Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: 20-hydroxyecdysone (20E; β-ecdysone; crustecdysone; ecdysterone; BIO101; CAS 5289-74-7; IUPAC 2β,3β,14α,20 R ,22 R ,25-hexahydroxy-5β-cholest-7-en-6-one).

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques:

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Selected examples of ecdysteroid-rich medicinal plants and their traditional uses. The names of ecdysteroids are underlined (see www.ecdybase.org for structures, accessed on 1 April 2021). Note that it is not established that all the reported biological activities are due totally or partly to the presence of ecdysteroids.

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques:

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Summary of the literature concerning 20E’s pharmacological effects in mammals.

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques:

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: ( A ) The effects of 20E (0.01–10 μM) on protein synthesis in C2C12 cells, showing the anabolic effect of 20E on optimal value for 1 µM 20E. C2C12 cells were grown on 24-well plates at a density of 30,000 cells/well in 0.5 mL of growth medium (Dulbecco’s Modified Eagle Medium (DMEM) 4.5 g/L glucose supplemented with 10% fetal bovine serum). Twenty-four hours after plating, the differentiation induction into multinucleated myotubes was carried out, and after 5 days, cells were pre-incubated in Krebs medium 1 h at 37 °C before being incubated in DMEM media without serum for 2.5 h in the presence of [ 3 H]-Leucine (5 µCi/mL) and DMSO (control condition) or IGF-1 (100 ng/mL) or 20E (0.01–0.1–1–10 µM). At the end of incubation, supernatants were discarded and cells were lysed in 0.1 N NaOH for 30 min. The cell soluble fraction-associated radioactivity was then counted and protein was quantified using the Lowry method (after ). ( B ) Effects of dexamethasone (Dexa 6 = 10 −6 M, Dexa 5 = 10 −5 M), IGF-1 (10 ng/mL), and 20E (10 −6 M) on the diameter of C2C12 myotubes. Four- to six-day-old myotubes were incubated for 48 h with test chemicals, and were fixed and photographed by glutaraldehyde-induced autofluorescence. *: p = < 0.05; **: p = 0.01. (redrawn and modified from ).

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Modification, Incubation, Control, Radioactivity

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Dose-dependent inhibition of myostatin gene expression in C2C12 cells by 20E. C2C12 mouse myoblasts were differentiated for 6 days into myotubes. They were then treated for 6 h with concentrations of 20E ranging from 0.001 to 10 μM. Myostatin gene expression was detected by qRT-PCR. Results are shown as means ± standard error of the mean (SEM) ().

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Inhibition, Gene Expression, Quantitative RT-PCR

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Effect of 20E on mice fed a high-fat diet (HF), when compared to mice fed a low-fat diet (LF). The animals received either pure 20E (50 mg/kg/day) or the same amount of 20E as a quinoa extract (Q). Panel ( A ) shows the impact on the mass of epididymal adipose tissue (*** p < 0.01 when compared to LF; ## p < 0.01 and ### p < 0.001 when compared to HF) and panel ( B ) shows the effect on adipocyte diameter (reproduced, with permission, from ).

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques:

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: 20E reduction of myostatin gene expression in C2C12 cells (differentiated for 6 days into myotubules) is mediated by binding to receptor sites on the external surface of the cells. The histogram compares the activities of IGF-1 (100 nM) and 20E (10 μM) with those of conjugates of 20E covalently bound to protein (HSA or BSA) through different C-atoms (C-2 and C-22-hemisuccinates or C-6 [6-carboxymethoxime]), all at nominal 10 μM hapten concentration. BSA bovine serum albumin; HSA: human serum albumin; error bars = standard error of the mean [ , ].

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Gene Expression, Binding Assay, Concentration Assay

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Diagrammatic representation of the proposed mode of action of 20E in the regulation of protein synthesis in C2C12 muscle cells in vitro ().

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: In Vitro

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Time-course of the distribution of radioactivity in the stomach/intestine/feces in mice after the oral application of [1α,2α- 3 H 2 ]20E. Note the logarithmic scale for abscissa. Each value is a mean of 2 animals. Note the plateau of small intestine content that is best explained by an entero-hepatic cycle and consistent with the prolonged concentration of radioactivity in bile as observed by Wu et al. (reproduced, with permission, from ).

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Radioactivity, Concentration Assay

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Comparison of the temporal ( A ) and cumulative ( B ) urinary and fecal elimination of radioactivity after the oral application of [5,7,9- 3 H]20E to 6–7 week-old male Wistar rats. After oral application of [ 3 H]20E, elimination of radioactively labelled 20E and its metabolites is completed within 48 h. The amount of radioactivity recovered from the feces is by far the major route of excretion, since the amount in the urine corresponds to only 1.40% of the total radioactivity recovered. (Reproduced, with permission, from ).

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Comparison, Radioactivity

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Kinetic parameters of BIO101 (=97% pure 20E) after a single oral administration ( n = 6, fasted). Values in parentheses indicate the SEM (C max , AUC) or the range (t max ).

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques:

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Pharmacokinetics of 20E in young and elderly humans given a single dose of 1400 mg. 20E was quantified by HPLC-MS [ , ].

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Drug discovery

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: The principal routes of metabolism of 20E in rodents and humans (modified from Kumpun et al., 2011). The circles and arrows in red highlight the changes associated with 14-dehydroxylation, while the boxes and arrows in blue highlight the changes associated with side-chain cleavage.

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Modification

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: A representative flow-diagram for the large-scale extraction and purification of 20E from roots of Cyanotis sp.

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Extraction, Purification

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Drugability scores for ecdysteroids.

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques:

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: Clinical studies on humans using pure 20E.

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Activity Assay, Clinical Proteomics, Control

Journal: Biomedicines

Article Title: 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

doi: 10.3390/biomedicines9050492

Figure Lengend Snippet: SARS-CoV-2 infection will result in a strong impairment of the activity of angiotensin converting enzyme 2 (ACE2), hence a lack of angiotensin-(1-7) production and a disequilibrium between the harmful and protective arms of the renin–angiotensin system (RAS). Treatment with BIO101 (20E) is expected to activate Mas receptor and the protective arm of RAS, thus preventing inflammation and lung damage.

Article Snippet: It is proposed that RAS balance could be restored in COVID-19 patients through Mas1 activation downstream of ACE2 activity, with 20E (BIO101), a non-peptidic Mas receptor (Mas1) activator developed by Biophytis ( ).

Techniques: Infection, Activity Assay