Anti-inflammatory effect of nestorone in a lipopolysaccharide-induced acute lung injury model through regulation of the TLR-4/Myd88/NF-κB signaling pathway

• DOI: 10.1007/s10787-024-01625-6
• Publication Date: 2024-12-17T18:39:00Z
• Authors: Aying Ma; Jieyun Zhou; Hui Zou; Li Yuan; Ruihua Zhong; Yan Zhu; Chao Gao
• Keywords: Proinflammatory cytokine

Progesterone plays a crucial and indispensable role in regulating immunity attenuating inflammation. Nestorone® (NES, segesterone acetate) is steroidal progestin 19-norprogesterone derivative with no -CH3 group radical at the 6-position. Here, we showed that NES enhanced viability of lipopolysaccharide (LPS)-stimulated THP-1 cell-derived macrophages, potently inhibiting both arms Toll-like receptor 4 (TLR-4) signaling cascade triggered by LPS, especially TLR-4/MyD88/NF-κB pathway. In addition, exerted an anti-inflammatory effect significantly decreasing secretion inflammatory cytokines chemokines type II alveolar epithelial A549 cells macrophages stimulated LPS. Furthermore, evaluated potential pre-treatment, administered 2 h prior to LPS exposure, mitigate acute lung injury induced using LPS-induced (ALI) mouse model. this study, alleviated inflammation damage reducing leukocyte infiltration bronchoalveolar lavage fluid (BALF) tissues mice. Interestingly, our findings indicate dosage 1 mg/kg (91.67%) was more effective than dosages 0.1 (70.83%) or 10 (87.50%), as well dexamethasone (DEX, 5 mg/kg, 83.34%), extending survival mice subjected lethal injury. Additionally, successful alleviating diffuse lungs C57 Our study indicates concentration critical determinant efficacy NES. Consequently, emerges potentially promising therapeutic agent for treatment pulmonary conditions through modulation TLR-4 pathways.