![Competition binding curves of compounds: A) 3,17-Estradiol () (Ki: 0.3910-10 M), 20E () (Ki: 2.5310-5 M), Polypodine B (o) (Ki: 6.9510-5 M) and 20E 22-acetate (+) (Ki: 1.3510-6 M) on rat estrogen receptor. The radioligand was [ 3 H]17-Estradiol; B) Testosterone () (Ki: 1.0910-9 M) and 9,11Didehydropoststerone () (Ki: 5.1510-7 M) on rat prostate cytosol. The radioligand was [ 3 H]Dihydrotestosterone.](https://www.researchgate.net/profile/Ernoe-Zador/publication/5630573/figure/fig1/AS:601681104490511@1520463362613/Fig-4-Competition-binding-curves-of-compounds-A-3-17-Estradiol-Ki-03910-10_Q320.jpg)
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Phytoecdysteroids and Anabolic-Androgenic Steroids - Structure and Effects on Humans
Abstract and Figures
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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... Derivada de la Ecdisona, la Ecdisterona (Ec), β-Ecdisona o 20-Hidroxiecdisona (BE) fue catalogada como la molécula estándar de esta familia de compuestos cíclicos perhidrogenados. Ec es el ecdiesteroide con mayor actividad biológica en insectos (14,15,16) . Del mismo modo, es el PE más común, pudiendo ser aislado de los extractos de diversas especies de plantas con una relación coste/beneficio aceptable (13) . ...
... Sin embargo, aunque la actividad de Ec en mamíferos es la más evidenciada, se han llegado a identificar 571 análogos (17) , de los cuales algunos también están siendo objeto de estudio. Muchos de estos compuestos vienen siendo utilizados en medicina tradicional desde hace milenios, utilizando extractos de diferentes secciones de plantas (5,14,18) . ...
... De mismo modo, la respuesta celular es dosis dependiente ya que con una posología inferior a 5ug/Kg de peso corporal no mostraban actividad significativa (27) . En modelos animales, principalmente ratas y ratones, la suplementación de la dieta con Ec durante periodos de 20 a 30 días y, en combinación con pruebas de natación, mostró que aquellos individuos suplementados eran capaces de nadar tramos más largos (14,15,25) . Estas conclusiones llevaron a la Ec a ser propuesta como molécula de estudio en humanos y dilucidar si realmente ejerce un poder anabólico y de mejora del rendimiento físico. ...
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.
... Ecdysteroids are a group of polyhydroxylated sterols, structurally similar to androgens ( Figure 1) [24,27,28]. PDs possess a wide range of pharmacological properties, including antidiabetic and hepatoprotective properties [24,29]. Previous studies reported that 20E possesses anabolic, neuroprotective, and antitumor effects, restores renal dysfunction, and decreases triglycerides [28][29][30][31][32][33][34]. ...
... PDs possess a wide range of pharmacological properties, including antidiabetic and hepatoprotective properties [24,29]. Previous studies reported that 20E possesses anabolic, neuroprotective, and antitumor effects, restores renal dysfunction, and decreases triglycerides [28][29][30][31][32][33][34]. It has the potential to prevent adiposity, dyslipidemia, and hyperglycemia [35,36], while PA possesses anabolic activity [29]. ...
... The current study aimed to evaluate the phytochemical profile of R. carthamoides rhizomes and roots extract (RCE) via an innovative high-performance thin layer chromatog- PDs possess a wide range of pharmacological properties, including antidiabetic and hepatoprotective properties [24,29]. Previous studies reported that 20E possesses anabolic, neuroprotective, and antitumor effects, restores renal dysfunction, and decreases triglycerides [28][29][30][31][32][33][34]. ...
