β-Ecdysone has bone protective but no estrogenic effects in ovariectomized rats
Abstract
Estrogens exert beneficial effects in the bone. Their chronic use however bares several risks. Therefore intensive search for non-estrogenic, bone protective compounds is going on. We observed that an extract of Tinospora cordifolia has antiosteoporotic effects and identified 20-OH-Ecdysone (beta-Ecdysone=Ecd) as a possible candidate for this action. Ovariectomized (ovx) rats were treated orally over 3 months with no Ecd (control) or 18, 57 or 121 mg Ecd/day/animal. Estradiol-17beta benzoate (E2) 159 microg/day/animal) fed animals served as positive controls. Bone mineral density (BMD) of tibia was measured by quantitative computer tomography, serum Osteocalcin and CrossLaps were measured in a ligand binding assay. Utilizing an estrogen receptor (ER) containing cytosolic extract of porcine uteri the capability of Ecd to bind to ER was tested. Ecd did not bind to ER. BMD was reduced by more than 50% in the control. In the Ecd animals BMD was dose dependently higher. Serum CrossLaps was lower in the Ecd and E2 group while serum Osteocalcin levels were decreased in the E2 but increased in the Ecd fed animals. Ecd has an antiosteoporotic effect which does not involve activation of ER.
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In ovariectomized rats, 20E increased bone mineral density in the tibia in a dose-dependent manner but did not bind to the oestrogen receptor in porcine uterine cytosolic extract.
“In ovariectomized rats, an animal model of postmenopausal condition, 20E increased bone mineral density in the tibia in a dose-dependent manner but did not bind to the oestrogen receptor in porcine uterine cytosolic extract.”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [28]
Serum CrossLaps were lowered in both 20E and oestrogen treatment, but osteocalcin decreased in oestrogen-treated animals and increased in 20E-fed animals.
“Serum CrossLaps, an adjunct of diagnosis, were lowered in both 20E and oestrogen treatment, but the osteocalcin, a marker of mineralization, decreased in oestrogen-treated animals and increased in 20E-fed animals.”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [28]
20E is devoid of any feminizing activity and is probably inactive on estrogen-dependent cancer cells.
“Thus 20E is devoid of any feminizing activity (13,56) and is probably inactive on estrogen-dependent cancer cells.”
From 20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor (2020) · cites this paper as [13]
There is no direct evidence for the binding of 20E to nuclear estrogen (or androgen) receptors.
“There is in fact no direct evidence for the binding of 20E to nuclear estrogen (or androgen) receptors (12,13).”
From 20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor (2020) · cites this paper as [13]
Beta-ecdysone is reported to increase growth plate width in estrogen deficient rats and to have a marginal beneficial effect on trabecular bone and cartilage preserving following ovariectomy.
“βEcd is reported to increase the growth plate width in estrogen deficient rats and to have a marginal beneficial effect on trabecular bone and cartilage preserving following ovariectomy (OVX) [31, 32].”
From Prevention of glucocorticoid induced bone changes with beta-ecdysone (2015) · cites this paper as [32]
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References 51 · Cited by 51
- Authors
- Seidlova-Wuttke, D., Christel, D., Kapur, P., Nguyen, B. T., Jarry, H., & Wuttke, W.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Wuttke, Wolfgang
- ORCID
- Nguyen, Ba Tiep
- Venue
- Phytomedicine
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 17
- Issue
- 11
- Pages
- 884-889
- ISSN
- 0944-7113 (ISSN-L)
- OpenAlex
- W1977207984
- Cited by
- 51
- References
- 51
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 4 · 2012: 3
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Phytomedicine (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Medicinal Plant Pharmacodynamics Research
- Keywords
- 20-hydroxyecdysone, Tinospora cordifolia, anti-osteoporotic effect, bone mineral density, ovariectomy, estrogen receptor, osteocalcin, crosslaps, ecdysteroids
- MeSH terms
- Animals, Collagen, Dose-Response Relationship, Drug, Ecdysterone, Female, Phytotherapy, Osteoporosis, Ovariectomy, Peptide Fragments, Plant Extracts, Receptors, Estrogen, Swine, Uterus, Bone Density, Osteocalcin, Rats, Sprague-Dawley, Tinospora, Bone Density Conservation Agents, Rats
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