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Protective effect of 13-methylberberine against mouse enteritis caused by MRSA
Wei-Mei Wang1, Zhen Zhang1, Liang Sun1
1College of Veterinary Medicine, Qingdao Agricultural University, No.700 Changcheng Road, Qingdao, Shandong, 266109, China.
Ethnopharmacological Relevance:
The emergence and spread of antibiotic resistance bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), urgently need to develop alternative strategies or novel antibacterial drugs. Coptis chinensis Franch., one ancient Chinese herb, has been widely used for the treatment of intestine disease, such as diarrhea. Alkaloids are the major active compounds of Coptis chinensis Franch., and has anti-inflammatory, antioxidant, and antimicrobial effects.
Aim Of The Study:
The aim of the study was tried to investigate the potential antibacterial effects of the alkaloids from Coptis chinensis Franch. and explore the mechanism.
Materials And Methods:
A checkerboard assay, time-killing analysis, membrane functions assay, transcriptome analysis, and inducible resistance test showed the antibacterial effects and mechanisms of alkaloids from Coptis chinensis Franch. Hemolytic assay and MRSA-infected RAW264.7 cells were used to evaluate anti-virulence and anti-inflammatory activities of 13-methylberberine (13-MB). MRSA-infected Vero cells and mouse enteritis models were used to evaluate the anti-infectious effect of 13-MB against MRSA both in vitro and in vivo.
Results:
13-methylberberine (13-MB) displayed high bactericidal efficiency against methicillin-resistant S. aureus (MRSA). Mechanistic studies showed that 13-MB rapidly killed MRSA by interfering with the proton motive force, ROS generation and membrane fluidity via direct interaction with membrane phospholipids. 13-MB suppressed the virulence of MRSA, modulated the host immune response, and effectively eliminated MRSA in Vero cells. Importantly, 13-MB suppressed weight loss, inflammatory response, bacterial colonization and intestinal lesion in mouse enteritis caused by 13-MB susceptible and resistant S. aureus.
Conclusion:
These results supported the 13-MB has promising potential to be developed as natural drug with antibacterial activity, anti-virulence activity, and host modulation activity for the treatment of enteritis caused by MRSA.
