Rosanna T Basting1, Catarine M Nishijima1, Juliana A Lopes1, Raquel C Santos1, Larissa Lucena Périco1, Stefan Laufer2, Silke Bauer2, Miriam F Costa3, Lourdes C Santos3, Lúcia R M Rocha1, Wagner Vilegas4, Adair R S Santos5, Catarina Dos Santos6, Clélia A Hiruma-Lima7. 1. Univ. Estadual Paulista-UNESP, Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil. 2. Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany. 3. Univ. Estadual Paulista-UNESP, Departamento de Química Orgânica, Instituto de Química, CEP 14800-900, Araraquara, SP, Brazil. 4. Univ. Estadual Paulista-UNESP, Campus Experimental do Litoral Paulista, CEP 11330-900, São Vicente, SP, Brazil. 5. Universidade Federal de Santa Catarina, Departamento de Ciências Fisiológicas, CEP 88040-900, Florianópolis, SC, Brazil. 6. Univ. Estadual Paulista-UNESP, Departamento de Ciências Biológicas, Faculdade de Ciências e Letras, CEP 19806-900, Assis, SP, Brazil. Electronic address: csantos@assis.unesp.br. 7. Univ. Estadual Paulista-UNESP, Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil. Electronic address: hiruma@ibb.unesp.br.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: An ethnopharmacological survey indicated that leaves from Eugenia punicifolia (Kunth) DC. (Myrtaceae) are popularly used as a natural therapeutic agent to treat pain and inflammation. AIM OF THE STUDY: The overall objective of the present study was to evaluate the antinociceptive, anti-inflammatory and gastroprotective activities of a hydroalcoholic extract of leaves from Eugenia punicifolia (HEEP) in rodents. MATERIAL AND METHODS: The antinociceptive effects of HEEP were evaluated in mice after oral administration in chemical (formalin and glutamate) and thermal (hot-plate) tests. We evaluated the involvement of the glutamatergic, opioidergic and nitrergic pathways in the antinociception of HEEP and the effect of HEEP on the inhibition of p38α MAPK. The anti-inflammatory effect of HEEP was evaluated in mice and rats using xylene-induced ear edema and carrageenan-induced paw edema, respectively. Furthermore, the gastroprotective effect of HEEP was evaluated in rats with acute gastric lesions induced by ethanol or indomethacin. Finally, we performed a phytochemical analysis of HEEP. RESULTS: The oral administration of HEEP (125, 250 and 500mg/kg, p.o.) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, and HEEP (250mg/kg, p.o.) also significantly inhibited the nociception caused by glutamate. The antinociceptive effects of HEEP were significantly reversed by l-arginine (500mg/kg, i.p.) but not by naloxone (1mg/kg, i.p.) in the formalin test. HEEP did not affect animal motor performance in the rotarod model. In addition, HEEP also increased the paw withdraw latency in the hot-plate test. HEEP significantly inhibited ear edema induced by xylene (64%) and paw edema induced by carrageenan (50%) compared to the control group. Furthermore, HEEP (3-30mg/mL) also inhibited the phosphorylation of p38α MAPK by approximately 90%. In addition, HEEP (125, 250 and 500mg/kg, p.o.) protected the rats against ethanol (88.4-99.8%) and indomethacin (53-72.3%) and increased the mucus levels of the gastric mucosa without producing an antisecretory effect. The phytochemical profile of HEEP obtained using HPLC-PDA showed secondary metabolites already reported for the genus, mostly flavonoids, gallotannins and proanthocyanidins. CONCLUSIONS: These data show for the first time that HEEP has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system, the synthesis of nitric oxide and the inhibition of the phosphorylation of p38α MAPK. HEEP also has interesting gastroprotective effects related to the maintenance of protective factors, such as mucus production. These results support the use of Eugenia punicifolia in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive, anti-inflammatory and gastroprotective properties.
ETHNOPHARMACOLOGICAL RELEVANCE: An ethnopharmacological survey indicated that leaves from Eugenia punicifolia (Kunth) DC. (Myrtaceae) are popularly used as a natural therapeutic agent to treat pain and inflammation. AIM OF THE STUDY: The overall objective of the present study was to evaluate the antinociceptive, anti-inflammatory and gastroprotective activities of a hydroalcoholic extract of leaves from Eugenia punicifolia (HEEP) in rodents. MATERIAL AND METHODS: The antinociceptive effects of HEEP were evaluated in mice after oral administration in chemical (formalin and glutamate) and thermal (hot-plate) tests. We evaluated the involvement of the glutamatergic, opioidergic and nitrergic pathways in the antinociception of HEEP and the effect of HEEP on the inhibition of p38α MAPK. The anti-inflammatory effect of HEEP was evaluated in mice and rats using xylene-induced ear edema and carrageenan-induced paw edema, respectively. Furthermore, the gastroprotective effect of HEEP was evaluated in rats with acute gastric lesions induced by ethanol or indomethacin. Finally, we performed a phytochemical analysis of HEEP. RESULTS: The oral administration of HEEP (125, 250 and 500mg/kg, p.o.) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, and HEEP (250mg/kg, p.o.) also significantly inhibited the nociception caused by glutamate. The antinociceptive effects of HEEP were significantly reversed by l-arginine (500mg/kg, i.p.) but not by naloxone (1mg/kg, i.p.) in the formalin test. HEEP did not affect animal motor performance in the rotarod model. In addition, HEEP also increased the paw withdraw latency in the hot-plate test. HEEP significantly inhibited ear edema induced by xylene (64%) and paw edema induced by carrageenan (50%) compared to the control group. Furthermore, HEEP (3-30mg/mL) also inhibited the phosphorylation of p38α MAPK by approximately 90%. In addition, HEEP (125, 250 and 500mg/kg, p.o.) protected the rats against ethanol (88.4-99.8%) and indomethacin (53-72.3%) and increased the mucus levels of the gastric mucosa without producing an antisecretory effect. The phytochemical profile of HEEP obtained using HPLC-PDA showed secondary metabolites already reported for the genus, mostly flavonoids, gallotannins and proanthocyanidins. CONCLUSIONS: These data show for the first time that HEEP has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system, the synthesis of nitric oxide and the inhibition of the phosphorylation of p38α MAPK. HEEP also has interesting gastroprotective effects related to the maintenance of protective factors, such as mucus production. These results support the use of Eugenia punicifolia in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive, anti-inflammatory and gastroprotective properties.
Authors: Mírian Feliciano Costa; Tais Iara Jesus; Bruno Rafael Pereira Lopes; Célio Fernando Figueiredo Angolini; Abner Montagnolli; Lorraine de Paula Gomes; Gabriela Sterle Pereira; Ana Lucia Tasca Gois Ruiz; João Ernesto Carvalho; Marcos Nogueira Eberlin; Catarina Dos Santos; Karina Alves Toledo Journal: BMC Complement Altern Med Date: 2016-10-22 Impact factor: 3.659
Authors: Izabelly Bianca da Silva Santos; Bruno Santos Dos Santos; João Ricardhis Saturnino de Oliveira; Wêndeo Kennedy Costa; Adrielle Zagmignan; Luís Cláudio Nascimento da Silva; Magda Rhayanny Assunção Ferreira; Vilmar Luiz Lermen; Maria Silvanete Benedito de Sousa Lermen; Alexandre Gomes da Silva; Rafael Matos Ximenes; Luiz Alberto Lira Soares; Patrícia Maria Guedes Paiva; Vera Lúcia de Menezes Lima; Maria Tereza Dos Santos Correia; Márcia Vanusa da Silva Journal: Adv Pharmacol Pharm Sci Date: 2020-04-27