Comprehensive Bioactive Compound Profiling of Artocarpus heterophyllus Leaves: LC-MS/MS Analysis, Antioxidant Potential, and Molecular Insights.

PURPOSE: Artocarpus heterophyllus leaves, rich in phytochemicals, present a promising source of natural bioactive compounds for therapeutic and cosmetic applications. This study evaluated the phytochemical composition, antioxidant potential, and tyrosinase inhibition activities of leaf extracts while assessing the enzyme inhibition properties of key compounds through molecular docking and dynamics simulations. PATIENTS AND METHODS: Ethanol and ethyl acetate extracts were analyzed using Thin Layer Chromatography (TLC) and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS). Antioxidant activity was determined via DPPH radical scavenging and tyrosinase inhibition was compared against kojic acid. Molecular docking and molecular dynamics simulations explored binding interactions of Artocarpin and Sitosterol with matrix metalloproteinases (MMPs) and tyrosinase. RESULTS: Artocarpin and Sitosterol were identified as primary bioactive compounds. Ethanol extracts exhibited stronger tyrosinase inhibition (IC(50): 177.24 ppm), while ethyl acetate extracts showed superior antioxidant activity (IC(50): 117.64 ppm). Molecular docking highlighted high binding affinities of Artocarpin and Sitosterol with MMP-13 and tyrosinase. MD simulations confirmed stable interactions, particularly between Artocarpin and MMP-13, supporting its potential as a therapeutic agent. CONCLUSION: Artocarpin and Sitosterol from Artocarpus heterophyllus leaf extracts demonstrate potent antioxidant, enzyme inhibitory, and tyrosinase inhibition activities. These findings underscore their potential for managing oxidative stress, inflammation, and pigmentation disorders, warranting further investigation into their bioavailability and formulation for therapeutic and cosmetic uses.