Pharmacokinetics and antiangiogenic studies of potassium koetjapate in rats
| Autor: | Mohamed B. Khadeer Ahamed, Armaghan Shafaei, Yasser M Tabana, Muhammad Asif, Hussein M. Baharetha, Ashwaq Hamid Salem Yehya, Seyedeh Fatemeh Jafari, Fouad Saleih R. Al-Suede, Amin Malik Shah Abdul Majid |
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| Rok vydání: | 2020 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Bioavailability Angiogenesis Potassium koetjapate Cmax Biological Availability Mice Nude Angiogenesis Inhibitors RM1-950 Pharmacology Sandoricum koetjape Rats Sprague-Dawley Mice 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Oral administration Animals Humans IC50 Aorta Matrigel Neovascularization Pathologic biology Chemistry Endothelial Cells General Medicine biology.organism_classification Triterpenes Rats 030104 developmental biology Area Under Curve 030220 oncology & carcinogenesis Endothelium Vascular Koetjapic acid Therapeutics. Pharmacology HPLC |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 130, Iss, Pp 110602-(2020) |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2020.110602 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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