Phytoecdysteroids and Anabolic Androgenic Steroids--Structure and Effects on Humans
Open accessAbstract
Phytoecdysteroids are structural analogs of the insect molting hormone ecdysone. Plants comprise rich sources of ecdysteroids in high concentration and with broad structural diversity. Ecdysteroids have a number of proven beneficial effects on mammals but the hormonal effects of ecdysteroids have been proven only in arthropods. Their structures are somewhat similar to those of the vertebrate steroid hormones but there are several structural differences between the two steroid groups. Despite of these essential structural differences, ecdysteroids exert numerous effects in vertebrates that are similar to those of vertebrate hormonal steroids, and they may serve as effective anabolic, hepatoprotective, immunoprotective, antioxidant and hypoglycemic agents. Ecdysteroids do not bind to the cytosolic steroid receptors, instead, they are likely to influence signal transduction pathways, like the anabolic steroids, possibly via membrane bound receptors. The application of phytoecdysteroids is a promising alternative to the use of anabolic-androgenic steroids because of the apparent lack of adverse effects. The prospective use of phytoecdysteroids may extend to treatments of pathological conditions where anabolic steroids are routinely applied. One of the most cited aspects of phytoecdysteroid application (on the Internet) is the increase of muscle size. However in this field too stringent research is needed as an adequate cytological explanation is not yet available for the anabolic. This paper reports on the most important structural differences between androgenic hormones, their synthetic analogs and ecdysteroids. The anabolic/hormonal effects and the possible mechanisms of action of these compounds are also discussed as concerns the skeletal muscle.
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Ecdysterone exerts its anabolic effects primarily through interaction with nuclear receptors, though its mechanism differs from that of traditional anabolic steroids.
“Ecdysterone, like other ecdysteroids, exerts its anabolic effects primarily through interaction with nuclear receptors, though its mechanism differs from that of traditional anabolic steroids.”
From Molecular insights into the role of Estrogen Receptor Beta in Ecdysterone Mediated Anabolic Activity (2025) · cites this paper as [4]
The ‘Effects on Protein Synthesis’ section says ecdysteroids are not likely to act through the classical cytoplasmic-receptor pathway. ‘The Mechanism of Action of Anabolics’ instead suggests membrane-associated pathways. The paper supports a difference from traditional anabolic steroids, but contradicts the claim that ecdysterone acts primarily through nuclear receptors. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredEarlier in vitro and in vivo studies confirmed non-hormonal anabolic activities of 20E and other ecdysteroids, including stimulation of protein synthesis, increased body and organ weight, and improved skeletal muscle mass and fiber size.
“Earlier in vitro and in vivo studies confirmed the non-hormonal anabolic activities of 20E and other ecdysteroids [5] in terms of stimulation of protein synthesis, increased weight of the whole body and internal organs, and improved skeletal muscle mass and fiber size [8,9].”
From Prevention of Diet-Induced Obesity by Phytoecdysteroids 20-Hydroxyecdysone and Calonysterone—Unexpected Modulation of Androgen Balance in Normal and Obese Rats (2026) · cites this paper as [5]
The “Effects on Protein Synthesis” section (page unavailable) reports anabolic effects of 20-hydroxyecdysone and other ecdysteroids, and the “Hormonal Activity on Mammals” section says an absence of androgenic effects has been widely observed in experimental animals. But the review also identifies a study reporting androgen-like anabolic action, so it does not support the unqualified assertion that the activity was confirmed to be non-hormonal. The specific weight and muscle outcomes are attached to other citations in the citing sentence, not to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredEndogenous mammalian steroid hormones usually accompany a positive anabolic effect with a dangerous androgenic one.
“This is in contrast to steroid hormones that are endogenous in mammals that usually accompany the positive anabolic effect with an often dangerous androgenic one [4,5,6].”
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 [4]
The 'Anabolic Steroid Effect in Muscle' section reports anabolic effects of testosterone, and 'Anabolic-Androgenic Steroids' says complete separation of anabolic and androgenic effects was impossible. Those sections support the pairing of effects, but do not establish that the androgenic effect is often dangerous. Page numbers are unavailable in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredLower doses of 20-hydroxyecdysone showed no significant effects, but amounts more than 5 μg/kg body weight were considered effective.
