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内生真菌特异青霉提取物对致痘细菌的抗菌及抗炎活性

Antimicrobial and anti-inflammatory activities of endophytic fungi Talaromyces wortmannii extracts against acne-inducing bacteria.

作者信息

Pretsch Alexander, Nagl Michael, Schwendinger Katja, Kreiseder Birgit, Wiederstein Martina, Pretsch Dagmar, Genov Miroslav, Hollaus Ralph, Zinssmeister Daniela, Debbab Abdesamad, Hundsberger Harald, Eger Andreas, Proksch Peter, Wiesner Christoph

机构信息

SeaLife Pharma GmbH, Tulln, Austria.

Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University, Düsseldorf, Germany.

出版信息

PLoS One. 2014 Jun 2;9(6):e97929. doi: 10.1371/journal.pone.0097929. eCollection 2014.

Abstract

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.

摘要

寻常痤疮是最常见的皮肤病,会引发严重的心理社会问题,如焦虑和抑郁,对患者而言类似于慢性病。目前,可获得的痤疮治疗药物用途有限。因此,开发治疗该疾病的新型药物具有很高的医疗需求。痤疮丙酸杆菌这种厌氧菌通过核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)途径激活白细胞介素-8(IL-8)等促炎介质,从而参与寻常痤疮的炎症阶段。特异青霉是一种内生真菌,已知能产生具有高生物活性的天然化合物。我们推测化合物C以及特异青霉的粗提物可能具有抗菌活性,尤其是对痤疮丙酸杆菌,并且还具有抗炎特性,可通过抑制肿瘤坏死因子-α(TNF-α)诱导的细胞间黏附分子-1(ICAM-1)表达以及痤疮丙酸杆菌诱导的IL-8释放来实现。用痤疮丙酸杆菌处理角质形成细胞(HaCaT)可显著增加NF-κB和活化蛋白-1(AP-1)的激活以及IL-8的释放。化合物C通过抑制IκB降解以及细胞外调节蛋白激酶(ERK)和应激活化蛋白激酶(JNK)的磷酸化,以剂量依赖的方式抑制痤疮丙酸杆菌介导的NF-κB和AP-1激活以及IL-8释放。基于这些结果,化合物C对痤疮丙酸杆菌具有有效的抗菌活性和抗炎活性,我们认为该物质或粗提物可作为寻常痤疮抗生素/抗炎治疗的替代疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bee8/4041568/0a59ef579b1e/pone.0097929.g001.jpg

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