Ginsenoside Rg1 Alleviates Blood-Milk Barrier Disruption in Subclinical Bovine Mastitis by Regulating Oxidative Stress-Induced Excessive Autophagy

As a critical disease usually infected by Staphylococcus aureus, with a worldwide effect on dairy Animals, subclinical mastitis is characterized by persistence and treatment resistance. During mastitis, the blood-milk barrier (BMB)'s integrity is impaired, resulting in pathogen invasion and milk quality decline. In this study, it was found that ginsenoside Rg1 (Rg1), a natural anti-inflammatory and antioxidant compound derived from ginseng, inhibited the onset of tight junction (TJ) dysfunction and ameliorated lipoteichoic acid (LTA)-induced BMB disruption inside and outside the organisms. According to subsequent mechanistic studies, Rg1 inhibited excessive Autophagy and inactivated the NLRP3 inflammasome by blockading ROS generation, thereby alleviating TJ dysfunction. Peroxisome Proliferator-activated Receptor gamma (PPARγ) was identified as a potential target of Rg1 by means of molecular docking plus network pharmacology analysis. Furthermore, it was demonstrated that Rg1 inhibited the oxidative stress levels by activating PPARγ, and regulating the upstream autophagy-related AMPK/mTOR signaling pathway, thus decreasing excessive in vivo and in vitro Autophagy. The ROS/Autophagy/NLRP3 inflammasome axis was identified as a promising target for treating subclinical bovine mastitis in this study. In conclusion, Rg1 is proven to alleviate BMB disruption by activating PPARγ to inhibit oxidative stress and subsequent excessive Autophagy in the case of subclinical bovine mastitis.

NLRP3 inflammasome; autophagy; blood–milk barrier; ginsenoside Rg1; reactive oxygen species; subclinical bovine mastitis.