Mechanistic Investigation of Cryptotanshinone and Curcumin Combination in Attenuating BVDV-1-Induced Injury in Bovine Ovarian Granulosa Cells

Abstract

Bovine viral diarrhea virus (BVDV) is a widespread pathogen causing significant economic losses in cattle. There is an urgent need for drugs to treat BVDV-induced reproductive dysfunction. This study investigated the mechanisms and targets of the cryptotanshinone–curcumin (CRY-CUR) combination against BVDV-1. Overlapping targets of CRY, CUR, and BVDV were screened using TCMSP, ChEMBL, and GeneCards databases. A Venn diagram was generated, followed by GO and KEGG enrichment analyses via DAVID. A PPI network was constructed using Cytoscape, and molecular docking was performed with AutoDock. Anti-BVDV-1 activity was verified in bovine ovarian granulosa cells (BOGCs) using RT-qPCR and immunofluorescence. A total of 108 overlapping targets were identified, with four core targets (STAT3, TNF, BCL-2, and EGFR) selected. Molecular docking showed strong binding affinities. Enrichment analysis indicated involvement in calcium ion binding, apoptosis, and TNF/NF-κB pathways. In vitro, the CRY-CUR combination suppressed BVDV-1 replication and reversed abnormal mRNA expression of the core targets. The CRY-CUR combination may inhibit BVDV-1 replication, potentially through modulation of BVDV-1-related targets such as STAT3, TNF, BCL-2, and EGFR and their associated signaling pathways.