Design and Evaluation of Ethylene Glycol Monopiperate as a Novel Antihyperlipidemic Prodrug: Synthesis, Antihyperlipidemic Activity, and Pharmacokinetics.
4 affiliations
- 1Department of Chemistry and Environment Hohhot Minzu College Hohhot China.
- 2School of Chemistry sand Chemical Engineering Yan'an University Yan'an China yau.edu.cn.
- 3School of Chemistry and Chemical Engineering Institute of Mongolian Medicine Chemistry Inner Mongolia University Hohhot China imu.edu.cn.
- 4Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency Faculty of Medicine School of Pharmaceutical Science and Technology Collaborative Innovation Center of Chemical Science and Engineering Tianjin University Tianjin China tju.edu.cn.
Abstract
Piperine, a major active component isolated from the traditional Mongolian medicine Piper longum L., exhibits antihyperlipidemic activity but also demonstrates inherent toxicity. In this study, ethylene glycol monopiperate (EGM), a piperine derivative, was synthesized via concentrated H₂SO₄-catalyzed esterification. Its structure was systematically characterized by FTIR, MS, ¹³C NMR, and ¹H NMR, with a yield of 60% and a purity of 99.2%. Subsequently, the in vitro cytotoxicity of EGM on HepG2 cells was evaluated, and the results indicated that over 90% cell viability was observed at concentrations up to 150 μg/mL. It was also investigated in male Wistar rats, and a sensitive, rapid, and accurate solid-phase extraction (SPE)-UPLC method was developed and validated for the quantification of EGM in rat plasma. The novel method showed good linearity over the concentration range of 1-16 µg/mL, a limit of detection (LOD) of 1 μg/mL, and high accuracy and precision (relative error [RE%] < 15%, relative standard deviation [RSD%] < 10%). In terms of antihyperlipidemic efficacy, EGM demonstrated excellent performance in reducing total cholesterol (TC), glucose (GLU), and low-density lipoprotein cholesterol (LDL-C), as well as elevating high-density lipoprotein cholesterol (HDL-C); these effects were notably better than the conventional control drug simvastatin. Pharmacokinetic analysis revealed that the plasma concentration-time profile of EGM followed a first-order open one-compartment model. Calculations using WINNONLIN software (ver. 5.2) showed a half-life (t 1/2) of 1.46 ± 0.67 h and an area under the curve (AUC₀-∞) of 7,15,530 ± 522.4 ng h/mL. EGM was stable in plasma over 24 h at room temperature and one month at -20°C, after three freeze-thaw cycles. These results verified that EGM may serve as a promising candidate for an antihyperlipidemic prodrug.
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BibTeX
@article{borijihan2026design,
title = {{Design and Evaluation of Ethylene Glycol Monopiperate as a Novel Antihyperlipidemic Prodrug: Synthesis, Antihyperlipidemic Activity, and Pharmacokinetics.}},
author = {Guirong Borijihan and Mimi Liu and Mingming Bao and Zhengkun Sun and Meng He and Youxin Li},
journal = {Journal of analytical methods in chemistry},
year = {2026},
month = oct,
doi = {10.1155/jamc/3258325},
url = {https://europepmc.org/article/MED/42948627},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design and Evaluation of Ethylene Glycol Monopiperate as a Novel Antihyperlipidemic Prodrug: Synthesis, Antihyperlipidemic Activity, and Pharmacokinetics.
AU - Guirong Borijihan
AU - Mimi Liu
AU - Mingming Bao
AU - Zhengkun Sun
AU - Meng He
AU - Youxin Li
PY - 2026
DA - 2026/10/27
JO - Journal of analytical methods in chemistry
DO - 10.1155/jamc/3258325
UR - https://europepmc.org/article/MED/42948627
AB - Piperine, a major active component isolated from the traditional Mongolian medicine Piper longum L., exhibits antihyperlipidemic activity but also demonstrates inherent toxicity. In this study, ethylene glycol monopiperate (EGM), a piperine derivative, was synthesized via concentrated H₂SO₄-catalyzed esterification. Its structure was systematically characterized by FTIR, MS, ¹³C NMR, and ¹H NMR, with a yield of 60% and a purity of 99.2%. Subsequently, the in vitro cytotoxicity of EGM on HepG2 cells was evaluated, and the results indicated that over 90% cell viability was observed at concentrations up to 150 μg/mL. It was also investigated in male Wistar rats, and a sensitive, rapid, and accurate solid-phase extraction (SPE)-UPLC method was developed and validated for the quantification of EGM in rat plasma. The novel method showed good linearity over the concentration range of 1-16 µg/mL, a limit of detection (LOD) of 1 μg/mL, and high accuracy and precision (relative error [RE%] < 15%, relative standard deviation [RSD%] < 10%). In terms of antihyperlipidemic efficacy, EGM demonstrated excellent performance in reducing total cholesterol (TC), glucose (GLU), and low-density lipoprotein cholesterol (LDL-C), as well as elevating high-density lipoprotein cholesterol (HDL-C); these effects were notably better than the conventional control drug simvastatin. Pharmacokinetic analysis revealed that the plasma concentration-time profile of EGM followed a first-order open one-compartment model. Calculations using WINNONLIN software (ver. 5.2) showed a half-life (t 1/2) of 1.46 ± 0.67 h and an area under the curve (AUC₀-∞) of 7,15,530 ± 522.4 ng h/mL. EGM was stable in plasma over 24 h at room temperature and one month at -20°C, after three freeze-thaw cycles. These results verified that EGM may serve as a promising candidate for an antihyperlipidemic prodrug.
SN - 2090-8865
SN - 2090-8873
ER -