Potential Interaction of Costunolide and Dehydrocostuslactone Compounds on Proteins Associated With Non-Alcoholic Fatty Liver Disease in An In-Silico Study

Abstract

Background: Non-alcoholic Fatty Liver Disease (NAFLD) is a growing health problem but there is no standard drug for its treatment. Costunolide and dehydrocostuslactone is the compound of Saussurea costus, and an antioxidant that has activities as anti-hepatotoxic, anti-inflammatory, and immunostimulants, which have been proven in-vivo and in-vitro.

Purpose: This study aims to identify the bioactive ingredients of S. costus that affect NAFLD and explore its therapeutic targets through pharmacological networking.

Methods: Various tissue databases were identified to get the bioactive material S. costus and identify NAFLD therapeutic targets. Gene ontology enrichment (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to enrich the functions and molecular pathways of common targets. The analysis was carried out through the Structure-Activity-Relationship (SAR) search, with the determination of a range score of 0-1, where the closer to 1 the better the value.

Results: The results of the Structure-Activity-Relationship (SAR) analysis were that the costunolide and dehydrocostuslactone compounds had scored <0.5 as a hepatoprotector and as a regulator of fat metabolism. The potential of these two compounds as TNF-alpha inhibitors and Interleukin-6 antagonists also shows a score <0.5. Costunolide and Dehydrocostuslactone showed a score >0.5 for their activity as anti-inflammatory and NF-ĸB transcription inhibitors, indicating the existence of anti-inflammatory potential, and the potential as a candidate for NAFLD therapy indicated by the NF-ĸB transcription inhibitory pathway.

Conclusion: Costunolide, and Dehydrocostuslactone showed anti-inflammatory potential, and the presumed potential as a candidate for NAFLD therapy was shown to inhibit the transcription pathway of NF-ĸB