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A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects.
Bioorg Med Chem Lett. 2018 10 01; 28(18):3119-3122.BM

Abstract

Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.

Authors+Show Affiliations

College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China; Department of Medicine, Tibet University of Nationalities, No. 6 Wenhui East Road, Xianyang, Shaanxi Province 712082, People's Republic of China. Electronic address: xieshijiaoda405@stu.xjtu.edu.cn.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Shaanxi University of Chinese Medicine, Shiji Ave., Xi'an-xianyang New Ecomic Zone, Shaanxi Province 712046, People's Republic of China.Pharmacy Department, Xianyang Central Hospital, No. 78 Renmin East Road, Xianyang, Shaanxi Province 712000, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.College of Pharmacy, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30119959

Citation

Xie, Yun-Dong, et al. "A New Multifunctional Hydroxytyrosol-clofibrate With Hypolipidemic, Antioxidant, and Hepatoprotective Effects." Bioorganic & Medicinal Chemistry Letters, vol. 28, no. 18, 2018, pp. 3119-3122.
Xie YD, Chen ZZ, Shao LH, et al. A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects. Bioorg Med Chem Lett. 2018;28(18):3119-3122.
Xie, Y. D., Chen, Z. Z., Shao, L. H., Wang, Q. T., Li, N., Lu, W. F., Xu, Y. H., Gao, Y. Q., Guo, L. Y., Liu, H. L., Li, Y. P., Yang, G. D., & Bian, X. L. (2018). A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects. Bioorganic & Medicinal Chemistry Letters, 28(18), 3119-3122. https://doi.org/10.1016/j.bmcl.2018.06.010
Xie YD, et al. A New Multifunctional Hydroxytyrosol-clofibrate With Hypolipidemic, Antioxidant, and Hepatoprotective Effects. Bioorg Med Chem Lett. 2018 10 1;28(18):3119-3122. PubMed PMID: 30119959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects. AU - Xie,Yun-Dong, AU - Chen,Zi-Zhang, AU - Shao,Li-Hua, AU - Wang,Qiu-Tang, AU - Li,Na, AU - Lu,Wen-Fang, AU - Xu,Yan-Hong, AU - Gao,Yu-Qiong, AU - Guo,Li-Ying, AU - Liu,Hao-Le, AU - Li,Yi-Ping, AU - Yang,Guang-De, AU - Bian,Xiao-Li, Y1 - 2018/06/05/ PY - 2018/03/03/received PY - 2018/05/30/revised PY - 2018/06/04/accepted PY - 2018/8/19/pubmed PY - 2019/3/22/medline PY - 2018/8/19/entrez KW - Antioxidant KW - Hepatoprotective KW - Hydroxytyrosol-clofibrate KW - Hypolipidemic SP - 3119 EP - 3122 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 28 IS - 18 N2 - Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/30119959/A_new_multifunctional_hydroxytyrosol_clofibrate_with_hypolipidemic_antioxidant_and_hepatoprotective_effects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(18)30496-7 DB - PRIME DP - Unbound Medicine ER -