In silico analysis of ferulic acid against therapeutic target proteins PPAR-?, SIRT1, FOXO1 and LXR-? for the treatment of hyperlipidemia
Keywords:Ferulic acid, SIRT1, FOXO1, PPAR-gamma, LXR-alpha
Introduction and Aim: Hyperlipidemia is a worth-mentioning risk factor for a variety of rapidly spreading diseases such as cardio-vascular diseases, myocardial infarction, impaired glucose tolerance and metabolic syndrome. Peroxisome proliferator-activated receptor - gamma (PPAR-?), sirtuin 1 (SIRT1), forkhead box factor 1(FOXO1), and liver X receptor-alpha (LXR-?) are the important determinants of hyperlipidemia by regulating a plethora of transcriptional factors in metabolically active tissues such as adipose tissue, liver, and skeletal muscle. The present study aimed to evaluate the binding affinity of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) with therapeutic target proteins of hyperlipidemia using an in silico approach.
Materials and Methods: The in silico docking studies were performed between ferulic acid (PubChem CID: 445858) and PPAR-?, SIRT1, FOXO1, LXR-? with PDB ID of 3ADX – A chain, 4ZZI- A chain, 4LG0– A chain, and 3IPQ-A chain respectively by using Autodock 4.2 docking tool.
Results: The results revealed that ferulic acid exhibited maximum binding affinities with FOXO1 (-8.63) followed by SIRT1(-6.18), PPAR-? (-5.79), and LXR-? (-5.79) kcal/mol respectively. Ferulic acid interacted with FOXO1 with amino acids ASN 204, TYR 165 with a distance of 2.01 Å and 1.86 Å. Furthermore, the molecular interaction of ferulic acid with SIRT1 was at residues SER 441(2.20 Å), GLN 345(2.79 Å), and LXR-? was at amino acids ASP 444 (1.85 Å) and SER 418 (1.98 Å). Also, to activate the action of PPAR-? ferulic acid interacts with it at residues VAL 450(2.04) and GLN 454 (2.80).
Conclusion: These in vitro findings suggest that ferulic acid could be used as a lead structure for designing and developing more powerful hypolipidemic medicines.
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