20-Hydroxyecdysone

20-Hydroxyecdysone
Skeletal formula of 20-hydroxyecdysone
Ball-and-stick model of the 20-hydroxyecdysone molecule
Clinical data
Pregnancy
category
  • X
Routes of
administration		Oral
Legal status
Legal status
Pharmacokinetic data
MetabolismHepatic
Elimination half-life4-9 hours
ExcretionUrinary:?%
Identifiers
  • (2β,3β,5β,22R)-2,3,14,20,22,25-Hexahydroxycholest-7-en-6-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.241.312 Edit this at Wikidata
Chemical and physical data
FormulaC27H44O7
Molar mass480.642 g·mol−1
3D model (JSmol)
  • O=C1\C=C3/[C@@H]([C@]2(C[C@H](O)[C@H](O)C[C@@H]12)C)CC[C@]4([C@@]3(O)CC[C@@H]4[C@](O)(C)[C@H](O)CCC(O)(C)C)C
  • InChI=1S/C27H44O7/c1-23(2,32)9-8-22(31)26(5,33)21-7-11-27(34)16-12-18(28)17-13-19(29)20(30)14-24(17,3)15(16)6-10-25(21,27)4/h12,15,17,19-22,29-34H,6-11,13-14H2,1-5H3/t15-,17-,19+,20-,21-,22+,24+,25+,26+,27+/m0/s1 checkY
  • Key:NKDFYOWSKOHCCO-YPVLXUMRSA-N checkY
 ☒NcheckY (what is this?)  (verify)

20-Hydroxyecdysone (ecdysterone or 20E) is a naturally occurring ecdysteroid hormone which controls the ecdysis (moulting) and metamorphosis of arthropods. It is therefore one of the most common moulting hormones in insects, crabs, etc. A phytoecdysteroid produced by various plants, including Cyanotis vaga, Ajuga turkestanica and Rhaponticum carthamoides, its purpose is presumably to disrupt the development and reproduction of insect pests. In arthropods, 20-hydroxyecdysone acts through the ecdysone receptor. Although mammals lack this receptor, 20-hydroxyecdysone affects mammalian biological systems. 20-Hydroxyecdysone is an ingredient of some supplements that aim to enhance physical performance. In humans, it is hypothesized to bind to the estrogen receptor beta (ERβ) protein-coding gene.[1]

Sources in arthropods

The primary sources of 20-hydroxyecdysone in larvae are the prothoracic gland, ring gland, gut, and fat bodies. These tissues convert dietary cholesterol into the mature forms of the hormone 20-hydroxyecdysone.[2] For the most part, these glandular tissues are lost in the adult, with exception of the fat body, which is retained as a sheath of lipid tissue surrounding the brain and organs of the abdomen. In the adult female, the ovary is a substantial source of 20-hydroxyecdysone production.[3] Adult males are left with, so far as is currently known, one source of 20-hydroxyecdysone, which is the fat body tissue. These hormone-producing tissues express the ecdysone receptor throughout development, possibly indicating a functional feedback mechanism.[citation needed]

Ecdysteroid activity in arthropods

In insects, an ecdysteroid is a type of steroid hormone derived from enzymatic modification of cholesterol by p450 enzymes. This occurs by a mechanism similar to steroid synthesis in vertebrates. Ecdysone and 20-hydroxyecdysone regulate larval molts, onset of puparium formation, and metamorphosis. As these hormones are hydrophobic, they traverse lipid membranes and permeate the tissues of an organism. Indeed, the ecdysone receptor is an intracellular protein.

In humans and other mammals

Use as research tool

20-Hydroxyecdysone and other ecdysteroids are used in biochemistry research as inducers in transgenic animals, whereby a new gene is introduced into an animal so that its expression is under the control of an introduced ecdysone receptor. Adding or removing ecdysteroids from the animal's diet then gives a convenient way to turn the inserted gene on or off. At usual doses, 20-hydroxyecdysone appears to have little or no effect on animals that do not have extra genes inserted. Given its high oral bioavailability, therefore, it is useful for determining whether the transgene has been taken up effectively.[4] However, studies mentioned below show that 20E is not totally inert in non-transgenic mammals.

