December 2018Volume 37, Issue
6, Pages 769–782
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Declaration: The authors report no financial or commercial conflicts of interest.
Abstract
Research question
Can
carnosic acid, (CA) rosmarinic acid (RA) and wogonin (WG) inhibit the
growth of cultured human endometrial stromal cells and
endometriotic-like lesions induced in a BALB/c model of endometriosis?
Design
Primary
stromal cell cultures were established from endometrial biopsies from
women with endometriosis and controls. The human endometrial stromal
cell line T-HESC was also used for in-vitro experiments. Endometriosis
was surgically induced in BALB/c mice, which were randomly assigned to
CA 2 mg/kg/day (n = 11); CA 20 mg/kg/day (n = 10); RA 1 mg/kg/day (n = 11); RA 3 mg/kg/day (n = 10); WG 20 mg/kg/day (n = 12); intraperitoneal vehicle control (n = 8) or oral vehicle control (n = 11).
After surgery, CA and RA were administered intraperitoneally on days
14–28. WG was administered orally by intragastric gavage on days 14–26.
Results
CA, RA and WG significantly inhibited in-vitro cell proliferation in primary and T-HESC cell cultures (P < 0.05). CA and WG induced cell cycle arrest of T-HESC at the G2/M phase (P < 0.01). RA reduced intracellular ROS accumulation (P < 0.001), whereas WG increased it (P < 0.05). WG significantly inhibited oestrogen receptor alpha expression in T-HESC (P < 0.01). In-vivo, CA, RA and WG significantly reduced lesions size (P < 0.05). All compounds significantly decreased the percentage of cells in proliferation (P < 0.05) whereas RA and WG further increased the percentage of apoptotic cells (P < 0.05) in endometriotic-like lesions.
Conclusions
The results are promising; further investigation of these compounds as new therapeutics is needed.