In silico Assessment of Bioactive Compounds from Thaalisaathi Chooranam Targeting Alcohol Dehydrogenase in Alcoholic Liver Disease

Background

Alcoholic Liver Disease (ALD) is a major cause of cirrhosis-related morbidity and mortality, with limited therapies. Alcohol Dehydrogenase (ADH) plays a key role in ethanol metabolism and contributes to hepatic injury. Siddha formulations are rich in bioactive phytoconstituents with potential hepatoprotective effects.

Objectives

To evaluate the drug-likeness and inhibitory potential of bioactive phytoconstituents from Thaalisaathi Chooranam against Human Alcohol Dehydrogenase using in silico ADME analysis and molecular docking studies.

Materials and Methods

A total of 43 bioactive compounds were identified from previously published data of Thaalisaathi Chooranam. After excluding certain fatty acids, five small molecules were selected based on peak area percentage. Drug-likeness and lead-likeness were assessed using the Swiss-ADME web tool following Lipinski’s Rule of Five. Three compounds that met ADME criteria were docked against human alpha-type alcohol dehydrogenase (PDB ID: 1HSO) using iGEMDOCK v2.0. Binding energies and protein-ligand interactions were analyzed.

Results

Swiss-ADME analysis confirmed that the three selected compounds had favourable physicochemical and pharmacokinetic properties. Molecular docking demonstrated their activity against Alcohol Dehydrogenase, with Dihydroqinghaosu showing the strongest binding, stabilised by hydrogen bonds with active site residues, complemented by van der Waals interactions. The other two compounds, 4-Cyano-4-(3,4-methylenedioxyphenyl) cyclohexanone and Apiole, also exhibited strong binding, indicating potential inhibitory activity.

Conclusion

This study showed that bioactive compounds from Thaalisaathi Chooranam, particularly Dihydroqinghaosu, demonstrated strong inhibitory potential against human alcohol dehydrogenase and favourable ADME properties, endorsing their promise as therapeutic leads for ALD and supporting further in vivo and experimental validation.