title: Steroidal Alkaloids as an Emerging Therapeutic Alternative for Investigation of Their Immunosuppressive and Hepatoprotective Potential.
abstract: The compounds, sarcovagine-D, alkaloid-C, and holaphylline isolated fromSarcococca salignawere found to possess immunosuppressive activities. These compounds were characterized forin vitroinhibition on human T-cells proliferation and IL-2 production. The compounds showed significant immunosuppressive effect on IL-2 production as well as on phytohemagglutinin stimulated T-cell proliferation in a dose dependent manner. Of all the tested compounds holaphylline was found to be less toxic and safe. These compounds were then evaluated for theirin vivohepatoprotective potential against CCl4, in which alkaloid-C and holaphylline showed markedly reduced liver inflammation and biochemical parameter (ALT, AST, and ALP) of liver injury. The decrease in the activity of hepatic antioxidant enzyme (SOD) was significantly prevented by holaphylline, likewise gradually the levels of MDA and GSH were also normalized compared to silymarin. The CCl4induced inflammation and necrosis around the central vein of liver was reduced by sarcovagine-D, alkaloid-C and holaphylline, to 8%, 4% to 1% respectively as assessed by histopathology, thus having better hepatoprotective effect compared to positive control. Steroidal alkaloids attenuated the inflammation of liver around the injured central vein region by down regulating the CCl4induced activation of hepatic macrophages as well as their number respectively. Therefore, thein vitroandin vivoresults suggest that steroidal alkaloids fromS. salignacould be excellent immunosuppressive and hepatoprotective agents.
authors.affiliation: Center of Biotechnology and Microbiology, University of Peshawar, Peshawar Pakistan.
authors.forename: Naeem U
authors.initials: NU
authors.lastname: Jan
authors.affiliation: Center of Biotechnology and Microbiology, University of Peshawar, Peshawar Pakistan.
authors.forename: Bashir
authors.initials: B
authors.lastname: Ahmad
authors.affiliation: Pakistan Institute of Engineering and Applied Sciences, Islamabad Pakistan.
authors.forename: Safdar
authors.initials: S
authors.lastname: Ali
authors.affiliation: Hussain Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi Pakistan.
authors.forename: Achyut
authors.initials: A
authors.lastname: Adhikari
authors.affiliation: Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam University, Islamabad Pakistan.
authors.forename: Amjad
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Zoology, Abdul Wali Khan University, Mardan Pakistan.
authors.forename: Azra
authors.initials: A
authors.lastname: Jahan
authors.affiliation: Laboratory of Germplasm Innovation and Molecular Breeding, Department of Vegetable Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou China.
authors.forename: Abid
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, IslamabadPakistan; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, KarachiPakistan.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ali
keywords: IL-2; T-cells; cytotoxicity; hepatoprotection; immunosuppressive; steroidal alkaloids