Combination use of ferulic acid, ligustrazine and tetrahydropalmatine inhibits the growth of ectopic endometrial tissue: A multi-target therapy for endometriosis rats

摘要

Ethnopharmacological relevance Ferulic acid (FA), ligustrazine (LZ) and tetrahydropalmatine (THP) are separately isolated from Chinese Angelica, Szechwan Lovage Rhizome and Rhizoma in the Jiawei-Foshou-San formula, a popular traditional Chinese medicine for irregular menses. It has been reported that the combination use of FA+LZ+THP has similar effect on endometriosis, but the underlying mechanisms are unclear. This study was to investigate the combination effects and mechanisms of FA+LZ+THP on endometriosis rats. Materials and methods Fifty endometriosis rats were intragastricly treated with FA+LZ+THP for 4 wk. The volume of ectopic endometrial tissue was measured to evaluate the effects. Then the changes in hypothalamic-pituitary-ovarian axis and ERE pathway were indicated by the levels of E2, GnRH, FSH and LH, and the expressions of ER, HSP90 and COX-2, respectively. In addition, peritoneal macrophages of each rat were cultured in vitro and treated with (FA+LZ+THP)-medicated serum for 24 h. The proliferation and phagocytosis abilities, the levels of IL-1β and TNF-α, and the expression of IκBα were then measured for the changes of peritoneal macrophage activities. Results Combination use of FA+LZ+THP diminished the volume of the ectopic endometrial tissues (P0.05 or P0.01). It also decreased the E2 level, suppressed the expression of GnRH, FSH and LH, and decreased the protein expression of ER, HSP90 and COX-2 (all P0.05 or P0.01). The phagocytosis ability of peritoneal macrophage was enhanced by (FA+LZ+THP)-medicated serum (P0.05) with no change of proliferation (P0.05). Moreover, IL-1β and TNF-α were downregulated (both P0.05 or P0.01) and IκBα was upregulated by the (FA+LZ+THP)-medicated serum (P0.01). Conclusions The combination use of FA, LZ and THP could inhibit the growth of ectopic endometrial tissue in endometriosis rats. It might be related to the down-regulation of hypothalamic-pituitary-ovarian axis, the amelioration in ERE pathway and the improvement of peritoneal macrophage activities.