In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained fromBoehmeria caudataSw. Aerial Parts

Author(s):Show less -

de Paiva, Paula P. ; Nunes, Julia H. B. ; Nonato, Fabiana R. ; Ruiz, Ana L. T. G. ; Zafred, Rafael R. T. ; Sousa, Ilza M. O. ; Okubo, Marcia Y. ; Kawano, Daniel F. ; Monteiro, Paula A. ; Foglio, Mary A. ; Carvalho, Joao E.

• Document type: Journal article
• Source: Molecules; v. 25, n. 17, p. 20-pg., 2020-09-01.

Abstract

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction ofBoehmeriacaudata(BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine's binding site on beta-tubulin were performed, suggesting (-)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies. (AU)

• FAPESP's process: 12/19661-4 - Vouacapans and geranilgeraniol synergic effect evaluation on nociceptive pain, pharmacokinetic and preclinical toxicological studies
• Grantee: Mary Ann Foglio
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/21801-2 - Predictors of severity and new treatments for bone marrow neoplasias
• Grantee: Sara Teresinha Olalla Saad
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/22457-7 - Isolation, identification and mechanism of action of anticancer active principles of Croton campestris A.St.-Hil.
• Grantee: Paula Araujo Monteiro
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/22458-3 - Isolation, identification and mechanism of action of fractions and active principles of Boehmeria caudata Sw with anticancer activity.
• Grantee: Paula Pereira de Paiva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/06636-7 - In vitro antiproliferative activity of Coronarin-D
• Grantee: Márcia Yumi Okubo
• Support Opportunities: Scholarships in Brazil - Master