RESUMO
Kaempferia parviflora, referred to as black ginger, has traditionally been used as a health-promoting alternative medicine. In this study, we examined the anti-inflammatory, sebostatic, and anti-Propionibacterium acnes activities of K. parviflora extract. The extract significantly down-regulated the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) level. Moreover, the phosphorylation of IĸBα and nuclear factor-kappa B (NF-κB), and the enhanced nuclear translocation of NF-κB p65 in lipopolysaccharide-stimulated murine macrophage-like cell line (RAW 264.7) cells were markedly decreased by the extract. Notably, the main component of K. parviflora, 5,7-dimethoxyflavone, also modulated the expression of iNOS and NF-κB signal molecules in P. acnes-stimulated human keratinocyte (HaCaT) cells. Additionally, K. parviflora extract inhibited the lipogenesis of sebocytes, as evidenced by a reduced level of triglyceride and lipid accumulation in the sebocytes. The sebostatic effect was also confirmed by a reduced expression of peroxisome proliferation-activating receptors (PPAR-γ) and oil-red O staining in sebocytes. Taken together, this study suggests for the first time that K. parviflora extract could be developed as a potential natural anti-acne agent with anti-inflammatory, sebostatic, and anti-P. acnes activity.
Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Queratinócitos/efeitos dos fármacos , Propionibacterium acnes/efeitos dos fármacos , Zingiberaceae/química , Animais , Antibacterianos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Flavonoides/isolamento & purificação , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/química , Propionibacterium acnes/crescimento & desenvolvimento , Células RAW 264.7 , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In this study, we investigated the anti-microbial, anti-inflammatory, and anti-lipogenic effects of hemp (Cannabis sativa L.) seed hexane extracts, focusing on the Propionibacterium acnes-triggered inflammation and lipogenesis. Hemp seed hexane extracts (HSHE) showed anti-microbial activity against P. acnes. The expression of iNOS, COX-2, and the subsequent production of nitric oxide and prostaglandin increased after infection of P. acnes in HaCaT cells, however, upon treating with HSHE, their expressions were reduced. P. acnes-induced expressions of IL-1ß and IL-8 were also reduced. HSHE exerted anti-inflammatory effects by regulating NF-κB and MAPKs signaling and blunting the translocation of p-NF-κB to the nucleus in P. acnes-stimulated HaCaT cells. Moreover, P. acnes-induced phosphorylation of ERK and JNK, and their downstream targets c-Fos and c-Jun, was also inhibited by HSHE. In addition, the transactivation of AP-1 induced by P. acnes infection was also downregulated by HSHE. Notably, HSHE regulated inflammation and lipid biosynthesis via regulating AMPK and AKT/FoxO1 signaling in IGF-1-induced inflammation and lipogenesis of sebocytes. In addition, HSHE inhibited 5-lipoxygenase level and P. acnes-induced MMP-9 activity, and promoted collagen biosynthesis in vitro. Thus, HSHE could be utilized to treat acne vulgaris, through its anti-microbial, anti-inflammatory, anti-lipogenic, and collagen-promoting properties.
Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Cannabis/química , Inflamação/tratamento farmacológico , Lipogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Glândulas Sebáceas/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Araquidonato 5-Lipoxigenase/química , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Hexanos/química , Humanos , Inflamação/etiologia , Inflamação/patologia , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Inibidores de Lipoxigenase/isolamento & purificação , Inibidores de Lipoxigenase/farmacologia , Propionibacterium acnes/patogenicidade , Glândulas Sebáceas/citologia , Glândulas Sebáceas/metabolismo , Sementes/químicaRESUMO
Photodynamic therapy (PDT), consisting of photosensitizer, light, and oxygen has been used for the treatment of various diseases including cancers, microbial infections and skin disorders. In this study, we examined the anti-inflammatory effect of chlorin e6-mediated PDT in P. acnes-infected HaCaT cells using photosensitizer chlorin e6 (Ce6) and halogen light. The live and heat-killed P. acnes triggered an upregulation of inflammatory molecules such as iNOS, NO, and inflammatory cytokine in HaCaT cells and mouse model. Ce6-mediated PDT notably downregulated the expression of these inflammatory molecules in vitro and in vivo. Similarly, chlorin e6-mediated PDT was capable of regulating inflammatory response in both live and heat killed S. epidermidis exposed HaCaT cells. Moreover, phosphorylation of p38, JNK, and ERK were reduced by Ce6-mediated PDT. Ce6-mediated PDT also reduced the phosphorylation of IKKα/ß, IĸBα and NFκB p65 in P. acnes-stimulated HaCaT cells. In addition, the dramatic increase in the nuclear translocation of NFκB p65 observed upon stimulation with P. acnes was markedly impaired by Ce6-based PDT. This is the first suggestion that Ce6-mediated PDT suppresses P. acnes-induced inflammation through modulating NFκB and MAPKs signaling pathways.