RESUMO
Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density (BMD), which results in an increased risk of fracture. Melandrium firmum (Siebold & Zucc.) Rohrbach (MFR), 'Wangbulryuhaeng' in Korean, is the dried aerial portion of Melandrii Herba Rohrbach, which is a member of the Caryophyllaceae family and has been used to treat several gynecological conditions as a traditional medicine. However, to the best of our knowledge, the effect of MFR on osteoclast differentiation and osteoporosis has not been assessed. To evaluate the effects of MFR on osteoclast differentiation, tartrateresistant acid phosphatase staining, actin ring formation and bone resorption assays were used. Additionally, receptor activator of nuclear factorκB ligandinduced expression of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) and cFos were measured using western blotting and reverse transcriptionPCR. The expression levels of osteoclastrelated genes were also examined. To further investigate the antiosteoporotic effects of MFR in vivo, an ovariectomized (OVX) rat model of menopausal osteoporosis was established. Subsequently, the femoral head was scanned using microcomputed tomography. The results revealed that MFR suppressed osteoclast differentiation, formation and function. Specifically, MFR reduced the expression levels of osteoclastrelated genes by downregulating transcription factors, such as NFATc1 and cFos. Consistent with the in vitro results, administration of MFR water extract to OVX rats reduced BMD loss, and reduced the expression levels of NFATc1 and cathepsin K in the femoral head. In conclusion, MFR may contribute to alleviate osteoporosislike symptoms. These results suggested that MFR may exhibit potential for the prevention and treatment of postmenopausal osteoporosis.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Osteoclastos/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Silene/química , Actinas/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/toxicidade , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/sangue , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/patologia , Ovariectomia/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/toxicidade , Ratos Sprague-Dawley , Fator 6 Associado a Receptor de TNF/metabolismo , Fosfatase Ácida Resistente a Tartarato/metabolismoRESUMO
Cone of Pinus densiflora (CP), or Korean red pinecone, is a cluster of Pinus densiflora fruit. CP has also been verified in several studies to have anti-oxidation, anti-fungal, anti-bacterial, and anti-melanogenic effects. However, anti-inflammatory effects have not yet been confirmed in the inflammatory responses of pinecones to allergic contact dermatitis. The purpose of this study is to prove the anti-inflammatory effect of CP on allergic contact dermatitis (ACD) in vitro and in vivo. CP inhibited the expression of TSLP, TARC, MCP-1, TNF-α, and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells and MCP-1, GM-CSF, TNF-α, IL-6, and IL-8 in PMACI (phorbol-12-myristate-13-acetate plus A23187)-stimulated HMC-1 cells. CP inhibited the phosphorylation of mitogen-activated protein kinase (MAPKs), as well as the translocation of NF-κB on TNF-α/IFN-γ stimulated in HaCaT cells. In vivo, CP decreased major symptoms of ACD, levels of IL-6 in skin lesion, thickening of the epidermis and dermis, infiltration of eosinophils and mast cells, and the infiltration of CD4+ T cells and CD8+ T cells. This result suggests that CP represents a potential alternative medicine to ACD for diseases such as chronic skin inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Dermatite Alérgica de Contato/tratamento farmacológico , Pinus/química , Extratos Vegetais/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Dermatite Alérgica de Contato/etiologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Células HaCaT , Humanos , Interferon gama/metabolismo , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The present study aimed to investigate the effects of Solanum nigrum Linne (SNL) in a model of 1chloro2,4dinitrobenzene (DNCB)induced atopic dermatitis (AD) and in TNFα/IFNγstimulated HaCaT cells. AD is a chronic inflammatory skin disease and is characterized by erythema, edema, increased pruritus and eczema. Steroids are most commonly used for antiinflammatory therapy; however, their longterm use is limited due to sideeffects, such as osteoporosis, brittle skin, muscle weaknesses and diabetes. Therefore, patients with AD require alternative treatment strategies. In previous studies, SNL has been reported to be effective against oxidants and cancer. However, to the best of our knowledge, the effects of SNL on AD have not yet been investigated. The present study examined the effects of SNL ethanol extract on a model of DNCB induced AD and on TNFα/IFNγstimulated HaCaT cells. The skin tissue was sectioned to measure the thicknesses of the epidermis and dermis, as well as the numbers of eosinophils, mast cells and CD8 infiltration by H&E, toluidine blue, Masson's trichrome and IHC staining. ELISA was performed using serum to measure IgE levels. The present study also examined the expression of various inflammatory cytokines, MAPK and NFκB in TNFα/IFNγstimulated HaCaT cells. SNL significantly reduced the levels of cytokines released from HaCaT cells stimulated with TNFα/IFNγ. SNL also significantly reduced the levels of pp38 at 30 min and significantly reduced the activation of NFκB in a time course experiment. In addition, SNL significantly reduced the level of serum IgE and dermal thickness and the infiltration of mast cells and CD8 in the BALB/c mouse model of DNCBinduced AD. The results of the current study suggest that SNL exerts a suppressive effect on proinflammatory cytokines in vitro and in vivo through the regulation of the immune system.