Tellimagrandin II Stimulates Inflammasomes by Causing an Accumulation of 3-Aminopropanal, Which Promotes Apoptosis of Endometriotic Cells While Inhibiting Invasion

Weisen Fan,* Yongjia Zhang,* Ruihua Zhao Gynecology Department, Guang ‘anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China*These authors contributed equally to this workCorrespondence: Ruihua Zhao, Email [email protected]: Endometriosis is frequently treated with Paeoniae Radix. It contains Tellimagrandin II, which has the role of modulating immunity and anti-tumor. Therefore, we will explore the effects of Tellimagrandin II on the apoptosis and invasion/migration of ectopic endometrial cells (EECs).Methods: Tellimagrandin II was used to treat EECs, and transcriptomics and bioinformatics techniques were used to identify its main pathways and targets of Tellimagrandin II. Western blotting was used to confirm the expression of essential targets. Flow cytometry was applied, the impact of tellimagrandin II on EECs apoptosis was identified. Transwell assays were conducted the effects of Tellimagrandin II on EECs invasion and migration. Finally, the binding of tellimagrandin II to key targets was confirmed using molecular docking techniques.Results: Tellimagrandin II may inhibit pathways like beta-alanine metabolism and ECM-receptor interaction while activating JAK-STAT, NF-κB, and apoptotic pathways, according to transcriptomics and GSEA enrichment analysis. Tellimagrandin II can inhibit ALDH7A1 expression in EECs as well as increase SMOX expression, which may facilitate the accumulation of 3-Aminopropanal. This action becomes more pronounced as the dosage is increased. By upregulating the expression of NLRP3, TIMP-1, Caspase-3, BAX, and Caspase-1 in EECs while decreasing the expression of β-catenin and MMP2, tellimagrandin II can prevent EECs invasion and migration and encourage EECs apoptosis. Tellimagrandin II exhibited good docking with ALDH7A1 and SMOX, according to molecular docking.Conclusion: Tellimagrandin II may stimulate inflammasomes by encouraging 3-aminopropanal accumulation within EECs. The increase in inflammasomes may promote EECs apoptosis and inhibit EECs invasion and migration. However, its in vivo inhibitory effects on endometriosis require further investigation.Keywords: tellimagrandin II, 3-aminopropanal, inflammasome, endometriosis apoptosis, invasion