Combination therapy with Polygala tenuifolia Willd and Phellodendron chinense Schneid extracts provides effective protection against Micropterus Salmoides Rhabdovirus in largemouth bass

Abstract

Combination therapies are widely explored for treating diseases, as drug mixtures can interact synergistically. Combining various herbal extracts with individual antiviral activity can produce synergistic effects, resulting in a broader range of bioactive compounds and increasing the likelihood of preventing viral replication and transmission. The study investigated the inhibitory effects of Polygala tenuifolia Willd (PTW) and Phellodendron chinense Schneid (PCS) extracts on Micropterus Salmoides rhabdovirus (MSRV). The extracts individually showed effective inhibition, with PTW and PCS having half-maximal inhibitory concentration (IC50) values of 56.82 mg/L and 57.56 mg/L, respectively. Combining the extracts shifted the dose-response curves towards lower drug concentrations, reducing the IC50 values to 51.54 mg/L (PTW) and 46.28 mg/L (PCS). Also, PTW and PCS addition to the diets modifies antiviral gene expression, including interferon regulatory factor 3 (IRF3), IRF7, and interferon-γ (IFN-γ), and reduces viral load, increasing the survival rates of MSRV-infected largemouth bass (Micropterus Salmoides) to 20% and 14%, respectively. In parallel, the combination of PTW and PCS provided greater protection than monotherapy in fish infected with MSRV, improving survival rates by up to 22%. As well as enhancing the expression levels of IRF3 and IRF7 in the organs, the combination therapy significantly increased the IFN-γ expression in the tested organs, with a 17.8- and 24.77-fold rise in the liver and spleen, respectively, at day 9. In summary, the PTW and PCS aqueous extracts were shown to have anti-MSRV activity, and the use of combination therapy in aquaculture against viral diseases is promising.