Ecdiesteroides y su actividad farmacológica sobre el músculo esquelético

Autores/as

DOI:

https://doi.org/10.30827/ars.v64i4.28863

Palabras clave:

Ecdiesteroides, Ecdisterona, Tejido muscular esquelético, Receptor de estrógenos, GPCR, Receptor Mas

Resumen

Introducción: Los ecdiesteroides presentan cualidades únicas dentro del reino vegetal y animal. Su similitud a esteroides endógenos de mamíferos les otorga actividad biológica sobre el tejido muscular esquelético. Sin embargo, su mecanismo de acción está por definirse en su totalidad.

Método: Se realizó una revisión narrativa utilizando la evidencia científica más relevante. Se consultaron de las bases de datos Medline, Google Scholar, Scielo y Wiley, incluyéndose y excluyéndose trabajos acordes a los criterios del autor.

Resultados: La actividad de los ecdiesteroides, principalmente de la Ecdisterona (Ec), podría deberse a la interacción con Mas, receptor acoplado a proteína-G transmembrana (GPCR), y la posterior activación del receptor de estrógenos β (ER β) no nuclear. Dicho mecanismo de acción induce la activación de la ruta alternativa del Sistema Renina-Angiotensina-Aldosterona (RAA) aboliendo los mecanismos de degradación muscular y, mediante la activación indirecta de Erβ, se suprime la expresión del gen de la miostatina. Esta actividad biológica pudiera conferir a los ecdiesteroides propiedades farmacológicas óptimas para impedir la degradación proteico-muscular, tales como la regeneración y reparación del tejido.

Conclusiones: Ec ha demostrado poseer propiedades farmacológicas interesantes para el abordaje alternativo de patologías musculodegenerativas por sus efectos anticatabólicos. Aunque prosigue la investigación para su implementación en la clínica, esta siendo utilizada en la industria deportiva y en ensayos para el tratamiento de diferentes patologías.

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Lenaerts C, Van Wielendaele P, Peeters P, Vanden Broeck J, Marchal E. Ecdysteroid signalling components in metamorphosis and development of the desert locust, Schistocerca gregaria. Insect Biochem Mol Biol. 2016;75:10–23. doi: 10.1016/J.IBMB.2016.05.003.

Lafont R, Dinan L. Practical uses for ecdysteroids in mammals including humans: And update. J Insect Sci. 2003;3. doi: 10.1093/jis/3.1.7.

Dinan L. Phytoecdysteroids: biological aspects. Phytochemistry [Internet]. 2001;57:325–339. doi: 10.1016/S0031-9422(01)00078-4.

Wang Y chen, Zhao J jia, Chi D fu. β-Ecdysterone accumulation and regulation in Ajuga multiflora Bunge suspension culture. 3 Biotech [Internet]. 2018;8. doi: 10.1007/S13205-018-1117-2.

Zhao P, Soukup ST, Hegevoss J, Ngueu S, Kulling SE, Diel P. Anabolic effect of the traditional chinese medicine compound tanshinone iia on myotube hypertrophy is mediated by estrogen receptor. Planta Med. 2015;81:578–585. doi: 10.1055/s-0035-1545883.

Dinan L, Dioh W, Veillet S, Lafont R. 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases. Biomedicines. 2021;9(5):492. doi: 10.3390/biomedicines9050492.

Xia X, Zhang Q, Liu R, Wang Z, Tang N, Liu F, Huang G, Jiang X, Gui G, Wang L, et al. Effects of 20-hydroxyecdysone on improving memory deficits in streptozotocin-induced type 1 diabetes mellitus in rat. Eur J Pharmacol. 2014;740:45–52. doi: 10.1016/j.ejphar.2014.06.026.

Zhao XF. G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone. Cell Commun Signal [Internet]. 2020;18. doi: 10.1186/S12964-020-00620-Y.

Karlson P. Chemistry and Biochemistry of Insect Hormones. Angewandte Chemie International Edition in English [Internet]. 1963;2:175–182. doi: 10.1002/ANIE.196301751.

Cherbas P. The IVth Karlson Lecture: Ecdysone-responsive genes. Insect Biochem Mol Biol. 1993;23:3–11. doi: 10.1016/0965-1748(93)90076-5.

Huber R, Hoppe W. [On the chemistry of ecdysone. VII. Analysis of the crystal and molecular structure of the molting hormone in insects, ecdysone, using the automized folding molecule method. Chem Ber [Internet]. 1965 ; 98:2403–2424. doi: 10.1002/CBER.19650980744.

