Wang SR, Lu XY, Jin GJ, Cao TL, Jiang HZ. Resetting the fibrotic liver clock: NR1D1 couples Hedyotis diffusa to the HIF-1/urea-cycle-ammonia axis and stellate cell activation. World J Gastroenterol 2026; 32(25): 118561 [DOI: 10.3748/wjg.118561]
Corresponding Author of This Article
Hui-Zhong Jiang, PhD, Professor, Researcher, Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 11 North Third Ring Road East, Beijing 100700, China. jianghz93@126.com
Research Domain of This Article
Medicine, Research & Experimental
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editorial
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Wang SR, Lu XY, Jin GJ, Cao TL, Jiang HZ. Resetting the fibrotic liver clock: NR1D1 couples Hedyotis diffusa to the HIF-1/urea-cycle-ammonia axis and stellate cell activation. World J Gastroenterol 2026; 32(25): 118561 [DOI: 10.3748/wjg.118561]
Si-Rui Wang, Xin-Yu Lu, Hui-Zhong Jiang, Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Guo-Ju Jin, Department of Pathology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100007, China
Ting-Lan Cao, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Co-first authors: Si-Rui Wang and Xin-Yu Lu.
Author contributions: Wang SR and Lu XY contribute equally to this study as co-first authors; Wang SR, Lu XY, and Jin GJ wrote the original draft; Cao TL and Jiang HZ contributed to conceptualization, writing, reviewing and editing; Wang SR, Jiang HZ, Lu XY, Jin GJ, and Cao TL participated in drafting the manuscript; Wang SR, Lu XY, and Jin GJ made equal contributions to this paper; all authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Hui-Zhong Jiang, PhD, Professor, Researcher, Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 11 North Third Ring Road East, Beijing 100700, China. jianghz93@126.com
Received: January 6, 2026 Revised: February 14, 2026 Accepted: February 28, 2026 Published online: July 7, 2026 Processing time: 176 Days and 9.4 Hours
Core Tip
Core Tip: Hepatic fibrosis is a pivotal and potentially reversible stage of chronic liver disease, yet approved antifibrotic therapies remain scarce. Xia et al propose that Hedyotis diffusa injection mitigates fibrogenesis by engaging the core clock gene NR1D1, with two downstream branches—suppression of HIF-1 signaling and restoration of urea-cycle/ammonia homeostasis—converging on reduced hepatic stellate cell activation and collagen deposition. This work connects circadian regulation with hypoxia responses and nitrogen metabolism, addressing a key mechanistic gap in liver scarring. By highlighting a druggable clock node and clinically accessible metabolic readouts, it may inform clock-guided antifibrotic development and biomarker-based staging and response monitoring.
