This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.
Devipriya K.P,
Abstract
Primary Sclerosing Cholangitis (PSC) is a long-term liver disease where the bile ducts become inflamed and scarred over time. This scarring can block the flow of bile, leading to liver damage and, eventually, liver failure. The etiology of PSC remains largely unknown, and current treatment options are limited, highlighting the need for novel therapeutic strategies. This study aims to repurpose Liv-52, a traditional herbal formulation known for its hepatoprotective properties, to evaluate its potential in regulating bile flow and mitigating fibrosis in PSC through computational docking and pharmacokinetic studies. The project focuses on two critical proteins: Farnesoid X Receptor (FXR), which plays a pivotal role in bile acid homeostasis, and Transforming Growth Factor Beta-1 (TGF-β1), a key mediat or of fibrosis. Ligands from Liv-52’s active compounds were retrieved and analysed for their binding affinity to these proteins. The results indicated that several components of Liv-52 exhibit favorable docking profiles with FXR and TGF-β1, suggesting potential therapeutic mechanisms for enhancing bile flow and reducing fibrosis. Notably, compounds such as episesamin (-10.1 kcal/mol), (-)-acorenone (-9.2 kcal/mol), and apigenin (-8.5 kcal/mol) showed strong binding affinities to FXR and TGF-β1, further supporting their role in regulating bile flow and fibrosis. Pharmacokinetic analysis demonstrated adequate absorption and a favorable safety profile for Liv-52, supporting its viability as a therapeutic agent for PSC. However, the findings necessitate further validation through in vivo and clinical studies to confirm the therapeutic effects of Liv-52 in PSC patients. This research not only provides insights into the potential of Liv-52 as a treatment for PSC but also bridges the gap between traditional herbal medicine and modern pharmacology, paving the way for future studies on its broader applications in liver diseases.
Keywords: Primary Sclerosing Cholangitis (PSC), Liv-52, Hepatoprotective properties, Bile flow regulation Computational docking, Pharmacokinetic study, Farnesoid X Receptor (FXR), Transforming Growth Factor Beta-1 (TGF-β1)
[This article belongs to Research and Reviews : Journal of Computational Biology ]
Devipriya K.P. Repurposing Liv-52 For Primary Sclerosing Cholangitis: A Computational Docking And Pharmacokinetic Study To Evaluate Its Bile Flow-Regulating Potential. Research and Reviews : Journal of Computational Biology. 2025; 14(02):-.
Devipriya K.P. Repurposing Liv-52 For Primary Sclerosing Cholangitis: A Computational Docking And Pharmacokinetic Study To Evaluate Its Bile Flow-Regulating Potential. Research and Reviews : Journal of Computational Biology. 2025; 14(02):-. Available from: https://journals.stmjournals.com/rrjocb/article=2025/view=213117
References
1. van der Pol, K. H. et al. Drug Repurposing of Generic Drugs: Challenges and the Potential Role for Government. 2023; 21(6):831–840.
2. Shahini, E. et al. Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis. 2022; 10. CC BY 4.0.
3. Fu, K. et al. Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking. 2023; 25 April.
4. Tully, D. C. et al. Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Non-alcoholic Steatohepatitis (NASH). 2017; November 16.
5. Ashburn, T. T. et al. Drug repositioning: identifying and developing new uses for existing drugs. Nature Reviews Drug Discovery. 2004; 1 August.
6. Krishnamurthy, N. et al. Drug repurposing: a systematic review on root causes, barriers and facilitators. BMC Health Services Research. 2022; 29 July.
7. Asrani, S. K. et al. Burden of liver diseases in the world. 2019; 70(1):151-171.
8. Luo, H. et al. Biomedical data and computational models for drug repositioning: a comprehensive review. 2020; 10 February.
9. Johnson, T. O. et al. Modern drug discovery for inflammatory bowel disease: The role of computational methods. 2023; January 14. PMID:36687123.
10. Kainuma, M. et al. Farnesoid X Receptor Activation Enhances Transforming Growth Factor β-Induced Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells. 2018; June 28. PMID: 29958417.
11. Xu, J.-Y. et al. Recent insights into farnesoid X receptor in non-alcoholic fatty liver disease. 2014; October 7. PMID: 25309079.
12. Fiorucci, S. et al. The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis. 2004; 127(5):1497-1512.
13. Miraz, M. M. H. et al. Nigelladine A among Selected Compounds from Nigella sativa Exhibits Propitious Interaction with Omicron Variant of SARS-CoV-2: An In Silico Study. 2023; February 20. PMID:36861057.
14. Li, L. et al. Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Analysis Reveal Insights into the Molecular Mechanism of Cordia myxa in the Treatment of Liver Cancer. 2024; May 1. PMID:38785796.
15. Krishna Moorthy, C. et al. Phytocompounds of Salvia plebeia against SIRT1 targets in lung cancer. 2022; November. CC BY 4.0.
16. Ali, F. E. et al. Exploring the potential of drug repurposing for liver diseases: A comprehensive study. Life Sciences. 2024; 122642.
17. Ramírez-Marroquín, O. A. et al. Hepato-Protective Effect from Natural Compounds, Biological Products and Medicinal Plant Extracts on Antitubercular Drug-Induced Liver Injuries, A Systematic Review. Med Aromat Plants (Los Angeles). 2019; 8(339):2167-0412.
18. Shivnitwar, S. K. et al. Safety and Effectiveness of Liv. 52 DS in Patients With Varied Hepatic Disorders: An Open-Label, Multi-centre, Phase IV Study. Cureus. 2024; 16(5).
19. Hirschfield, G. M. et al. Primary sclerosing cholangitis. The Lancet. 2013; 382(9904):1587-1599.
20. Lazaridis, K. N. et al. Primary sclerosing cholangitis. New England Journal of Medicine. 2016; 375(12):1161-1170.
Research and Reviews : Journal of Computational Biology
| Volume | 14 |
| Issue | 02 |
| Received | 27/02/2025 |
| Accepted | 25/03/2025 |
| Published | 12/06/2025 |
| Publication Time | 105 Days |
Login
PlumX Metrics