Antae-eum, a herbal formula, relieves LPS-induced inflammatory response in macrophages via suppression of autophagic...

Antae-eum (ATE), a traditional herbal formula consisting of ten medicinal herbs, has been primarily used for fetal health and the alleviation of abdominal pain during pregnancy. However, comprehensive experimental studies on its pharmacological effects and mechanisms of action are lacking. Local inflammatory responses in the uterus play a crucial role in embryo implantation and early placental development, while excessive inflammation can lead to implantation failure, recurrent miscarriage, and preeclampsia. In the present study, we hypothesized that ATE may help promote pregnancy stability by modulating the inflammatory responses during pregnancy, and investigated the effect of ATE on the inflammatory response. First, the marker compounds in ATE were identified using a high-performance liquid chromatography system. Then, we assessed inflammatory cytokine production, expression changes related to inflammatory signaling, as well as the expression and flux of autophagic markers in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In ATE, the nineteen marker compounds including baicalin, hesperidin, paeoniflorin, and wogonoside were detected, and the most abundant was baicalin. The anti-inflammatory effect of ATE is achieved by reducing pro-inflammatory cytokine production and further downregulating the TLR4-mediated MAPK and NF-κB signalings. ATE suppressed autophagic flux by disrupting the accumulation of FOXO3a. In summary, our results indicate that ATE exerts anti-inflammatory effects by the blockade of autophagic flux. These findings suggest that ATE has potential as a therapeutic agent for various inflammatory diseases, including inflammatory-related reproductive disorders.