title: Phytosterols isolated from Clinacanthus nutans induce immunosuppressive activity in murine cells.
abstract: Clinacanthus nutans (Burm. f.) Lindau is a traditional medicinal plant belonging to the Acanthaceae family. Its therapeutic potentials have been increasingly documented particularly the antiviral activity against Herpes Simplex Virus (HSV), anti-cancer, anti-oxidant, anti-inflammatory and immunomodulatory activities. However, majority of these studies used crude or fractionated extracts and not much is known about individual compounds from these extracts and their biological activities. In the present study, we have isolated four compounds (CN1, CN2, CN3 and CN4) from the hexane fractions of C. nutans leaves. Using NMR spectroscopic analysis, these compounds were identified to be shaftoside (CN1), stigmasterol (CN2), β-sitosterol (CN3) and a triterpenoid lupeol (CN4). To determine the immunosuppressive potential of these compounds, their effects on mitogens induced T and B lymphocyte proliferation and the secretion of helper T cell cytokines were examined. Among the four compounds, stigmasterol (CN2) and β-sitosterol (CN3) were shown to readily inhibit T cell proliferation mediated by Concanavalin A (ConA). However, only β-sitosterol (CN3) and not stigmasterol (CN2) blocks the secretion of T helper 2 (Th2) cytokines (IL-4 and IL-10). Both compounds have no effect on the secretion of Th1 cytokines (IL-2 and IFN-γ), suggesting that β-sitosterol treatment selectively suppresses Th2 activity and promotes a Th1 bias. CN3 was also found to significantly reduce the proliferation of both T helper cells (CD4+CD25+) and cytotoxic T cells (CD8+CD25+) following T cell activation induced by ConA. These results suggested that phytosterols isolated from C. nutans possess immunomodulatory effects with potential development as immunotherapeutics.
authors.affiliation: School of Pharmacy, Faculty of Science, The University of Nottingham Malaysia Campus, 43500 Semenyih, Selangor, Malaysia.
authors.forename: Cheng-Foh
authors.initials: CF
authors.lastname: Le
authors.affiliation: School of Pharmacy, Faculty of Science, The University of Nottingham Malaysia Campus, 43500 Semenyih, Selangor, Malaysia.
authors.forename: Thina Hareesh
authors.initials: TH
authors.lastname: Kailaivasan
authors.affiliation: School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia.
authors.forename: Sek-Chuen
authors.initials: SC
authors.lastname: Chow
authors.affiliation: Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia.
authors.forename: Zunoliza
authors.initials: Z
authors.lastname: Abdullah
authors.affiliation: Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia. Electronic address: lingsk@frim.gov.my.
authors.forename: Sui-Kiong
authors.initials: SK
authors.lastname: Ling
authors.affiliation: School of Pharmacy, Faculty of Science, The University of Nottingham Malaysia Campus, 43500 Semenyih, Selangor, Malaysia. Electronic address: CheeMun.Fang@nottingham.edu.my.
authors.forename: Chee-Mun
authors.initials: CM
authors.lastname: Fang
mesh_terms: D027901:Acanthaceae / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010840:Phytosterols / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D010840:Phytosterols; D010936:Plant Extracts
keywords: Clinacanthus nutans; Cytokines; Flow cytometry; Immunosuppression; Stigmasterol; β-Sitosterol