Csábi J, Rafai T, Hunyadi A, Zádor E. Poststerone increases muscle fibre size partly similar to its metabolically parent compound, 20-hydroxyecdysone. Fitoterapia [Internet]. 2019;134:459–464. doi: 10.1016/J.FITOTE.2019.03.017.

Lafont R, Serova M, Didry-Barca B, Raynal S, Guibout L, Dinan L, Veillet S, Latil M, Dioh W, Dilda PJ. 20-Hydroxyecdysone activates the protective arm of the RAAS via the MAS receptor. J Mol Endocrinol [Internet]. 2021;68:77–87. doi: 10.1530/JME-21-0033.

Bathori M, Toth N, Hunyadi A, Marki A, Zador E. Phytoecdysteroids and anabolic-androgenic steroids--structure and effects on humans. Curr Med Chem [Internet]. 2008;15:75–91. doi: 10.2174/092986708783330674.

Wilborn CD, Taylor LW, Campbell BI, Kerksick C, Rasmussen CJ, Greenwood M, Kreider RB. Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males. J Int Soc Sports Nutr [Internet]. 2006;3. doi: 10.1186/1550-2783-3-2-19.

Gorelick-Feldman J, MacLean D, Ilic N, Poulev A, Lila MA, Cheng D, Raskin I. Phytoecdysteroids increase protein synthesis in skeletal muscle cells. J Agric Food Chem [Internet]. 2008;56:3532–3537. doi: 10.1021/JF073059Z.

Ecdybase (The Ecdysone Handbook) - a free online ecdysteroids database [Internet]. Ecdybase.org. Disponible en: https://ecdybase.org/

Jung K, Kim IH, Han D. Effect of medicinal plant extracts on forced swimming capacity in mice. J Ethnopharmacol. 2004;93:75–81. doi: 10.1016/j.jep.2004.03.022.

Liu JJ, Zhang HY, Chen X, Zhang GB, Lin JK, Feng H, Chu WH. 20-Hydroxyecdysone Improves Neuronal Differentiation of Adult Hippocampal Neural Stem Cells in High Power Microwave Radiation-Exposed Rats. Biomed Environ Sci. 2022;35:504–517. doi: 10.3967/bes2022.068.

Jian CX, Liu XF, Hu J, Li CJ, Zhang G, Li Y, Zhu JW, Tan YH. 20-hydroxyecdysone-induced bone morphogenetic protein-2-dependent osteogenic differentiation through the ERK pathway in human periodontal ligament stem cells. Eur J Pharmacol. 2013;698:48–56. doi: 10.1016/J.EJPHAR.2012.07.044.

Testing the efficacy and safety of BIO101, for the prevention of respiratory deterioration, in patients with COVID-19 pneumonia (COVA study): a structured summary of a study protocol for a randomised controlled trial - PMC [Internet]. doi: 10.1186/s13063-020-04998-5

Parr MK, Zhao P, Haupt O, Ngueu ST, Hengevoss J, Fritzemeier KH, Piechotta M, Schlörer N, Muhn P, Zheng WY, et al. Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone. Mol Nutr Food Res [Internet]. 2014;58:1861–1872. doi: 10.1002/MNFR.201300806.

Sobrino A, Vallejo S, Novella S, Lázaro-Franco M, Mompeón A, Bueno-Betí C, Walther T, Sánchez-Ferrer C, Peiró C, Hermenegildo C. Mas receptor is involved in the estrogen-receptor induced nitric oxide-dependent vasorelaxation. Biochem Pharmacol. 2017;129:67–72. doi: 10.1016/J.BCP.2017.01.012.

Schaltmann K, Pongs O. Identification and characterization of the ecdysterone receptor in Drosophila melanogaster by photoaffinity labeling. Proceedings of the National Academy of Sciences [Internet]. 1982 ;79:6–10. doi: 10.1073/PNAS.79.1.6.

Isenmann E, Ambrosio G, Joseph JF, Mazzarino M, de la Torre X, Zimmer P, Kazlauskas R, Goebel C, Botrè F, Diel P, et al. Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans. Arch Toxicol. 2019;93:1807–1816. doi: 10.1007/s00204-019-02490-x.

Bathori M. Phytoecdysteroids Effects on Mammalians, Isolation and Analysis. Mini-Reviews in Medicinal Chemistry. 2005;2:285–293. doi: 10.2174/1389557023406269.

