RESUMEN
Lactobacillus plantarum CJLP55 has anti-pathogenic bacterial and anti-inflammatory activities in vitro. We investigated the dietary effect of CJLP55 supplement in patients with acne vulgaris, a prevalent inflammatory skin condition. Subjects ingested CJLP55 or placebo (n = 14 per group) supplements for 12 weeks in this double-blind, placebo-controlled randomized study. Acne lesion count and grade, skin sebum, hydration, pH and surface lipids were assessed. Metagenomic DNA analysis was performed on urine extracellular vesicles (EV), which indirectly reflect systemic bacterial flora. Compared to the placebo supplement, CJLP55 supplement improved acne lesion count and grade, decreased sebum triglycerides (TG), and increased hydration and ceramide 2, the major ceramide species that maintains the epidermal lipid barrier for hydration. In addition, CJLP55 supplement decreased the prevalence of Proteobacteria and increased Firmicutes, which were correlated with decreased TG, the major skin surface lipid of sebum origin. CJLP55 supplement further decreased the Bacteroidetes:Firmicutes ratio, a relevant marker of bacterial dysbiosis. No differences in skin pH, other skin surface lipids or urine bacterial EV phylum were noted between CJLP55 and placebo supplements. Dietary Lactobacillus plantarum CJLP55 was beneficial to clinical state, skin sebum, and hydration and urine bacterial EV phylum flora in patients with acne vulgaris.
Asunto(s)
Acné Vulgar/microbiología , Acné Vulgar/terapia , Suplementos Dietéticos , Vesículas Extracelulares/microbiología , Lactobacillus plantarum , Método Doble Ciego , Disbiosis/microbiología , Disbiosis/terapia , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Sebo/química , Piel/química , Piel/microbiología , Resultado del Tratamiento , Triglicéridos/metabolismo , Orina/microbiología , Adulto JovenRESUMEN
When anti-acne alternatives from dietary and plant sources are ingested, systemic alterations of interleukin (IL)-4, IL-10, IL-12 and interferon (IFN)-γ, individually or simultaneously, are induced at a 0.1-10.0-fold (×) range of normal physiological concentrations (1×). However, little is known about the effects of these cytokines on excess sebum, a pathophysiological factor of acne development. In this study, human sebocytes were treated with 0.1-10.0× of IL-4, IL-10, IL-12 and IFN-γ for 3 or 5 days to elucidate the effects on lipid content. Treatment with individual cytokines decreased the lipid content at specific concentrations rather than in a concentration-dependent manner. Specifically, 5.0× of IL-4, 5.0× of IFN-γ (5.0IFN), and 0.5×, 5.0× and 10.0× of IL-10 for 3 days, and 0.5× of IL-4 (0.5IL4) for 5 days decreased lipid content to 87.6-93.0% of the control. Treatment with other concentrations of IL-4, IL-10 and IFN-γ, and 0.1-10.0× of IL-12 did not alter lipid content. Combined treatment with 0.5IL4, 5.0IFN and 0.5× of IL-10 for 3 or 5 days decreased the lipid content more than each individual treatment. However, this effect was more evident after 3 days, in parallel with decreased levels of triglycerides, cholesterol esters and free fatty acids, the major lipid compositions of sebocytes, and decreased protein expression of fatty acid synthase (FAS) and mature sterol response element-binding protein-1 (SREBP-1), the lipogenesis-related factors, without altered cell proliferation. We demonstrated that suppressed IL-4 and IL-10 with enhanced IFN-γ synergistically decreased lipid content and protein expression of FAS and mature SREBP-1 in human sebocytes.
Asunto(s)
Ácido Graso Sintasas/metabolismo , Glándulas Sebáceas/metabolismo , Sebo/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Acné Vulgar/dietoterapia , Acné Vulgar/inmunología , Acné Vulgar/patología , Línea Celular , Proliferación Celular , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-10/inmunología , Interleucina-10/metabolismo , Interleucina-4/inmunología , Interleucina-4/metabolismo , Lípidos/análisis , Lipogénesis/inmunología , Cultivo Primario de Células , Glándulas Sebáceas/citología , Glándulas Sebáceas/inmunología , Sebo/química , Sebo/inmunologíaRESUMEN
The root of Panax ginseng C.A. Meyer has been shown to induce nitric oxide (NO) release resulting in a hypotensive effect. However, the main active component contributing to vascular endothelium relaxation remains uncertain. In this study, we hypothesized that multiple components of ginseng extract might have combinatory effects providing greater health benefits than a single ginsenosides. To test this hypothesis, we compared the NO-releasing and endothelial NO synthase (eNOS) activating potency of wide range of ginseng extracts (crude extract, CE; protopanaxatriol-enriched extract, TE; protopanaxadiol-enriched extract, DE) and individual ginsenosides (Rg1, Re and Rb1) in human umbilical vein endothelial cells. We found that TE had the highest potency in NO production, followed by CE, DE, and Rg1. We also observed that TE-treatment resulted in rapid activation of intracellular signaling pathways, immediate linear rise of NO, and increased eNOS activation. TE-induced activation of eNOS was abolished by pretreatment with wortmannin (inhibitor for PI3K-Akt), compound C (inhibitor for AMP activated protein kinase, AMPK) or L-NAME (inhibitor for NOS), whereas Rg1-induced eNOS phosphorylation was only partially attenuated. Further analysis revealed that TE, but not Rg1, results in AMPK phosphorylation at Thr(172). These novel finding add evidence that the multiple components of Panax ginseng extract rich in protopanaxatriol offers combinatorial effects in NO production and vascular endothelium relaxation via multiple signaling pathways.
RESUMEN
Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a fundamental regulator of systemic blood pressure. Ginsenosides from Panax ginseng have been investigated in vitro for the molecular and biochemical mechanisms by which they stimulate NO release in vascular endothelial cells; however, little research has been done to confirm the physiological relevance of these in vitro studies. To address this research gap, the effects of a P. ginseng extract rich in ginsenosides from protopanaxatriol on spontaneously hypertensive rats (SHRs) was examined. Ginseng extract administration stimulated nongenomic Akt-mediated eNOS activation, enhanced NO production, improved vessel wall thickening, and alleviated hypertension in SHRs, confirming the physiological relevance of previous in vitro studies with ginsenosides.