Poststerone increases muscle fibre size partly similar to its metabolically parent compound, 20-hydroxyecdysone

Csábi, József; Rafai, Tímea; Hunyadi, Attila; Zádor, Ernö

doi:10.1016/j.fitote.2019.03.017

Cited by 7 publications

(8 citation statements)

References 20 publications

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“…However, the 13 C NMR spectrum of 6 showed several differences with respect to that of 5; that is, the δC-14 signal shifted from 53.5 to 84.5 ppm, proving an OH substitution, and the δC-22 resonance shifted from 77.9 to 217. 4 13 C NMR spectrum of 7 indicated the presence of five methyl, seven methylene, three sp 3 HC−O, three CH methine, and two sp 2 CH groups and four quaternary sp 3 and three quaternary sp 2 carbon atoms, one of which is a conjugated CO (δ 202.2 ppm). The δC-4 signal at 34.8 ppm was rather broad probably due to hindered conformational motion; however, the H 2 C-4 signals were detectable in the edHSQC spectrum.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Nevertheless, these compounds serve as models for the rational design of synthetic analogues, 1 , 2 rendering the study of their structure–activity relationships important. Ecdysteroids are also bioactive in mammals; some of their representatives, including 20E and its metabolite poststerone, 3 , 4 act as nonhormonal, green anabolic agents and adaptogens and offer a wide range of metabolic benefits. As a result, their consumption is typically considered “healthy”.…”

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confidence: 99%

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A Commercial Extract of Cyanotis arachnoidea Roots as a Source of Unusual Ecdysteroid Derivatives with Insect Hormone Receptor Binding Activity

Tóth

Herke

Gáti³

et al. 2021

J. Nat. Prod.

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Ecdysteroids act as molting hormones in insects and as nonhormonal anabolic agents and adaptogens in mammals. A wide range of ecdysteroid-containing herbal extracts are available worldwide as food supplements. The aim of this work was to study such an extract as a possible industrial source of new bioactive ecdysteroids. A large-scale chromatographic isolation was performed from an extract of Cyanotis arachnoidea roots. Ten ecdysteroids ( 1 – 10 ) including eight new compounds were isolated and characterized by extensive nuclear magnetic resonance studies. Highly unusual structures were identified, including a H-14β ( 1 , 2 , 4 , and 10 ) moiety, among which a 14β(H)17β(H) phytosteroid ( 1 ) is reported for the first time. Compounds with an intact side chain ( 4 – 10 ) and 11 other natural or semisynthetic ecdysteroids ( 11 – 21 ) were tested for insect ecdysteroid receptor (EcR) binding activity. Two new compounds, i.e., 14-deoxydacryhainansterone ( 5 ) and 22-oxodacryhainansterone ( 6 ), showed strong EcR binding activity (IC 50 = 41.7 and 380 nM, respectively). Six compounds were identified as EcR agonists and another two as antagonists using a transgenic ecdysteroid reporter gene assay. The present results demonstrate that commercial C. arachnoidea extracts are rich in new, unusual bioactive ecdysteroids. Because of the lack of an authentic plant material, the truly biosynthetic or artifactual nature of these compounds cannot be confirmed.

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Section: ■ Results and Discussionmentioning

confidence: 99%

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confidence: 99%

A Commercial Extract of Cyanotis arachnoidea Roots as a Source of Unusual Ecdysteroid Derivatives with Insect Hormone Receptor Binding Activity

Tóth

Herke

Gáti³

et al. 2021

J. Nat. Prod.

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“…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 …”

Section: Discussionmentioning

confidence: 99%

A Phase 1 study for safety and pharmacokinetics of BIO101 (20‐hydroxyecdysone) in healthy young and older adults

