Pharmacokinetics and cytotoxic study of euphol from Euphorbia umbellata (Bruyns) Pax latex - PubMed
- ️Mon Jan 01 2018
doi: 10.1016/j.phymed.2018.04.055. Epub 2018 May 11.
Thais L de Oliveira 2 , Carla C Kanunfre 3 , Katia S Paludo 3 , Bruno R Minozzo 1 , Ana P Prestes 1 , Mei Wang 4 , Daniel Fernandes 1 , Fábio A Dos Santos 5 , Vamshi K Manda 4 , Shabana I Khan 4 , Zulfiqar Ali 4 , Iara J de Messias-Reason 2 , Bharathi Avula 4 , Ikhlas A Khan 4 , Flávio L Beltrame 6
Affiliations
- PMID: 30166094
- DOI: 10.1016/j.phymed.2018.04.055
Pharmacokinetics and cytotoxic study of euphol from Euphorbia umbellata (Bruyns) Pax latex
Luiza S Cruz et al. Phytomedicine. 2018.
Abstract
Background: Medicinal plants are an important source to identify new active pharmaceutical compounds. Traditionally, the sap of Euphorbia umbellata is widely used to treat cancer and inflammatory conditions. These effects have been attributed to the presence of terpenes and phenolic compounds in the extracts of this plant. Euphol, a tetracyclic triterpene alcohol, is one of the major compounds present in Euphorbia species, and some biological activities have been attributed to this compound.
Purpose: This study aimed to evaluate the in vitro cytotoxicity of euphol against Jurkat, HL-60, K-562, B16F10, and HRT-18 cells lines, as well as the biological stability, distribution, metabolism properties in vitro, and the determination of the concentration of euphol in the plasma and liver of rats.
Methods: The MTT reduction assay was used to evaluate the cytotoxicity of euphol against cancer cell lines, and the selectivity index, the morphology and cell cycle assays to evaluate the death mechanisms in K-562 and B16F10 lineages. UHPLC-MS was applied for the in vivo evaluation of the concentration of euphol in plasma and liver, and in vitro metabolic stability in human liver microsomes and S9 fraction, plasma protein binding, and stability in simulated gastric and intestinal fluids assays.
Conclusions: This study demonstrated that euphol exhibited cytotoxic effects against a variety of cancer cells lines, selectivity against leukemia and possibly, the mechanism involved is apoptosis. The evaluation of stability, distribution, and metabolism properties showed that euphol was unstable in gastric and intestinal fluids, presenting moderate plasma protein binding with two hours elimination half-life and possible phase II liver metabolism. All the results suggested that further studies could be developed to prove the viability of euphol as an anticancer agent.
Keywords: Cell culture; Cytotoxic activity; Euphol; Euphorbia; Pharmacokinetics; UHPLC-MS.
Copyright © 2018 Elsevier GmbH. All rights reserved.
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