Besides their common use as an adaptogen, Rhaponticum carthamoides (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main characteristic secondary metabolites of RCE are phytoecdysteroids. In order to determine an RCE’s phytoecdysteroid profile, a novel, sensitive, and robust high-performance thin-layer chromatography (HPTLC) method was developed and validated. Moreover, a comparative analysis was conducted to investigate the effects of RCE and its secondary metabolites on adipogenesis and adipolysis. The evaluation of the anti-adipogenic and lipolytic effects was performed using human Simpson–Golabi–Behmel syndrome cells, where lipid staining and measurement of released glycerol and free fatty acids were employed. The HPTLC method confirmed the presence of 20-hydroxyecdysone (20E), ponasterone A (PA), and turkesterone (TU) in RCE. The observed results revealed that RCE, 20E, and TU significantly reduced lipid accumulation in human adipocytes, demonstrating their anti-adipogenic activity. Moreover, RCE and 20E were found to effectively stimulate basal lipolysis. However, no significant effects were observed with PA and TU applications. Based on our findings, RCE and 20E affect both lipogenesis and lipolysis, while TU only restrains adipogenesis. These results are fundamental for further investigations.
... Since ecdysteroids are not endogenously synthesized in rodents and humans, its receptor is not present in mammalian species. Nevertheless, the pharmacological effects of 20E in mammals have been documented [3][4][5][6]. Various studies demonstrated the effects of 20E on skeletal muscle including increased muscle mass and fiber size [7][8][9], increased protein synthesis and associated protein signaling [10,11], increased myonuclear number during muscle regeneration [7], alleviated disuse muscle atrophy [12], and increased muscle strength [10]. ...
Purpose: To investigate the effect of 20-hydroxyecdysone (20E) and its metabolites and their synergistic effect with IGF-1 on regulation of skeletal muscle cell growth. Methods: Mouse skeletal muscle cell line (C2C12) was solely treated with 20E and its metabolites (14- deoxy- 20-hydroxyecdysone, poststerone, and 14-deoxypoststerone) at doses of 0.1, 1, and 10 µM or co-treated with IGF-1 (10 ng/ml). Cell viability and proliferative capacity were evaluated using MTT and BrdU incorporation assays, respectively. Myogenic differentiation proteins [embryonic myosin heavy chain (EbMHC) and MHC], androgen receptor (AR), and IGF-1 receptor (IGF-1R) protein expression were investigated using immunocytochemistry. Results: Treatments of 20E and its metabolites had no toxicity on skeletal muscle cells or induced AR/IGF-1R expression. In addition, solely treatment of 20E and its metabolites or co-treatment with IGF-1 had no significant effect on cell proliferation and myogenic differentiation capacity. In contrast, IGF-1 treatment alone significantly increased EbMHC expression (p<0.0001), MHC expression (p<0.05), and myotube number (p<0.05). Conclusion: These results indicate that 20E and its metabolites have no direct or synergistic effect with IGF-1 on skeletal muscle cell growth. Nevertheless, the pharmacological effects of 20E on skeletal muscle mass and strength in vivo that raises its therapeutic potential may associate with its indirect action.
... In plants, phytoecdysteroids act as either antifeedants or endocrine disruptors against invertebrate predators. [49][50][51][52] The general chemical structure of ecdysteroids is shown in Fig. 4. Turkesterone (from A. turkestanica), and ecdysterone from different sources e.g. R. carthamoides or C. arachnoidea are commercially available in dietary supplements. ...
Testosterone boosters (TB) are multi-ingredient dietary supplements that have gained popularity among athletes and the general population. However, certain ingredients in TB are associated with adverse events. The aim of the present study was to analyze dietary TB supplements available for sale online on shop.bodybuilding.com and amazon.com in ten distribution area markets. We evaluated the top five best-selling TB and the most frequently used ingredients of 50 selected TB and the evidence for their efficacy and safety, as well as legislation, statements in the European Union (EU) and sports organizations such as International Olympic Committee (IOC), International Society of Sports Nutrition (ISSN), Australian Institute of Sport (AIS) and World Anti- Doping Agency (WADA). Among 50 TB, 361 components and 98 ingredients were identified. The following ingredients were included in the final review: fenugreek, D- aspartic acid (DAA), 3,3′-diindolylmethane (DIM) or indole-3-carbinol (I3C), Eurycoma longifolia, Cordyceps spp., and ecdysteroids. In EU an authorized health claims refer to few ingredients in TB, mainly minerals, vitamins. Some ingredients were recognized by international sports organizations such as the ISSN, AIS, and WADA and some were identified as unauthorized ingredients/novel food in the EU. Selected ingredients can possibly increase the risk of endocrine system dysregulation.
