Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 17;20(1):369-375.
doi: 10.1007/s40200-021-00754-x. eCollection 2021 Jun.

Gene set enrichment analysis of PPAR-γ regulators from Murraya odorata Blanco

Prarambh Sr Dwivedi  1 , V P Rasal  1 , Ekta Kotharkar #  1 , Shailaja Nare #  1 , Pukar Khanal  1
Affiliations

Gene set enrichment analysis of PPAR-γ regulators from Murraya odorata Blanco

Prarambh Sr Dwivedi et al. J Diabetes Metab Disord. .

Abstract

Background: Peroxisome proliferator-activated receptor gamma (PPAR-γ) is reported to regulate insulin sensitivity and progression of Type 2 diabetes mellitus (T2DM). Hence the present study is aimed to identify PPAR-γ regulators from Murraya odorata Blanco and predict their role to manage T2DM.

Methods: Multiple in-silico tools and databases like SwissTargetPrediction, ADVERPred, PubChem, and MolSoft, were used to retrieve the information related to bioactives, targets, druglikeness character, and probable side effects as applicable. Similarly, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to identify the regulated pathways. Further, the bioactives-protein-pathways network interaction was constructed using Cytoscape. Finally, molecular docking was performed using Autodock4.

Results: Twenty-five bioactives were shortlisted in which six were predicted as PPAR-γ modulators. Among them, stigmasterol was predicted to possess the best binding affinity towards PPAR-γ and possessed no side effects. Similarly, n-hexadecanoic acid was predicted to modulate the highest number of proteins, and protein CD14 was targeted by the highest number of bioactives. Further, the PI3K-Akt pathway was predicted as the maximum modulated genes.

Conclusions: The anti-diabetic property of the Murraya odorata Blanco of fruit pulp may be due to the presence of n-hexadecanoic acid and stigmasterol; may also involve in the regulation of the PI3K-Akt pathway which needs further investigated by in-vitro and in-vivo protocols.

Keywords: Murraya odorata Blanco; Gene set enrichment; Network pharmacology; PPAR-γ; Stigmasterol.

PubMed Disclaimer

Conflict of interest statement

Conflict of interestNil.

Figures

Fig. 1
Fig. 1
Interaction of bioactives from Murraya odorata Blanco with respective targets and regulated pathways with respective proteins. In the network the triangle, circle and square represent pathways, proteins and bioactives respectively
Fig. 2
Fig. 2
(a) 3D and (b) 2D interaction of Stigmasterol (pose with lowest binding energy) with PPAR-γ
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Baynes HW. Classification, pathophysiology, diagnosis and management of diabetes mellitus. J Diabetes Metab. 2015;6(5):1–9. doi: 10.4172/2155-6156.1000541. - DOI
    1. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ) J Biol Chem. 1995;270(22):12953–6. doi: 10.1074/jbc.270.22.12953. - DOI - PubMed
    1. Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. J Diabetes. 1998;47(4):507–14. doi: 10.2337/diabetes.47.4.507. - DOI - PubMed
    1. Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obes (Lond) 2003;27(2):147–61. doi: 10.1038/sj.ijo.802223. - DOI - PubMed
    1. Krentz AJ, Bailey CJ. Oral antidiabetic agents. Drugs. 2005;65(3):385–411. doi: 10.2165/00003495-200565030-00005. - DOI - PubMed