Bovine viral diarrhea (BVD) is a common viral disease in cattle that causes huge economic losses in naïve herds that are introduced to bovine viral diarrhea virus (BVDV). Currently, there are no available anti-BVDV drugs due to the variety and mutability of strains; therefore, developing new anti-BVDV drugs is of great significance. The aim of this study was to investigate the anti-BVDV effects and immunomodulatory activities of Codonopsis pilosula polysaccharides (CPPs) in BVDV-infected bovine macrophage (BoMac) cells. CPPs directly inactivated BVDV particles and intervened in BVDV absorption process. The immunity suppression resulting from BVDV in BoMac cells was restored by CPPs, as was verified by phagocytosis increase, the expression up-regulation of cell surface co-stimulatory molecules (CD40, CD80, and CD86), and antigen-presenting function recovery. Furthermore, the expressions of cytokines including TNF-α, IFN-γ, IL-6, IL-18, IL-1β, Caspase-3, Bim, and Bcl-xL at the mRNA and proteins levels were modulated, and a reduction in the apoptosis rate was observed, which demonstrates that CPPs attenuated inflammation and apoptosis induced by BVDV. Collectively, our findings reveal new pharmacological properties of CPPs, which exert anti-BVDV efficacy and regulate immune injury induced by BVDV in BoMac cells, indicating that CPPs are a potential option for BVDV prevention in clinical application.

Curcumin, the principal bioactive compound derived from turmeric, possesses a wide range of therapeutic properties such as anti-inflammatory, antioxidant, and wound-healing properties. Recent studies suggest that curcumin may alleviate HMGB1-mediated inflammation in ovarian cells. However, its role in modulating dysfunction in HMGB1-driven ovarian granulosa cells (OGCs) remains to be elucidated. In the present study, curcumin suppresses the HMGB1-induced overexpression of toll-like receptor 2 (TLR2) and ovulation-related factors such as EGFR, VEGF, STAR, and TIMP1/2 genes. Additionally, the elevated levels of TLR2, TLR1, TLR6, and phospho-NF-κB p65 proteins were significantly inhibited by curcumin. Further mechanistic analysis reveals that the interaction between HMGB1 and the TLR1-TLR2/TLR6 complex, as well as phospho-NF-κB p65, was restrained. This resulted in the suppression of the pro-inflammatory cytokine IL-6 production and the alleviation of the HMGB1-induced inflammation response in OGCs. Collectively, our findings demonstrate that curcumin modulates the upregulation of ovulation-related genes and pro-inflammatory cytokines in OGCs by inhibiting the TLR2-NF-κB pathway, providing a mechanistic basis for its potential application as a therapeutic agent against OGC inflammation.

Objective: The objective of this study was to evaluate the function of the reactive oxygen species (ROS)-mitochondrial pathway in attenuating Escherichia coli (E. coli) induced apoptosis in bovine endometrial epithelial cells (BENDs) by Lactobacillus rhamnosus (L. rhamnosus) GR-1.Methods: The BENDs were exposed to preincubation with and without L. rhamnosus GR-1 for 3 hours (h) and they were later subject to E. coli for 6 h. The release of lactate dehydrogenase (LDH), the expression of oxidative factors, adhesion and invasion of E. coli, the expression of mitochondrial membrane potential (MMP), apoptotic rate and apoptosis-associated protein expression were observed. Then, ROS expression, MMP level and cell rate apoptosis rate were further detected after the intervention of antioxidant n-acetyl-l-cysteine (NAC).Results: L. rhamnosus GR-1 was capable of obviously alleviating the content of LDH, ROS expression, E. coli adhesion and invasion, the apoptotic rate and MDA concentrations in BENDs induced by E. coli (p<0.01). In addition, L. rhamnosus GR-1 could notably promote the levels of antioxidant factors (SOD, GSH, T-AOC) (p<0.01), inhibit the depolarization of MMP (p<0.01), and levels of apoptosis-related factors (Bax, Caspase-3 and Cyt-c), and promote anti-apoptosis factor (Bcl-2) (p<0.01). Moreover, after the intervention of antioxidant NAC, ROS expression, MMP depolarization, and apoptotic rate induced by E. coli in BENDs were decreased (p<0.01).Conclusion: In E. coli-induced apoptosis in BENDs, therapeutic strategies aimed at down-regulating ROS and MDA and up-regulating antioxidant factors may maintain mitochondrial function and provide theoretical support for the use of probiotics in bovine endometritis.

Bovine viral diarrhea virus (BVDV) constitutes a significant pathogen adversely threatening reproductive performance in the cattle industry, primarily by inducing ovarian dysfunction characterized by aberrant hormone synthesis and impaired follicular development. Although several commercial vaccines are available, they are insufficient for prevention and control BVDV infection, underscoring the necessity for the development of novel therapeutic drugs. This study aimed to investigate the antiviral activity of cryptotanshinone (CRY) against BVDV infection and its protective effects on bovine ovarian granulosa cells (BOGCs). An in vitro infection model was established by exposing BOGCs to BVDV. The results demonstrated that CRY exhibits anti-BVDV activity and alleviates detrimental effects on BOGCs through multiple mechanisms. Comparative analysis revealed that therapeutic administration of CRY constitutes the most effective mode of intervention. Furthermore, CRY promotes the secretion of estradiol (E₂) and progesterone (P₄) in BOGCs, counteracting the BVDV-induced reduction in these hormones. Moreover, CRY shows protective activity by mitigating BVDV-induced apoptosis in BOGCs. In summary, this study is the first to elucidate the inhibitory effect of CRY on BVDV and its regulatory role in BOGCs function, suggesting that CRY holds potential application value in the clinical treatment of BVDV-related reproductive disorders.

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.

Acute lung injury (ALI) is a common clinical acute respiratory disorder driven primarily by a diffuse pulmonary inflammatory response. Cordycepin (COR) is a bioactive metabolite extracted from the fungus Cordyceps militaris, which possesses antioxidant and anti-inflammatory properties. However, its underlying molecular mechanism remains to be elucidated. This study evaluated the therapeutic effect of COR on ALI and the underlying molecular mechanisms. MH-S cells were primed with lipopolysaccharide (LPS) at 1 µg/mL for 24 h and then treated with varying doses of COR for an additional 24 h. WB and RT-qPCR analyses showed that COR inhibited the phosphorylation of TGF-β-activated kinase 1 (TAK1) as well as the key kinases in the MAPK and NF-κB pathways in LPS-induced MH-S cells, as evidenced by decreased TAK1, p38, JNK, IκB-α and P65 expression levels, as well as decreased TNF-α, IL-6, IL-1β, MAP3K7, MAPK8 and MAPK14 relative expression. Six-week-old BALB/c mice were intranasally instilled with LPS at 3 mg/kg, followed 24 h later by oral gavage administration of various concentrations of COR. The results showed that COR can effectively suppress the progression of pulmonary tissue injury; similarly, the expression levels of key proteins and inflammatory factors in the TAK1-MAPK and NF-κB signaling pathways were downregulated. In summary, COR exerts a therapeutic effect on ALI by directly targeting TAK1 to inhibit the activation of the MAPK and NF-κB signaling pathways and concurrently suppressing key inflammatory cytokines.