Investigation of the metabolism of ecdysteroids and their human physiological effects

Abstract

Phytoecdysteroids have anabolic effects in humans and especially popular among athletes as sport performance enhancers. This study investigated the metabolism of an ecdysteroid, 20-Hydroxyecdysone (20HE), and its physiological effects, at concentrations not expected to be anabolic.
The uPA (+/+)-SCID chimeric mice were administered 20HE. An excretion study was conducted on a male volunteer, after administration of low and high doses of supplement-derived 20HE. The effect of a 20HE containing supplement for two months was recorded in male athletes, with samples before and after consuming a 20HE supplement (n=4) or placebo (n=4). The detection of urinary 20HE was determined. Anthropometric changes were measured, as well as glucose, lipids and haematology, and an index of aerobic fitness (VO2 max). The hepatic transcriptome and proteome were analysed in RNA and protein extracted from the SCID mice treated with 20HE. Effects on Mitochondrial Membrane Potential (MMP) were tested in-vitro in human skeletal muscle cells and adipocytes treated with 20HE (5 and 10µM).
Fifteen drug metabolizing genes were overexpressed, including NOS3, and, 29 were under expressed, including CYP17A1, in the 20HE treated group. In mice, following multiple doses, 20HE was detectable for up to 24h. In a human subject, following a high dose of supplement-derived 20HE, the ecdysteroid was first detected after 2 hours, with peak detection between 4-5 hours, and remained detectable for up to 48 hours. The lower concentration was only detectable for 36 hours. 20HE supplement decreased diastolic blood pressure (p=0.05), with no significant changes in muscle mass and aerobic fitness. Seventy proteins were only detected in the 20HE group, while 37 genes were significantly differentially expressed. Upregulation of NOS3 was a consistent finding, and, validated at both the protein and RNA levels in human endothelial cells.
Low dose, supplement-derived 20HE was detectable in human urine for at least 36 hours, and its administration (2 months) was not anabolic, but, was still able to alter systemic blood pressure and the expression of vasocrine genes (NOS3).

Date of Award	21 Jan 2021
Original language	English
Awarding Institution	The University of Bristol
Supervisor	David J Morgan (Supervisor) & Wael Kafienah (Supervisor)