关键词: Gram-negative bacteria Rhizoma Paridis acne vulgaris anti-inflammation kelch-like ECH-associated protein 1 mitogen-activated protein kinase polyphyllin H

Mesh : Humans Mitogen-Activated Protein Kinases / metabolism NF-E2-Related Factor 2 / genetics metabolism Kelch-Like ECH-Associated Protein 1 / genetics metabolism Lipopolysaccharides / adverse effects Saponins / pharmacology therapeutic use Molecular Docking Simulation Anti-Inflammatory Agents / therapeutic use NF-kappa B / metabolism Gram-Negative Bacteria / metabolism Acne Vulgaris / drug therapy Heme Oxygenase-1 / genetics metabolism Inflammation / metabolism

来  源:   DOI:10.1111/jcmm.18146   PDF(Pubmed)

Abstract:
Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1β and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic.
摘要:
寻常痤疮代表慢性炎症,其发病机制与皮肤微生物组的改变密切相关。最近的研究表明,革兰氏阴性菌在痤疮发展中起着深远的作用,但是缺乏针对这些细菌的抗痤疮剂。Polyphyllins是阴蒂的主要成分,具有很大的抗炎潜力。在这项研究中,我们的目的是评估PPH和富含PPH的重晶石提取物(RPE)治疗革兰氏阴性菌诱导的痤疮的抗痤疮作用和潜在机制.PPH和RPE处理显著抑制脂多糖(LPS)诱导的RAW264.7和HaCaT细胞白细胞介素(IL)-1β和IL-6的mRNA和蛋白表达,随着细胞内活性氧(ROS)的产生。此外,PPH和RPE抑制LPS诱导的RAW264.7细胞中核因子κB(NF-κB)P65的核转位。基于分子对接,PPH可与海带样ECH相关蛋白1(KEAP1)蛋白结合。PPH和RPE处理可以激活核因子红系2相关因子2(NRF2)并上调血红素加氧酶-1(HO-1)。此外,RPE抑制丝裂原活化蛋白激酶(MAPK)途径。因此,富含PPH的RPE在体外显示抗炎和抗氧化作用,这是有希望的替代抗痤疮治疗。
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