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

Abstract

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 × 109 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.

Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection

“…Nrf2 as a crucial transcription factor regulates cellular oxidative stress responses and modulates intracellular redox homeostasis. Evidences are accumulating that Nrf2 signaling pathway has attracted increasing interest in diverse bacterial infection; hence, the application of Nrf2 activators might represent a novel therapeutic strategy against pathogens infection ( 7 ). In the present study, we investigated the efficacies and mechanisms of atractylodin on the L. monocytogenes -induced oxidative stress response, regulated by Nrf2.…”

“…Atractylodin enhances Nrf2/HO-1 signaling pathway and downregulates L. monocytogenes-activated NLRP3 inflammasome in mice Recently, Nrf2 signaling pathway has attracted increasing interest in diverse bacterial infection; hence, the application of Nrf2 inducers might represent a novel therapy against pathogens infection (7). Notably, in light of the critical role of Nrf2 in NLRP3 inflammasome activation, Nrf2/NLRP3 signaling pathway was identified as regulators of multiple inflammatory diseases (24).…”

“…Nuclear factor erythroid 2-related factor 2 (Nrf2), as a transcription factor, plays a crucial role in cellular survival and defense against various stresses through antioxidant gene regulation, including classical enzymes (superoxide dismutases (SODs), catalase, and glutathione peroxidase (GPx)), typical phase 2 detoxifying enzymes (glutamatecysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM) and NADP(H):quinone oxidoreductase-1 (NQO1)), the stress response protein heme oxygenase-1 (HO-1) (6). Recent evidences emphasized the beneficial role of Nrf2 in bacterial infection (7). Intriguingly, Nrf2 activation contributed to the suppression of NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3) inflammasome activation in macrophages, suggesting that activation of Nrf2 is a potential therapeutic strategy for N L R P 3 -a s s o c i a t e d i n fl a m m a t o r y d i s e a s e s .…”

Mulberry plant as a source of functional food with therapeutic and nutritional applications: A review

“…The aqueous leaves extract downregulated the NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3) inflammasome, pro-inflammatory cytokines, and upregulation of erythroid 2-related factor to reduce S. aureus-induced conjunctivitis in rabbits (Ying et al, 2022).…”

“…In vitro soluble epoxide hydrolase inhibitory activity of isolated compounds (coumarin and moracin derivatives) from mulberry leaves exhibited significant inhibitory activity to target vascular diseases (Li, Heo, et al, 2020). The aqueous leaves extract downregulated the NOD‐like receptor leucine‐rich pyrin domain‐containing protein 3 (NLRP3) inflammasome, pro‐inflammatory cytokines, and upregulation of erythroid 2‐related factor to reduce S. aureus ‐induced conjunctivitis in rabbits (Ying et al, 2022).…”