Molecular Docking Study of Phytosterols in Lygodium microphyllum Towards SIRT1 and AMPK, the in vitro Brine Shrimp Toxicity Test, and the Phenols and Sterols Levels in the Extract.

BACKGROUND: Lygodium microphyllum is a fern plant with various pharmacological activities, and phytosterols were reported contained in the n-hexane and ethyl acetate extract of this plant. Phytosterols are known to inhibit steatosis, oxidative stress, and inflammation. Sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) are the key proteins that control lipogenesis. However, information about L. microphyllum on SIRT1 and AMPK is still lacking.

PURPOSE: This study aims to investigate the binding mode of phytosterols in L. microphyllum extract towards AMPK and SIRT1, and the toxicity of the extract against brine shrimp ( Artemia salina ) larvae, and to determine the phenols and sterols levels in the extract.

METHODS: The molecular docking was performed towards SIRT1 and AMPK using AutoDock v4.2.6, the toxicity of the extract was assayed against brine shrimp ( Artemia salina ) larvae, and the phytosterols were analyzed by employing a thin layer chromatography densitometry, and the total phenols were by spectrophotometry.

RESULTS: The molecular docking study revealed that β-sitosterol and stigmasterol could occupy the active allosteric-binding site of SIRT1 and AMPK by binding to important residues similar to the protein's activators. The cold extraction of the plant yields 15.86% w/w. Phytochemical screening revealed the presence of phenols, steroids, flavonoids, alkaloids, and saponins. The total phenols are equivalent to 126 mg gallic acid (GAE)/g dry extract, the total sterols are 954.04 µg/g, and the β-sitosterol level is 283.55 µg/g. The LC50 value of the extract towards A. salina larvae is 203.704 ppm.

CONCLUSION: Lygodium microphyllum extract may have the potential to be further explored for its pharmacology activities, particularly in the discovery of plant-based anti-dyslipidemic drug candidates. However, further studies are needed to confirm their roles in alleviating lipid disorders.