Curcusinol from the fruit of Carex baccans with antibacterial activity against multidrug-resistant strains

Abstract

Ethnopharmacological relevanceCarex baccans, known as Shan-Bai-Zi or Ye-Gao-Liang in China, is a traditional medicinal herb used by several ethnic groups in Yunnan Province. It is utilized for the treatment of wound infections, ulcers, and dysentery. However, there is currently a dearth of research reports on its antimicrobial potential. Aim of the studyThe substance basis of the antimicrobial activity of C. baccans will be unveiled, and the in vitro and in vivo antibacterial activities against multidrug-resistant bacteria of its major active compounds, as well as their preliminary mechanisms of action, will be investigated. Materials and methodsAn antibacterial bioactivity-guided isolation method was used to isolate and identify the active compound curcusinol from C. baccans. UPLC-DAD-MS was employed for the quantitative analysis of curcusinol. The antibacterial activity, resistance profile, synergistic effects, anti-biofilm activity, and potential mechanisms of action of curcusinol against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and other multidrug-resistant bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii) were investigated using various methods, including the broth microdilution method, scanning electron microscopy, time kill assay, multi-generational resistance induction assay, checkerboard synergy assay, anti-biofilm assay, and metabolomics. Furthermore, the therapeutic efficacy of curcusinol was assessed in vivo by establishing an animal skin wound infection model of MRSA. ResultsCurcusinol was isolated from the fruit of C. baccans, which accounts for 3.1% of the dry weight of the fruit. Curcusinol exhibited significant bactericidal and anti-biofilm activities against antibiotic-resistant Gram-positive bacteria in vitro. Furthermore, curcusinol acted as an antibiotic adjuvant to enhance the activity of various commonly used antibiotics against both Gram-positive and Gram-negative antibiotic-resistant bacteria without cytotoxicity to mammalian cells (A549 and RAW264.7) at 64 μM. Moreover, curcusinol affected arginine biosynthesis, cysteine and methionine metabolism, and alanine, aspartate, and glutamate metabolism significantly in MRSA cells under stress. Additionally, curcusinol effectively treated MRSA-infected mouse skin wounds and accelerated wound healing in vivo. ConclusionsThe results of this study not only support the traditional uses of C. baccans but also demonstrate that its major active compound, curcusinol, is an effective plant-derived bactericidal agent and antibacterial adjuvant with potential applications in the treatment of skin infections.