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Title: In vitro effects of selected medicinal plants shortlisted for clinical use in the Brazilian public health system in CYP3A4 mRNA gene expression, glutathione levels and P-glycoprotein activity and their implications for herb-drug interactions
Author: Dias Araujo Mazzari, A. L.
ISNI:       0000 0004 7231 4877
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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The Brazilian Unified Public Health System (SUS) shortlisted various plant species of interest (RENISUS) for future clinical use. However, very little is known about their effects on metabolic and transporter proteins, which could potentially lead to herb-drug interactions (HDI). To evaluate this, we conducted in vitro preclinical studies on twenty-four plant extracts to disclose their effects on CYP3A4 mRNA gene expression, intracellular glutathione (GSH) levels, inhibition of γ-glutamyl transferase (GGT) in HepG2 cells and P- glycoprotein (P-gp) activity in vincristine resistant Caco-2 (Caco-2 VCR) cells. We also investigated whether four Brazilian native species were able to activate the human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells. This preclinical research showed that all but two plant extracts were able to modulate at least one of the selected targets. CYP3A4 mRNA gene expression in HepG2 cells was significantly affected by half of the extracts. The antagonistic effect of Solanum paniculatum L. on hPXR could explain its ability to inhibit CYP3A4. GSH levels were affected by 80% of the extracts. There was depletion of intracellular GSH levels by Cordia verbenacea A. DC., Costus spicatus (Jacq.) Sw., Persea americana Mill., Salix alba L., Schinus terebinthifolia Raddi and Syzygium jambolanum (Lam.) DC. accompanied because of the inhibition of GGT activity. P-gp activity was modulated in a significant manner by 17% of the extracts. The approaches used for the conduction of in vitro preclinical studies in herbal medicines revealed a series of challenges faced especially by academics in order to anticipate cases of HDI. Clinicians have also to consider the presence of intrinsic factors such as genetic polymorphisms in each patient. The possible presence of undesirable interactions between RENISUS herbal medicines and essential drugs in SUS need eventually be clinically confirmed to attest our observed in vitro effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available