Betamethasone Acetate

The pharmacokinetics and pharmacodynamics of betamethasone following intra‐articular administration to horses have been described; however, studies characterizing intramuscular administration are lacking. Twenty‐four horses received an intramuscular dose of 12 mg betamethasone sodium phosphate/betamethasone acetate. Blood and urine were collected at post administration for up to 408 h. Concentrations of betamethasone were determined using LC–MS/MS and pharmacokinetic parameters determined using a Population PK three‐compartment model. The duration of pharmacodynamic effects was assessed by measuring changes in cortisol and inflammatory biomarkers utilizing an ex vivo model. The Cmax , Tmax , and terminal half‐life of betamethasone were 6.43 ± 1.70 ng/mL, 0.75 (0.5–2.0 h; median and range), and 30.5 ± 20.4 h, respectively. Covariates were not found to have significant effects on the variability of pharmacokinetic parameters. Based on Monte Carlo simulations, for 1000 horses, a detection time of 23 days is recommended for concentrations to fall below the screening limit of 10 pg/mL in 99% of the population. Urine concentrations were above the limit of quantitation in 2/24 horses at 408 h. Suppression of cortisol lasted for 360 h. Effects on inflammatory biomarker production lasted for a prolonged period. An extended withdrawal time for intramuscular administration prior to competition is warranted.

Pulmonary sarcoidosis (PS) is an immune-mediated disorder characterised by a significant association with various immune cell types including macrophages, T-helper 1 (TH1) cells, and TH17 cells. Dysregulation of immune cell differentiation leads to pronounced inflammatory responses in the pulmonary system, resulting in granuloma formation. Currently, the therapeutic approach for PS predominantly involves the use of immunosuppressive agents. However, the considerable adverse effects associated with these treatments underscore the urgent need to develop novel anti-PS pharmacological interventions.

To investigate whether essential oil from Radix Curcumae (RCEO) improves pulmonary function in PS mice by inhibiting inflammation mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) (TLR4/MyD88/NF-κB) pathway.

Bioinformatics and network pharmacology methodologies were used to predict potential therapeutic targets of RCEO in the context of PS. The primary components of RCEO were analysed using gas chromatography-mass spectrometry. A murine model of PS was established by induction with Propionibacterium acnes, and alterations in pulmonary function were evaluated using whole-body plethysmography. An enzyme-linked immunosorbent assay was used to measure changes in inflammatory mediators in the blood and bronchoalveolar lavage fluid. Additionally, flow cytometry was performed to determine the differentiation of CD4+ T cells into TH1 and TH17 subsets in the lung tissues of mice in the model group. Immunofluorescence analysis was used to quantify the differentiation of macrophages into M1 and M2 phenotypes in the lung tissues. Polymerase chain reaction (PCR) and western blotting (WB) were used to assess alterations in the mRNAs expression levels and proteins associated with the TLR4/MyD88/NF-κB signalling pathway in pulmonary tissues.

Bioinformatics and network pharmacology predictions suggested that the therapeutic effects of RCEO on PS are linked to the modulation of inflammation via the TLR4/MyD88/NF-κB pathway. In a murine model of PS, RCEO significantly reduced pathological alterations in lung tissue and enhanced pulmonary function. Subsequent experimental analyses revealed that RCEO inhibited the differentiation of macrophages into M1-type macrophages and reduced the differentiation of CD4+ T cells into TH1 and TH17 cells, thereby preventing granuloma formation in the mouse pulmonary tissue. Further PCR and WB analyses indicated that RCEO modulated immune cell differentiation by inhibiting inflammation mediated through the TLR4/MyD88/NF-κB signalling pathway. Immunofluorescence experiments demonstrated that RCEO conferred a protective effect against PS by attenuating inflammation in macrophages.

RCEO inhibited the differentiation of macrophages into M1-type macrophages and suppressed the differentiation of CD4+T cells into TH1 and TH17 cells by blocking the inflammatory response mediated by the TLR4/MyD88/NF-κB pathway. This further reduced the formation of granulomas in lung tissue and improved lung function in PS mice.