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柏木脑:治疗鲍曼不动杆菌感染引起肺炎的有前景的抗菌剂。

Perillaldehyde: A promising antibacterial agent for the treatment of pneumonia caused by Acinetobacter baumannii infection.

机构信息

School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi, PR China; College of Life Science and Technology, Xinjiang University, Urumqi 830046, Xinjiang, PR China.

School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi, PR China.

出版信息

Int Immunopharmacol. 2024 Jan 5;126:111311. doi: 10.1016/j.intimp.2023.111311. Epub 2023 Dec 4.

Abstract

Perillaldehyde is a monoterpene compound mainly from the medicinal plant Perilla frutescens (L.) Britt., which has hypolipidemic, antioxidant, antibacterial and anti-inflammatory functions. In this investigation, we discovered that Perillaldehyde had powerful antimicrobial activity against Acinetobacter baumannii 5F1, and its minimum inhibitory concentration was 287.08 μg/mL. A. baumannii is a conditionally pathogenic bacterium with a high clinical resistance rate and is a major source of hospital infections, especially in intensive care units, which is one of the main causes of pneumonia. Inflammatory immune response is characteristic of pneumonia caused by A. baumannii infection. The results of our in vitro experiments indicate that Perillaldehyde disrupts the cell membrane of A. baumannii 5F1 and inhibits its quorum sensing to inhibit biofilm formation, among other effects. With an experimental model of murine pneumonia, we investigated that Perillaldehyde decreased NLRP3 inflammasome activation and TNF-α expression in lung tissues by inhibiting the NF-κB pathway, and also impacted MAPKs protein signaling pathway through the activation of TLR4. Notably, the use of high doses of Perillaldehyde for the treatment of pneumonia caused by A. baumannii 5F1 infection resulted in a survival rate of up to 80 % in mice. In summary, we demonstrated that Perillaldehyde is promising as a new drug for the treatment of pneumonia caused by A. baumannii 5F1 infection.

摘要

芳樟醇醛是一种单萜化合物,主要来源于药用植物紫苏(Perilla frutescens (L.) Britt.),具有降血脂、抗氧化、抗菌和抗炎作用。在这项研究中,我们发现芳樟醇醛对鲍曼不动杆菌 5F1 具有强大的抗菌活性,其最小抑菌浓度为 287.08μg/ml。鲍曼不动杆菌是一种条件致病菌,临床耐药率高,是医院感染的主要来源,尤其是在重症监护病房,是肺炎的主要病因之一。炎症免疫反应是鲍曼不动杆菌感染引起肺炎的特征。我们的体外实验结果表明,芳樟醇醛破坏鲍曼不动杆菌 5F1 的细胞膜,并通过抑制群体感应来抑制生物膜的形成,等等。通过小鼠肺炎实验模型,我们发现芳樟醇醛通过抑制 NF-κB 通路,降低肺组织中 NLRP3 炎性小体的激活和 TNF-α 的表达,同时通过 TLR4 的激活影响 MAPKs 蛋白信号通路。值得注意的是,使用高剂量的芳樟醇醛治疗由鲍曼不动杆菌 5F1 感染引起的肺炎,可使小鼠的存活率高达 80%。综上所述,我们证明芳樟醇醛有望成为治疗鲍曼不动杆菌 5F1 感染引起肺炎的新药。

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