During acute ruminal acidosis, the manifestation of aseptic polysynovitis and lameness in cattle has been observed. Evidence suggests that joint inflammation can be attributed to the metabolic alterations induced by D-lactate in fibroblast-like synoviocytes (FLSs). We aimed to investigate whether andrographolide could mitigate the inflammation and metabolic alterations induced by D-lactate in bovine fibroblast-like synoviocytes (bFLSs). To assess this, bFLSs were cultured in the presence or absence of andrographolide. We evaluated its potential interference with the expression of proinflammatory cytokines, COX-2, HIF-1α, and LDHA using RT-qPCR. Furthermore, we investigated its potential interference with PI3K/Akt signaling and IκBα degradation through immunoblotting and flow cytometry, respectively. Our observations revealed that andrographolide reduced the elevation of IL-6, IL-8, COX-2, HIF-1α, and LDHA induced by D-lactate. Additionally, andrographolide demonstrated interference with the PI3K/Akt and NF-κB pathways in bFLSs. In conclusion, our findings suggest that andrographolide can potentially reverse the inflammatory effects and metabolic changes induced by D-lactate in bFLSs, showing promise as a therapeutic intervention for managing these conditions associated with lameness.

Bovine mastitis is a major bioeconomic and animal health challenge in dairy systems and is traditionally managed with intensive antibiotic therapy, contributing to antimicrobial resistance (AMR). This study explored the therapeutic potential of essential oils (EOs) from two native species of the Valdivian temperate rainforest, Laureliopsis philippiana (Tepa; LP_EO) and Drimys winteri (Canelo; DW_EO), against priority mastitis pathogens. Gas Chromatography–Mass Spectrometry (GC–MS) was used to characterize EO composition, and in vitro antibacterial and antifungal activities were evaluated against clinical isolates of Staphylococcus aureus, Streptococcus uberis and the azole-resistant yeast Pichia kudriavzevii by disk diffusion and broth microdilution assays. Both EOs were dominated by monoterpenes; LP_EO was richer in oxygenated monoterpenes (eucalyptol, terpinen-4-ol), whereas DW_EO showed a pinene-rich profile (β-pinene, α-pinene). DW_EO produced significantly larger inhibition zones than LP_EO against S. aureus and P. kudriavzevii and exhibited lower MIC₅₀/MIC₉₀ values for S. aureus, S. uberis and P. kudriavzevii. Notably, DW_EO showed a higher inhibitory activity against P. kudriavzevii with a MIC₉₀ of 4 mg/mL. These findings support DW_EO as a high-potential dual-action phytotherapeutic candidate for developing formulations and complementary tools within sustainable bovine udder health and antimicrobial stewardship frameworks.