1. Dibenzocyclooctadiene lignans from Kadsura coccinea alleviate APAP-induced hepatotoxicity via oxidative stress inhibition and activating the Nrf2 pathway in vitro.
- Author
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Yang Y, Jian Y, Cheng S, Jia Y, Liu Y, Yu H, Cao L, Li B, Peng C, Iqbal Choudhary M, Rahman AU, and Wang W
- Subjects
- Acetaminophen pharmacology, Cell Survival drug effects, Cyclooctanes chemical synthesis, Cyclooctanes chemistry, Dose-Response Relationship, Drug, Hep G2 Cells, Humans, Lignans chemical synthesis, Lignans chemistry, Molecular Structure, NF-E2-Related Factor 2 metabolism, Oxidative Stress drug effects, Protective Agents chemical synthesis, Protective Agents chemistry, Structure-Activity Relationship, Acetaminophen antagonists & inhibitors, Cyclooctanes pharmacology, Kadsura chemistry, Lignans pharmacology, NF-E2-Related Factor 2 antagonists & inhibitors, Protective Agents pharmacology
- Abstract
Phytochemical investigation on the roots of Kadsura coccinea led to the isolation five previously unknown dibenzocyclooctadiene lignans, named heilaohusuins A-E (1-5). Their structures determined by NMR spectroscopy, HR-ESI-MS, and ECD spectra. Hepatoprotection effects of a series of dibenzocyclooctadiene derivatives (1-68) were investigated against acetaminophen (APAP) induced HepG2 cells. Compounds 2, 10, 13, 21, 32, 41, 46, and 49 showed remarkable protective effects, increasing the viabilities to > 52.2% (bicyclol, 52.1 ± 1.3%) at 10 μM. The structure-activity relationships (SAR) for hepatoprotective activity were summarized, according to the activity results of dibenzocyclooctadiene derivatives. Furthermore, we found that one new dibenzocyclooctadiene lignan heilaohusuin B attenuates hepatotoxicity, the mechanism might be closely correlated with oxidative stress inhibition via activating the Nrf2 pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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