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Molecules 2018, 23(9), 2287; https://doi.org/10.3390/molecules23092287

Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury

1
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Jichang Road 12, Guangzhou 510405, China
2
College of Food and Drug, Anhui Science and Technology of University, Fengyang 233100, Anhui, China
3
Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Beijing Road, Guiyang 550004, China
4
College of Chinese Medicine, Guangzhou University of Chinese Medicine, Jichang Road 12, Guangzhou 510405, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 16 July 2018 / Revised: 18 August 2018 / Accepted: 29 August 2018 / Published: 7 September 2018
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Abstract

The objective of this study was to evaluate the hepatoprotective and metabolic effects of rosmarinic acid (RA) in rats. RA [100 mg/kg body weight (BW)] was intragastrically (i.g.) administered to Sprague-Dawley (SD) rats once a day for seven consecutive days. The rats were then i.g. administered α-naphthylisothiocyanate (ANIT) (80 mg/kg once on the 5th day) to induce acute intrahepatic cholestasis after the last administration of RA. Blood samples were collected at different time points (0.083 h, 0.17 h, 0.33 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 20 h) after administration, and the levels of RA were estimated by HPLC. Plasma and bile biochemical analysis, bile flow rate, and liver histopathology were measured to evaluate the hepatoprotective effect of RA. The PK-PD curves showed obviously clockwise (AST and ALT) or anticlockwise (TBA, TBIL). Pretreatment with RA at different doses significantly restrained ANIT-induced pathological changes in bile rate, TBA, TBIL, ALT, AST (p < 0.05 or p < 0.01). The relationship between RA concentration and its hepatoprotective effects on acute cholestasis responses was assessed by PK-PD modeling. View Full-Text
Keywords: rosmarinic acid; cholestasis; pharmacodynamics; pharmacokinetics rosmarinic acid; cholestasis; pharmacodynamics; pharmacokinetics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Min, J.; Chen, H.; Gong, Z.; Liu, X.; Wu, T.; Li, W.; Fang, J.; Huang, T.; Zhang, Y.; Zhao, W.; Zhu, C.; Wang, Q.; Mi, S.; Wang, N. Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury. Molecules 2018, 23, 2287.

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