Extracts of Vitex agnus-castus (VAC) are used for the treatment of premenstrual symptoms. The mechanism of action was proposed to be dopaminergic and estrogenic in nature. To isolate these endocrinologically active substances, receptor ligand binding assays and cell cultures were used as in vitro systems to monitor the bioactivity-guided chromatographic separation.
Estrogen receptor (ER) and Dopamine D2-receptor ligand binding assays were performed with human recombinant receptor protein. Both known ERs (ERα and ERβ) were used. Cultures of anterior pituitary cells were prepared from 3 months old female rats. The concentrations of prolactin (PRL) and of cAMP in the supernatants were measured by radio immunoassay (RIA). Starting material for the isolation of single constituents was the aqueous ethanol 70% (v/v) VAC extract BNO 1095. The fractionations were performed with high speed counter current or Sephadex-LH-20 chromatography. Structure elucidation was conducted with GC–MS, LC–MS, 1H NMR and 13C NMR.
The bio-guided fractionation of BNO 1095 resulted in the isolation of dopaminergic bicyclic diterpenes. The fraction with the highest dopaminergic activity was a mixture of diterpenes of the clerodane type, designated as “BNO-diterpenes”. These newly isolated diterpenes inhibited cAMP formation and PRL-release in rat pituitary cell cultures. The estrogenic compounds in BNO 1095 were identified as the flavonoids penduletin and apigenin. Both substances are specific ligands for the ERβ.
Using the strategy of bioactivity-guided fractionation we were able to isolate new dopaminergic diterpenes with a high specific activity which contribute significantly to the PRL-lowering activity of VAC. The therapeutical potential of the ERβ specific ligands penduletin and apigenin needs further investigation.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Maturitas
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The premenstrual syndrome.Obstet Gynecol Surv. 1990; 45: 220-228
- Neuroendocrine control of prolactin secretion.Ann Rev Physiol. 1983; 45: 109-127
- Chaste tree ( Vitex agnus-castus) – pharmacology and clinical indications.Phytomedicine. 2003; 10: 348-357
- Effectiveness of Vitex agnus-castus preparations.Wien Med Wochenschr. 2002; 152: 364-372
- Treatment of cyclical mastalgia with a solution containing a Vitex agnus-castus extract: results of a placebo-controlled double-blind study.The Breast. 1999; 8: 175-181
- In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of agnus-castus: direct evidence for a dopaminergic principle by the dopamine receptor assay.Exp Clin Endocrinol. 1994; 102: 448-454
- First evidence for estrogenic compounds in Vitex agnus-castus: effects on in vitro steroid secretion from human granulosa and porcine luteal cells.J Menopause. 2000; 7: 12
- Growth inhibition of human breast cancer cells by herbs and phytoestrogens.Oncol Rep. 1999; 6: 1383-1387
- Dopamine: a prolactin-inhibiting hormone.Endocr Rev. 1985; 6: 564-589
- Comparison of the uterotrophic activities of various steroids with their utilization in in vitro estrogen biosynthetic systems.Endocrinology. 1960; 67: 843-848
- Cloning of a novel receptor expressed in rat prostate and ovary.Proc Natl Acad Sci USA. 1996; 93: 5925-5930
- Effects of estradiol, benzophenone-2 and benzophenone-3 on the expression pattern of the estrogen receptors (ER) alpha and beta, the estrogen receptor-related receptor 1 (ERR1) and the aryl hydrocarbon receptor (AhR) in adult ovariectomized rats.Toxicology. 2004; 205: 123-130
- Studies on the endocrine effects of the contents of Cimicifuga racemosa. 2. In vitro binding of compounds to estrogen receptors.Planta medica. 1985; 51: 316-319
- Radioimmunoassay for rat prolactin.Proc Soc Exp Biol Med. 1969; 130: 793-797
- Diterpenoids from the fruits of Vitex agnus-castus.Phytochemistry. 1999; 52: 1555-1558
- Reflections on the discovery and significance of estrogen receptor beta.Endocr Rev. 2005; 26: 465-478
- Estrogen receptor beta in health and disease.Biol Reprod. 2005; 73: 866-871
- Radioimmunoassay for rat luteinizing hormone with antiovine LH serum and LH J-131.Proc Soc Exp Biol Med. 1968; 128: 807-811
Published online: July 20, 2006
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.