The Alexipharmic Mechanisms of Five Licorice Ingredients Involved in CYP450 and Nrf2 Pathways in Paraquat-Induced Mice Acute Lung Injury
Joint Authors
Chen, Ze-Hui
Liu, Zi-Jing
Zhong, Jing
Zhang, Mei
Wang, Ji-Ye
Chen, Han-Ying
Wang, Xiao-Qin
Zhang, Bo
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-28
Country of Publication
Egypt
No. of Pages
20
Main Subjects
Abstract EN
Oxidative stress is an important mechanism in acute lung injury (ALI) induced by paraquat (PQ), one of the most widely used herbicides in developing countries.
In clinical prophylaxis and treatment, licorice is a widely used herbal medicine in China due to its strong alexipharmic characteristics.
However, the corresponding biochemical mechanism of antioxidation and detoxification enzymes induced by licorice’s ingredients is still not fully demonstrated.
In this study, the detoxification effect of licorice was evaluated in vivo and in vitro.
The detoxification and antioxidation effect of its active ingredients involved in the treatment was screened systematically according to Absorption, Distribution, Metabolism, and Excretion (ADME): predictions and evidence-based literature mining methods in silico approach.
Data shows that licorice alleviate pulmonary edema and fibrosis, decrease Malondialdehyde (MDA) contents and increase Superoxide Dismutase (SOD) activity in PQ-induced ALI mice, protect the morphologic appearance of lung tissues, induce cytochrome 3A4 (CYA3A4) and Nuclear factor erythroid 2-related factor 2 (Nrf2) expression to active detoxification pathways, reduce the accumulation of PQ in vivo, protect or improve the liver and renal function of mice, and increase the survival rate.
The 104 genes of PPI network contained all targets of licorice ingredients and PQ, which displayed the two redox regulatory enzymatic group modules cytochrome P450 (CYP450) and Nrf2 via a score-related graphic theoretic clustering algorithm in silico.
According to ADME properties, glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A were employed due to their oral bioavailability OB≥30%, drug-likeness DL≥0.1, and being highly associated with CYP450 and Nrf2 pathways, as potential activators to halt PQ-induced cells death in vitro.
Both 3A4 inhibitor and silenced Nrf2 gene decreased the alexipharmic effects of those ingredients significantly.
All these disclosed the detoxification and antioxidation effects of licorice on acute lung injury induced by PQ, and glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A upregulated CYP450 and Nrf2 pathways underlying the alexipharmic mechanisms of licorice.
American Psychological Association (APA)
Liu, Zi-Jing& Zhong, Jing& Zhang, Mei& Chen, Ze-Hui& Wang, Ji-Ye& Chen, Han-Ying…[et al.]. 2019. The Alexipharmic Mechanisms of Five Licorice Ingredients Involved in CYP450 and Nrf2 Pathways in Paraquat-Induced Mice Acute Lung Injury. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-20.
https://search.emarefa.net/detail/BIM-1205072
Modern Language Association (MLA)
Liu, Zi-Jing…[et al.]. The Alexipharmic Mechanisms of Five Licorice Ingredients Involved in CYP450 and Nrf2 Pathways in Paraquat-Induced Mice Acute Lung Injury. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-20.
https://search.emarefa.net/detail/BIM-1205072
American Medical Association (AMA)
Liu, Zi-Jing& Zhong, Jing& Zhang, Mei& Chen, Ze-Hui& Wang, Ji-Ye& Chen, Han-Ying…[et al.]. The Alexipharmic Mechanisms of Five Licorice Ingredients Involved in CYP450 and Nrf2 Pathways in Paraquat-Induced Mice Acute Lung Injury. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-20.
https://search.emarefa.net/detail/BIM-1205072
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205072