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Métodos Terapêuticos e Terapias MTCI
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1.
Int Immunopharmacol ; 101(Pt A): 108177, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34626872

RESUMO

Osteoporosis, characterized by bone loss and microstructure damage, occurs when osteoclast activity outstrips osteoblast activity. Natural compounds with inhibitory effect on osteoclast differentiation and function have been evidenced to protect from osteoporosis. After multiple compounds screening, 12-deoxyphorbol 13-acetate (DPA) was found to decline RANKL-induced osteoclastogenesis dose-dependently by attenuating activities of NFATc1 and c-Fos, followed by decreasing the level of osteoclast function-associated genes and proteins including Acp5, V-ATPase-d2 and CTSK. Mechanistically, we found that DPA suppressing RANKL-induced downstream signaling pathways, including MAPK signaling pathway and calcium oscillations. Furthermore, the in vivo efficacy of DPA was further confirmed in an OVX-induced osteoporosis mice model. Collectively, the results in our presentation reveal that DPA might be a promising compound to manage osteoporosis.


Assuntos
Fatores de Transcrição NFATC/antagonistas & inibidores , Osteoporose/tratamento farmacológico , Ésteres de Forbol/farmacologia , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Osteogênese/efeitos dos fármacos , Osteogênese/imunologia , Osteoporose/imunologia , Ésteres de Forbol/uso terapêutico , Células RAW 264.7
2.
Phytother Res ; 35(10): 5754-5766, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34431562

RESUMO

Spinal cord injury (SCI) is a devastating neurological occurrence that usually leads to a loss of motor and sensory function in patients. Axon regeneration has been reported to be crucial for recovery after trauma to the nervous system. Morin, a natural bioflavonoid obtained from the Moraceae family, has previously been reported to exert neuroprotective effects. In our study, we investigated the protective effects of morin on PC12 cells and primary neurons treated with oxygen-glucose deprivation (OGD) and its function in an SCI model. In vitro experiments showed that treating neuronal cells with morin enhanced axonal regeneration after OGD treatment by regulating microtubule stabilization and protecting mitochondrial function. Mechanistically, morin protected neuronal cells exposed to OGD by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. An in vivo study illustrated that oral morin administration improved microtubule stability and promoted axon regeneration in SCI rats. Taken together, this study showed that treatment with morin improves functional recovery after SCI and that morin may serve as a potential agent for treating SCI.


Assuntos
Heme Oxigenase-1 , Traumatismos da Medula Espinal , Animais , Axônios , Flavonoides/farmacologia , Humanos , Fator 2 Relacionado a NF-E2 , Regeneração Nervosa , Ratos , Ratos Sprague-Dawley , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico
3.
J Cell Mol Med ; 23(12): 8355-8368, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31603626

RESUMO

Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti-inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, V-ATPase-d2 and integrin ß3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.


Assuntos
Reabsorção Óssea/prevenção & controle , Flavonóis/farmacologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/farmacologia , Animais , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Integrina beta3/genética , Integrina beta3/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Ovariectomia , Fitoterapia/métodos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/metabolismo
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