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

Jianbin Min,Suiqing Mi,Xian Liu,Tianlai Huang,Hao Chen,Ningsheng Wang,Wei Zhao,Tian Wu,Yingfeng Zhang,Chenchen Zhu,Weirong Li,Qi Wang,Zipeng Gong,Jiansong Fang

doi:10.3390/molecules23092287

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.

Highlights

Cholestasis, a hallmark feature of hepatobiliary disease, is characterized by impairment of bile and bilirubin secretion [1,2,3] and alterations in the expression levels of hepatic membrane transporters and bile acid metabolic enzymes [2,4]
rosmarinic acid (RA) is the in a water extract of we reported that serra imparts distinct hepatoprotective predominant active component in a water extract of R. serra
We reported that R. serra effects [25]

Summary

Introduction

Cholestasis, a hallmark feature of hepatobiliary disease, is characterized by impairment of bile and bilirubin secretion [1,2,3] and alterations in the expression levels of hepatic membrane transporters and bile acid metabolic enzymes [2,4]. Cholestasis is often divided into two categories based on etiology, namely, intrahepatic and extrahepatic. Surgical removal of primary foci remains the main treatment for extrahepatic cholestasis, whereas the therapeutic options for intrahepatic cholestasis are limited because liver transplantation is only appropriate for certain patients. A better understanding of the molecular mechanisms underlying intrahepatic cholestasis is required to identify novel drug targets and improve current therapies. 1) is is one of the most important and well-known polyphenolic polyphenolic antioxidants antioxidants that that is is abundant abundant in in various various medicinal medicinal plants plants of of the the Lamiaceae. Lamiaceae family family and and have have historically been used in Traditional Chinese

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Conclusion