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PLoS One ; 9(6): e97929, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24887557

RESUMO

Acne vulgaris is the most common skin disease, causing significant psychosocial problems such as anxiety and depression similar to a chronic illness for those afflicted. Currently, obtainable agents for acne treatment have limited use. Thus, development of novel agents to treat this disease is a high medical need. The anaerobic bacterium Propionibacterium acnes has been implicated in the inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such as the interleukin-8 (IL-8) via the NF-κB and MAPK pathways. Talaromyces wortmannii is an endophytic fungus, which is known to produce high bioactive natural compounds. We hypothesize that compound C but also the crude extract from T. wortmannii may possess both antibacterial activity especially against P. acnes and also anti-inflammatory properties by inhibiting TNF-α-induced ICAM-1 expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT) with P. acnes significantly increased NF-κB and activator protein-1 (AP-1) activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated activation of NF-κB and AP-1 by inhibiting IκB degradation and the phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent manner. Based on these results, compound C has effective antimicrobial activity against P. acnes and anti-inflammatory activity, and we suggest that this substance or the crude extract are alternative treatments for antibiotic/anti-inflammatory therapy for acne vulgaris.


Assuntos
Acne Vulgar/microbiologia , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Misturas Complexas/farmacologia , Endófitos/química , Propionibacterium acnes/fisiologia , Talaromyces/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-8/metabolismo , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Propionibacterium acnes/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
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