Hu Cong, Wang Yuheng, Liu Yu, Wang Xiaojing, Song Peifang, Ma Hong, Yang Ling
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2025 Jul 10;16:1582644. doi: 10.3389/fphar.2025.1582644. eCollection 2025.
Ginsenoside Rh3 (GRh), a rare ginsenoside, demonstrates diverse pharmacological activities ; however, the lack of pharmacokinetic and tissue distribution data has limited its translation to applications. This study aimed to develop and validate a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying GRh in rat biological matrices and to characterize its pharmacokinetic profile and tissue distribution following oral administration.
A validated LC-MS/MS method was established for the quantification of GRh in rat plasma and tissues. Male Sprague-Dawley rats received an oral dose of GRh (100 mg/kg), and plasma samples were collected up to 72 h post-dose for pharmacokinetic analysis. Tissue samples (intestine, stomach, liver, brain, etc.) were collected at the time corresponding to the maximum plasma concentration for distribution analysis.
The LC-MS/MS method showed excellent precision, accuracy, and extraction recovery (≥ 85%), with minimal matrix effects. GRh exhibited a prolonged elimination half-life (14.7 ± 1.7 h), a low clearance rate (13.0 ± 3.8 L/h/kg), and a high volume of distribution (280.4 ± 109.3 L/kg). Tissue distribution analysis revealed the highest GRh concentrations in the intestine (15445.2 ng/g), followed by the stomach (2906.7 ng/g) and liver (1930.8 ng/g). Notably, GRh was able to cross the blood-brain barrier, with significant accumulation observed in the hippocampus (520.0 ng/g).
The prolonged elimination and extensive tissue distribution of GRh, particularly its ability to penetrate the brain, indicate potential therapeutic benefits or neurotoxic risks involving the central nervous system. The mechanism underlying its blood-brain barrier permeability warrants further investigation, potentially involving transporter-mediated uptake or modulation of barrier integrity. These findings provide a foundation for optimizing GRh dosing regimens and guiding future preclinical studies.
人参皂苷Rh3（GRh）是一种稀有人参皂苷，具有多种药理活性；然而，缺乏药代动力学和组织分布数据限制了其在实际应用中的转化。本研究旨在开发并验证一种用于定量大鼠生物基质中GRh的新型液相色谱-串联质谱（LC-MS/MS）方法，并表征其口服给药后的药代动力学特征和组织分布。
建立了一种经过验证的LC-MS/MS方法，用于定量大鼠血浆和组织中的GRh。雄性Sprague-Dawley大鼠口服给予GRh（100 mg/kg），给药后长达72小时收集血浆样本进行药代动力学分析。在对应最大血浆浓度的时间点收集组织样本（肠道、胃、肝脏、脑等）进行分布分析。
LC-MS/MS方法显示出优异的精密度、准确度和提取回收率（≥85%），基质效应最小。GRh表现出较长的消除半衰期（14.7±1.7小时）、较低的清除率（13.0±3.8 L/h/kg）和较高的分布容积（280.4±109.3 L/kg）。组织分布分析显示，GRh在肠道中的浓度最高（15445.2 ng/g），其次是胃（2906.7 ng/g）和肝脏（1930.8 ng/g）。值得注意的是，GRh能够穿过血脑屏障，在海马体中观察到显著蓄积（520.0 ng/g）。
GRh的消除时间延长和广泛的组织分布，特别是其穿透大脑的能力，表明其对中枢神经系统具有潜在的治疗益处或神经毒性风险。其血脑屏障通透性的潜在机制值得进一步研究，可能涉及转运体介导的摄取或屏障完整性的调节。这些发现为优化GRh给药方案和指导未来的临床前研究奠定了基础。
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