LC-MS/MS-based metabolomics and PK/PD correlation analysis reveal the mechanism of hyperlipidemia treatment with Gastrodia elata fine powder.
- 1Department of Clinical Pharmacy, The Second Hospital of Hebei Medical University 215 West Heping Road Shijiazhuang Hebei 050000 China [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected].
- 2Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University 361 East Zhongshan Road Shijiazhuang Hebei 050017 China [email protected].
Abstract
Gastrodia elata Blume is used as both a food and a traditional medicine in East Asia. This study evaluated the lipid-lowering effects of G. elata fine powder (GFP) and the associated metabolic responses in Sprague-Dawley rats with high-fat diet (HFD)-induced hyperlipidemia. Thirty-five rats were assigned to seven groups: a normal-diet control, an untreated HFD model, three GFP groups (150, 300, or 500 mg kg⁻¹ per administration, three times daily), and two positive-control groups receiving simvastatin or fenofibrate. Following a 6 week modeling period and a 2 week intervention, serum biochemical parameters, liver histology, and serum, urinary, and fecal metabolic profiles were assessed using biochemical assays, histological examination, and untargeted liquid chromatography-high-resolution mass spectrometry. A separate cohort of six hyperlipidemic rats received gastrodin (25 mg kg⁻¹) for pharmacokinetic/pharmacodynamic (PK/PD) analysis. Compared with the untreated HFD group, medium- and high-dose GFP improved serum lipid profiles, reduced serum aminotransferase activities, and ameliorated hepatic histopathological changes. Metabolomic profiling revealed 14 urinary, 8 fecal, and 16 serum metabolites whose HFD-associated alterations shifted toward normal-control levels following high-dose GFP treatment. The associated pathways included phenylalanine metabolism, taurine and hypotaurine metabolism, and the tricarboxylic acid cycle. Gastrodin exhibited a biphasic plasma concentration-time profile, whereas responses of five endogenous metabolic markers lagged behind systemic drug exposure. These findings support the short-term lipid-lowering activity of GFP in HFD-fed rats and its association with changes in amino acid, bile-acid-related, and energy metabolism.
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BibTeX
@article{xie2026lcmsmsbased,
title = {{LC-MS/MS-based metabolomics and PK/PD correlation analysis reveal the mechanism of hyperlipidemia treatment with Gastrodia elata fine powder.}},
author = {Weiwei Xie and Meijuan Liu and Jiajun Li and Yuqian Zhang and Jingpu Xu and Chenyuan Wang and Ye Yuan and Yiran Jin and Yingfeng Du and Deqiang Li},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra07137f},
url = {https://europepmc.org/article/MED/42910039},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - LC-MS/MS-based metabolomics and PK/PD correlation analysis reveal the mechanism of hyperlipidemia treatment with Gastrodia elata fine powder.
AU - Weiwei Xie
AU - Meijuan Liu
AU - Jiajun Li
AU - Yuqian Zhang
AU - Jingpu Xu
AU - Chenyuan Wang
AU - Ye Yuan
AU - Yiran Jin
AU - Yingfeng Du
AU - Deqiang Li
PY - 2026
DA - 2026/10/21
JO - RSC advances
DO - 10.1039/d6ra07137f
UR - https://europepmc.org/article/MED/42910039
AB - Gastrodia elata Blume is used as both a food and a traditional medicine in East Asia. This study evaluated the lipid-lowering effects of G. elata fine powder (GFP) and the associated metabolic responses in Sprague-Dawley rats with high-fat diet (HFD)-induced hyperlipidemia. Thirty-five rats were assigned to seven groups: a normal-diet control, an untreated HFD model, three GFP groups (150, 300, or 500 mg kg⁻¹ per administration, three times daily), and two positive-control groups receiving simvastatin or fenofibrate. Following a 6 week modeling period and a 2 week intervention, serum biochemical parameters, liver histology, and serum, urinary, and fecal metabolic profiles were assessed using biochemical assays, histological examination, and untargeted liquid chromatography-high-resolution mass spectrometry. A separate cohort of six hyperlipidemic rats received gastrodin (25 mg kg⁻¹) for pharmacokinetic/pharmacodynamic (PK/PD) analysis. Compared with the untreated HFD group, medium- and high-dose GFP improved serum lipid profiles, reduced serum aminotransferase activities, and ameliorated hepatic histopathological changes. Metabolomic profiling revealed 14 urinary, 8 fecal, and 16 serum metabolites whose HFD-associated alterations shifted toward normal-control levels following high-dose GFP treatment. The associated pathways included phenylalanine metabolism, taurine and hypotaurine metabolism, and the tricarboxylic acid cycle. Gastrodin exhibited a biphasic plasma concentration-time profile, whereas responses of five endogenous metabolic markers lagged behind systemic drug exposure. These findings support the short-term lipid-lowering activity of GFP in HFD-fed rats and its association with changes in amino acid, bile-acid-related, and energy metabolism.
SN - 2046-2069
ER -