Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2023; 29(1): 171-189
Published online Jan 7, 2023. doi: 10.3748/wjg.v29.i1.171
In vivo recognition of bioactive substances of Polygonum multiflorum for protecting mitochondria against metabolic dysfunction-associated fatty liver disease
Li-Ping Yu, Yan-Juan Li, Tao Wang, Yu-Xuan Tao, Mei Zhang, Wen Gu, Jie Yu, Xing-Xin Yang
Li-Ping Yu, Yan-Juan Li, Tao Wang, Yu-Xuan Tao, Mei Zhang, Wen Gu, Jie Yu, Xing-Xin Yang, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
Li-Ping Yu, Yan-Juan Li, Tao Wang, Yu-Xuan Tao, Mei Zhang, Wen Gu, Jie Yu, Xing-Xin Yang, College of Pharmaceutical Science, Yunnan Key Laboratory of Southern Medicine Utilization, Kunming 650500, Yunnan Province, China
Author contributions: Yu LP, Li YJ, and Wang T contributed equally to this work; Li YJ wrote the manuscript; Li YJ, Yu LP, and Wang T performed the experiments; Tao YX and Zhang M provided technical support and suggestions; Yang XX, Yu LP, Zhang M, and Gu W participated in writing and modifying the manuscript; Yang XX and Yu J designed the study; and all authors approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82060707 and 82104381; the Application and Basis Research Project of Yunnan China, No. 202201AW070016, 202001AZ070001-006, and 2019IB009; and the Young and Middle-aged Academic and Technological Leader of Yunnan, No. 202005AC160059.
Institutional animal care and use committee statement: Approval was obtained from the Ethical Committee on Animal Care and Experimentation of the Yunnan University of Chinese Medicine (R-06201965).
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: All data used to support the findings of this study are available from the corresponding author upon reasonable request.
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: Xing-Xin Yang, PharmD, Professor, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, No. 1076 Yuhua Road, Kunming 650500, Yunnan Province, China. yxx78945@163.com
Received: September 7, 2022
Peer-review started: September 7, 2022
First decision: October 19, 2022
Revised: November 1, 2022
Accepted: December 5, 2022
Article in press: December 5, 2022
Published online: January 7, 2023
ARTICLE HIGHLIGHTS
Research background

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a serious threat to human health. Mitochondrial dysfunction is a mechanism involved in MAFLD. Modulation of mitochondrial function may become a novel strategy for the treatment of MAFLD. For centuries, Polygonum multiflorum (PM) has been used as a common traditional Chinese medicine and nutritional ingredient in China and has been proven to remedy mitochondria and further relieve MAFLD.

Research motivation

To date, the main pharmacodynamic ingredients of PM for regulating mitochondria against MAFLD remain unclear.

Research objectives

To investigate the pharmacodynamic ingredients for the mitochondrial remedy action of PM against high-fat diet (HFD)-induced MAFLD in rats.

Research methods

Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to evaluate the anti-MAFLD ability of PM and the mechanism of action involved. The adipocyte model was also used to determine the activities of PM-derived constituents in liver mitochondria from HFD-fed rats (mitochondrial pharmacology). PM-derived constituents in liver mitochondria were recognized by ultra-high performance liquid chromatography/mass spectrometry (mitochondrial pharmacochemistry). The abilities of the PM-derived monomer and the monomer group were evaluated by adipocyte model and MAFLD mouse model, respectively.

Research results

PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD. PM-derived constituents that entered the mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis. Eight chemicals were found in the mitochondria of PM-administrated rats. The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated.

Research conclusions

PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production. The identified eight chemicals may be the main bioactive ingredients in PM that adjust mitochondria to prevent MAFLD.

Research perspectives

PM treatment provided a new approach to prevent MAFLD-related mitochondrial dysfunction from alleviating MAFLD. Mitochondrial pharmacology and pharmacochemistry are efficient strategies for identifying the bioactive ingredients of traditional Chinese medicines regulating mitochondria to prevent disease.