The phytosteroid ecdysterone is included on the monitoring list of the World Anti-Doping Agency. Therefore, the consumption of food rich in ecdysterone is the focus of a lively debate. Thus, urinary excretion of ecdysterone and its metabolites in humans was investigated following quinoa consumption alone and in combination with spinach.
After intake of both preparations, ecdysterone and two metabolites were excreted in urine. Maximum concentrations of ecdysterone ranged from 0.44–5.50µg/mL after quinoa and 0.34– 4.09µg/mL after quinoa with spinach. The total urinary excreted amount as parent drug plus metabolites was 2.60(1.09)% following quinoa and 1.71(0.86)% after combination. Significant differences were found in total urinary excreted amounts of ecdysterone, 14-deoxy-ecdysterone, and 14-deoxy-poststerone. In conclusion, only small proportions of ecdysterone from quinoa and the combination with spinach were excreted in urine. The results indicate that both, quinoa and spinach, are poor sources of ecdysterone.
A novel flavone glycoside was isolated from the methanolic extract of Cynotis axillaris Schult. Various analysis and characterization techniques were used to determine its structure and properties. The compound exhibited a melting point range of 231‐2320C and had a molecular formula of C27H30O14. Several spectral characterization techniques were employed to establish the isolated compound's structure. These included UV‒visible spectroscopy, FT‐IR, LC‐ESI‐MS, and NMR spectroscopy. Based on these analyses, the structure of the isolated compound was determined to be 5,7,4’‐trihydroxyflavone‐8‐α‐L‐rhamnopyranoside‐4’‐O‐β‐D‐galactopyranosyl. This structure indicates that it is a flavone glycoside consisting of a flavone (5,7,4’‐trihydroxyflavone) moiety attached to a sugar molecule (galactopyranosyl) at position 4’, which further bears a rhamnose group at position 8 of the flavone. In addition, to the structural characterization, the compound also demonstrated significant antibacterial efficacy against various bacterial pathogens, including gram‐positive bacteria such as Bacillus subtilis MTCC441 and gram‐negative bacteria such as Escherichia coli MTCC1098, Proteus vulgarize MTCC426, and SalmonellaTyphimurium MTCC3224. The antimicrobial activity was evaluated by measuring the zone of inhibition in millimeters, which provides an indication of the compound’s ability to inhibit bacterial growth. The study successfully identified and characterized a novel flavone glycoside from Cynotis axillaris Schult. and its antimicrobial activity.
The phytoecdysteroid 20-hydroxyecdysone (20E) is widely used for resistance training (RT). Little is known about its potential ergogenic value and detraining effects post-RT. This study aimed to examine the effects of 20E extracted from Asparagus officinalis (A. officinalis) on muscle strength and mass, as well as anabolic and catabolic hormones following RT and detraining. Twenty males, aged 20.1 ± 1.1 years, were matched and randomly assigned to consume double-blind supplements containing either a placebo (PLA) or 30 mg/day of 20E for 12 weeks of RT and detraining. Before and after RT and detraining, muscle strength and mass and anabolic and catabolic hormones were measured. This study found that 20E reduced cortisol levels significantly (p < 0.05) compared to the PLA, yet no effect was observed on muscle mass, strength, or anabolic hormones after RT. Subsequent to 6 weeks of detraining, the 20E demonstrated a lower percentage change in 1RM bench press/FFM than the PLA (p < 0.05). Compared to the PLA, detraining throughout the 12 weeks resulted in a lower percentage change in thigh (p < 0.05) and chest (p < 0.01) circumferences, as well as reduced cortisol levels (p < 0.01), with 20E. Our findings demonstrate that 20E supplementation is a promising way to maintain muscle mass and strength during detraining. Accordingly, 20E may prevent muscle mass and strength loss due to detraining by lowering catabolic hormone levels.
Rationale
Recently, there has been a report suggesting that ecdysteroids can enhance sports performance, making them relevant substances in doping control. Hence, it is imperative to examine the analytical characteristics of ecdysteroids in biological samples to identify their misuse in competitive sports.
