Improved Bioavailablity of Curcumin by Derivatisation with Isoleucine in Plasma and Reproductive Tissues of Female Rats is Mainly Due to Altered Affinity for P-gp Transporter

Abstract

Aim: The present study aimed to investigate the bioavailability of curcumin conjugated with isoleucine. Background: Curcumin has various health beneficiary properties; however, it is poorly bioavailable because of its insolubility in water, poor absorption and quick systemic elimination. Hence, any approach that could improve bioavailability is necessary. Objective: The objective of the present study is to examine whether the bioavailability and biodistribution of curcumin is improved upon derivatisation with isoleucine than that of native curcumin. Methods: About 0.1 g/kg bw of curcumin and its isoleucine-derivative were administered to fasting rats. Then the blood and tissue samples were collected at different time intervals (0, 1800, 3600, 7200, 14400, 28800, 43200, 86400, and 172800 seconds) and processed for the extraction of curcumin and its derivative with methanol. The processed samples were subjected to HPLC analysis and compared with the standard curcumin and its derivative. The results were analysed using the software, PKSolver, for determining the bioavailability and biodistribution. Further, the docking studies were carried out to better understand the results obtained. Results: We found that isoleucine-curcumin conjugates have better bioavailable in plasma, ovary and uterus in the experimental rats. The curcumin and its isoleucine-derivative was detected to be maximum at 14400 seconds. However, the concentration of isoleucine-derivative of curcumin was significantly high at Tmax compared to native curcumin. Further, curcumin and its derivative were found in the reproductive organs only at 28800 seconds, 43200 seconds and 86400 seconds. The binding energy of isoleucine-derivative of curcumin with p-glycoprotein transporter was found to be more compared to the native form. This may be the reason for the increased bioavailability of isoleucine-derivative of curcumin. Conclusion: The isoleucine-curcumin conjugate has better bioavailability compared to curcumin both in plasma and reproductive organs.