Immunosuppressive Activity of Buxidin and E-Buxenone from Buxus hyrcana

Authors

  • M. Ahmed Mesaik,

    Corresponding author
    1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
    Search for more papers by this author
  • Sobia A. Halim,

    1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
    Search for more papers by this author
  • Zaheer Ul-Haq,

    Corresponding author
    1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
    Search for more papers by this author
  • M. Iqbal Choudhary,

    1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
    Search for more papers by this author
  • Salma Shahnaz,

    1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
    Search for more papers by this author
  • S. A. M Ayatollahi,

    1. School of Pharmacy, Shaheed Beheshti University of Medical Sciences. PO Box 14155-61-53, Tehran, Iran
    Search for more papers by this author
  • Shahnaz Murad,

    1. Institute for Medical Research, Kula Lumpur-50588, Malaysia
    Search for more papers by this author
  • Aqeel Ahmad

    1. Department of Microbiology, University of Karachi, Karachi-75270, Pakistan
    Search for more papers by this author

* Corresponding author: M. Ahmed Mesaik; mmesaik@hotmail.com; Zaheer Ul-Haq; zaheer.qasmi@iccs.edu

Abstract

Buxidin (1) and E-Buxenone (2), steroidal alkaloids from Buxus hyrcana, are found to possess potent immunosuppressive properties. The activity was tested in vitro on oxidative burst, chemotaxis, T-cell proliferation, and cytokine production. Both compounds showed a significant immunomodulatory activity with clear suppressive effect on oxidative burst and chemotaxis in a dose-dependent manner. They also exhibited suppressive effect on the phytohemagglutinin-stimulated T-cell proliferation. The immunomodulatory activity was further confirmed by the suppression of IL-2 and IL-4 production. Furthermore, molecular docking studies were performed to investigate the binding mode of Buxidin (1) and E-Buxenone (2) with IL-2. Despite the structural differences between Buxidin (1) and E-Buxenone (2), docking results revealed that they adopt a similar binding pattern at the active site of the IL-2. A good agreement between practical and theoretic results indicates that the current docking study could provide an alternate tool for the structural optimization of recently identified ligand as more potent IL-2 inhibitors.

Ancillary