Dioh

Tourette

Signore

et al. 2023

J cachexia sarcopenia muscle

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Background Sarcopenia is an age-related skeletal muscle disorder characterized by loss of muscle mass and strength leading to mobility disability. 20-Hydroxyecdysone (20E) is a polyhydroxylated plant steroid that demonstrates pharmacological effects in many disease animal models including ageing/sarcopenia. BIO101 is a 20E purified investigational drug (≥97%) that previously demonstrated good toxicology profiles in rat and dog. BIO101 is evaluated in healthy young and older adults in a Phase 1 study. Methods This study is a Single Ascending Dose (SAD) followed by a 14-day Multiple Ascending Dose (MAD). In SAD, BIO101 was administered orally to 16 young adults at doses from 100 to 1400 mg and to 8 older adults (age ≥65 years) at 1400 mg. In MAD, doses of 350 mg once daily (qd), 350 mg twice daily (bid) and 450 mg bid were administered to 10 older adults. The primary objective was to evaluate safety and pharmacokinetics (PK), including dosing of circulating metabolites. Pharmacodynamic effects were investigated with regard to myostatin, procollagen-III-amino-terminal propeptide (PIIINP), myoglobin, creatine-kinase Muscle Brain (CKMB), renin and aldosterone plasma/serum levels. Results BIO101 showed a good safety profile with only mild to moderate adverse events and a satisfactory pharmacokinetic profile. In SAD, at 100 mg to 1400 mg, mean Cmax and areas under the curve increased less than doseproportionally. Mean half-life was short (2.4-4.9 h), and mean renal clearance was comparable in all doses (4.05-5.05 L/h). Mean plasma exposure was slightly lower in older adults (22% lower for Cmax and 13%-15% lower for AUCs) compared with young subjects. In MAD, 350 and 450 mg bid led to a slight accumulation over 14 days (mean ratio of accumulation [Rac] of 1.31 in both cohorts). Reduction of biomarkers (myoglobin, CK-MB) mean serum levels (vs. baseline) was observed at 450 mg bid. Two major metabolites of 20E (14-deoxy-20-hydroxyecdysone and 14deoxypoststerone) were identified and quantified. Conclusions BIO101 shows a good safety and pharmacokinetic profile that led to the selection of doses for the subsequent interventional clinical trials of Phase 2 in age-related sarcopenia (SARA-INT) and Phase 3 in Covid-19 (COVA).

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“…Further microarray RNA analysis exhibited alterations in genes associated with skeletal muscle cells development, growth, and morphogenesis ( Gdfs , Gdf5 , Tor2a , Pten , Traf6 ), but after false discovery rate (FDR) correction, no significant difference has been detected in the expression level of these genes between the treated and the control animals [ 86 ]. An in vivo study of 20β-OH-ecdysone transformation in mammalian system revealed that the main metabolic product, poststerone, also fosters the increase of muscle type fiber cross-sectional area but in a relatively lower degree compared to its parental compound per se [ 119 ]. However, this evidence emphasizes the putative anabolic property of ecdysterone caused by the steroidal nucleus of this compound.…”

Section: Dietary Sterols In Sportmentioning

confidence: 99%

Diversity of Plant Sterols Metabolism: The Impact on Human Health, Sport, and Accumulation of Contaminating Sterols

et al. 2021

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The way of plant sterols transformation and their benefits for humans is still a question under the massive continuing revision. In fact, there are no receptors for binding with sterols in mammalians. However, possible biotransformation to steroids that can be catalyzed by gastro-intestinal microflora, microbial cells in prebiotics or cytochromes system were repeatedly reported. Some products of sterols metabolization are capable to imitate resident human steroids and compete with them for the binding with corresponding receptors, thus affecting endocrine balance and entire physiology condition. There are also tremendous reports about the natural origination of mammalian steroid hormones in plants and corresponding receptors for their binding. Some investigations and reports warn about anabolic effect of sterols, however, there are many researchers who are reluctant to believe in and have strong opposing arguments. We encounter plant sterols everywhere: in food, in pharmacy, in cosmetics, but still know little about their diverse properties and, hence, their exact impact on our life. Most of our knowledge is limited to their cholesterol-lowering influence and protective effect against cardiovascular disease. However, the world of plant sterols is significantly wider if we consider the thousands of publications released over the past 10 years.

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Poststerone increases muscle fibre size partly similar to its metabolically parent compound, 20-hydroxyecdysone

Cited by 7 publications

References 20 publications

A Commercial Extract of Cyanotis arachnoidea Roots as a Source of Unusual Ecdysteroid Derivatives with Insect Hormone Receptor Binding Activity

A Commercial Extract of Cyanotis arachnoidea Roots as a Source of Unusual Ecdysteroid Derivatives with Insect Hormone Receptor Binding Activity

A Phase 1 study for safety and pharmacokinetics of BIO101 (20‐hydroxyecdysone) in healthy young and older adults

Diversity of Plant Sterols Metabolism: The Impact on Human Health, Sport, and Accumulation of Contaminating Sterols

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