RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Morus bombycis Koidzumi (M. bombycis, Moraceae) has been used in Asian countries as a traditional medicine for the treatment of hypertension, diabetes, and inflammation-related disorders. AIM OF STUDY: Although its anti-inflammatory actions have been partly documented, scientific evidence involving its molecular mechanisms related to inflammasome activation signaling pathways remains unknown. MATERIALS AND METHODS: Lipopolysaccharide-stimulated RAW 264.7 cells and bone marrow-derived murine macrophages were used to study the in vitro effect of methanolic extract of M. bombycis (MB) on inflammatory responses. A monosodium urate crystal (MSU)-induced peritonitis murine model was used to study the in vivo effects. RESULTS: MB attenuated the production of nitric oxide and interleukin-6, through the regulation of the interferon-ß receptor signaling pathway. MB also inhibited IL-1ß secretion via attenuation of NLRP3 inflammasome activation. Furthermore, MB inhibited MSU-induced peritonitis in the in vivo murine model. CONCLUSIONS: This study provides the key molecular mechanisms involved in the anti-inflammatory effects of M. bombycis, substantiating the traditional claims of its use in the treatment of inflammation-related disorders.
Assuntos
Anti-Inflamatórios/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Interferon beta/antagonistas & inibidores , Morus , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Proteínas de Transporte/metabolismo , Linhagem Celular , Células Cultivadas , Feminino , Inflamassomos , Interferon beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Óxido Nítrico/metabolismo , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Ácido ÚricoRESUMO
Carpesium macrocephalum (CM) Fr. et Sav. (Compositae) has been used in Chinese folk medicine as an analgesic, hemostatic, antipyretic, and to suppress inflammatory conditions. In the present study we aimed to provide scientific evidence for the anti-inflammatory properties of CM extract and evaluate the intrinsic mechanisms involved in both in vitro and in vivo experimental models. In in vitro findings, CM significantly inhibited the LPS-stimulated release of proinflammatory mediators such as nitric oxide, tumor necrosis factor-alpha, prostaglandin E2, and interleukin-6 in RAW264.7 macrophages in a concentration-dependent fashion. The attenuation of inflammatory responses in LPS-activated RAW264.7 cells by CM was closely associated with the suppression of nuclear factor-kappa B (NF-κB) phosphorylation, IκB-α degradation, and phosphorylation of Akt. CM treatment also attenuated the phosphorylation of STAT through TRIF dependent pathways in LPS-activated RAW264.7 cells. In vivo studies revealed that CM extract concentration dependently suppressed the acetic acid-induced vascular permeability in mice. Considering the data obtained regulation of multiple signaling mechanisms involving TRIF and Akt/NF-κB pathways might be responsible for the potent anti-inflammatory action of CM, substantiating its traditional use in inflammatory diseases.
Assuntos
Asteraceae , Permeabilidade Capilar/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Dinoprostona/imunologia , Endotoxinas/imunologia , Endotoxinas/toxicidade , Proteínas I-kappa B/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Interleucina-6/imunologia , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Camundongos , Inibidor de NF-kappaB alfa , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição STAT/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Acorus gramineus Solander (Acoraceae, AG), is a widely distributed plant in Asian countries. Rhizome part of this plant has long been used as a traditional medicine for treating various symptoms including central nervous system (CNS) disorders. AIM OF STUDY: The anti-neuroinflammatory effect of AG aqueous extract was investigated using in vitro cellular and in vivo Parkinson's disease (PD) mouse model. MATERIALS AND METHODS: Lipopolysaccharide (LPS) is used to stimulate BV-2 microglial cells in vitro and the changes in neuroinflammatory expressional levels were measured using ELISA, Western blotting, RT-PCR and immunofluorescence techniques. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD was developed followed by immunohistochemical analysis of specific brain tissues. RESULTS: LPS-stimulation to BV-2 cells increased the production of nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß. Pretreatment with AG extract inhibited the increased levels of NO and pro-inflammatory cytokines in LPS-stimulated BV-2 cells. Mechanistic study revealed that AG acts via the regulation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and TRIF-dependent signaling pathways. Further, AG protected MPTP-induced neuronal cell death and inhibited neuroinflammation in vivo. CONCLUSION: Our results indicated that AG extract exerted anti-neuroinflammatory effects against activated microglia mediated insults through multiple signaling pathways and prevented in vivo neuronal cell death in mouse model of PD substantiating the traditional claims for its use in CNS disorders.