Duda-Madej Anna, Viscardi Szymon, Bazan Hanna, Sobieraj Jakub
Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Chałubińskiego 4, 50-368 Wrocław, Poland.
Faculty of Medicine, Wroclaw Medical University, Ludwika Pasteura 1, 50-367 Wrocław, Poland.
Pharmaceuticals (Basel). 2025 Jun 24;18(7):947. doi: 10.3390/ph18070947.
In recent years, one of the most important issues in public health is the rapid growth of antibiotic resistance among pathogens. Multidrug-resistant (MDR) strains (mainly and non-fermenting bacilli) cause severe infections, against which commonly used pharmaceuticals are ineffective. Therefore, there is an urgent need for new treatment options and drugs with innovative mechanisms of action. Natural compounds, especially alkaloids, are showing promising potential in this area. This review focuses on the ability of the isoquinoline alkaloid berberine (BRB) to overcome various resistance mechanisms against conventional antimicrobial agents. BRB has demonstrated significant activity in inhibiting efflux pumps of the RND (Resistance-Nodulation-Cell Division) family, such as MexAB-OprM () and AdeABC (). Moreover, BRB was able to decrease quorum sensing activity in both Gram-positive and Gram-negative pathogens, resulting in reduced biofilm formation and lower bacterial virulence. Additionally, BRB has been identified as a potential inhibitor of FtsZ, a key protein responsible for bacterial cell division. Particularly noteworthy, though requiring further investigation, are reports suggesting that BRB might inhibit β-lactamase enzymes, including NDM, AmpC, and ESβL types. The pleiotropic antibacterial actions of BRB, distinct from the mechanisms of traditional antibiotics, offer hope for breaking bacterial resistance. However, more extensive studies, especially in vivo, are necessary to fully evaluate the clinical potential of BRB and determine its practical applicability in combating antibiotic-resistant infections.
近年来,公共卫生领域最重要的问题之一是病原体对抗生素的耐药性迅速增长。多重耐药(MDR)菌株(主要是肠杆菌科细菌和非发酵菌)会引发严重感染,常用药物对其无效。因此,迫切需要新的治疗方案和具有创新作用机制的药物。天然化合物,尤其是生物碱,在这一领域显示出了有前景的潜力。本综述聚焦于异喹啉生物碱黄连素(BRB)克服针对传统抗菌药物的各种耐药机制的能力。BRB已证明在抑制RND(耐药-结瘤-细胞分裂)家族的外排泵方面具有显著活性,如MexAB-OprM(铜绿假单胞菌)和AdeABC(鲍曼不动杆菌)。此外,BRB能够降低革兰氏阳性和革兰氏阴性病原体中的群体感应活性,从而减少生物膜形成并降低细菌毒力。此外,BRB已被确定为FtsZ的潜在抑制剂,FtsZ是负责细菌细胞分裂的关键蛋白。特别值得注意的是,尽管需要进一步研究,但有报道表明BRB可能抑制β-内酰胺酶,包括NDM、AmpC和ESβL类型。BRB的多效抗菌作用不同于传统抗生素的作用机制,为打破细菌耐药性带来了希望。然而,需要更广泛的研究,尤其是体内研究,以充分评估BRB的临床潜力并确定其在对抗耐药感染中的实际适用性。