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

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,...

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Main Authors: Yao Li, Sheng Guo, Quanjin Ren, Dandan Wei, Ming Zhao, Shulan Su, Zhishu Tang, Jin-Ao Duan
Format: Article
Language:English
Published: MDPI AG 2018-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/19/7/2047
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spelling doaj-d059cc3bc2294b8aa01ca7c5394b7d872020-11-24T23:58:12ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-07-01197204710.3390/ijms19072047ijms19072047Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury RatsYao Li0Sheng Guo1Quanjin Ren2Dandan Wei3Ming Zhao4Shulan Su5Zhishu Tang6Jin-Ao Duan7Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/State Key Laboratory Cultivation Base for Traditional Chinese Medicine Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/State Key Laboratory Cultivation Base for Traditional Chinese Medicine Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaInstitute of Botany, Jiangsu Province and Chinese Academy of Science, Nanjing 210014, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/State Key Laboratory Cultivation Base for Traditional Chinese Medicine Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/State Key Laboratory Cultivation Base for Traditional Chinese Medicine Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/State Key Laboratory Cultivation Base for Traditional Chinese Medicine Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaShaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/State Key Laboratory Cultivation Base for Traditional Chinese Medicine Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJujubae 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.http://www.mdpi.com/1422-0067/19/7/2047Ziziphus jujubatriterpenic acidspharmacokinetic studyacute liver injury
collection DOAJ
language English
format Article
sources DOAJ
author Yao Li
Sheng Guo
Quanjin Ren
Dandan Wei
Ming Zhao
Shulan Su
Zhishu Tang
Jin-Ao Duan
spellingShingle Yao Li
Sheng Guo
Quanjin Ren
Dandan Wei
Ming Zhao
Shulan Su
Zhishu Tang
Jin-Ao Duan
Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats
International Journal of Molecular Sciences
Ziziphus jujuba
triterpenic acids
pharmacokinetic study
acute liver injury
author_facet Yao Li
Sheng Guo
Quanjin Ren
Dandan Wei
Ming Zhao
Shulan Su
Zhishu Tang
Jin-Ao Duan
author_sort Yao Li
title Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats
title_short Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats
title_full Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats
title_fullStr Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats
title_full_unstemmed Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats
title_sort pharmacokinetic comparisons of multiple triterpenic acids from jujubae fructus extract following oral delivery in normal and acute liver injury rats
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2018-07-01
description 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.
topic Ziziphus jujuba
triterpenic acids
pharmacokinetic study
acute liver injury
url http://www.mdpi.com/1422-0067/19/7/2047
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