Mulberry Leaf Extract Alleviates <b><i>Staphylococcus aureus</i></b>-Induced Conjunctivitis in Rabbits via Downregulation of NLRP3 Inflammasome and Upregulation of the Nrf2 System and Suppression of Pro-Inflammatory Cytokines

Abstract

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Mulberry (&lt;i&gt;Morus alba L&lt;/i&gt;.) leaves are widely used in traditional Chinese medicine for their antioxidant, anti-inflammatory, antibacterial, anti-obesity, antidiabetic, antiatherosclerotic, and anticancer properties. The current study aimed to investigate the effect of mulberry leaf extract (MLE) on &lt;i&gt;Staphylococcus aureus&lt;/i&gt; (&lt;i&gt;S&lt;/i&gt;. &lt;i&gt;aureus&lt;/i&gt;)-induced conjunctivitis (5 × 10&lt;sup&gt;9&lt;/sup&gt; colony-forming units, 0.5 mL/eye) in a rabbit model. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Rabbits were treated with MLE (5 mL/kg·d&lt;sup&gt;−1&lt;/sup&gt; and 10 mL/kg·d&lt;sup&gt;−1&lt;/sup&gt;), 0.9% saline, pearl bright eye (PBE) drops, or erythromycin eye ointment (EEO) group for 5 days. The ocular infection symptoms, bacterial negative conversion rate, and conjunctival histopathological changes of rabbits in each group were observed. The expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-18, IL-6, IL-1β, TNFα, Keap1, and nuclear factor erythroid 2-related factor 2 (Nrf2) in conjunctival tissue of rabbits were detected by quantitative real-time reverse transcription PCR and/or Western blot analysis. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; 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 was compared to that in the control group. The antibacterial and anti-inflammatory activities of MLE (10 mL/kg·d&lt;sup&gt;−1&lt;/sup&gt;) were similar to those of the positive control drug PBE and EEO. In addition, MLE significantly decreased the levels of pro-inflammatory cytokines, downregulated the NLRP3 inflammasome, and upregulated the Nrf2 system. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; MLE is effective in alleviating &lt;i&gt;S&lt;/i&gt;. &lt;i&gt;aureus&lt;/i&gt;-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.

NLRP3 inflammasome-a likely target for the treatment of immunologic conjunctivitis: A protocol for systematic review and meta-analysis

“…The NLRP3 inflammasome has been extensively studied for its activation pathways and pathogenic mechanisms in recent publications in Nature and Science, as it plays a pivotal role in pathogen infections, autoimmune inflammatory reactions, neurodegenerative diseases, cancer, type 2 diabetes, and other conditions [9][10][11]. Recently, accumulating evidence from human and mouse experiments has demonstrated the outstanding potential of NLRP3-related treatments, including NLRP3 inflammasome inhibitors, Interleukin-1 beta, Interleukin-18, and Caspase-1, in treating immunologic conjunctivitis [12][13][14][15][16][17][18][19]. Specific NLRP3 inflammasome and its related inhibitors may serve as potential therapeutic agents for immunologic conjunctivitis [12][13][14][15][16][17][18][19].…”

“…Recently, accumulating evidence from human and mouse experiments has demonstrated the outstanding potential of NLRP3-related treatments, including NLRP3 inflammasome inhibitors, Interleukin-1 beta, Interleukin-18, and Caspase-1, in treating immunologic conjunctivitis [12][13][14][15][16][17][18][19]. Specific NLRP3 inflammasome and its related inhibitors may serve as potential therapeutic agents for immunologic conjunctivitis [12][13][14][15][16][17][18][19]. Therefore, in this study, we aim to collect clinical evidence of NLRP3-related treatments for immunologic conjunctivitis and conduct a systematic review and meta-analysis to evaluate their efficacy and safety.…”