Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats

Abstract

Jujubae Fructus, the dried fruit of Ziziphus jujuba, has been used as Chinese medicine and food for centuries. Triterpenic acids have been found to be the major bioactive constituents in Jujubae Fructus responsible for their hepatoprotective activity in previous phytochemical and biological studies, while few pharmacokinetic studies have been conducted. To reveal the kinetics of the triterpenic acids under the pathological liver injury state, an established ultra-performance liquid chromatography coupled with a mass spectrometry method was applied for the simultaneous quantitation of seven triterpenic acids (ceanothic acid, epiceanothic acid, pomonic acid, alphitolic acid, maslinic acid, betulinic acid, and betulonic acid) in plasma samples of normal and acute liver injury rats induced by CCl4. The results showed that there were significant differences (p < 0.05) in the pharmacokinetic parameters of seven triterpenic acids between model and normal groups. The AUC0–t and AUC0–∞ of epiceanothic acid (5227 ± 334 μg⋅h/L vs. 1478 ± 255 μg⋅h/L and 6127 ± 423 μg⋅h/L vs. 1482 ± 255 μg⋅h/L, respectively) and pomonic acid (4654 ± 349 μg⋅h/L vs. 1834 ± 225 μg⋅h/L and 4776 ± 322 μg⋅h/L vs. 1859 ± 230 μg⋅h/L, respectively) in model rats were significantly higher than those in normal rats, and the CLz/F of them were significantly decreased (0.28 ± 0.02 L/h/kg vs. 1.36 ± 0.18 L/h/kg and 19.96 ± 1.30 L/h/kg vs. 53.15 ± 5.60 L/h/kg, respectively). In contrast, the above parameters for alphitolic acid, betulinic acid and betulonic acid exhibited the quite different trend. This pharmacokinetic research might provide useful information for the clinical usage of triterpenic acids from Jujubae Fructus.