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Phytoecdysteroids 20-hydroxyecdysone and calonysterone prevent diet-

induced obesity and unexpectedly modulate steroid hormonal balance in rats

2
1
2
2
1
Alaa AM Osman, Noémi Tóth, Dávid Laczkó, Máté Vágvölgyi, Kata Kira Kemény,
1
*,1
Péter Szatmári, Attila Hunyadi, 2,3,4 Eszter Ducza

1 Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of
Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
2 Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, 6720,
Szeged, Hungary
3 HUN-REN-SZTE Biologically Active Natural Products Research Group, Eötvös u. 6, H-6720
Szeged, Hungary
4 Graduate Institute of Natural Products, Kaohsiung Medical University, Shih-Chuan 1st Rd.
100, Kaohsiung 807, Taiwan R.O.C
* E-mail: ducza.eszter@szte.hu

Abstract
Phytoecdysteroids such as 20-hydroxyecdysone (20E) are marketed as natural anabolic
agents with metabolic benefits, yet their structural similarity to steroid hormones raises
concerns regarding endocrine disruption, particularly during puberty. Calonysterone (CAL), a
rare derivative of 20E, exhibits enhanced anabolic potential in vitro, but its in vivo actions
remain poorly understood. We investigated the metabolic and endocrine effects of oral 20E and
CAL (10 mg/kg/day, 12 weeks) in pre- and peripubertal male Sprague-Dawley rats maintained
on standard or high-fat, high-sugar diets (HFHSD). Body and organ weights, glucose tolerance,
plasma adipokine and hormone concentrations, liver antioxidant status, global DNA
methylation were measured and determined. Testicular expression of androgen receptor (AR),
estrogen receptor β (ERβ), and liver expression of IL-6 was assessed by RT-PCR. Both
phytoecdysteroids attenuated HFHSD-induced weight gain and muscle atrophy without altering
food intake, while restoring adiponectin and leptin levels. They increased global DNA
methylation and normalized corticosterone and estrogen concentrations. However, systemic
testosterone was consistently suppressed. CAL uniquely preserved testicular and levator ani
mass and upregulated ERβ in obese rats, while both compounds induced compensatory AR
overexpression. In summary, 20E and CAL exert tissue-selective anabolic and metabolic
effects but simultaneously disrupt androgen homeostasis during a critical developmental
window. CAL demonstrated superior protection of androgen-sensitive tissues, indicating
distinct activity compared to 20E. These findings highlight the need for caution in the use of
phytoecdysteroids as supplements and their use in adolescents warrants further mechanistic and
long-term evaluation.

Keywords: 20-Hydroxyecdysone; Calonysterone; Metabolic syndrome; Hormonal balance;
Obesity prevention