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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1582644

This article is part of the Research TopicTraditional, Complementary and Integrative Medicine – Opportunities for Managing and Treating Neurodegenerative Diseases and Ischaemic StrokeView all 13 articles

Pharmacokinetics and tissue distribution analysis of Ginsenoside Rh3 in rats using a novel LC-MS/MS quantification strategy

Provisionally accepted
Cong  HuCong Hu1,2Yuheng  WangYuheng Wang3Yu  LiuYu Liu2Xiaojing  WangXiaojing Wang2Peifang  SongPeifang Song2Hong  MaHong Ma2*Ling  YangLing Yang1,2*
  • 1Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • 2Zunyi Medical University, Zunyi, Guizhou Province, China
  • 3First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning Province, China

The final, formatted version of the article will be published soon.

Ginsenoside Rh3 (GRh3), a rare ginsenoside, exhibits various pharmacological activities in vitro. However, the lack of pharmacokinetics and tissue distribution data has limited its transition from in vitro studies to in vivo applications. In this study, a method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the quantification of GRh3 in rat plasma and tissues. The method exhibited excellent precision, accuracy, extraction recovery, and minimal matrix effects.Subsequently, the pharmacokinetics and tissue distribution of GRh3 following oral administration in rats were investigated using this method. The pharmacokinetics analysis revealed that GRh3 exhibited a relatively prolonged Tmax (8.0 h) and half-life (14.7 ± 1.7 h), a low clearance rate (13.0 ± 3.8 L/h/kg), and a high apparent volume of distribution (280.4 ± 109.3 L/kg). The tissue distribution result indicated that GRh3 had extensive tissue penetration, with the highest concentration observed in the intestine, followed by the stomach and liver. It is noteworthy that GRh3 was detected in the brain, most significantly in the hippocampus, which departure from the conventional theory that only small molecules (< 500 Da) are capable of traversing the blood-brain barrier (BBB). The underlying mechanisms of this observation requires further investigation.These findings provide a valuable foundation for further in vivo studies on GRh3.

Keywords: GRh3, pharmacokinetics, Tissue Distribution, Blood-Brain Barrier, LC-MS/MS

Received: 24 Feb 2025; Accepted: 26 Jun 2025.

Copyright: © 2025 Hu, Wang, Liu, Wang, Song, Ma and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Hong Ma, Zunyi Medical University, Zunyi, 563000, Guizhou Province, China
Ling Yang, Zunyi Medical University, Zunyi, 563000, Guizhou Province, China

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