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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway
Bao-Fei Yan, Lan-Fen Pan, Yi-Fang Quan, Qian Sha, Jing-Zheng Zhang, Yi-Feng Zhang, Li-Bing Zhou, Xi-Long Qian, Xiao-Mei Gu, Feng-Tao Li, Ting Wang, Jia Liu, Xian Zheng
Bao-Fei Yan, Jing-Zheng Zhang, Feng-Tao Li, Jia Liu, College of Pharmacy, Jiangsu Health Vocational College, Nanjing 211800, Jiangsu Province, China
Lan-Fen Pan, Department of Pathology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu Province, China
Yi-Fang Quan, Department of Education and Science, The First People's Hospital of Taicang, Kunshan 215400, Jiangsu Province, China
Qian Sha, Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, Jiangsu Province, China
Yi-Feng Zhang, School of Pharmacy, Nantong University, Nantong 226019, Jiangsu Province, China
Li-Bing Zhou, Xiao-Mei Gu, Ting Wang, Xian Zheng, Department of Pharmacy, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu Province, China
Xi-Long Qian, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Author contributions: Yan BF, Pan LF, and Quan YF contributed equally to this work and performed the research; Liu J and Zheng X designed the research and proofread the manuscript; Sha Q, Zhang JZ, and Zhou LB analyzed the data; Zhang YF carefully revised the manuscript; Qian XL, Gu XM, Li FT, and Wang T interpreted the data; All authors approved the final version of the article.
Supported by the Scientific Research Project of Jiangsu Health Commission, No. Z2022078; the Natural Science Foundation of Jiangsu Province, No. BK20220299.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Jiangsu Health Vocational College.
Institutional animal care and use committee statement: The experimental protocols strictly complied with the European Community criteria and were authorized by the Animal Ethics Committee of Jiangsu Health Vocational College (Permission No. JHVC-IACUC-2022-B007).
Conflict-of-interest statement: The authors declare that they have no competing interests.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Xian Zheng, PhD, Pharmacist, Postdoc, Department of Pharmacy, Affiliated Kunshan Hospital of Jiangsu University, No. 566 Qianjin East Road, Development Zone, Kunshan 215300, Jiangsu Province, China. zhengxiannew@163.com
Received: April 27, 2023
Peer-review started: April 27, 2023
First decision: July 9, 2023
Revised: July 23, 2023
Accepted: July 31, 2023
Article in press: July 31, 2023
Published online: August 21, 2023
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity characterized by intrahepatic ectopic steatosis. As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle, the incidence of NAFLD has surpassed that of viral hepatitis, making it the most common cause of chronic liver disease globally. Huangqin decoction (HQD), a Chinese medicinal formulation that has been used clinically for thousands of years, has beneficial outcomes in patients with liver diseases, including NAFLD. However, the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.
AIM
To evaluate the ameliorative effects of HQD in NAFLD, with a focus on lipid metabolism and insulin resistance, and to elucidate the underlying mechanism of action.
METHODS
High-fat diet-induced NAFLD rats and palmitic acid (PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action. Phytochemicals in HQD were analyzed by high-performance liquid chromatography (HPLC) to identify the key components.
RESULTS
Ten primary chemical components of HQD were identified by HPLC analysis. In vivo, HQD effectively prevented rats from gaining body and liver weight, improved the liver index, ameliorated hepatic histological aberrations, decreased transaminase and lipid profile disorders, and reduced the levels of pro-inflammatory factors and insulin resistance. In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation, inflammation, and insulin resistance in HepG2 cells. In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathway-modulated lipogenesis and inflammation, contributing to its beneficial actions, which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.
CONCLUSION
In summary, our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
Core Tip: Huangqin decoction (HQD) has substantial therapeutic effects in liver diseases. We previously showed that HQD mitigates hepatic inflammation in a rat model of High-fat diet (HFD)-induced Nonalcoholic fatty liver disease (NAFLD) by inhibiting the TLR4/NF-κB/NLRP3 pathway. Here, we investigated the effects of HQD on lipid metabolism disorders and insulin resistance in NAFLD. Our results demonstrated that HQD effectively antagonizes hepatocyte steatosis and insulin resistance in HFD-fed rats and palmitic acid-challenged HepG2 cells by triggering Sirt1/NF-κB pathway-modulated lipogenesis and inflammation. These data will significantly promote the clinical application of HQD in the treatment of NAFLD.
