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.

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.

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.