Yin DY, Liu XY, Li A, Ren ZG. From the brain to the liver: A pharmacokinetic dilemma and safety barriers in levodopa-based antifibrotic therapy. World J Gastroenterol 2026; 32(42): 117873 [DOI: 10.3748/wjg.117873]
Corresponding Author of This Article
Zhi-Gang Ren, MD, Doctor, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Jianshe East Road, Zhengzhou 450052, Henan Province, China. fccrenzg@zzu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
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review-article
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Yin DY, Liu XY, Li A, Ren ZG. From the brain to the liver: A pharmacokinetic dilemma and safety barriers in levodopa-based antifibrotic therapy. World J Gastroenterol 2026; 32(42): 117873 [DOI: 10.3748/wjg.117873]
World J Gastroenterol. Nov 14, 2026; 32(42): 117873 Published online Nov 14, 2026. doi: 10.3748/wjg.117873
From the brain to the liver: A pharmacokinetic dilemma and safety barriers in levodopa-based antifibrotic therapy
Dan-Yu Yin, Xiang-Yi Liu, Ang Li, Zhi-Gang Ren
Dan-Yu Yin, College of Medicine, Zhengzhou University, Zhengzhou 450052, Henan Province, China
Xiang-Yi Liu, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Ang Li, Zhi-Gang Ren, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Zhengzhou 450052, Henan Province, China
Author contributions: Yin DY contributed to visualization, prepared the figures, and wrote the manuscript; Liu XY contributed to formal analysis and revised the manuscript; Ren ZG and Li A contributed to conceptualization, supervision, and validation and critically revised the manuscript; and all authors reviewed and edited the draft, and have read and agreed to the published version of the manuscript.
AI contribution statement: We would like to clarify that the scientific content of the manuscript, including the study design, analysis, interpretation, and conclusions, was entirely developed and written by the authors. AI-based tools were used only to assist with language polishing and to improve the clarity and readability of the manuscript. These tools did not contribute to the generation of scientific ideas, data interpretation, or conclusions. When responding point by point to the reviewers' comments, AI tools were only used for translation, improving English expression, and language polishing. All revisions to the academic content were based on the authors' own understanding and completed independently by the authors.
Supported by the National Natural Science Foundation of China, No. 82470654; Natural Science Foundation Key Project of Henan Province, No. 232300421124; and Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation, No. ZYYC202301ZD.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Corresponding author: Zhi-Gang Ren, MD, Doctor, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Jianshe East Road, Zhengzhou 450052, Henan Province, China. fccrenzg@zzu.edu.cn
Received: December 18, 2025 Revised: January 30, 2026 Accepted: May 12, 2026 Published online: November 14, 2026 Processing time: 278 Days and 9.2 Hours
Core Tip
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 opinion review 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.
