Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2023; 29(34): 5054-5074
Published online Sep 14, 2023. doi: 10.3748/wjg.v29.i34.5054
Green tea polyphenols alleviate di-(2-ethylhexyl) phthalate-induced liver injury in mice
Heng Shi, Xin-Hai Zhao, Qin Peng, Xian-Ling Zhou, Si-Si Liu, Chuan-Chuan Sun, Qiu-Yu Cao, Shi-Ping Zhu, Sheng-Yun Sun
Heng Shi, Xin-Hai Zhao, Xian-Ling Zhou, Chuan-Chuan Sun, Qiu-Yu Cao, Shi-Ping Zhu, Sheng-Yun Sun, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 522000, Guangdong Province, China
Heng Shi, Qin Peng, Department of Gastroenterology, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China
Si-Si Liu, Department of Pathology, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China
Author contributions: Shi H performed the conceptualization, software, data curation, software, writing; Zhao XH, Zhou XL, Sun CC, Cao QY, and Zhu SP contributed to the supervision and writing; Liu SS contributed to the pathology and analysis; Sun SY performed the review, editing, and supervision; all authors approved the final version of the article.
Supported by Guangdong Provincial Department of Science and Technology, Science and Technology Plan Project, Journal of Jinan University High-Level Science and Technology Journal Construction Project, No. 2021B121020012; and Guangdong Provincial Administration of Traditional Chinese Medicine, Traditional Chinese Medicine Research Project, No. 20213005.
Institutional review board statement: The study does not include Human subject research.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (licence No. IACUC-20210630-15; protocol no. 2021621-01, The Laboratory Animal Welfare and Ethic Commettee, Jinan University, Guangzhou, China).
Conflict-of-interest statement: The authors declare no competing financial interest.
Data sharing statement: The data that support the findings of this study are openly available in the NCBI GEO database at https://www.ncbi.nlm.nih.gov/geo/ with the accession number: GSE232128.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng-Yun Sun, MD, PhD, Chief Doctor, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 Huangpu Avenue West, Tianhe District, Guangzhou 522000, Guangdong Province, China. shengyunsun2020@163.com
Received: May 16, 2023
Peer-review started: May 16, 2023
First decision: July 10, 2023
Revised: July 19, 2023
Accepted: August 21, 2023
Article in press: August 21, 2023
Published online: September 14, 2023
Processing time: 115 Days and 2.1 Hours
Abstract
BACKGROUND

Di (2-ethylhexyl) phthalate (DEHP) is a common plasticizer known to cause liver injury. Green tea is reported to exert therapeutic effects on heavy metal exposure-induced organ damage. However, limited studies have examined the therapeutic effects of green tea polyphenols (GTPs) on DEHP-induced liver damage.

AIM

To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage.

METHODS

C57BL/6J mice were divided into the following five groups: Control, model [DEHP (1500 mg/kg bodyweight)], treatment [DEHP (1500 mg/kg bodyweight) + GTP (70 mg/kg bodyweight), oil, and GTP (70 mg/kg bodyweight)] groups. After 8 wk, the liver function, blood lipid profile, and liver histopathology were examined. Differentially expressed micro RNAs (miRNAs) and mRNAs in the liver tissues were examined using high-throughput sequencing. Additionally, functional enrichment analysis and immune infiltration prediction were performed. The miRNA-mRNA regulatory axis was elucidated using the starBase database. Protein expression was evaluated using immunohistochemistry.

RESULTS

GTPs alleviated DHEP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, liver fibrosis, and mitochondrial and endoplasmic reticulum lesions in mice. The infiltration of macrophages, mast cells, and natural killer cells varied between the model and treatment groups. mmu-miR-141-3p (a differentially expressed miRNA), Zcchc24 (a differentially expressed mRNA), and Zcchc24 (a differentially expressed protein) constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice.

CONCLUSION

This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, and partial liver fibrosis, and regulate immune cell infiltration. Additionally, an important miRNA-mRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.

Keywords: Green tea polyphenols; Di(2-ethylhexyl) phthalate; Liver fibrosis; Fatty liver disease; Mitochondria; Immune

Core Tip: Green tea polyphenols (GTPs) alleviated Di (2-ethylhexyl) phthalate (DEHP)-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, liver fibrosis, and mitochondrial and endoplasmic reticulum lesions in mice. The infiltration of macrophages, mast cell, and natural killer cells varied between the model and treatment groups. mmu-miR-141-3p (a differentially expressed miRNA), Zcchc24 (a differentially expressed mRNA), and Zcchc24 (a differentially expressed protein) constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice.