Rosmarinic Acid Inhibits PRV Replication by Regulating Oxidative Stress Through the Nrf2 Signaling Pathway

Area of Science:

• Veterinary Virology
• Natural Product Chemistry
• Molecular Pharmacology

Background:

• Pseudorabies (PR) is a highly contagious viral disease caused by the pseudorabies virus (PRV), leading to significant economic losses in the swine industry.
• Rosmarinic acid, a natural compound, is known for its antioxidant and antiviral properties, but its efficacy against PRV was previously uninvestigated.

Purpose of the Study:

• To evaluate the anti-PRV activity of rosmarinic acid.
• To elucidate the mechanism of rosmarinic acid's action against PRV, focusing on the Nrf2 signaling pathway.

Main Methods:

• In vitro antiviral assays to determine efficacy (IC50, CC50, SI).
• Inhibition assays targeting virus adsorption, entry, and replication.
• In vivo studies using a mouse model to assess survival rates and viral load.
• Biochemical assays to measure oxidative stress markers (SOD, CAT, MDA).
• Network pharmacology and molecular studies to investigate the Nrf2 signaling pathway.

Main Results:

• Rosmarinic acid demonstrated potent in vitro antiviral activity against PRV (IC50=0.02654 mg/mL, SI=3.9).
• It inhibited PRV adsorption, entry, replication, and suppressed gB protein expression.
• In vivo, rosmarinic acid increased mouse survival rates, reduced viral loads, and alleviated tissue damage.
• The compound counteracted oxidative stress by enhancing antioxidant factors and activating the Nrf2 signaling pathway, upregulating Nrf2, HO-1, GPX, SOD, and CAT.

Conclusions:

• Rosmarinic acid exhibits significant anti-PRV activity through multi-phase viral inhibition.
• Its mechanism involves activating the Nrf2-mediated antioxidant defense system.
• Rosmarinic acid represents a potential novel pharmacological agent for managing PRV infections.