• 1 EMAN Research and Testing Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
  • 2 EMAN Biodiscoveries Sdn. Bhd., Halal Park, 08000, Sungai Petani, Kedah, Malaysia
  • 3 EMAN Biodiscoveries Sdn. Bhd., Halal Park, 08000, Sungai Petani, Kedah, Malaysia. Electronic address:
  • 4 Centre for Integrative Metabolomics and Computational Biology, School of Sciences, Edith Cowan University Joondalup, WA, 6027, Australia
  • 5 Department of Pharmacy, The Islamia University of Bahawalpur, 63100, Pakistan
  • 6 Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, 116 St & 85 Ave, Edmonton, AB, T6G 2R3, Canada
  • 7 John Curtin School of Medical Research, College of Medicine, Australian National University, Australia
  • 8 Department of Pharmacy, College of Medicine and Health Sciences, Hadhramout University, Mukalla, Hadhramout, Yemen
Biomed Pharmacother, 2020 Oct;130:110602.
PMID: 32771894 DOI: 10.1016/j.biopha.2020.110602


PURPOSE: Koetjapic acid is an active compound of a traditional medicinal plant, Sandoricum koetjape. Although koetjapic acid has a promising anticancer potential, yet it is highly insoluble in aqueous solutions. To increase aqueous solubility of koetjapic acid, we have previously reported a chemical modification of koetjapic acid to potassium koetjapate (KKA). However, pharmacokinetics of KKA has not been studied. In this study, pharmacokinetics and antiangiogenic efficacy of KKA are investigated.

METHODS: Pharmacokinetics of KKA was studied after intravenous and oral administration in SD rats using HPLC. Anti-angiogenic efficacy of KKA was investigated in rat aorta, human endothelial cells (EA.hy926) and nude mice implanted with matrigel.

RESULTS: Pharmacokinetic study revealed that KKA was readily absorbed into blood and stayed for a long time in the body with Tmax 2.89 ± 0.12 h, Cmax 7.24 ± 0.36 μg/mL and T1/2 1.46 ± 0.03 h. The pharmacological results showed that KKA significantly suppressed sprouting of microvessels in rat aorta with IC50 18.4 ± 4.2 μM and demonstrated remarkable inhibition of major endothelial functions such as migration, differentiation and VEGF expression in endothelial cells. Further, KKA significantly inhibited vascularization in matrigel plugs implanted in nude mice.

CONCLUSIONS: The results indicate that bioabsorption of KKA from oral route was considerably efficient with longer retention in body than compared to that of the intravenous route. Further, improved antiangiogenic activity of KKA was recorded which could probably be due to its increased solubility and bioavailability. The results revealed that KKA inhibits angiogenesis by suppressing endothelial functions and expression of VEGF.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.