Publication Name	World Journal of Gastroenterology
Manuscript ID	115334
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Integrative study reveals NR1D1 mediates Hedyotis diffusa’s antifibrosis via hypoxia inducible factor-1/ammonia axis
Manuscript Source	Unsolicited Manuscript
All Author List	Si-Wei Xia, Huan Liu, Kai-Yao Yang, Yi-Jie Gao, Meng-Ru Zhang, Jing-Wen Zhou, De-Song Kong, Hong-Yan Wu, Feng Zhang and Li Chen
Funding Agency and Grant Number	Funding Agency Grant Number Jiangsu Province Traditional Chinese Medicine Science and Technology Development Plan Project No. QN202304 Jiangsu Province Traditional Chinese Medicine Science and Technology Development Plan Project No. ZD202402 Jiangsu Province Traditional Chinese Medicine Science and Technology Development Plan Project No. QN202112 National Natural Science Foundation of China No. 82173874 National Natural Science Foundation of China No. 82274339 Noncommunicable Chronic Diseases-National Science and Technology Major Project No. 2024ZD0530800 Jiangsu Higher Education Institution Innovative Research Team for Science and Technology (2023) No. 56 Jiangsu Province Engineering Research Center for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control (2022) No. 85 Postgraduate Research and Practice Innovation Program of Jiangsu Province No. KYCX242311 Natural Science Foundation for Colleges and Universities in Jiangsu Province No. 23KJB360005
Corresponding Author	Li Chen, Lecturer, PhD, Jiangsu Key Laboratory for Pharmacology and Safety Research of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing 210023, Jiangsu Province, China. 300643@njucm.edu.cn
Key Words	Hedyotis diffusa; Hepatic fibrosis; NR1D1; Hypoxia inducible factor-1; Urea cycle; Ammonia metabolism
Core Tip	This study reveals a novel antifibrotic mechanism of Hedyotis diffusa, demonstrating that its bioactive components alleviate hepatic fibrosis by restoring expression of the circadian rhythm gene NR1D1 expression. NR1D1 acts as an upstream regulator, inhibiting hypoxia inducible factor-1 signaling and restoring urea cycle function, thereby reducing hepatic ammonia accumulation and interrupting the vicious cycle of ammonia-induced hepatic stellate cell activation. These findings position circadian rhythm-metabolism interplay as a promising therapeutic axis for liver fibrosis treatment.
Citation	Xia SW, Liu H, Yang KY, Gao YJ, Zhang MR, Zhou JW, Kong DS, Wu HY, Zhang F, Chen L. Integrative study reveals NR1D1 mediates Hedyotis diffusa’s antifibrosis via hypoxia inducible factor-1/ammonia axis. World J Gastroenterol 2025; In press

Received	2025-10-17 05:19
Peer-Review Started	2025-10-17 05:19
First Decision by Editorial Office Director	2025-10-28 10:30
Return for Revision	2025-10-28 10:30
Revised	2025-11-10 01:02
Publication Fee Transferred	2025-11-11 03:11
Second Decision by Editor	2025-12-16 02:39
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2025-12-16 07:47
Articles in Press	2025-12-16 07:47
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
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