Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats

Phytomedicine. 2010 Feb;17(2):116-25. doi: 10.1016/j.phymed.2009.05.012. Epub 2009 Jul 3.


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.

Publication types

  • Comparative Study

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Biomarkers / blood
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use
  • Bone and Bones / anatomy & histology
  • Bone and Bones / drug effects
  • Calcium / blood
  • Endometrial Hyperplasia / etiology
  • Estradiol / pharmacology*
  • Estrogen Receptor beta / metabolism
  • Ethinyl Estradiol / adverse effects
  • Ethinyl Estradiol / pharmacology*
  • Ethinyl Estradiol / therapeutic use
  • Female
  • Hormones / blood
  • Lipids / blood
  • Organ Size / drug effects
  • Osteocalcin / blood
  • Osteoporosis / prevention & control*
  • Ovariectomy
  • Phosphorus / blood
  • Phytoestrogens / adverse effects
  • Phytoestrogens / pharmacology
  • Phytoestrogens / therapeutic use
  • Phytotherapy
  • Plant Extracts / adverse effects
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rats
  • Selective Estrogen Receptor Modulators / adverse effects
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Silybum marianum / chemistry*
  • Silymarin / adverse effects
  • Silymarin / pharmacology*
  • Silymarin / therapeutic use
  • Uterus / drug effects
  • Weight Gain / drug effects


  • Biomarkers
  • Bone Density Conservation Agents
  • Estrogen Receptor beta
  • Hormones
  • Lipids
  • Phytoestrogens
  • Plant Extracts
  • Selective Estrogen Receptor Modulators
  • Silymarin
  • Osteocalcin
  • Phosphorus
  • Ethinyl Estradiol
  • Estradiol
  • Alkaline Phosphatase
  • Calcium