RESUMO
Cutibacterium acnes (formerly Propionibacterium acnes) is one of the major bacterial species responsible for acne vulgaris. Numerous bioactive compounds from Momordica charantia Linn. var. abbreviata Ser. have been isolated and examined for many years. In this study, we evaluated the suppressive effect of two cucurbitane-type triterpenoids, 5ß,19-epoxycucurbita-6,23-dien-3ß,19,25-triol (Kuguacin R; KR) and 3ß,7ß,25-trihydroxycucurbita-5,23-dien-19-al (TCD) on live C. acnes-stimulated in vitro and in vivo inflammatory responses. Using human THP-1 monocytes, KR or TCD suppressed C. acnes-induced production of interleukin (IL)-1ß, IL-6 and IL-8 at least above 56% or 45%, as well as gene expression of these three pro-inflammatory cytokines. However, a significantly strong inhibitory effect on production and expression of tumor necrosis factor (TNF)-α was not observed. Both cucurbitanes inhibited C. acnes-induced activation of the myeloid differentiation primary response 88 (MyD88) (up to 62%) and mitogen-activated protein kinases (MAPK) (at least 36%). Furthermore, TCD suppressed the expression of pro-caspase-1 and cleaved caspase-1 (p10). In a separate study, KR or TCD decreased C. acnes-stimulated mouse ear edema by ear thickness (20% or 14%), and reduced IL-1ß-expressing leukocytes and neutrophils in mouse ears. We demonstrated that KR and TCD are potential anti-inflammatory agents for modulating C. acnes-induced inflammation in vitro and in vivo.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cucurbitacinas/química , Cucurbitacinas/farmacologia , Inflamação/tratamento farmacológico , Momordica charantia/química , Triterpenos/química , Triterpenos/farmacologia , Acne Vulgar/tratamento farmacológico , Acne Vulgar/imunologia , Acne Vulgar/microbiologia , Animais , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Glicosídeos/química , Glicosídeos/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Propionibacteriaceae/patogenicidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células THP-1RESUMO
Cutibacterium acnes (formerly Propionibacterium acnes) is a key pathogen involved in the development and progression of acne inflammation. The numerous bioactive properties of wild bitter melon (WBM) leaf extract and their medicinal applications have been recognized for many years. In this study, we examined the suppressive effect of a methanolic extract (ME) of WBM leaf and fractionated components thereof on live C. acnes-induced in vitro and in vivo inflammation. Following methanol extraction of WBM leaves, we confirmed anti-inflammatory properties of ME in C. acnes-treated human THP-1 monocyte and mouse ear edema models. Using a bioassay-monitored isolation approach and a combination of liquid-liquid extraction and column chromatography, the ME was then separated into n-hexane, ethyl acetate, n-butanol and water-soluble fractions. The hexane fraction exerted the most potent anti-inflammatory effect, suppressing C. acnes-induced interleukin-8 (IL-8) production by 36%. The ethanol-soluble fraction (ESF), which was separated from the n-hexane fraction, significantly inhibited C. acnes-induced activation of mitogen-activated protein kinase (MAPK)-mediated cellular IL-8 production. Similarly, the ESF protected against C. acnes-stimulated mouse ear swelling, as measured by ear thickness (20%) and biopsy weight (23%). Twenty-four compounds in the ESF were identified using gas chromatograph-mass spectrum (GC/MS) analysis. Using co-cultures of C. acnes and THP-1 cells, ß-ionone, a compound of the ESF, reduced the production of IL-1ß and IL-8 up to 40% and 18%, respectively. ß-ionone also reduced epidermal microabscess, neutrophilic infiltration and IL-1ß expression in mouse ear. We also found evidence of the presence of anti-inflammatory substances in an unfractionated phenolic extract of WBM leaf, and demonstrated that the ESF is a potential anti-inflammatory agent for modulating in vitro and in vivo C. acnes-induced inflammatory responses.
Assuntos
Anti-Inflamatórios/química , Momordica charantia/química , Extratos Vegetais/química , Propionibacteriaceae/patogenicidade , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/microbiologia , Edema/patologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Masculino , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Momordica charantia/metabolismo , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/microbiologia , Extratos Vegetais/análise , Folhas de Planta/química , Folhas de Planta/metabolismoRESUMO
Acne vulgaris (acne) is a common inflammatory skin disorder, and Propionibacterium acnes plays a major role in the development and progression of acne inflammation. Herbs possessing antimicrobial and anti-inflammatory activity have been applied as a medical option for centuries. In this study, we examined the suppressive effect of ethanolic oregano (Origanum vulgare) extract on live P. acnes-induced in vivo and in vitro inflammation. Following ethanol extraction of oregano leaves, four compounds with strong antioxidant activity, including rosmarinic acid, quercetin, apigenin, and carvacrol, were identified by high-performance liquid chromatography. Using the mouse ear edema model, we demonstrated that ethanol oregano extracts (EOE) significantly suppressed P. acnes-induced skin inflammation, as measured by ear thickness (32%) and biopsy weight (37%). In a separate study, using the co-culture of P. acnes and human THP-1 monocytes, EOE reduced the production of interleukin (IL)-8, IL-1ß and tumor necrosis factor (TNF)-α up to 40%, 37%, and 18%, respectively, as well as the expression of these three pro-inflammatory mediators at the transcriptional level. Furthermore, EOE inhibited the translocation of nuclear factor-kappa B (NF-κB) into the nucleus possibly by inactivating toll-like receptor-2 (TLR2). The suppressive effect of EOE on live P. acnes-induced inflammatory responses could be due, in part, to the anti-inflammatory and antioxidant properties, but not the anti-microbial effect of EOE.
