Skip to main navigation menu Skip to main content Skip to site footer

Research Articles

Vol. 10 No. 2 (2023)

DMPK studies in rat model for comparative evaluation of bioavailability of alpha-mangostin and its formulated solid lipid nanoparticle using a validated LC-MS/MS method

DOI
https://doi.org/10.14719/pst.2217
Submitted
2 November 2022
Published
19-03-2023 — Updated on 01-04-2023
Versions

Abstract

Garcinia mangostana L., contains the xanthone ?-mangostin, which is a bioactive secondary metabolite. The Caco-2 cell line transport of ?-mangostin was explored to see whether it could be used to study oral uptake. There has been little in-vivo research on the drug metabolism and pharmacokinetics of solid lipid nanoparticles of ?-mangostin. The ?-mangostin content estimation in plasma of rat was accomplished using a validated LC-MS/MS technique. The Papp (permeability coefficient apparent) across the Caco-2 cell monolayer is used to predict the absorption of orally administered ?-mangostin and ?-mangostin solid lipid nanoparticles (AM-SLNP). In the presence of the solid lipid and emulsifiers, AM-SLNP had 3.72 times higher Papp than ?-mangostin after 4 hours of study across the Caco-2 cell line. In-vivo rat model study show that formulated AM-SLNP has a 3.3-fold higher bioavailability than pure ?-mangostin. High tissue distribution of the AM-SLNP is observed compared to ?-mangostin, which may improve the efficacy of the product when compared to pure extract, as the available drug at the site of distribution is high. Because both cell monolayer and animal studies demonstrate the same pattern of drug intake mechanism for SLNP’s and as it is almost identical, nanotechnology can be utilized in avoiding hepatic metabolism and improving bioavailability.

