CAPSULE PROPOSAL

Pharma299

INVESTIGATOR Kerstin Mariae G. Ponsaran

TITLE OF THE Molecular Docking Studies and Determination of the Effect of α-Mangostin
STUDY on Selected Cytochrome P450 Enzymes using Probe Drugs In Vivo

Review of literature revealed that there were no current studies done on α-

Mangostin and its effect on cytochrome P450 enzymes. Therefore, the
investigator would like to seek answers for the following questions:
1. What is the concentration of α-Mangostin in the capsulated Garcinia
mangostana pericarp available in the market?
RESEARCH
2. Does α-mangostin affects the metabolism of midazolam,
QUESTIONS
dextromethorphan, losartan, and chlorzoxazone in vivo which are
the probe drugs for CYP3A4, CYP2D6, CYP2C9, and CYP2E1,
respectively?
3. On what amino acid/s of the cytochrome P450 enzymes can α-
Mangostin be bound? What is the affinity of the bond?

Mangosteen (Garcinia mangostana) is a tree usually planted in several

parts of Mindanao and Sulu Archipelago [1]. The pericarp of its fruit
recently became a popular herbal supplement marketed in various forms
such as capsules and teas. Studies have shown that its dried pericarp extract
exhibited a wide range of therapeutic properties which includes anti-
diabetic, anti-cancer, neuroprotective and anti-obesity which were largely
attributed to the xanthone content of the extract [2].
BACKGROUND
OF THE STUDY α-Mangostin, one of the most abundant [3] and most studied xanthone
derivatives of the pericarp of mangosteen fruit was been reported to
possess antioxidant, antiproliferative, pro-apoptotic, anticarcinogenic and
antimicrobial properties [4, 5]. Although, α-Mangostin was found to be
generally safe [5], there’s a lack of evidence on its drug interaction which is
significant to patients who are taking mangosteen supplement along with
their medication. Therefore, this study would like to investigate the effect of
α-Mangostin on the activity of cytochrome P450 enzymes.

The aim of the study is:

1. To determine the amount of α-Mangostin present in capsulized
Garcinia mangostana dried pericarp available in the market using
LC-MS;
2. To evaluate the effect of α-Mangostin on the metabolism of
OBJECTIVES
midazolam, dextromethorphan, losartan, and chlorzoxazone (probe
drugs for CYP3A4, CYP2D6, CYP2C9, and CYP2E1, respectively) in
Sprague-Dawley rats; and
3. To identify the binding sites of α-Mangostin on the selected
cytochrome P450 enzymes using molecular studies

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 CAPSULE PROPOSAL
Pharma299

Determination of α-Mangostin concentration on capsuled Garcinia

mangostana dried pericarp available in the market using LC-MS (for the
concentration of pure α-mangostin to be used in the succeeding tests)

Determination of α-Mangostin effect on the metabolism of midazolam,

dextromethorphan, losartan, and chlorzoxazone (probe drugs for
CYP3A4, CYP2D6, CYP2C9, and CYP2E1, respectively) in Sprague-Dawley
Rats*
RESEARCH
*appropriate gender will be confirmed
DESIGN

Molecular docking* studies:

- identify which amino acid/s does α-Mangostin binds and
compare the binding site for the probe drugs
- determine the affinity of α-Mangostin on the binding site of the
cytochrome P450 isoforms
*software to be used for the molecular docking will be confirmed

Data Analysis
[1]. Philippine Medicinal Plants: Mangosteen. Retrieved from
http://www.stuartxchange.org/Mangosteen.html on February 28,
2017.
[2]. Magallanes BO, Perez DE, Chaverri JP. 2017. Medicinal Properties of
Mangosteen (Garcinia mangostana L.): A Comprehensive Update. Food
and Chemical Toxicology, DOI: 10.1016/j.fct.2017.08.021
[3]. Foti RS, Pearson JT, Rock DA, Wahlstrom JL, Wienkers LC. 2009. In
Vitro Inhibition of Multiple Cytochrome P450 Isoforms by Xanthone
REFERENCES
Derivatives from Mangosteen Extract. Pharmacokinetics and Drug
Metabolism, DOI: 10.1124/dmd.109.028043
[4]. Orozco FG, Failla ML. 2013. Biological Activities and Bioavailability of
Mangosteen Xanthones: A Critical Review of the Current Evidence.
Nutrients, DOI: 10.3390/nu5083163
[5]. Wang MH, Zhang KJ, Gu QL, Bi XL, Wang JX. 2017. Pharmacology of
Mangostins and Their Derivatives: A Comprehensive Review. Chinese
Journal of Natural Medicines, 15(2): 81-93.

Comment: Are these CYP enzymes the most for many of the drugs that are used especially those that
are used chornically?

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