Pharmacokinetics and antioxidant activity of dihydrocaffeic acid grafted chitosan nanomicelles loaded with chicoric acid in broilers

Juan Ren; Xin Ren; Leying Ma; Juxiang Liu; Sikun Yuan; Gengnan Wang

doi:10.1016/j.psj.2024.103776

Pharmacokinetics and antioxidant activity of dihydrocaffeic acid grafted chitosan nanomicelles loaded with chicoric acid in broilers

Poult Sci. 2024 Apr 16;103(7):103776. doi: 10.1016/j.psj.2024.103776. Online ahead of print.

Authors

Juan Ren¹, Xin Ren¹, Leying Ma¹, Juxiang Liu¹, Sikun Yuan², Gengnan Wang³

Affiliations

¹ College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei 071000, People's Republic of China.
² Baoding Institute for Food and Drug Control, Baoding, Hebei 071000, People's Republic of China.
³ College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei 071000, People's Republic of China. Electronic address: wanggengnan@hebau.edu.cn.

Abstract

Chicoric acid (CA) is a natural nutrient found in plants, showcasing diverse biological activities, including anti-inflammatory and antioxidant properties. Despite its valuable properties, CA faces limitations in bioavailability and susceptibility to oxidative breakdown during utilization. Previous research introduced synthesized dihydrocaffeic acid grafted chitosan self-assembled nanomicelles (DA-g-CS), demonstrating its potential to enhance CA absorption. This study aims to investigate the pharmacokinetics, tissue distribution, and antioxidant activity of both CA and DA-g-CS loaded CA (DA-g-CS/CA) in broilers. An IPEC-J2 cell model was established and evaluated to delve deeper into the transport mechanism and antioxidant potential. The in vivo pharmacokinetic analysis in broilers highlighted a substantial difference: the maximum plasma concentration (Cmax) of DA-g-CS/CA exceeded CA by 2.6-fold, yielding a notable increased relative bioavailability to 214%. This evidence underscores the significant enhancement in CA's oral absorption, facilitated by DA-g-CS. The collective evaluation outcomes affirm the successful development of the cell model, indicating its suitability for drug transporter experiments. The findings from the intestinal transit analysis revealed that both CA and DA-g-CS/CA underwent passive entry into IPEC-J2 cells. Notably, the cellular uptake rate of DA-g-CS loaded with CA was significantly amplified, reaching 2.1 times higher than that of CA alone. Intracellular transport mechanisms involved microtubules, lysosomes, and the endoplasmic reticulum, with an additional pathway involving the endoplasmic reticulum observed specifically for DA-g-CS/CA, distinguishing it from CA. Moreover, the results from both in vivo and in vitro antioxidant assessments highlight the potent antioxidant activity of DA-g-CS/CA, showcasing its efficacy in preventing and treating cellular damage induced by oxidative stress. In summary, these findings underscore the significant enhancement of CA's efficacy facilitated by DA-g-CS, establishing a robust theoretical foundation for the prospective application of CA within livestock and poultry farming.

Keywords: IPEC-J2 cell; antioxidant; broiler; chicoric acid; pharmacokinetic.