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Article

In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts

by
Paula P. de Paiva
1,2,3,*,†,
Julia H. B. Nunes
2,4,†,
Fabiana R. Nonato
2,
Ana L. T. G. Ruiz
2,3,
Rafael R. T. Zafred
1,2,
Ilza M. O. Sousa
2,3,
Márcia Y. Okubo
2,5,
Daniel F. Kawano
3,
Paula A. Monteiro
1,2,
Mary A. Foglio
3 and
João E. Carvalho
1,3
1
Institute of Biology, University of Campinas-UNICAMP, Campinas-SP 13083-862, Brazil
2
Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas-UNICAMP, Paulínia-SP 13148-218, Brazil
3
Faculty of Pharmaceutical Sciences, University of Campinas-UNICAMP, Campinas-SP 13083-871, Brazil
4
Institute of Chemistry, University of Campinas-UNICAMP, Campinas-SP 13083-970, Brazil
5
Piracicaba Dental School, University of Campinas, UNICAMP, Piracicaba-SP 13414-903, Brazil
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2020, 25(17), 4018; https://doi.org/10.3390/molecules25174018
Submission received: 12 August 2020 / Revised: 28 August 2020 / Accepted: 1 September 2020 / Published: 3 September 2020
(This article belongs to the Special Issue Current Trends in the Analysis of Medicinal Plants)
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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 of Boehmeriacaudata (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 β-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.
Keywords: molecular docking; edema; phenanthroquinolizidine; Urticaceae; NCI-H460 cell line; myeloperoxidase molecular docking; edema; phenanthroquinolizidine; Urticaceae; NCI-H460 cell line; myeloperoxidase
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MDPI and ACS Style

Paiva, P.P.d.; Nunes, J.H.B.; Nonato, F.R.; Ruiz, A.L.T.G.; Zafred, R.R.T.; Sousa, I.M.O.; Okubo, M.Y.; Kawano, D.F.; Monteiro, P.A.; Foglio, M.A.; et al. In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts. Molecules 2020, 25, 4018. https://doi.org/10.3390/molecules25174018

AMA Style

Paiva PPd, Nunes JHB, Nonato FR, Ruiz ALTG, Zafred RRT, Sousa IMO, Okubo MY, Kawano DF, Monteiro PA, Foglio MA, et al. In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts. Molecules. 2020; 25(17):4018. https://doi.org/10.3390/molecules25174018

Chicago/Turabian Style

Paiva, Paula P. de, Julia H. B. Nunes, Fabiana R. Nonato, Ana L. T. G. Ruiz, Rafael R. T. Zafred, Ilza M. O. Sousa, Márcia Y. Okubo, Daniel F. Kawano, Paula A. Monteiro, Mary A. Foglio, and et al. 2020. "In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts" Molecules 25, no. 17: 4018. https://doi.org/10.3390/molecules25174018

APA Style

Paiva, P. P. d., Nunes, J. H. B., Nonato, F. R., Ruiz, A. L. T. G., Zafred, R. R. T., Sousa, I. M. O., Okubo, M. Y., Kawano, D. F., Monteiro, P. A., Foglio, M. A., & Carvalho, J. E. (2020). In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts. Molecules, 25(17), 4018. https://doi.org/10.3390/molecules25174018

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