Anti-endometriotic Effects of Ceratonia Siliqua L. Pod on Endometrial Mesenchymal Stromal/stem Cells Isolated from Women with Endometriosis-associated Infertility

Abstract: This study investigated the effects of carob (Ceratonia siliqua L.) pod extract (CPE) on human endometrial stem cells (ESCs) viability and to examine its impact on mRNA expression of methyltransferase (DNMT-1, DNMT-3A and DNMT-3B), histone deacetylase-1 (HDAC-1), matrix metalloproteinase-2 (MMP-2) and cyclooxygenase-2 (COX-2) in endometriotic patients. The ESCs were derived from endometrium of patients with endometrioma (OMA-ESCs) and deep infiltrative endometriosis samples of 10 women with endometriosis associated infertility (E-ESCs) were compared to the ESCs derived from endometrium of endometriosis free, normal women as control group (C-ESCs). The metabolic activity of control and case groups was evaluated by treating them with different concentrations of CPE. In the E-ESCs, treatment with 0.8 and 2 µg/mL of CPE resulted in downregulation of COX-2 and HDAC-1 compared to the control group (p = 0.02 and p = 0.02, respectively). Treatment with 0.8 µg/mL of CPE decreased MMP-2 and DNMT-3B genes expression (p = 0.02 and p = 0.03, respectively). Furthermore, COX-2 and DNMT-3A genes were significantly upregulated after treatment with 2 µg/mL of CPE. Expression of the COX-2, HDAC-1, DNMT-1, DNMT-3A, and DNMT-3B peptides decreased in E-ESCs, OMA-ESCs and C-ESCs after treatment with 0.8 and 2 µg/mL concentrations of the CPE. The GC analysis of the CPE resulted in 14 compounds with interactions with the target proteins through the docking process. In vitro CPE treatment significantly downregulated cell inflammatory pathway involved in the pathophysiology of endometriosis and may be a potential agent for treatment of endometriosis.