Publication Name	World Journal of Gastroenterology
Manuscript ID	117873
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Opinion Review
Article Title	From the brain to the liver: Pharmacokinetic dilemmas and safety barriers in levodopa-based antifibrotic therapy
Manuscript Source	Unsolicited Manuscript
All Author List	Dan-Yu Yin, Xiang-Yi Liu, Ang Li and Zhi-Gang Ren
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China No. 82470654 Natural Science Foundation Key Project of Henan Province No. 232300421124 Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation No. ZYYC202301ZD
Corresponding Author	Zhi-Gang Ren, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Jianshe East Road, Zhengzhou 450052, Henan Province, China. fccrenzg@zzu.edu.cn
Key Words	Levodopa; Liver fibrosis; Dopamine receptor D1; Drug repurposing; Pharmacokinetic mismatch
Core Tip	There is a lack of approved direct antifibrotic therapies for liver fibrosis. Levodopa has been reported to exert antifibrotic effects by activating hepatic dopamine receptor D1 (DRD1) and suppressing yes-associated protein signaling in hepatic stellate cells. However, its standard Parkinson’s disease regimen includes peripheral aromatic L-amino acid decarboxylase inhibitors, which limit the generation of the hepatic dopamine required for this mechanism. This letter highlights this pharmacokinetic contradiction and additional translational barriers, including receptor nonselectivity, regeneration-related safety concerns, and portal hypertension risk, and proposes liver-targeted or DRD1-selective strategies as more rational alternatives.
Citation	Yin DY, Liu XY, Li A, Ren ZG. From the brain to the liver: Pharmacokinetic dilemmas and safety barriers in levodopa-based antifibrotic therapy. World J Gastroenterol 2026; In press

Received	2025-12-18 02:12
Peer-Review Started	2025-12-18 02:12
First Decision by Editorial Office Director	2026-01-21 09:22
Return for Revision	2026-01-21 09:22
Revised	2026-01-30 16:44
Publication Fee Transferred
Second Decision by Editor	2026-05-12 02:41
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-05-12 10:56
Articles in Press	2026-05-12 10:56
Edit the Manuscript by Language Editor	2026-05-13 03:02
Typeset the Manuscript

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