Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2019; 25(43): 6404-6415
Published online Nov 21, 2019. doi: 10.3748/wjg.v25.i43.6404
Mitochondrial metabolomic profiling for elucidating the alleviating potential of Polygonatum kingianum against high-fat diet-induced nonalcoholic fatty liver disease
Xing-Xin Yang, Jia-Di Wei, Jian-Kang Mu, Xin Liu, Feng-Jiao Li, Yan-Qin Li, Wen Gu, Jing-Ping Li, Jie Yu
Xing-Xin Yang, Jia-Di Wei, Jian-Kang Mu, Feng-Jiao Li, Yan-Qin Li, Wen Gu, Jing-Ping Li, Jie Yu, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
Xin Liu, Beijing Entry-Exit Inspection and Quarantine Bureau, Beijing 100026, China
Author contributions: Yang XX and Mu JK wrote the manuscript; Wei JD, Yang XX, and Li FJ performed the experiments; Liu X provided technical support and suggestions; Mu JK, Li YQ, Gu W, and Li JP participated in writing and modifying the manuscript; Yang XX and Yu J designed the study; The final manuscript has been approved by all the co-authors; Yang XX, Wei JD and Mu JK contributed equally to this work.
Supported by the National Natural Science Foundation of China, No. 81660596; the National Natural Science Foundation of China, No. 81760733; the Application and Basis Research Project of Yunnan, China, No. 2017FF117-013; the Application and Basis Research Project of Yunnan, China, No. 201801CH00227; and the Application and Basis Research Project of Yunnan, China, No. 2016FD050.
Institutional review board statement: This study was reviewed and approved by the Institutional Ethical Committee on Animal Care and Experimentations of Yunnan University of Chinese Medicine.
Institutional animal care and use committee statement: Approval from the Institutional Ethical Committee on Animal Care and Experimentations of Yunnan University of Chinese Medicine was obtained for this study.
Conflict-of-interest statement: The authors declare no conflict of interest associated with this manuscript.
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 which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Jie Yu, PhD, Professor, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, Yunnan Province, China. cz.yujie@gmail.com
Telephone: +86-871-65933303 Fax: +86-871-65933303
Received: September 2, 2019
Peer-review started: September 2, 2019
First decision: September 19, 2019
Revised: October 15, 2019
Accepted: October 30, 2019
Article in press: October 30, 2019
Published online: November 21, 2019
Abstract
BACKGROUND

Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for therapy of non-alcoholic fatty liver disease (NAFLD). Polygonatum kingianum (PK) has been traditionally used in China as a medicinal and nutritional ingredient for centuries and can alleviate high-fat diet (HFD)-induced NAFLD by promoting mitochondrial functions. To date, the underlying molecular mechanism of PK for treating mitochondrial dysfunctions and thus alleviating NAFLD remains unclear.

AIM

To identify the molecular mechanism behind the mitochondrial regulatory action of PK against HFD-induced NAFLD in rats.

METHODS

NAFLD model was induced in rats with HFD. The rats were intragastrically administered PK (4 g/kg per day) for 14 wk. Metabolites in hepatic mitochondrial samples were profiled through ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to find the potential biomarkers and metabolic pathways.

RESULTS

PK significantly restored the metabolites’ levels in the mitochondrial samples. Ten potential biomarkers were identified in the analyzed samples. These biomarkers are involved in riboflavin metabolism.

CONCLUSION

PK can alleviate HFD-induced NAFLD by regulating the riboflavin metabolism and further improving the mitochondrial functions. Thus, PK is a promising mitochondrial regulator/nutrient for alleviating NAFLD-associated diseases.

Keywords: Metabolomics, Mitochondria, Multivariate statistical analysis, Non-alcoholic fatty liver, Polygonatum kingianum, Ultra-high performance liquid chromatography/mass spectrometry

Core tip: We identified the molecular mechanism behind the mitochondrial regulatory action of Polygonatum kingianum against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats using an integrated mitochondrial metabolomic method. The results indicated that Polygonatum kingianum can alleviate HFD-induced NAFLD by regulating riboflavin metabolism, increasing flavin mononucleotide content and further improving mitochondrial functions. Polygonatum kingianum as a promising mitochondrial regulator/nutrient can alleviate NAFLD-associated diseases.