References

  1. Morton J. Roselle. In: Fruits of Warm Climate. Julia F. Morton: Miami, FL; 1987. p. 281-286. http://www.hort.purdue.edu/newcrop/mortonne/roselle.html
  2. Chin YW, Jung HA, Chai H, Keller WJ, Kinghorn AD. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (mangosteen). Phytochemistry. 2008; 69(3):754-8. https://doi.org/10.1016/j.phytochem.2007.09.023
  3. Obolskiy D, Pischel I, Siriwatanametanon N, Heinrich M. Garcinia mangostana L.: a phytochemical and pharmacological review. Phytotherapy research. 2009; 23(8): 1047–1065. https://doi.org/10.1002/ptr.2730
  4. Han AR, Kim JA, Lantvit DD, Kardono LB, Riswan S, Chai H, Carcache de Blanco EJ, Farnsworth NR, Swanson SM, Kinghorn AD. Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen). J Nat Prod. 2009; 72(11):2028-31. https://doi.org/10.1021/np900517h
  5. Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD. Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem. 2006; 54(6):2077-82. https://doi.org/10.1021/jf052649z
  6. Pothitirat W, Chomnawang MT, Supabphol R, Gritsanapan W. Comparison of bioactive compounds content, free radical scavenging and anti-acne inducing bacteria activities of extracts from the mangosteen fruit rind at two stages of maturity. Fitoterapia. 2009; 80(7):442-7.https://doi.org/10.1016/j.fitote.2009.06.005
  7. Yoshikawa M, Harada E, Miki A, Tsukamoto K, Liang SQ, Yamahara J, Murakami N. Antioxidant constituents from the fruit hulls of mangosteen (Garcinia mangostana L.) originating in Vietnam. Yakugaku Zasshi. 1994; 114: 129–133. https://www.cabi.org/isc/abstract/19940310889
  8. Han SY, Chin YW, Choi YH. A new approach for pharmacokinetic studies of natural products: measurement of isoliquiritigenin levels in mice plasma, urine and feces using modified automated dosing/blood sampling system. Biomed Chromatogr. 2013; 27(6):741-9. https://doi.org/10.1002/bmc.2854
  9. Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y. Histaminergic and serotonergic receptor blocking substances from the medicinal plant Garcinia mangostana. Planta Med. 1996; 62(5):471-2.. https://doi.org/10.1055/s-2006-957943
  10. Chomnawang MT, Surassmo S, Wongsariya K, Bunyapraphatsara N. Antibacterial activity of Thai medicinal plants against methicillin-resistant Staphylococcus aureus. Fitoterapia. 2009; 80(2):102-4. https://doi.org/10.1016/j.fitote.2008.10.007
  11. Puripattanavong J, Khajorndetkun W, Chansathirapanich W. Improved isolation of ?-mangostin from the fruit hull of Garcinia mangostana and its antioxidant and antifungal activity. Planta Medica. 2006; 72. https://doi.org/10.1055/s-2006-950128
  12. Chen SX, Wan M, Loh BN. Active constituents against HIV-1 protease from Garcinia mangostana. Planta Med. 1996;62(4):381-2 https://doi.org/10.1055/s-2006-957916
  13. Vlietinck AJ, De Bruyne T, Apers S, Pieters LA. Plant-derived leading compounds for chemotherapy of human immunodeficiency virus (HIV) infection. Planta Med. 1998; 64(2):97-109. https://doi.org/10.1055/s-2006-957384
  14. Balunas MJ, Su B, Brueggemeier RW, Kinghorn AD. Xanthones from the botanical dietary supplement mangosteen (Garcinia mangostana) with aromatase inhibitory activity. J Nat Prod. 2008; 71(7):1161-6. https://doi.org/10.1021/np8000255
  15. Chin YW, Jung HA, Chai H, Keller WJ, Kinghorn AD. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (Mangosteen). Phytochemistry. 2008; 69(3):754-8. https://doi.org/10.1016/j.phytochem.2007.09.023
  16. Chin YW, Kinghorn AD. Structural Characterization, Biological Effects, and Synthetic Studies on Xanthones from Mangosteen (Garcinia mangostana), a Popular Botanical Dietary Supplement. Mini Rev Org Chem. 2008; 5(4):355-364. https://doi.org/10.2174/157019308786242223
  17. Nilar, Harrison LJ. Xanthones from the heartwood of Garcinia mangostana. Phytochemistry. 2002; 60(5):541-8. https://doi.org/10.1016/s0031-9422(02)00142-5
  18. Suksamrarn S, Suwannapoch N, Ratananukul P, Aroonlerk N, Suksamrarn A. Xanthones from the green fruit hulls of Garcinia mangostana. Journal of natural products. 2002; 65(5): 761–763. https://doi.org/10.1021/np010566g
  19. Peres V, Nagem TJ, de Oliveira FF. Tetraoxygenated naturally occurring xanthones. Phytochemistry. 2000; 55(7):683-710. https://doi.org/10.1016/s0031-9422(00)00303-4
  20. Walker EB. HPLC analysis of selected xanthones in mangosteen fruit. J Sep Sci. 2007; 30(9):1229-34. https://doi.org/10.1002/jssc.200700024
  21. Devi Sampath P, Vijayaraghavan K. Cardioprotective effect of alpha-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats. J Biochem Mol Toxicol. 2007; 21(6):336-9. https://doi.org/10.1002/jbt.20199
  22. Gopalakrishnan C, Shankaranarayanan D, Kameswaran L, Nazimudeen SK. Effect of mangostin, a xanthone from Garcinia mangostana Linn. in immunopathological & inflammatory reactions. Indian J Exp Biol. 1980; 18(8):843-6. https://pubmed.ncbi.nlm.nih.gov/7461736/
  23. Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y. Characterized mechanism of alpha-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg Med Chem. 2007; 15(16):5620-8. https://doi.org/10.1016/j.bmc.2007.04.071
  24. Sakagami Y, Iinuma M, Piyasena KG, Dharmaratne HR. Antibacterial activity of alpha-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics. Phytomedicine. 2005; 12(3):203-8.https://doi.org/10.1016/j.phymed.2003.09.012
  25. Sampath PD, Vijayaragavan K. Ameliorative prospective of alpha-mangostin, a xanthone derivative from Garcinia mangostana against beta-adrenergic cathecolamine-induced myocardial toxicity and anomalous cardiac TNF-alpha and COX-2 expressions in rats. Exp Toxicol Pathol. 2008; 60(4-5):357-64.https://doi.org/10.1016/j.etp.2008.02.006
  26. Sampath PD, Kannan V. Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin, a xanthonic derivative from Garcinia mangostana. Drug Chem Toxicol. 2009;32(4):344-52 https://doi.org/10.1080/01480540903159210
  27. Kondo M, Zhang L, Ji H, Kou Y, Ou B. Bioavailability and antioxidant effects of a xanthone-rich mangosteen (Garcinia mangostana) product in humans. J Agric Food Chem. 2009; 57(19):8788-92. https://doi.org/10.1021/jf901012f
  28. Han SY, Chin YW, Kim DY, Choi YH. Simultaneous determination of ?- and-? mangostins in mouse plasma by HPLC-MS/MS method: application to a pharmacokinetic study of mangosteen extract in mouse. Chromatographia. 2013; 76: 643–650. https://doi.org/10.1007/s10337-013-2437-3

Downloads

Download data is not yet available.