Ethnopharmacological relevanceTaohong Siwu Decoction (TSD) is a well-known traditional Chinese medicine (TCM) prescription. It consists of six crude herbs, including Rehmannia glutinosa Libosch, Paeonia lactiflora Pall, Angelica sinensis (Oliv.) Diels, Ligusticum chuanxiong Hort., Prunus persica (L.) Batsch, Cauthamus tinctorius L. It has been used to treat blood stasis syndrome in Chinese clinics for thousands of years. According to recent research, TSD may be useful in the management of abnormal uterine bleeding (AUB). The aim of the present study is to investigate the possible mechanism of TSD on AUB after drug-induced incomplete abortion. Aim of the studyTo investigate whether TSD could be effective in ameliorating AUB through inhibiting acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated ferroptosis. Materials and methodsAn incomplete medical aborting model was established and Ishikawa cell lines were utilized in vitro. The quantity of uterine bleeding was measured by alkaline hemoglobin photometry. Pathological results were observed by hematoxylin-eosin staining (HE). Mitochondrial morphology and function were measured by transmission electron microscopy. The related protein and mRNA were detected by western blot, the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). We used knockdown and overexpression of ACSL4 to investigate the influence of ferroptosis in Ishikawa cells and the impact of TSD on ferroptosis. ResultsTSD dramatically reduced the amount and duration of bleeding as well as the endometrial inflammation of AUB. TSD improved mitochondrial characteristics, decreased ACSL4 protein and mRNA levels. The ferroptosis marker glutathione (GSH) levels were increased, on the contrary, reactive oxygen species (ROS) and iron levels decreased when TSD intervened. TSD decreased levels of the inflammatory factors and the oxidative products. ConclusionTSD alleviated endometrial inflammation by inhibiting ACSL4-mediated ferroptosis and exerts a protective effect of AUB.
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