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Int Immunopharmacol ; 132: 111971, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38565040

RESUMO

DNA damage resulting from UV irradiation on the skin has been extensively documented in numerous studies. In our prior investigations, we demonstrated that UVB-induced DNA breakage from keratinocytes can activate the cGAS-STING pathway in macrophages. The cGAS-STING signaling pathway serves as the principal effector for detecting and responding to abnormal double-stranded DNA in the cytoplasm. Expanding on our previous findings, we have further validated that STING knockout significantly diminishes UVB-induced skin damage, emphasizing the critical role of cGAS-STING activation in this context. Salvianolic acid A, a principal active constituent of Salvia miltiorrhiza Burge, has been extensively studied for its therapeutic effects in conditions such as coronary heart disease, angina pectoris, and diabetic peripheral neuropathy. However, its effect on cGAS-STING pathway and its ability to alleviate skin damage have not been previously reported. In a co-culture system, supernatant from UVB-treated keratinocytes induced IRF3 activation in macrophages, and this activation was inhibited by salvianolic acid A. Our investigation, employing photodamage and photoaging models, establishes that salvianolic acid A effectively mitigates UV-induced epidermal thickening and collagen degeneration. Treatment with salvianolic acid A significantly reduced skin damage, epidermal thickness increase, and keratinocyte hyperproliferation compared to the untreated photo-damage and photoaging model groups. In summary, salvianolic acid A emerges as a promising candidate for preventing UV-induced skin damage by inhibiting cGAS-STING activation. This research enhances our understanding of the intricate mechanisms underlying skin photodamage and provides a potential avenue for the development of therapeutic interventions.


Assuntos
Ácidos Cafeicos , Queratinócitos , Lactatos , Proteínas de Membrana , Nucleotidiltransferases , Transdução de Sinais , Pele , Raios Ultravioleta , Raios Ultravioleta/efeitos adversos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Animais , Transdução de Sinais/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Pele/efeitos dos fármacos , Pele/patologia , Pele/efeitos da radiação , Nucleotidiltransferases/metabolismo , Ácidos Cafeicos/farmacologia , Humanos , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Fator Regulador 3 de Interferon/metabolismo , Feminino , Células RAW 264.7
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