TY - JOUR

T1 - Pharmacokinetic Characteristics of Ecdystene and Ursolic Acid in Plant Extracts After Oral Administration In Vivo

AU - Kiseleva, D. A.

AU - An’kov, S. V.

AU - Tolstikova, T. G.

AU - Okhina, A. A.

AU - Rogachev, A. D.

N1 - The research was funded within the framework of the planned research theme of the Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences: “Modern approaches to the study of toxicological and pharmacological properties of biologically active substances, pharmaceutical formulations, and medical materials,” no. 122040400038-4.

PY - 2025/8

Y1 - 2025/8

N2 - Objective: Bioavailability determination is critically important when studying the therapeutic potential of plant extracts, as it indicates whether active compounds retain their biological activity or gradually lose efficacy under various physiological conditions. Rosemary (Rosmarinus officinalis L.) represents the richest source of the pentacyclic triterpenoid ursolic acid, while ecdystene (20-hydroxyecdysone) is a principal phytoecdysteroid present in Rhaponticum (Rhaponticum carthamoides Willd.). Both plant sources are approved for pharmaceutical distribution as dietary supplements and metabolic therapy agents. However, limited information exists regarding the pharmacokinetic profiles of ecdystene and ursolic acid in plant extracts and multicomponent formulations. This study aimed to comparatively evaluate the pharmacokinetic parameters of ecdystene, ursolic acid, Rhaponticum and Rosemary extracts, and a combination formulation containing both extracts after oral administration in vivo. Methods: Test substances and their extracts were administered as single intragastric doses to CD-1 outbred mice at doses standardized to equivalent concentrations of the primary active compounds. Ursolic acid and ecdystene concentrations in animal blood were quantified using HPLC-MS/MS for subsequent pharmacokinetic parameter calculations (Cmax, Tmax, AUC). Results and Discussion: Both compounds demonstrated decreased bioavailability in animal blood when administered as plant extracts compared to pure substances. In the combination formulation, only trace amounts of ecdystene were detected, while ursolic acid pharmacokinetic parameters showed no significant differences between the combination and rosemary extract. These findings demonstrate that combining plant extracts in multicomponent formulations can reduce bioavailability of active compounds through various physicochemical and biological mechanisms. Conclusions: This study confirms that plant extract combinations in multicomponent formulations may significantly decrease bioavailability of primary active substances through multiple factors. Development of plant extract-based products should incorporate comprehensive pharmacokinetic studies to ensure finished product quality and therapeutic efficacy.

AB - Objective: Bioavailability determination is critically important when studying the therapeutic potential of plant extracts, as it indicates whether active compounds retain their biological activity or gradually lose efficacy under various physiological conditions. Rosemary (Rosmarinus officinalis L.) represents the richest source of the pentacyclic triterpenoid ursolic acid, while ecdystene (20-hydroxyecdysone) is a principal phytoecdysteroid present in Rhaponticum (Rhaponticum carthamoides Willd.). Both plant sources are approved for pharmaceutical distribution as dietary supplements and metabolic therapy agents. However, limited information exists regarding the pharmacokinetic profiles of ecdystene and ursolic acid in plant extracts and multicomponent formulations. This study aimed to comparatively evaluate the pharmacokinetic parameters of ecdystene, ursolic acid, Rhaponticum and Rosemary extracts, and a combination formulation containing both extracts after oral administration in vivo. Methods: Test substances and their extracts were administered as single intragastric doses to CD-1 outbred mice at doses standardized to equivalent concentrations of the primary active compounds. Ursolic acid and ecdystene concentrations in animal blood were quantified using HPLC-MS/MS for subsequent pharmacokinetic parameter calculations (Cmax, Tmax, AUC). Results and Discussion: Both compounds demonstrated decreased bioavailability in animal blood when administered as plant extracts compared to pure substances. In the combination formulation, only trace amounts of ecdystene were detected, while ursolic acid pharmacokinetic parameters showed no significant differences between the combination and rosemary extract. These findings demonstrate that combining plant extracts in multicomponent formulations can reduce bioavailability of active compounds through various physicochemical and biological mechanisms. Conclusions: This study confirms that plant extract combinations in multicomponent formulations may significantly decrease bioavailability of primary active substances through multiple factors. Development of plant extract-based products should incorporate comprehensive pharmacokinetic studies to ensure finished product quality and therapeutic efficacy.

KW - Rhaponticum carthamoides

KW - Rosmarinus officinalis

KW - ecdystene

KW - extract

KW - mice

KW - pharmacokinetics

KW - ursolic acid

UR - https://www.scopus.com/pages/publications/105012024447

UR - https://www.mendeley.com/catalogue/66ec5d2b-13e4-3871-8358-01268b203300/

U2 - 10.1134/S1068162024607316

DO - 10.1134/S1068162024607316

M3 - Article

VL - 51

SP - 1645

EP - 1653

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 4

M1 - 18

ER -