In silico analysis of ferulic acid against therapeutic target proteins PPAR-?, SIRT1, FOXO1 and LXR-? for the treatment of hyperlipidemia

Authors

  • V. Ramamurthy
  • Mumtaz Begum T.A.K

DOI:

https://doi.org/10.51248/.v42i2.1124

Keywords:

Ferulic acid, SIRT1, FOXO1, PPAR-gamma, LXR-alpha

Abstract

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.

Author Biographies

V. Ramamurthy

Department of Biochemistry, Marudupandiyar College, Thanjavur, Tamil Nadu, India (Affiliated to Bharathidasan University)

Mumtaz Begum T.A.K

Department of Biochemistry, Marudupandiyar College, Thanjavur, Tamil Nadu, India (Affiliated to Bharathidasan University)

References

Monika, P., Geetha, A. The modulating effect of Perseaamericana fruit extract on the level of expression of fatty acid synthase complex, lipoprotein lipase, fibroblast growth factor-21 and leptin--A biochemical study in rats subjected to experimental hyperlipidemia and obesity. Phytomedicine. 2015; 22(10): 939-945.

Khan, S.,&Ahemad, N.,&Chuah, L.,& Naidu, Rakesh&Hta,, T. Illustrated step by step protocol to perform molecular docking: Human estrogen receptor complex with 4-hydroxytamoxifen as a case study. Prog. Drug. Discov. Biomed. Sci. 2020; 3(1): a0000054.

Idehen, E., Tang, Y., Sang, S. Bioactive phytochemicals in barley. J. Food. Drug. Anal. 2017; 25(1):148-161.

Mancuso, C., Santangelo, R. Ferulic acid: pharmacological and toxicological aspects. Food. Chem. Toxicol. 2014; 65:185-195.

Salazar-López, N., Astiazarán-García, H., González-Aguilar, G.A., Loarca-Piña, G., Ezquerra-Braue, J.M., Domínguez Avila, J.A., Robles-Sánchez, M. Ferulic Acid on Glucose Dysregulation, Dyslipidemia, and Inflammation in Diet-Induced Obese Rats: An Integrated Study. Nutrients. 2017; 9:675.

Schug, T.T., Li, X. Sirtuin 1 in lipid metabolism and obesity. Ann. Med. 2011; 43(3):198-211.

Tontonoz, P., Spiegelman, B.M. Fat and beyond: the diverse biology of PPAR gamma. Annu. Rev. Biochem. 2008; 77:289-312.

Dowell, P., Otto, T.C., Adi, S., Lane, M.D. Convergence of peroxisome proliferator-activated receptor gamma and FOXO 1 signalling pathways. J. Biol. Chem. 2003; 278: 45485-45491.

Laurencikiene, J., Rydén, M. Liver X receptors and fat cell metabolism. Int. J.Obes. 2012; 36: 1494-1502.

Lipinski, C.A. Lead-and drug-like compounds: the rule-of-five revolution. Drug. Discov. Today. Technol. 2004; 1(4):337-341.

Vasileva, L.V., Savova, M.S., Amirova, K.M., Balcheva-Sivenova, Z., Ferrante, C., Orlando, G., Wabitsch, M., Georgiev, M.I. Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways. Int. J. Mol. Sci. 2020; 21: 9740.

Sin, T.K., Yung, B.Y., Siu, P.M. Modulation of SIRT1-Foxo1 signaling axis by resveratrol: implications in skeletal muscle aging and insulin resistance. Cell. Physiol. Biochem. 2015;35(2):541-552.

Rodgers, J.T., Puigserver, P. Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc. Natl. Acad. Sci. USA. 2007; 104(31):12861- 12866.

Ge, C.X., Yu, R., Xu, M.X., Li, P.Q., Fan, C.Y., Li, J.M., et al., Betaine prevented fructose-induced NAFLD by regulating LXR?/PPAR? pathway and alleviating ER stress in rats. Eur. J. Pharmacol. 2016;770:154-164.

Downloads

Published

2022-05-01

How to Cite

1.
V. R, T.A.K MB. In silico analysis of ferulic acid against therapeutic target proteins PPAR-?, SIRT1, FOXO1 and LXR-? for the treatment of hyperlipidemia. Biomedicine [Internet]. 2022 May 1 [cited 2022 Nov. 27];42(2):247-51. Available from: https://biomedicineonline.org/home/article/view/1124

Issue

Section

Original Research Articles

Plum Analytics