El-Shiekh Riham A, Radi Mai Hussin, Elshimy Rana, Abdel-Sattar Essam, El-Halawany Ali M, Ibrahim Marwa A, Ali Merhan E, Hassanen Eman I
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Herbal Department, Egyptian Drug Authority, Cairo, 15301, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 18. doi: 10.1007/s00210-025-03965-8.
Methicillin-resistant Staphylococcus aureus (MRSA) is primarily recognized as a pathogen responsible for skin, soft tissue, and multiple organs infection. The colonization of the skin and mucous membranes by hypervirulent resistant bacteria like MRSA during hospitalization significantly contributes to life-threatening conditions. Friedelin (FRN) is a pentacyclic triterpene (CHO) isolated from Euphorbia grantii Oliv. The current work aims to determine the efficacy of FRN against MRSA-infected wounds in mice besides the in vitro study to evaluate its bactericidal activity. The in vitro study revealed that FRN was strongly active against MRSA which had a wide zone of MRSA growth inhibition and promising minimum inhibitory concentration (MIC). Moreover, FRN downregulated the major virulence genes seb and icaD, responsible for the production of staphylococcal enterotoxin SED and biofilm formation, respectively in contrast to the untreated group. The dressing of MRSA-infected wound with 40 ppm FRN significantly reduced the wound size and bacterial count and accelerated the process of wound healing which had a higher immune expression of both VEGF (vascular endothelial growth factor) and α-SMA (alpha smooth muscle actin) compared with other treated groups. Additionally, FRN could reduce the inflammatory response of MRSA in a dose-dependent manner by downregulating the TNF-α (tumor necrosis factor-α) and PGS-2 (prostaglandin synthase-2) gene expression levels. FRN is effective against MRSA-infected wounds via its potent bactericidal and anti-inflammatory activities that accelerate angiogenesis and wound maturation.
耐甲氧西林金黄色葡萄球菌（MRSA）主要被认为是引起皮肤、软组织和多器官感染的病原体。住院期间，像MRSA这样的高毒力耐药菌在皮肤和黏膜上定植，会显著导致危及生命的情况。Friedelin（FRN）是从大戟科大戟属植物大戟中分离出的一种五环三萜（CHO）。目前的工作旨在确定FRN对小鼠MRSA感染伤口的疗效，同时进行体外研究以评估其杀菌活性。体外研究表明，FRN对MRSA具有很强的活性，对MRSA的生长抑制区域很宽，且最小抑菌浓度（MIC）很有前景。此外，与未处理组相比，FRN下调了主要毒力基因seb和icaD，它们分别负责葡萄球菌肠毒素SED的产生和生物膜的形成。用40 ppm的FRN处理MRSA感染的伤口，与其他处理组相比，显著减小了伤口大小，减少了细菌数量，并加速了伤口愈合过程，同时VEGF（血管内皮生长因子）和α-SMA（α平滑肌肌动蛋白）的免疫表达更高。此外，FRN可以通过下调TNF-α（肿瘤坏死因子-α）和PGS-2（前列腺素合成酶-2）基因表达水平，以剂量依赖的方式降低MRSA的炎症反应。FRN通过其强大的杀菌和抗炎活性，加速血管生成和伤口成熟，对MRSA感染的伤口有效。