“It is considered that lower doses showed no significant effects but reported that amounts more than 5 μg/kg body weight were considered effective [102].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [102]
The Effects on Protein Synthesis section reports effects of 20-hydroxyecdysone, and the Ecdysteroid Containing Preparations section says 5 mg/kg body weight per day is generally recommended. Neither passage says lower doses had no significant effect or establishes an effective threshold above 5 μg/kg; the recommended dose is 1,000 times that figure. Page numbers are unavailable in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredUp to now, structure activity relationship studies have been limited to a comparison of various natural phytoecdysteroids, and the biological activity of metabolites is not much documented, with the exception of Post, which showed an anabolic activity similar to that of 20E.
“Up to now, structure activity relationship studies have been limited to a comparison of various natural phytoecdysteroids, 30 and the biological activity of metabolites is not much documented, with the exception of Post, which showed an anabolic activity similar to that of 20E. 31”
From A Phase 1 study for safety and pharmacokinetics of BIO101 (20‐hydroxyecdysone) in healthy young and older adults (2023) · cites this paper as [30]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
20E does not bind directly to the androgen receptor.
“Although 20E does not bind directly to the androgen receptor (Ar) [5], emerging evidence suggests it may exert some of its effects via estrogen receptor beta (ERβ) signaling [10,11].”
The mitigation of muscle atrophy by both ecdysteroids is consistent with their anabolic activity.
“In our study, both ecdysteroids mitigated muscle atrophy in the tibialis anterior and soleus, which effect is consistent with their anabolic activity [5,6,8].”
20E affects major metabolic pathways, including protein synthesis.
“Notably, 20E affects major metabolic pathways, including protein synthesis [10].”
Significant structural differences between ecdysteroids and anabolic-androgenic steroids may account for their distinct anabolic mechanisms.
“The significant structural differences between ecdysteroids and anabolic-androgenic steroids may account for their distinct anabolic mechanisms [4,5].”
From Molecular insights into the role of Estrogen Receptor Beta in Ecdysterone Mediated Anabolic Activity (2025) · cites this paper as [4]
The extensive range of ecdysteroid analogues provides an excellent natural resource for SAR studies in arthropods and mammals.
“In addition to providing reference compounds for biochemical studies, the extensive range of ecdysteroid analogues provides an excellent natural resource for SAR studies in arthropods (reviewed in [37]) and mammals [38].”
From Ecdysteroids (2021) · cites this paper as [38]
The chemical space provided by natural ecdysteroids is being extended by the preparation and biological assessment of numerous semi-synthetic analogues.
“The chemical space provided by the natural ecdysteroids is being extended by the preparation and biological assessment of numerous semi-synthetic analogues (e.g., [37][38][39][40][41]).”
From Ecdysteroids (2021) · cites this paper as [38]
Ecdysteroids have a wide array of physiological and pharmacological effects in animals and insects, including modulation of protein synthesis and carbohydrate metabolism.
“At the same time, brassinosteroids share some similarities with ecdysteroids that have a wide array of physiological and pharmacological effects in animals and insects (4), including modulation of protein synthesis (14) and carbohydrate metabolism (21).”
From Hypoglycemic effects of brassinosteroid in diet-induced obese mice (2012) · cites this paper as [4]
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 [12]
Brassinosteroids share some similarities with ecdysteroids that have a wide array of physiological and pharmacological effects in animals and insects, including modulation of protein synthesis and carbohydrate metabolism.
“At the same time, brassinosteroids share some similarities with ecdysteroids (Fig. 1C) that have a wide array of physiological and pharmacological effects in animals and insects (46), including modulation of protein synthesis (47) and carbohydrate metabolism (48).”
From Anabolic effect of plant brassinosteroid (2011) · cites this paper as [46]
Ecd has protein anabolic effects and increases muscle mass in mammals.
“In mammals, Ecd has protein anabolic effects and increases muscle mass of unexercised and exercised muscle [11,12].”
From Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β- induced catabolic gene expression in cartilage (2015) · cites this paper as [11]
Ecdysterone possesses a variety of beneficial pharmacological effects on humans, including anabolic and adaptogenic ones.
“However, ecdysterone possesses a variety of beneficial pharmacological effects on humans, including anabolic and adaptogenic ones (Báthori et al., 2008).”
From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Báthori et al., 2008
Doses of ecdysteroids higher than 5 μg/kg body weight were reported as active, while lower doses did not result in anabolic activities.
“Doses higher than 5 µg/kg body weight were reported as active while lower doses did not result in anabolic activities [21].”
Ecdy enhances the ability to cope with stress and enhances resistance to tiredness.
