Longistylin A, a natural stilbene isolated from the leaves of Cajanus cajan, exhibits significant anti-MRSA activity

Longistylin A (LLA) is an abundant stilbene isolated from the leaves of Cajanus cajan (L.) Millsp. However, the antibacterial effect of LLA is not yet understood. Therefore, in this study, a detailed investigation of the antibacterial effect of LLA, particularly against methicillin-resistant Staphylococcus aureus (MRSA), was conducted. In vitro, LLA exhibited strong antibacterial activity against MRSA with a minimum inhibitory concentration (MIC) of 1.56 µg/mL and displayed much more rapid bactericidal activity (3-log decrease in MRSA survival within 8 h) than vancomycin. A membrane-targeting experiment suggested that the antibacterial activity of LLA is associated with perturbation of the bacterial membrane potential and increased membrane permeability. Notably, LLA had relatively weak cytotoxicity to murine macrophages [50% cytotoxic concentration (CC50) = 8.61 ± 0.57 µg/mL]. In vivo, topical treatment of a skin injury with LLA improved wound healing and closure in an MRSA-infected wound healing mouse model. After 3 days treatment, LLA decreased MRSA bacterial counts in the wounded region, reduced the accumulation of immune cells at the injury site, and alleviated induction of the inflammatory cytokines tumour necrosis factor-alpha (180.74 ± 10.78 pg/mL vs. 606.57 ± 68.99 pg/mL) and interleukin-6 (87.25 ± 10.19 pg/mL vs. 280.58 ± 42.27 pg/mL) in serum.