Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2020; 26(24): 3432-3446
Published online Jun 28, 2020. doi: 10.3748/wjg.v26.i24.3432
Hepatoprotective effects of Hovenia dulcis seeds against alcoholic liver injury and related mechanisms investigated via network pharmacology
Xiao Meng, Guo-Yi Tang, Cai-Ning Zhao, Qing Liu, Xiao-Yu Xu, Shi-Yu Cao
Xiao Meng, Guo-Yi Tang, Cai-Ning Zhao, Qing Liu, Xiao-Yu Xu, Shi-Yu Cao, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Meng X, Tang GY, and Zhao CN contributed to the conception and design of the study; Meng X, Tang GY, Zhao CN, Liu Q, Xu XY, and Cao SY performed the experiments and acquired data; Meng X drafted the manuscript; Tang GY, Zhao CN, and Liu Q made critical revisions; all authors approved the final version of the manuscript.
Institutional animal care and use committee statement: All experimental procedures were performed based on the approval of Animal Ethics Committee of School of Public Health, Sun Yat-Sen University (No. 2017-011).
Conflict-of-interest statement: The authors declared that they have no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xiao Meng, PhD, Lecturer, Department of Nutrition, School of Public Health, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, Guangdong Province, China. mengx7@mail2.sysu.edu.cn
Received: March 4, 2020
Peer-review started: March 4, 2020
First decision: April 12, 2020
Revised: April 24, 2020
Accepted: May 30, 2020
Article in press: May 30, 2020
Published online: June 28, 2020
Abstract
BACKGROUND

Alcoholic liver disease (ALD) is a worldwide health problem, and natural products have been shown to improve ALD due to their antioxidant activities. Some parts of Hovenia dulcis (H. dulcis), such as roots, peduncles, and stems, provide health benefits. Nevertheless, the effects and mechanisms of H. dulcis seeds on ALD have not yet been fully elucidated.

AIM

To determine H. dulcis antioxidant activity, evaluate its effects against ALD, and investigate the related mechanisms via network pharmacology.

METHODS

The antioxidant activity of H. dulcis seed was determined by both ferric-reducing antioxidant power and trolox equivalent antioxidant capacity assays. The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry, respectively, and polysaccharide was determined by phenol-sulfuric acid method. The effects of H. dulcis seeds against alcoholic liver injury were investigated in mice with water extract pretreatment for 7 days followed by alcohol administration. Moreover, the mechanisms of action were explored with network pharmacology.

RESULTS

The results showed that H. dulcis seeds possessed strong antioxidant activity (245.11 ± 10.17 μmol Fe2+/g by ferric-reducing antioxidant power and 284.35 ± 23.57 μmol TE/g by trolox equivalent antioxidant capacity) and contained remarkable phenols and flavonoids, as well as a few polysaccharides. H. dulcis seeds attenuated alcohol-induced oxidative liver injury, showing reduced serum alanine and aspartate aminotransferases, alkaline phosphatase, and triglyceride, elevated hepatic glutathione, increased activities of superoxide dismutase and catalase, and reduced malondialdehyde and hepatic triglyceride. The results of network pharmacology analysis indicated that kaempferol, stigmasterol, and naringenin were the main bioactive compounds in H. dulcis seeds and that modulation of oxidative stress, inflammation, gut-derived products, and apoptosis were underlying mechanisms of the protective effects of H. dulcis seeds on ALD.

CONCLUSION

The results of this study demonstrate that H. dulcis seeds could be a good natural antioxidant source with protective effects on oxidative diseases such as ALD.

Keywords: Hovenia dulcis, Alcoholic liver disease, Antioxidant activity, Hepatoprotection, Oxidative stress, Network pharmacology

Core tip: Although some parts of Hovenia dulcis (H. dulcis) provide health impacts, the effects and mechanisms of H. dulcis seeds on alcoholic liver disease (ALD) have not been fully elucidated. In this study, we found that H. dulcis seeds possessed strong antioxidant activity and contained considerable phenols and flavonoids. H. dulcis seeds attenuated ALD and improved hepatic antioxidant capacity. Furthermore, results of network pharmacology analyses indicated that kaempferol, stigmasterol, and naringenin were the main bioactive compounds in H. dulcis seeds and that modulating oxidative stress, inflammation, gut-derived products, and apoptosis were involved in the mechanisms underlying the protective effects of H. dulcis seeds on ALD.