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Cited by 428Phytoestrogen effects and researchEstrogen and related hormone effectsMenopause: Health Impacts and Treatments

Evaluation of Estrogenic Activity of Plant Extracts for the Potential Treatment of Menopausal Symptoms

Liu, Jianghua, Burdette, Joanna E., Xu, Haiyan, Gu, Chungang, van Breemen, Richard B., Bhat, Krishna P. L., Booth, Nancy, Constantinou, Andreas I. +4 more·2001·Journal of Agricultural and Food Chemistry
DOI 10.1021/jf0014157
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Abstract

Eight botanical preparations that are commonly used for the treatment of menopausal symptoms were tested for estrogenic activity. Methanol extracts of red clover (Trifolium pratense L.), chasteberry (Vitex agnus-castus L.), and hops (Humulus lupulus L.) showed significant competitive binding to estrogen receptors alpha (ER alpha) and beta (ER beta). With cultured Ishikawa (endometrial) cells, red clover and hops exhibited estrogenic activity as indicated by induction of alkaline phosphatase (AP) activity and up-regulation of progesterone receptor (PR) mRNA. Chasteberry also stimulated PR expression, but no induction of AP activity was observed. In S30 breast cancer cells, pS2 (presenelin-2), another estrogen-inducible gene, was up-regulated in the presence of red clover, hops, and chasteberry. Interestingly, extracts of Asian ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax quinquefolius L.) induced pS2 mRNA expression in S30 cells, but no significant ER binding affinity, AP induction, or PR expression was noted in Ishikawa cells. Dong quai [Angelica sinensis (Oliv.) Diels] and licorice (Glycyrrhiza glabra L.) showed only weak ER binding and PR and pS2 mRNA induction. Black cohosh [Cimicifuga racemosa (L.) Nutt.] showed no activity in any of the above in vitro assays. Bioassay-guided isolation utilizing ER competitive binding as a monitor and screening using ultrafiltration LC-MS revealed that genistein was the most active component of red clover. Consistent with this observation, genistein was found to be the most effective of four red clover isoflavones tested in the above in vitro assays. Therefore, estrogenic components of plant extracts can be identified using assays for estrogenic activity along with screening and identification of the active components using ultrafiltration LC-MS. These data suggest a potential use for some dietary supplements, ingested by human beings, in the treatment of menopausal symptoms.

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Crossref · 10.1021/jf0014157

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  • Glabridin remarkably reduced brain cholinesterase activity in mice compared to control.

    “there was a remarkable reduction of the enzyme break down of choline ester in the brain with glabridin when administered to mice as assessed to the control group.”

    From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [89]

  • Glabridin, a compound from Glycyrrhiza glabra roots, significantly abridged scopolamine-induced memory lack at a higher dose in mice.

    “The lack of memory caused by scopolamine (0.5 mg/kg) tested employing the passive avoidance test was abridged significantly with a higher dose of glabridin.”

    From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [89]

  • Red clover extractions increased the level of estrogen-inducible gene presenelin-2 (pS2) in S30 cells.

    “The extractions from the red clover also increased the level of estrogen inducible gene presenelin-2 (pS2) in S30 cells.”

    From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [89]

  • Isoflavone genistein was the extremely potent phytoestrogen in red clover.

    “the estrogen activity estimation of the potency of red clover by bioassay displayed that the extremely potent phytoestrogen was isoflavone genistein [89]”

    From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [89]

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Authors
Liu, J., Burdette, J. E., Xu, H., Gu, C., van Breemen, R. B., Bhat, K. P. L., Booth, N., Constantinou, A. I., Pezzuto, J. M., Fong, H. H. S., Farnsworth, N. R., & Bolton, J. L.
Affiliations
  • University of Illinois Chicago (US)
  • Department of Medicinal Chemistry and Pharmacognosy, Program for Collaborative Research in the Pharmaceutical Sciences, UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, M/C 781, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, and Department of Surgical Oncology, University of Illinois at Chicago, 840 South Wood Street, Chicago, Illinois 60612
Corresponding author
Bolton, Judy L.
ORCID
Venue
Journal of Agricultural and Food Chemistry
Publisher
American Chemical Society (ACS)
Published
2001-03-24
Volume
49
Issue
5
Pages
2472-2479
ISSN
  • 0021-8561 (ISSN-L)
  • 1520-5118
DOI
10.1021/jf0014157
OpenAlex
W2057747591
Cited by
428
References
53
Citations by year
2026: 6 · 2025: 5 · 2024: 11 · 2023: 7 · 2022: 12 · 2021: 15 · 2020: 11 · 2019: 6 · 2018: 9 · 2017: 11 · 2016: 14 · 2015: 16 · 2014: 14 · 2013: 20 · 2012: 21
FWCI
16.75
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Agricultural and Food Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Center for Complementary and Integrative Health (P50-AT00155, P50AT000155)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
estrogenic activity, menopausal symptoms, herbal products, red clover, Vitex agnus-castus, Humulus lupulus, estrogen receptor alpha, estrogen receptor beta, progesterone receptor, pS2 gene expression, genistein, isoflavones, Panax ginseng, Panax quinquefolius, Angelica sinensis, licorice, black cohosh, dietary supplements, bioassay-guided isolation
MeSH terms
Binding, Competitive, Cells, Cultured, Estrogens, Estrogens, Non-Steroidal, Humans, Isoflavones, Menopause, Plant Extracts, Receptors, Estrogen, Receptors, Progesterone, Up-Regulation, Dietary Supplements, Plant Preparations, Phytoestrogens

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