Mulberry Leaf Extract Alleviates Staphylococcus Aureus-Induced Conjunctivitis in Rabbits via Downregulation of NLRP3 Inflammaome and Upregulation of the Nrf2 System and Suppression of Pro-Inflammatory Cytokines

Mulberry leaves are widely used in traditional Chinese medicine for their antioxidant, anti-inflammatory, antibacterial, antiobesity, antidiabetic, antiatherosclerotic, and anticancer properties. The current study aimed to investigate the effect of mulberry leaf extract (MLE) on Staphylococcus aureus ( S. aureus )-induced conjunctivitis (5 × 10 9 CFU, 0.5 mL/eye) in a rabbit model. Rabbits were treated with MLE (5 mL/kg·d -1 and 10 mL/kg·d -1 ), 0.9% saline, or pearl bright eye drops (PBE) for 5 days. The results showed that MLE treatment significantly reduced the clinical sign scores of conjunctivitis, alleviated clinical signs, and decreased bacterial load and histological damage in a time- and dose-dependent manner compared to that in the conjunctivitis control group. The antibacterial and anti-inflammatory activities of MLE (10 mL/kg·d -1 ) were equal to or greater than those of the positive control drug PBE. In addition, MLE significantly decreased the levels of pro-inflammatory cytokines, downregulated the NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3) inflammasome, and upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) system. Overall, MLE is effective in alleviating S. aureus -induced conjunctivitis in rabbits and this mechanism is associated with the inhibition of the NLRP3 inflammasome and activation of the Nrf2 system to regulate pro-inflammatory signaling.