RESUMO
Our previous studies suggested that paeonol, the active constituent of the traditional Chinese medicine Cortex Moutan, may be an effective treatment for inflammatory disorders. In the present study, the therapeutic potential of paeonol on atopic dermatitis (AD) was investigated using animal and cell experiments. ADlike lesions were induced by repeated application of 1chloro2,4dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice, and P815 cells were used for in vitro assays. The skin lesions, serum and spleens of the mice were analyzed using lesion severity scoring, histological analysis, flow cytometry, reverse transcriptionquantitative polymerase chain reaction, western blotting and ELISA, in order to investigate the antiAD effects of paeonol. In addition, western blotting and ELISA were conducted for in vitro analysis of P815 cells. The results demonstrated that oral administration of paeonol inhibited the development of DNCBinduced ADlike lesions in the BALB/c mice by reducing severity of the lesions, epidermal thickness and mast cell infiltration; this was accompanied by reduced levels of immunoglobulin E and inflammatory cytokines [interleukin (IL)4, histamine, IL13, IL31 and thymic stromal lymphopoietin], along with regulation of the T helper (Th) cell subset (Th1/Th2) ratio. Application of paeonol also reduced the protein expression levels of phosphorylated (p)p38 and pextracellular signalregulated kinase (ERK) in skin lesions. In vitro, paeonol reduced the expression levels of tumor necrosis factorα and histamine in P815 cells, and inhibited p38/ERK/mitogenactivated protein kinase signaling. The present findings indicated that paeonol may relieve dermatitis by acting on cluster of differentiation 4+ T and mast cells; therefore, paeonol may represent a potential therapeutic strategy for the treatment of allergic inflammatory conditions via immunoregulation.
Assuntos
Acetofenonas/farmacologia , Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/efeitos adversos , Mastócitos/imunologia , Mastócitos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Biomarcadores , Linhagem Celular , Citocinas/genética , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Camundongos , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
Matrine, is a bioactive compound isolated from Sophora flavescens (Ku shen), an herb used in Chinese traditional medicine that possesses wide-reaching pharmacological action. Psoriasis is a chronic relapsing inflammatory disorder with an incompletely understood pathophysiology, and dendritic cells (DCs) play a central role in the disease. This study aimed to explore DCs related potential mechanisms based on the effect of matrine on imiquimod (IMQ)-induced psoriasiform dermatitis in BALB/c mice and DCs simulated by resiquimod. Mice with IMQ-induced psoriasiform cutaneous lesions were treated with matrine [12.5, 25 or 50 mg/(kg·d), for 6 days]. Morphology, histological changes, keratinocyte proliferation and differentiation, inflammatory cell infiltration, protein expression levels of myeloid differentiation factor 88 (MyD88), and mRNA expression levels of inflammatory factors [interleukin (IL)-12, IL-23, and IL-1ß] in lesional skin were assessed. The application of matrine decreased the proliferation of IMQ-induced keratinocytes. The treatment attenuated the infiltration of PCNA+ and CD3+ cells in the lesions. Matrine reduced the expression of the MyD88 protein and the inflammatory factors' mRNA in lesional skin, but also in BMDCs (bone marrow derived dendritic cells). These results indicated that matrine suppressed expression of the inflammatory factors by decreasing the expression of the MyD88 protein on the surface of BMDCs, finally alleviating psoriasiform skin lesions. Therefore, the findings suggest that matrine might be a potential candidate for treating psoriasis.
RESUMO
Dauricine, a bioactive component of Asiatic Moonseed Rhizome, has been widely used to treat a large number of inflammatory diseases in traditional Chinese medicine. In our study, we demonstrated that dauricine inhibited colon cancer cell proliferation and invasion, and induced apoptosis by suppressing nuclear factor-kappaB (NF-kappaB) activation in a dose- and time-dependent manner. Addition of dauricine inhibited the phosphorylation and degradation of IkappaBalpha, and the phosphorylation and translocation of p65. Moreover, dauricine down-regulated the expression of various NF-kappaB-regulated genes, including genes involved cell proliferation (cyclinD1, COX2, and c-Myc), anti-apoptosis (survivin, Bcl-2, XIAP, and IAP1), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). In athymic nu/nu mouse model, we further demonstrated that dauricine significantly suppressed colonic tumor growth. Taken together, our results demonstrated that dauricine inhibited colon cancer cell proliferation, invasion, and induced cell apoptosis by suppressing NF-kappaB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of dauricine in preventing or treating colon cancer through modulation of NF-kappaB singling pathway.