title: Immunosuppressive and hepatoprotective potential of Sarcococca saligna and its biomarker components.
abstract: Sarcococca saligna methanolic extract, fractions and isolated pure compounds saracocine (1), saracodine (2), pachyximine-A (3) and terminaline (4) were found to possess potent immunosuppressive activities. The fractions and compounds were tested in-vitro for their effects on human T-cell proliferation, and cytokine (IL-2) production. All the fractions, sub-fractions and purified compounds showed significant suppressive effect on IL-2 production in a dose-dependent manner. They also exhibited a suppressive effect on the phytohemagglutinin-stimulated T-cell proliferation. None of the extracts and purified compounds showed any cytotoxicity effects on the 3T3 mice fibroblast cell line. The crude extract, DCM fraction (pH9), DCM fractions (pH7) and one of the steroidal alkaloids (terminaline) were checked in-vivo for their hepato-protective potential against CCl4-induced liver injury. In in-vivo experiments, the basic and neutral DCM fractions and terminaline (4) significantly reduced inflammation in the liver. DCM fraction (pH9), DCM fractions (pH7) and compound 4 reduced the serum enzyme levels (ALT, AST, and ALP) down to control levels despite CCl4 treatment. They also reduced the CCl4-induced damaged area to almost zero as assessed by histopathology. The pale necrotic areas and mixed inflammatory infiltrate which are seen after CCl4 treatment were absent in the cases of basic, neutral fractions and terminaline treatment. These hepato-protective effects were better than the positive control silymarin. Our results suggest the therapeutic effect of S. saligna extract, fractions and bioactive steroidal alkaloids against CCl4-induced liver injury in vivo and their immunosuppressive function in vitro.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ali
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan; HEJ, Research Institute of Chemistry, International Center for Chemical Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan.
authors.forename: Syed Ghulam
authors.initials: SG
authors.lastname: Musharraf
authors.affiliation: HEJ, Research Institute of Chemistry, International Center for Chemical Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan.
authors.forename: Naveed
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: HEJ, Research Institute of Chemistry, International Center for Chemical Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan.
authors.forename: Achyut
authors.initials: A
authors.lastname: Adhikari
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan.
authors.forename: Omer Mohamed
authors.initials: OM
authors.lastname: Abdalla
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan; Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.
authors.forename: M
authors.initials: M
authors.lastname: Ahmed Mesaik
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: nurul.kabir@um.edu.my.
authors.forename: Nurul
authors.initials: N
authors.lastname: Kabir
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D031234:Buxaceae / Q000737:chemistry*; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D015415:Biomarkers; C508594:IL2 protein, human; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010936:Plant Extracts; D020011:Protective Agents
keywords: Cytotoxicity; Histopathology; IL-2; S. saligna; T-cell proliferation