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Comparative pharmacokinetic investigation on crocetin in hyperlipidemia and normal rats after oral administration

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Abstract

Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication.

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Data availability

All data are available from the corresponding author if requested by the journal or the readers.

Abbreviations

TC:

Total cholesterol

TG:

Triglyceride

LDL-C:

Low-density lipoprotein cholesterol

HDL-C:

High-density lipoprotein cholesterol

CHD:

Coronary heart disease

CVD:

Cardiovascular disease

CYP:

Cytochrome P450

MRP:

Multidrug resistance related protein

MDR:

Multidrug resistance

NADPH:

Nicotinamide adenine dinucleotide phosphate

HPLC:

High-performance liquid chromatography

C max :

Maximum plasma concentration

T max :

The time to reach Cmax

AUC:

The area under the plasma concentration–time curve

RSD:

Relative standard deviation

QC:

Quality control

RE:

Relative error

SD:

Standard deviation

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Acknowledgements

This research has been supported by the Animal Center of Medical College of Hunan Normal University and the Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province (Hunan Normal University).

Funding

This work was supported by the Hunan Provincial Natural Science Foundation of China (no. 2020JJ4437), Scientific Research Fund of Hunan Provincial Education Department (no. 18A033), the Opening Fund of Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Hunan Normal University), Ministry of Education (no. KLCBTCMR18-05), and the Opening Fund of Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province (no. 2019CG05).

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Authors and Affiliations

  1. Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, 410013, China

    Cheng-Ye She, Yuan-Xiong Deng, Qin-Yu Wu & Jing Li

  2. Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Hunan Normal University), Ministry of Education, Changsha, 410081, China

    Cheng-Ye She, Yuan-Xiong Deng, Qin-Yu Wu & Jing Li

  3. Department of Pharmaceutical Science, Medical College of Hunan Normal University, Changsha, 410013, China

    Cheng-Ye She, Yuan-Xiong Deng, Qin-Yu Wu & Jing Li

Authors
  1. Cheng-Ye She
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Contributions

Cheng-Ye She performed the HPLC assay, analyzed the data, and wrote the original draft. Yuan-Xiong Deng acquired funding, designed and supervised the investigation, and checked and revised the manuscript. Cheng-Ye She, Qin-Yu Wu, and Jing Li performed animal experiment, everted gut sac experiment, and the experiment of liver microsomes incubation. Yuan-Xiong Deng submitted the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Yuan-Xiong Deng.

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Ethical approval

The experimental protocol was approved by the Animal Ethics Committee of Hunan Normal University (approval number: D2021026) and complied with the Guide for the Care and Use of Laboratory Animals of Hunan Normal University. The committee approved the publication of the research.

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The authors declare no competing interests.

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She, CY., Deng, YX., Wu, QY. et al. Comparative pharmacokinetic investigation on crocetin in hyperlipidemia and normal rats after oral administration. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03012-y

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