Azizov AP, Seĭfulla RD, Chubarova AV, et al. Effects of leuzea tincture and leveton on humoral immunity of athletes. Eksp Klin Farmakol. 1997 Nov-Dec;60(6):47-8. Russian. PMID: 9460599.

Chermnykh NS, Shimanovskiĭ NL, Shutko GV, et al. The action of methandrostenolone and ecdysterone on the physical endurance of animals and on protein metabolism in the skeletal muscles. Farmakol Toksikol. 1988;51(6):57-60. Russian. PMID: 3234543.

Gao L, Cai G, Shi X. β-Ecdysterone Induces Osteogenic Differentiation in Mouse Mesenchymal Stem Cells and Relieves Osteoporosis. Biol Pharm Bull. 2008;31:2245–2249. doi: 10.1248/BPB.31.2245.

Seidlova-Wuttke D, Christel D, Kapur P, Nguyen BT, Jarry H, Wuttke W. β-Ecdysone has bone protective but no estrogenic effects in ovariectomized rats. Phytomedicine. 2010;17:884–889. doi: 10.1016/J.PHYMED.2010.03.021.

Mykhaylyk OM, Kotzuruba A V., Buchanevich OM, Korduban AM, Meged EF, Gulaya NM. Signal transduction of erythrocytes after specific binding of ecdysterone and cholesterol immobilized on nanodispersed magnetite. J Magn Magn Mater. 2001;225:226–234. doi: 10.1016/S0304-8853(00)01262-2.

Kotsiuruba AB, Tuhanova AV, Bukhanevich OM, Tarakanov SS. Mechanisms of the early effect of biologically active hydroxysterols: calcitriol and ecdysterone. Identification of sphingomyelin as the effector mechanism of the early effect. Ukr Biokhim Zh (1978). 1995;67(2):53-8. Ukrainian. PMID: 8592786.

Gorelick-Feldman J, Cohick W, Raskin I. Ecdysteroids elicit a rapid Ca2+ flux leading to Akt activation and increased protein synthesis in skeletal muscle cells. Steroids. 2010;75:632–637. doi: 10.1016/J.STEROIDS.2010.03.008.

Murphy KT, Hossain MI, Swiderski K, Chee A, Naim T, Trieu J, Haynes V, Read SJ, Stapleton DI, Judge SM, et al. Mas Receptor Activation Slows Tumor Growth and Attenuates Muscle Wasting in Cancer. Cancer Res [Internet]. 2019;79:706–719. doi: 10.1158/0008-5472.CAN-18-1207.

Rupert JE, Koniaris LG, Zimmers TA. Multimodal action of MAS activation for systemic cancer cachexia therapy. Cancer Res. 2019;79:699–700. doi: 10.1158/0008-5472.CAN-18-3910.

Yamamoto K, Takeshita H, Rakugi H. ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19. Clin Sci (Lond) [Internet]. 2020;134:3047–3062. doi: 10.1042/CS20200486.

Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, Campagnole-Santo MJ. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiol Rev [Internet]. 2018;98:505–553. doi: 10.1152/PHYSREV.00023.2016.

Omanakuttan A, Bose C, Pandurangan N, Kumar GB, Banerji A, Nair BG. Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone. Exp Cell Res. 2016;346:167–175. doi: 10.1016/J.YEXCR.2016.07.019.

Arif Y, Singh P, Bajguz A, Hayat S. Phytoecdysteroids: Distribution, Structural Diversity, Biosynthesis, Activity, and Crosstalk with Phytohormones. Int J Mol Sci. 2022;23. doi: 10.3390/ijms23158664.

Dreier SI, Towers GHN. Activity of Ecdysterone in Selected Plant Growth Bioassays. J Plant Physiol. 1988;132:509–512. doi: 10.1016/S0176-1617(88)80073-7.

Gholipour P, Komaki A, Parsa H, Ramezani M. Therapeutic Effects of High-Intensity Interval Training Exercise Alone and Its Combination with Ecdysterone Against Amyloid Beta-Induced Rat Model of Alzheimer’s Disease: A Behavioral, Biochemical, and Histological Study. Neurochem Res [Internet]. 2022;47:2090–2108. doi: 10.1007/S11064-022-03603-2.

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Publicado

2023-09-22

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1.
Otero Egocheaga V. Ecdiesteroides y su actividad farmacológica sobre el músculo esquelético. Ars Pharm [Internet]. 22 de septiembre de 2023 [citado 26 de diciembre de 2024];64(4):376-84. Disponible en: https://revistaseug.ugr.es/index.php/ars/article/view/28863

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