Methods
To assess the doping of ecdysteroids such as ecdysone, ecdysterone, ponasterone A, turkesterone, and ajugasterone C, a fast and sensitive extraction and detection method was developed, optimized, and validated using equine urine and plasma. Different extraction techniques, namely, solid‐phase extraction, liquid–liquid extraction, and dilute‐and‐inject, were explored to detect ecdysteroids from equine urine and plasma.
Results
The most suitable method of detection was solid‐phase extraction using ABS Elut‐NEXUS, while liquid–liquid extraction and dilute‐and‐inject methods encountered difficulties due to the high polarity of ecdysteroids and the presence of significant matrix interferences. Mass spectrometric parameters are optimized on both the Q Exactive high‐resolution mass spectrometer and the TSQ Altis triple quadrupole mass spectrometer. However, the study indicated that the triple quadrupole mass spectrometer exhibited improved limit of detection when analyzing samples. To achieve optimal separation of the analytes under investigation from the matrix interferences, various liquid chromatography columns were compared. The Selectra PFPP LC column with a mobile phase consisting of 0.2% formic acid in water (mobile phase A) and acetonitrile (mobile phase B) at a flow rate of 0.5 mL/min demonstrated superior performance.
Conclusions
The findings of this study will significantly contribute to the accurate identification of ecdysteroids, facilitating the investigation of their illicit use in horse racing.
Gut microbiota dysbiosis plays a crucial role in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD), which may be influenced by nutritional supplementation. Quinoa, a type of pseudocereal, has gained prominence due to its high nutritional value and diverse applications. This study aimed to determine whether yogurt containing quinoa can ameliorate NAFLD and alleviate metabolic disorders by protecting against the divergence of gut microbiota. Our findings suggested that quinoa yogurt could significantly reduce the body weight gain and fat tissue weight of high-fat diet (HFD)-fed obese mice. In addition, quinoa yogurt significantly reduced liver steatosis and enhanced glucose homeostasis and insulin sensitivity. Additional research indicates that quinoa yogurt can reduce the levels of proinflammatory cytokines (i.e., tumor necrosis factor α, IL-1β, and IL-6) and inhibit endotoxemia and systemic inflammation. The characteristics of the gut microbiota were then determined by analyzing 16S rRNA. In addition, we discovered that the gut microbiota was disturbed by HFD consumption. Particularly, intestinal probiotics and beneficial intestinal secretions were increased, leading to the expression of glucagon-like peptide-1 in the colon, contributing to NAFLD. Furthermore, endotoxemia and systemic inflammation in HFD-fed mice were restored to the level of control mice when they were fed yogurt and quinoa. Therefore, yogurt containing quinoa can effectively alleviate NAFLD symptoms and may exert its effects via microbiome-gut-liver axis mechanisms. According to some research, the role of the enteric-liver axis may also influence metabolic disorders to reduce the development of NAFLD.
Ecdysteroids are insect moulting hormones that regulate metamorphosis. Coincidentally, these compounds also show therapeutic benefits in both humans and animals. Some, particularly 20-hydroxyecdysone, are found at surprisingly high levels in certain plants, which have subsequently been subjected to intensive research as the possibility of their use in health preparations is investigated. Research on plant ecdyteroids (phytoecdysteroids) includes the analysis of known and new substances (hitherto unknown ecdysteroids), and isolation of known and new compounds. In this article the use of high performance liquid chromatography, thin-layer chromatography and classic column chromatography of ecdysteroids will be discussed.
