally used for fever, malaria, and diabetes mellitus treatments and has an extensive ethnobotanical history in Asia. Hence, the ability of andrographolide and 14-deoxy-11,12-didehydroandrographolide, the most medicinally active compound isolated from A. paniculata to modulate the CYP1A2, CYP2D6, and CYP3A4 mRNA and protein expressions were examined in HepG2 cells. After treatment of HepG2 cells for 48hr, the qRT-PCR and western blot analysis showed that 20μg/mL andrographolide and 5μg/mL 14-deoxy-11,12- didehydroandrographolide resulted in significant decreased in CYP1A2, CYP2D6, and CYP3A4 mRNA and protein expressions respectively. Interestingly, concurrent treatment of diterpenoid and CYP inducer (β-naphthoflavone and dexamethasone) also resulted in significant decreased in CYP1A2 and CYP3A4 mRNA and protein expressions implicating that both diterpenoids were able to inhibit the induction ability of CYP1A2 and CYP3A4 inducers. As for CYP3A4, both diterpenoids also caused a decrease in CYP3A4 enzymatic activity.
format Thesis
qualification_level Master's degree
author Ooi , Jer Ping
author_facet Ooi , Jer Ping
author_sort Ooi , Jer Ping
title The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions
title_short The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions
title_full The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions
title_fullStr The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions
title_full_unstemmed The Cytochrome P450 Inhibitory Effects Of Andrographolide And 14-Deoxy-11,12- Didehydroandrographolide In HEPG2 Cells: Development Of Model In Vitro Studies Ofdrug-Herb Interactions
title_sort cytochrome p450 inhibitory effects of andrographolide and 14-deoxy-11,12- didehydroandrographolide in hepg2 cells: development of model in vitro studies ofdrug-herb interactions
granting_institution Universiti Sains Malaysia
granting_department Institut Perubatan & Pergigian Termaju
publishDate 2010
url http://eprints.usm.my/41697/1/Ooi_Jer_Ping_HJ.pdf
_version_ 1747820957568860160