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The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity.
Bioorg Med Chem Lett. 2021 May 17; 44:128121.BM

Abstract

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.

Authors+Show Affiliations

College of Pharmacy, Shaanxi University of Chinese Medicine, Shiji Ave., Xi'an-xianyang New Ecomic Zone, Shaanxi Province 712046, 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; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, 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; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, 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; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, 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.College of Pharmacy, Shaanxi University of Chinese Medicine, Shiji Ave., Xi'an-xianyang New Ecomic Zone, Shaanxi Province 712046, 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.College of Pharmacy, Shaanxi University of Chinese Medicine, Shiji Ave., Xi'an-xianyang New Ecomic Zone, Shaanxi Province 712046, 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.College of Pharmacy, Shaanxi University of Chinese Medicine, Shiji Ave., Xi'an-xianyang New Ecomic Zone, Shaanxi Province 712046, 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.First Hospital of Xi'an, Xi'an, Shaanxi Province 710002, People's Republic of China. Electronic address: rcc1990@163.com.Shaanxi Traffic Hospital, 276 Daxue South Road, Beilin District, Xi'an, Shannxi Province 710068, People's Republic of China. Electronic address: 532413532@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34015506

Citation

Xie, Yundong, et al. "The Combination of Sesamol and Clofibric Acid Moieties Leads to a Novel Potent Hypolipidemic Agent With Antioxidant, Anti-inflammatory and Hepatoprotective Activity." Bioorganic & Medicinal Chemistry Letters, vol. 44, 2021, p. 128121.
Xie Y, Liu J, Shi Y, et al. The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity. Bioorg Med Chem Lett. 2021;44:128121.
Xie, Y., Liu, J., Shi, Y., Wang, B., Wang, X., Wang, W., Sun, M., Xu, X., Jiang, H., Guo, M., He, Y., Ren, C., & Cheng, L. (2021). The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity. Bioorganic & Medicinal Chemistry Letters, 44, 128121. https://doi.org/10.1016/j.bmcl.2021.128121
Xie Y, et al. The Combination of Sesamol and Clofibric Acid Moieties Leads to a Novel Potent Hypolipidemic Agent With Antioxidant, Anti-inflammatory and Hepatoprotective Activity. Bioorg Med Chem Lett. 2021 May 17;44:128121. PubMed PMID: 34015506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity. AU - Xie,Yundong, AU - Liu,Jiping, AU - Shi,Yongheng, AU - Wang,Bin, AU - Wang,Xiaoping, AU - Wang,Wei, AU - Sun,Meng, AU - Xu,Xinya, AU - Jiang,Haihui, AU - Guo,Min, AU - He,Yiyi, AU - Ren,Cuicui, AU - Cheng,Lifei, Y1 - 2021/05/17/ PY - 2021/03/17/received PY - 2021/05/10/revised PY - 2021/05/13/accepted PY - 2021/5/21/pubmed PY - 2021/5/21/medline PY - 2021/5/20/entrez KW - CF-Sesamol KW - Hepatoprotection KW - Hypolipidemic KW - Nrf2/NF-κB signaling pathway SP - 128121 EP - 128121 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 44 N2 - Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/34015506/The_combination_of_sesamol_and_clofibric_acid_moieties_leads_to_a_novel_potent_hypolipidemic_agent_with_antioxidant L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(21)00347-4 DB - PRIME DP - Unbound Medicine ER -
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