“Furthermore, since Ecdy enhances the ability to cope with stress and enhances resistance to tiredness (Báthori et al., 2008; Dinan et al., 2009), it seems beneficial to administer it as part of cytotoxic therapy with doxorubicin.”
From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Báthori et al., 2008
The anabolic effect of these compounds is influenced by the presence of diol groups at the C-20 and C-22 positions, whereas an additional hydroxyl group at C-11 significantly enhances protein synthesis.
“The anabolic effect of these compounds is influenced by the presence of diol groups at the C-20 and C-22 positions, whereas an additional hydroxyl group at C-11 significantly enhances protein synthesis [6].”
From Phytoecdysteroids: Quantification in Selected Plant Species and Evaluation of Some Effects on Gastric Smooth Muscles (2024) · cites this paper as [6]
Phytoecdysteroids have an effect on anabolic and steroidal growth regulations.
“and an effect on anabolic and steroidal growth regulations13.”
From The Phytochemical, Biological, and Medicinal Attributes of Phytoecdysteroids: An Updated Review (2021) · cites this paper as [13]
The mechanism by which ecdysteroids act is binding with signal transduction pathways, rather than with steroid and estrogen receptors.
“The mechanism by which ecdysteroids act is binding with signal transduction pathways, rather than with steroid and estrogen receptors [58].”
From Plant Adaptogens—History and Future Perspectives (2021) · cites this paper as [58]
20-HE improves dermal thickness and promotes wound-healing in vivo.
“20-HE has been shown to improve dermal thickness151,158 and promote wound-healing in vivo13,150.”
From The Phytochemical, Biological, and Medicinal Attributes of Phytoecdysteroids: An Updated Review (2021) · cites this paper as [13]
Phytoecdysteroid derivatives have shown non-hormonal anabolic and adaptogenic effects in mammals, including humans, through a probable mechanism involving activation of Akt.
“Recently, PE derivatives have shown their non-hormonal anabolic and adaptogenic effects in mammals, including humans13, through a probable mechanism involving the activation of protein kinase B (also known as Akt)105.”
From The Phytochemical, Biological, and Medicinal Attributes of Phytoecdysteroids: An Updated Review (2021) · cites this paper as [13]
No significant binding affinity of phytoecdysteroids to androgen receptors has been observed.
“Besides that, no significant binding affinity of PEs to the androgen receptors (ARs) has been observed13,157.”
From The Phytochemical, Biological, and Medicinal Attributes of Phytoecdysteroids: An Updated Review (2021) · cites this paper as [13]
20-HE has low acute toxicity.
“the most widely investigated ecdysteroid was 20-HE due to its low acute toxicity [8,19].”
From Phytoecdysteroids and Anabolic Effect of Atriplex dimorphostegia: UPLC-PDA-MS/MS Profiling, In Silico and In Vivo Models (2023) · cites this paper as [8]
Ecdysteroids do not bind to androgenic receptors (ARs).
“When compared to AAS, ecdysteroids do not bind to androgenic receptors (ARs).”
From Phytoecdysteroids and Anabolic Effect of Atriplex dimorphostegia: UPLC-PDA-MS/MS Profiling, In Silico and In Vivo Models (2023) · cites this paper as [8]
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- Authors
- Bathori, M., Toth, N., Hunyadi, A., Marki, A., & Zador, E.
- Affiliations
- University of Szeged (HU)
- ORCID
- Hunyadi, Attila
- Venue
- Current Medicinal Chemistry
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2008-01-01
- Volume
- 15
- Issue
- 1
- Pages
- 75-91
- ISSN
- 0929-8673 (ISSN-L)
- OpenAlex
- W2122262893
- Cited by
- 201
- References
- 10
- Citations by year
- 2026: 13 · 2025: 10 · 2024: 15 · 2023: 24 · 2022: 10 · 2021: 19 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 12 · 2014: 12 · 2013: 7 · 2012: 8
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Current Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- phytoecdysteroids, ecdysteroids, anabolic steroids, ecdysone, steroid structure, anabolic effects, muscle hypertrophy, skeletal muscle, cell surface receptors, signal transduction, hepatoprotection, immunoprotection, antioxidant activity, hypoglycemic effect
- MeSH terms
- Androgens, Animals, Ecdysone, Humans, Phytosterols, Structure-Activity Relationship, Protein Biosynthesis, Molecular Structure, Signal Transduction, Muscle, Skeletal, Anabolic Agents
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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