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

Ooi , Jer Ping (2010) 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. Masters thesis, Universiti Sains Malaysia.

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Abstract

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.

Item Type: Thesis (Masters)
Subjects: R Medicine > R Medicine (General)
Divisions: Institut Perubatan & Pergigian Termaju (Advanced Medical & Dental Institute) > Thesis
Depositing User: HJ Hazwani Jamaluddin
Date Deposited: 04 Sep 2018 07:27
Last Modified: 12 Apr 2019 05:26
URI: http://eprints.usm.my/id/eprint/41697

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