Anti-inflammatory activity of Eugenia punicifolia extract on muscular lesion of mdx dystrophic mice.
Eugenia punicifolia known as "pedra-ume caá" is a shrub largely distributed in the Amazon region popularly used in decoctions or infusions as a natural therapeutic agent, which can interfere on cholinergic nicotinic neurotransmission. This work aimed to investigate a putative anti-inflammatory effect of dichloromethane fraction of E. punicifolia extract (Ep-CM) in the muscular lesion of mdx dystrophic mice, considering that activation of cholinergic mechanisms mitigates inflammation. A polymer containing the Ep-CM was implanted in mdx gastrocnemius muscle before onset of myonecrosis for local slow and gradual release of bioactive compounds and mice sacrificed 7 days or 9 weeks after surgery. Comparing to control muscle, treatment did not alter choline acetyltransferase and acetylcholinesterase enzymatic activities, but decreased metaloproteases-9 and -2 activities and levels of tumor necrosis factor α and NFκB transcription factor. In addition, treatment also reduced levels of bioactive IL-1β form and cleaved caspase-3, related to early events of cellular death and inflammatory activation and further increased myogenin expression without affecting collagen production which is associated with fibrosis. In vivo treatment of mdx dystrophic mice with Ep-CM caused significant reduction of muscular inflammation and improved skeletal muscle regeneration without inducing fibrosis.
Departamento de Biologia Celular e Molecular, Universidade Federal Fluminense, Niterói, Rio de Janeiro 24020-141, Brazil.
Paulo Emílio Corrêa
PE
Leite
Kessiane Belshoff
KB
de Almeida
Jussara
J
Lagrota-Candido
Pablo
P
Trindade
Rafael Ferreira
RF
da Silva
Manuel Gustavo L
MG
Ribeiro
Katia G
KG
Lima-Araújo
Wilson C
WC
Santos
Thereza
T
Quirico-Santos
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D027842:Syzygium / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D002795:Choline O-Acetyltransferase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9