Network pharmacology based investigation of the multi target mechanisms of Murraya koenigii (curry leaves) in non-alcoholic steatohepatitis (NASH).

Objectives: Non-alcoholic steatohepatitis (NASH) is a multifactorial chronic liver disease with limited treatment options. Murraya koenigii has reported hepato-protective effects against NASH in humans, but the bioactive compounds and mechanisms remain unknown. In this study, we explored the bioactive compounds of M. koenigii and their potential mechanisms for combating NASH using network pharmacology and molecular docking approach.

Methods: Using online platforms such as IMPPAT, GeneCards, KEGG, and DisGeNET, we identified the phytochemicals, target proteins, and genes associated with NASH. Through Venn diagram analysis, we determined 31 common targets between the bioactive compounds and NASH-related genes. Gene Ontology (GO) and KEGG pathway enrichment analyses further revealed the key targets and underlying mechanisms. Molecular docking validated the binding interactions between the identified phytochemicals and core target proteins.

Results: Nine key targets (NFKB, HSP90, TLR4, ESR1, STAT3, MTOR, HIF1A, PI3KA, and PKCD) were identified that interacts with 16 selected phytochemicals. Molecular docking studies indicated phytochemicals, Osthole and Spathulenol to be the promising binders to the core targets especially NF-kB and STAT3. The results represented the muti-target, multi-compound and multi-pathway mechanisms of M. koenigii against NASH.

Conclusions: This study provides the evidence for further research into the mechanisms of M. koenigii bioactive compounds as complementary therapies for NASH. Our study also identifies the novel drug candidates based on M. koenigii active compounds.