Use as supplement

20-Hydroxyecdysone and other ecdysteroids are marketed as ingredients in nutritional supplements for various sports, particularly bodybuilding.[5] Although a number of early studies supported the anabolic effects of 20-hydroxyecdysone,[6][7][8][9][10][11] a 2006 study concluded that the use of 30 mg per day of 20-hydroxyecdysone administered orally did not significantly affect anabolic or catabolic responses to resistance training, body composition, or training adaptations.[12] However, a 2019 study found significantly higher increases in muscle mass and one-repetition bench press performance in participants dosed with ecdysterone. The study, funded by the World Anti-Doping Agency, demonstrated a significant dose-responsive anabolic effect.[13] Other studies have elucidated the mechanism of action of 20-hydroxyecdysone on human muscle cells, which appears to involve relatively selective activation of estrogen receptor beta (ERβ), known to result in muscle hypertrophy.[14]

Drug development

In 2024, the Food and Drug Administration approved a study on the efficacy of BIO101 (20-hydroxyecdysone) in treating obesity, focusing on muscle strength improvement in the lower limbs.[15]

  • Ecdybase, The Ecdysone Handbook - a free online ecdysteroids database

References

  1. ^ Isenmann E, Ambrosio G, Joseph JF, Mazzarino M, de la Torre X, Zimmer P, et al. (July 2019). "Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans". Archives of Toxicology. 93 (7): 1807–1816. doi:10.1007/s00204-019-02490-x. hdl:11573/1291269. PMID 31123801. S2CID 163166547.
  2. ^ Thummel CS, Chory J (December 2002). "Steroid signaling in plants and insects--common themes, different pathways". Genes & Development. 16 (24): 3113–29. doi:10.1101/gad.1042102. PMID 12502734.
  3. ^ Handler AM (September 1982). "Ecdysteroid titers during pupal and adult development in Drosophila melanogaster". Developmental Biology. 93 (1): 73–82. doi:10.1016/0012-1606(82)90240-8. PMID 6813165.
  4. ^ Saez E, Nelson MC, Eshelman B, Banayo E, Koder A, Cho GJ, Evans RM (December 2000). "Identification of ligands and coligands for the ecdysone-regulated gene switch" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 97 (26): 14512–7. Bibcode:2000PNAS...9714512S. doi:10.1073/pnas.260499497. PMC 18950. PMID 11114195.
  5. ^ Cohen PA, Sharfstein J, Kamugisha A, Vanhee C (April 2020). "Analysis of Ingredients of Supplements in the National Institutes of Health Supplement Database Marketed as Containing a Novel Alternative to Anabolic Steroids". JAMA Network Open. 3 (4): e202818. doi:10.1001/jamanetworkopen.2020.2818. PMC 7160690. PMID 32293681.
  6. ^ Simakin SY (1988). "The Combined Use of Ecdisten and the Product'Bodrost'during Training in Cyclical Types of Sport". Scientific Sports Bulletin: 2.
  7. ^ Gadzhieva RM, Portugalov SN, Paniushkin VV, Kondrat'eva II (1995). "[A comparative study of the anabolic action of ecdysten, leveton and Prime Plus, preparations of plant origin.]". Eksperimental'naia i Klinicheskaia Farmakologiia. 58 (5): 46–8. PMID 8704590.
  8. ^ Báthori M, Tóth N, Hunyadi A, Márki A, Zádor E (2008). "Phytoecdysteroids and anabolic-androgenic steroids--structure and effects on humans" (PDF). Current Medicinal Chemistry. 15 (1): 75–91. doi:10.2174/092986708783330674. PMID 18220764.
  9. ^ Smetanin BY (1986). The influence of preparations of plant origin on physical work capacity (Report). The Russian Ministry of Public Health.
  10. ^ Fadeev BG. Comments on the Results of Retibol in the Practice of Athletic Training and Rehabilitation (Report). Natural Sports Research Institute.
  11. ^ Azizov AP, Seĭfulla RD, Ankudinova IA, Kondrat'eva II, Borisova IG (1998). "[The effect of the antioxidants elton and leveton on the physical work capacity of athletes]". Eksperimental'naia i Klinicheskaia Farmakologiia (in Russian). 61 (1): 60–2. PMID 9575416.
  12. ^ Wilborn CD, Taylor LW, Campbell BI, Kerksick C, Rasmussen CJ, Greenwood M, Kreider RB (December 2006). "Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males". Journal of the International Society of Sports Nutrition. 3 (2): 19–27. doi:10.1186/1550-2783-3-2-19. PMC 2129166. PMID 18500969.
  13. ^ Isenmann E, Ambrosio G, Joseph JF, Mazzarino M, de la Torre X, Zimmer P, et al. (July 2019). "Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans". Archives of Toxicology. 93 (7): 1807–1816. doi:10.1007/s00204-019-02490-x. hdl:11573/1291269. PMID 31123801. S2CID 163166547.
  14. ^ Parr MK, Zhao P, Haupt O, Ngueu ST, Hengevoss J, Fritzemeier KH, Piechotta M, Schlörer N, Muhn P, Zheng WY, Xie MY, Diel P (September 2014). "Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone". Molecular Nutrition & Food Research. 58 (9): 1861–72. doi:10.1002/mnfr.201300806. PMID 24974955.
  15. ^ Sharma, Soumya (2024-07-12). "FDA approves Biophytis' Phase II OBA obesity study". Clinical Trials Arena. Retrieved 2024-07-13.