Inhibitory effects of Morus nigra L. (Moraceae) against local paw edema and mechanical hypernociception induced by Bothrops jararacussu snake venom in mice

Anita Eugênia Alencar Santos Ribeiro; Juliana Mikaely Dias Soares; Helder Anderson Lima Silva; Carlos Wagner de Souza Wanderley; Celuane Alves Moura; Raimundo Gonçalves de Oliveira-Junior; Ana Paula de Oliveira; Larissa Araújo Rolim; Emmanoel Vilaça Costa; Jackson Roberto Guedes da Silva Almeida; Helinando Pequeno de Oliveira; Raimundo Campos Palheta-Junior

doi:10.1016/j.biopha.2019.01.011

Inhibitory effects of Morus nigra L. (Moraceae) against local paw edema and mechanical hypernociception induced by Bothrops jararacussu snake venom in mice

Biomed Pharmacother. 2019 Mar:111:1046-1056. doi: 10.1016/j.biopha.2019.01.011. Epub 2019 Jan 11.

Authors

Affiliations

¹ Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: anita_alencar@hotmail.com.
² Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: juliana_mikaelly@hotmail.com.
³ Pós-Graduação em Ciências Veterinárias no Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: helderals@hotmail.com.
⁴ Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900, Ribeirão Preto, São Paulo, Brazil. Electronic address: cwswanderley@gmail.com.
⁵ Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: ce-lu93@hotmail.com.
⁶ Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: oliveira.farma.junior@gmail.com.
⁷ Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: ana_tecquimica@yahoo.com.br.
⁸ Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: larissa.rolim@univasf.edu.br.
⁹ Departamento de Química, Universidade Federal do Amazonas, 69067-005, Manaus, Amazonas, Brazil. Electronic address: emmanoelvilaca@yahoo.com.br.
¹⁰ Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: jackson.guedes@univasf.edu.br.
¹¹ Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil; Pós-Graduação em Ciência dos Materiais, Universidade Federal do Vale do São Francisco, 48902-300, Juazeiro, Bahia, Brazil. Electronic address: helinando.oliveira@univasf.edu.br.
¹² Pós-Graduação em Recursos Naturais do Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil; Pós-Graduação em Ciências Veterinárias no Semiárido, Universidade Federal do Vale do São Francisco, 56300-990, Petrolina, Pernambuco, Brazil. Electronic address: raimundo.palheta@univasf.edu.br.

PMID: 30841418
DOI: 10.1016/j.biopha.2019.01.011

Abstract

Background: Bothropic venoms cause intense local damage, pain, edema, and myonecrosis. Morus nigra L. (Moraceae) has several uses in folk medicine and can be a promising candidate for the treatment of several inflammatory disorders.

Hypothesis/purpose: The present study aims to evaluate the anti-inflammatory and antinociceptive effects of the ethanolic extract of Morus nigra L. (Mn-EtOH) on paw lesions induced by Bothrops jararacussu snake venom (BjcuV) in mice.

Methods: UV-vis absorption of BjcuV was evaluated. A phytochemical study was performed, which led to the isolation and characterization of three compounds. These compounds were identified using spectrometric methods, namely LC-MS and NMR (1D and 2D), followed by the validation of their spectra with the data available in the literature. Further, the flavonoids i.e. rutin and quercetin (chemical markers of M. nigra), Mn-EtOH or Mn-EtOH-encapsulated electrospun fibers of Eudragit L100 (FB/Mn-EtOH), and Mn-EtOH-encapsulated microparticles of Eudragit L100 (MP/Mn-EtOH) were evaluated, in paw edema test induced by BjcuV.

Results: UV-vis spectra showed the presence of phospholipases A₂ as component of BjcuV. The chemical examination resulted in the isolation of β-sitosterol, quercetin-3-O-glucopyranoside, and kaempferol-3-O-glucopyranoside. Mn-EtOH, FB/Mn-EtOH, MP/Mn-EtOH, rutin, and quercetin reduced the local edema induced by BjcuV. The Mn-EtOH also prevented edema provoked by serotonin and bradykinin. Moreover, it reduced paw edema and peritoneal leukocyte infiltration induced by carrageenan, and decreased the mechanical hypernociception of BjcuV. Mn-EtOH exerted anti-inflammatory and antinociceptive effects, possibly by the inhibition of leukocyte migration and the modulation of serotonin and bradykinin actions. This anti-inflammatory activity was maintained even upon incorporation of the M. nigra extract into the drug delivery systems (i.e., Mn-EtOH-encapsulated FBs and MPs of Eudragit L100).

Conclusion: These results reinforce the therapeutic potential of M. nigra in the treatment of inflammatory conditions, in addition to, its role as a complementary treatment of snakebites.

Keywords: Bothrops jararacussu; Edema; Electrospun fibers; Inflammation; Morus nigra; Pain.

MeSH terms

Animals
Bothrops
Carrageenan / pharmacology
Cell Movement / drug effects
Edema / chemically induced
Edema / drug therapy*
Female
Leukocytes / drug effects
Medicine, Traditional / methods
Mice
Moraceae / chemistry*
Morus / chemistry*
Nociception / drug effects*
Phytochemicals / chemistry
Phytochemicals / pharmacology
Plant Extracts / chemistry
Plant Extracts / pharmacology*
Snake Venoms / pharmacology*

Substances

Phytochemicals
Plant Extracts
Snake Venoms
Carrageenan