Recently, growing multiple uses of silymarin (SIL) as a complementary and alternative
medicine, for alcohol-induced liver disease, acute and chronic viral hepatitis, as
well as some other nonhepatic indications have been reported. Therefore, more attention
should be paid for the hormonal side effects of SIL. Since the available data on the
possible estrogenic effects of SIL is rather rare, this study aimed to further elucidate
the different estrogenic effects and antiosteoporotic activity of SIL in ovariectomized
(OVX) rats. OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE)
or SIL. Uterine and body weight were measured in all animals. Biochemical markers
of bone formation (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin),
endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle stimulating
hormone (FSH) and parathyroid hormone (PTH)) and serum total cholesterol and total
lipids were estimated. Formalin fixed femora and uteri specimens were used for histopathological
examination. In addition, the binding property of SIL to the two estrogen receptors
(ER) subtypes was tested by molecular docking. EE (strong) and SIL (mild) stimulated
uterine weight (increased uterus hyperplastic endometrial glands) but EE only prevented
body weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted
in protection of trabecula thickness, decreased serum levels of ALP and increased
serum levels of both calcium and phosphorus. In contrast to EE, SIL did not decrease
OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol, total lipids,
LH and FSH and increased serum E2. Both EE and SIL increased serum PTH. The docking
study revealed a high affinity of SIL towards ERbeta. In conclusion, findings derived
in the present study presented an overview of SIL many estrogenic effects in OVX rats.
SIL significantly prevents the bone loss in rats induced by OVX with mild proliferative
effects in uterus. The observed effects may be due to additive beneficial effect of
SIL on bone either due to direct interaction with ERbeta or increasing bone formation
parameters including calcium, phosphorus, osteocalcin and PTH.
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