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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

Preclinical Pharmacokinetics and CYP Modulation Activity of Chebulinic Acid: A Potent Molecule Against Metabolic Disease

Author(s): Arpon Biswas, Sarvesh Kumar Verma, Shiv Kumar, Tripti Mishra, Mukesh Kumar, Abhijit Deb Choudhury, Sristi Agrawal, Sachin Nashik Sanap, Amol Chhatrapati Bisen, Anjali Mishra, Tadigoppula Narender and Rabi Sankar Bhatta*

Volume 24, Issue 8, 2023

Published on: 11 September, 2023

Page: [587 - 598] Pages: 12

DOI: 10.2174/1389200224666230817101950

Price: $65


Background: Chebulinic acid (CA) is an active constituent of Terminalia chebula fruits with therapeutic potential against multiple metabolic diseases, including dementia, benign prostate hyperplasia, and osteoporosis.

Objective: The present work intends to explore the preclinical pharmacokinetics, including the absolute bioavailability of CA and its influence on the gene expression of cytochrome P450 enzymes in the liver.

Methods: Quantifying CA and probe drugs in vitro samples and preclinical serum samples of male SD rats were performed using LC-MS/MS. The influence of CA on the hepatic CYPs and their gene expression was analyzed in rat liver by quantitative real-time polymerase chain reaction.

Results: The plasma protein binding was found to be 84.81 ± 7.70 and 96.34 ± 3.12, blood-to-plasma ratio of 0.62 ± 0.16 and 0.80 ± 0.23 at 1 μM and 10 μM concentrations, respectively. Again, the absolute oral bioavailability of CA at 100 mg/kg was found to be 37.56 ± 7.3%. The in-vivo pharmacokinetic profile of probe drugs revealed CA to have significant inducing effects on CYP1A2, 2C11, 2D2, and 2E1 after 14 days, which correlates to both in-vitro rat microsomal data and gene expression results.

Conclusion: Altogether, pharmacokinetic parameters reveal CA to have an affinity to distribute across different extravascular tissues and induce rat liver CYP enzymes.

Keywords: Natural product, pharmacokinetics, bioavailability, chebulinic acid, CYP enzyme, LC-MS/MS.

Graphical Abstract

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