title: Immunosuppressive activity of buxidin and E-buxenone from Buxus hyrcana.
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.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. mmesaik@hotmail.com
authors.forename: M Ahmed
authors.initials: MA
authors.lastname: Mesaik
authors.forename: Sobia A
authors.initials: SA
authors.lastname: Halim
authors.forename: Zaheer
authors.initials: Z
authors.lastname: Ul-Haq
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Salma
authors.initials: S
authors.lastname: Shahnaz
authors.forename: S A M
authors.initials: SA
authors.lastname: Ayatollahi
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Murad
authors.forename: Aqeel
authors.initials: A
authors.lastname: Ahmad
mesh_terms: D001665:Binding Sites; D031235:Buxus / Q000737:chemistry*; D020134:Catalytic Domain; D003198:Computer Simulation; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013256:Steroids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: C553147:E-buxenone; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D013256:Steroids; C553146:buxidin; D015847:Interleukin-4