Among natural substances, of considerable interest are the so-called phytoecdysteroids. Some compounds of this class, which are structurally analogous or even identical to the hormones of ecdysis (molting) and metamorphosis in insects, were recently found to be capable of significantly affecting metabolic processes in mammals. Most interesting is the anabolic action of phytoecdysteroids [1 – 3]. The purpose of this study was to establish the relationship between the anabolic effect and chemical structure of phytoecdysteroids extracted from local plant material. The experiments were performed both with natural phytoecdysteroids isolated from plants of the genus Silene, Ajuga, and Rhaponticum and with a series of derivatives obtained by chemical methods. EXPERIMENTAL CHEMICAL PART Samples of Silene praemixta M. Pop. were collected in May in the vicinity of Alimtau Mountain (Chimkent Region, Kazakhstan). Separated from stems, the air-dry leaves and racemes (about 6 kg) were crushed and extracted with ethanol (30 liters). The ethanol extract fractions were combined, concentrated until obtaining a syrup-like mass, and diluted with water. The precipitate (not containing ecdysteroids) was separated by filtration, and the remaining solution was allowed to stand for 24 h. The precipitated crystals (~5 g) represent 2-deoxy--ecdysone. In order to isolate the other ecdysteroids, excess ethanol was distilled off under vacuum and the aqueous residue was treated with chloroform so as to remove hydrophobic impurities. Ecdysteroids present in this purified solution are exhaustively extracted with ethyl acetate. The residue (120 g) obtained after evaporation of the solvent under vacuum represents a purified total extract containing (by the data of TLC in chloroform – methanol system, 9 : 1) several phytoecdysteroids. This total extract (120 g) was chromatographed using an aluminum oxide column (3 kg) eluted sequentially with chloroform and a chloroform – methanol (9 : 1) mixture. The fractions containing ecdysteroids were combined and chromatographed using a silica gel column. Elution with an ethanol gradient (2 – 10%) in chloroform yielded a sequence of the following individual ecdysteroids: 2-deoxy--ecdysone (7.48 g, 0.12%); viticosterone E (100 mg, 0.0017%); 2-deoxyecdysterone (4.92 g, 0.082%); -ecdysone (1.5 g, 0.025%); here and below, the yields are calculated for the initial air-dry material. Final elution with a
Die vollständige Struktur und Konfiguration des Insektenverpuppungshormons Ecdyson wird durch Röntgenstrukturanalyse der natürlichen, schweratomfreien Verbindung als 2β.3β.14α.22βF.25-Pentahydroxy-Δ7-5β-cholestenon-(6) ermittelt.
Adult skeletal muscle fibers are among the few cell types that are truly multinucleated. Recently, evidence has accumulated supporting a role for the modulation of myonuclear number during muscle remodeling in response to injury, adaptation, and disease. These studies have demonstrated that muscle hypertrophy is associated with, and is dependent on, the addition of newly formed myonuclei via the fusion of myogenic cells to the adult myofiber, whereas muscle atrophy and disease appear to be associated with the loss of myonuclei, possibly through apoptotic-like mechanisms. Moreover, these studies also have demonstrated that myonuclear domain size, i.e., the amount of cytoplasm per myonucleus, is unchanged following the acute phase of hypertrophy but is reduced following atrophy. Together these data demonstrate that modulation of myonuclear number or myonuclear domain size (or both) is a mechanism contributing to the remodeling of adult skeletal muscle in response to alterations in the level of normal neuromuscular activity. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1350–1360, 1999
Ecdysteroids, polyhydroxylated Δ7–8-6-ketosteroids, are widespread in plants and invertebrates, especially arthropods. As early as the 1960s, several studies underlined the potential of ecdysterone to enhance the rate of protein synthesis in mammalian tissue. For these suspected anabolic properties, ecdysteroids such as ecdysone or ajugasterone, are widely diffused on the Internet and are presented as powerful growth promoters without any hormonal consequences. Because these compounds would be potentially used as anabolizing agents in food producing animals, it was necessary to develop an efficient analytical method dedicated to their analysis in biological matrices gas chromatography–mass spectrometry (GC–MS) was compared to liquid chromatography (LC)–MS for this purpose. Ecdysteroids, because of their numerous alcohol functions produced, after derivatisation, various by-products, making the GC–MS interpretation difficult. LC–MS was more appropriate, especially when positive electrospray ionization (ESI) and MS/MS acquisition were used; detection and identification (4 MRM transitions) limits were determined in the pg range.
Study of 44 athletes of various sport skill undergoing training for endurance showed the chemiluminescence method to be an important parameter indicating that a person is trained for physical exertion. The broad-spectrum adaptogenic agents elton and leveton reduced in in-vitro experiments the superweak luminescence of urine, which is evidence of their direct antioxidant effect. Twenty-day administration of elton and leveton reduced chemiluminescence and the level of malonic dialdehyde in the urine of highly skilled athletes and increased their physical working capacity tested by bicycle ergometry with gradually increasing physical loads.