Predicting activities of Clinacanthus nutans (Burm.f.) Lindau metabolites against molecular targets in metabolic dysfunction-associated steatotic liver disease

Abstract

Context: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder worldwide, yet pharmacological treatment options remain limited. Therapeutic agents that modulate both metabolic and hepatic pathological pathways are urgently needed. Aims: To identify chemical constituents from the ethanolic extract of Clinacanthus nutans and predict their interactions with validated molecular targets implicated in MASLD using in silico methodologies. Methods: Metabolite profiling was conducted using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC–MS). Identified compounds were evaluated for drug-likeness based on Lipinski, Ghose, and Veber criteria. Compounds meeting these criteria were subjected to ADMET profiling and molecular docking against 20 MASLD-associated targets using validated docking protocols. The potential compound underwent molecular dynamics analysis. Results: Seventeen compounds were identified from the C. nutans extract. Six metabolites, along with stearidonic acid, demonstrated favorable pharmacokinetic properties. Among these, a thiophene-based benzoic acid derivative and tagalsin Q exhibited strong binding affinities toward CCR2, ChREBP, and SGLT2, with interaction profiles comparable to native ligands. Conclusions: Metabolites of C. nutans possess predicted bioactivity against CCR2, ChREBP, and SGLT2, supporting their potential utility as multi-target phytotherapeutic agents for MASLD.