Anita Eugênia Alencar Santos Ribeiro1, Juliana Mikaely Dias Soares2, Helder Anderson Lima Silva3, Carlos Wagner de Souza Wanderley4, Celuane Alves Moura5, Raimundo Gonçalves de Oliveira-Junior6, Ana Paula de Oliveira7, Larissa Araújo Rolim8, Emmanoel Vilaça Costa9, Jackson Roberto Guedes da Silva Almeida10, Helinando Pequeno de Oliveira11, Raimundo Campos Palheta-Junior12. 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.
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.
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.
Authors: Asenate A X Adrião; Aline O Dos Santos; Emilly J S P de Lima; Jéssica B Maciel; Weider H P Paz; Felipe M A da Silva; Manuela B Pucca; Ana M Moura-da-Silva; Wuelton M Monteiro; Marco A Sartim; Hector H F Koolen Journal: Front Immunol Date: 2022-05-09 Impact factor: 8.786