Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA

  • Nageen Hussain Institute of Microbiology and Molecular Genetics, University of the Punjab Lahore-54590, Pakistan
  • Mohsin Mumtaz School of Women’s and Children’s Health, Faculty of Medicine and Health, the University of New South Wales, Australia
  • Mohammad Adil Institute of Microbiology and Molecular Genetics, University of the Punjab Lahore-54590, Pakistan
  • Abad Ali Nadeem Food and Biotechnology Research Center PCSIR Laboratories, Lahore, Pakistan
  • Abid Sarwar Food and Biotechnology Research Center PCSIR Laboratories, Lahore, Pakistan
  • Tariq Aziz Department of Agriculture, University of Ioannina, 47100 Arta, Greece
  • Metab Alharbi Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
  • Abdulrahman Alshammari Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
  • Abdullah F Alasmari Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
  • Mousa Essa Alharbi Ministry of Health King of Saudi Arabia Riyadh, King of Saudi Arabia

Abstract

Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton’s Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.

Published
2023-09-05
Section
Articles