Assuntos
Orelha/patologia , Edema/tratamento farmacológico , Etanol/química , Inflamação/tratamento farmacológico , Monócitos/microbiologia , Origanum/química , Extratos Vegetais/uso terapêutico , Propionibacterium acnes/efeitos dos fármacos , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Edema/microbiologia , Edema/patologia , Humanos , Inflamação/microbiologia , Inflamação/patologia , Masculino , Camundongos Endogâmicos ICR , Monócitos/efeitos dos fármacos , Monócitos/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Fenóis/análise , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor 2 Toll-Like/metabolismoRESUMO
Propionibacterium acnes is a key pathogen involved in acne inflammation. Wild bitter melon (WBM, Momordica charantia L. var. abbreviate Seringe) is consumed as both a vegetable and as folk medicine in Taiwan. We examined the inhibitory activity of the total phenolic extract (TPE) of WBM leaf on P. acnes-induced inflammatory responses in vivo and in vitro. Our data showed that TPE significantly attenuated P. acnes-induced ear swelling in mice along with microabscess. Flow cytometry analysis revealed that TPE treatment significantly decreased the migration of neutrophils and interleukin (IL)-1ß(+) populations in vivo. In P. acnes-stimulated human monocytic THP-1 cells, TPE suppressed the mRNA levels and production of IL-8, IL-1ß, and tumor necrosis factor (TNF)-αin vitro. In addition, TPE suppressed P. acnes-induced matrix metalloproteinase-9 levels. TPE blocked nuclear factor-κB (NF-κB) activation and inactivated mitogen-activated protein kinases (MAPK); these actions may partially account for its inhibitory effect on cytokine production. The quantitative HPLC analysis revealed gallic, chlorogenic, caffeic, ferulic, and cinnamic acids, myricetin, quercetin, luteolin, apigenin, and thymol in TPE. All these phenolics significantly suppressed P. acnes-induced IL-8 production in vitro. Our results suggest that WBM leaf extract effectively inhibits P. acnes-induced inflammatory responses and may be useful to relieve the inflammation of acne.
Assuntos
Acne Vulgar/tratamento farmacológico , Acne Vulgar/imunologia , Momordica charantia/química , Extratos Vegetais/administração & dosagem , Propionibacterium acnes/fisiologia , Acne Vulgar/genética , Acne Vulgar/microbiologia , Animais , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/imunologia , Camundongos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/imunologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Taiwan , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Propionibacterium acnes is a key pathogen involved in the progression of acne inflammation. The development of a new agent possessing antimicrobial and anti-inflammatory activity against P. acnes is therefore of interest. In this study, we investigated the inhibitory effect of rosemary (Rosmarinus officinalis) extract on P. acnes-induced inflammation in vitro and in vivo. The results showed that ethanolic rosemary extract (ERE) significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including interleukin (IL)-8, IL-1ß, and tumor necrosis factor-α in P. acnes-stimulated monocytic THP-1 cells. In an in vivo mouse model, concomitant intradermal injection of ERE attenuated the P. acnes-induced ear swelling and granulomatous inflammation. Since ERE suppressed the P. acnes-induced nuclear factor kappa-B (NF-κB) activation and mRNA expression of Toll-like receptor (TLR) 2, the suppressive effect of ERE might be due, at least partially, to diminished NF-κB activation and TLR2-mediated signaling pathways. Furthermore, three major constituents of ERE, carnosol, carnosic acid, and rosmarinic acid, exerted different immumodulatory activities in vitro. In brief, rosmarinic acid significantly suppressed IL-8 production, while the other two compounds inhibited IL-1ß production. Further study is needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes-induced inflammation.
Assuntos
Acne Vulgar/patologia , Anti-Inflamatórios/uso terapêutico , Mediadores da Inflamação/metabolismo , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Propionibacterium acnes , Rosmarinus/química , Abietanos/farmacologia , Abietanos/uso terapêutico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/metabolismo , Acne Vulgar/microbiologia , Animais , Anti-Inflamatórios/farmacologia , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Citocinas/genética , Citocinas/metabolismo , Depsídeos/farmacologia , Depsídeos/uso terapêutico , Humanos , Inflamação/genética , Inflamação/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fitoterapia , Extratos Vegetais/uso terapêutico , RNA Mensageiro/metabolismo , Transdução de Sinais , Ácido RosmarínicoRESUMO
In this study, we aimed to evaluate the inhibitory effect of wild bitter melons (WBM; Momordica charantia Linn. var. abbreviata Ser.) on Propionibacterium acnes-induced inflammation and to identify the bioactive components. Our results showed that ethyl acetate (EA) extract of WBM fruit in vitro potently suppressed pro-inflammatory cytokine and matrix metalloproteinase (MMP)-9 levels in P. acnes-stimulated THP-1 cells. Furthermore, concomitant intradermal injection of WBM EA extract in mice effectively attenuated P. acnes-induced ear swelling and granulomatous inflammation. To further investigate the bioactive components, we found that both saponifiable (S) and nonsaponifiable (NS) fractions of WBM EA extract significantly suppressed pro-inflammatory cytokine and MMP-9 levels. Phytol and lutein, identified in the NS fraction, also inhibited cytokine production. Moreover, S and NS fractions of EA extract, phytol and lutein, activated peroxisome proliferator-activated receptor (PPAR) α and ß in the transactivation assay. Our results suggested that PPARα or PPARγ signalling may contribute, at least in part, to the anti-inflammatory activity of WBM.