Silybum marianum acts as an organ selective estrogen receptor (ER) ß agonist without adverse effects on thyroid hormone release in ovariectomized (ovx) rats

Objectives: Recently it has been shown, that an extract of Silybum marianum (SM) has an estrogenic, anti-osteoporotic effect. SM contains a number of flavonoids, which may be responsible for this estrogenic action. If SM is considered as a phytoestrogen, the possibility exists that besides desirable effects these flavonoids may interfere with thyroid hormone synthesis as described for soy isoflavones. We therefore addressed two questions: a) Which flavonoids contribute to the estrogenic action of SM, b) does SM affect thyroid hormone levels in ovx rats. As a positive control parameter for an estrogenic effect, LH levels were also determined.

Methods: An ethanolic SM extract was fractionated by fast centrifugal partition chromatography and preparative HPLC. Recombinant human ER α or β was used for ligand binding assays. 3 months old, 14 days ovx rats were s.c. injected once per day with either 1ml of 5% cremophor (vehicle) or 3.5µg estradiol (E2) or 30mg dried SM extract for seven days. Each group consisted of 12 animals. Rats were were sacrificed 5h following the last injection.

Results: 4 flavonoids were isolated from SM. None of the isolated compounds interacted with ER α. In contrast, the flavonoids displaced E2 from the ERβ in the order silydianin > silibinin > isosilybinin. Silychristine was completely inactive. A 7 days treatment with either E2 or SM did not affect food intake, water consumption or bodyweight. Mean weigth of uteri were: vehicle 139mg, SM 102mg, E2 317mg (p<0.05 vs. vehicle). T4 and T3 levels were not affected by either E2 or SM. In contrast, LH levels were significantly reduced by both, E2 and SM (vehicle: 29.1 ng/ml, E2 8.8 ng/ml, SM 17.7 ng/ml, p<0.05)

Conclusions: SM proved to be a selective ERß agonist with no adverse on the uterus or thyroid. Since it is known that estrogenic compounds which reduce LH levels also ameliorate menopausal symptoms like hot flushes, SM may be considered as an organ specific phytoestrogen suitable as alternative treatment for hormone replacement therapy