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Steroids and triterpenoids from Eastern Nigeria mistletoe, Loranthus micranthus Linn. (Loranthaceae) parasitic on Kola acuminata with immunomodulatory potentials
Authors:Omeje Edwin Ogechukwu  Osadebe Patience Ogoamaka  Nworu Chukwuemeka Sylvester  Amal Hassan  Abdessamad Debbab  Esimone Charles Okechukwu  Akira Kawamura  Proksch Peter
Affiliation:aDepartment of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu, Nigeria;bDepartment of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu, Nigeria;cDepartment of Pharmaceutical Biology, Heinrich-Hein University, Bilk 40225, Düsseldorf, Germany;dDepartment of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, 420281 Awka, Nigeria;eDepartment of Chemistry, Hunter College of CUNY, The City University of New York, USA
Abstract:In search of immunomodulatory constituents from the Eastern Nigeria mistletoe, Loranthus micranthus Linn, two new stigmastane steroids: stigmast-7,20 (21)-diene-3β-hydroxy-6-one (1) and 3β-hydroxy-stigmast-23-ene (2); three (two new and one known) lupeol-based triterpenoid esters: 7β,15α-dihydroxyl-lup-20(29)-ene-3β-palmitate (3), 7β,15α-dihydroxyl-lup-20(29)-ene-3β-stearate (4) and 7β,15α-dihydroxyl-lup-20(29)-ene-3β-eicosanoate (5) were isolated and characterized following bioactivity-guided fractionation. The new compounds, 1, 2, 4 and 5 at concentrations of 10, 25 and 100 μg/ml were subjected to cell proliferation and early activation marker (CD69) expression studies in C57Bl/6 mice splenocytes using flow cytometry techniques against Lipopolysaccharide (LPS; 10 μg/ml) and Concanavalin A (ConA; 2 μg/ml) standards. The stigmastane steroids (1 and 2) at the highest concentration of 100 μg/ml showed statistically significantly (p < 0.05) stimulatory activity on the C57B1/6 splenocytes compared to the controls with values of 46 ± 0.76% and 43 ± 0.46% compared to 7.69 ± 0.41% recorded for the negative control. The novel lupeol esters, 4 and 5 at same concentration of 100 μg/ml exhibited lower stimulations of 30 ± 0.41% and 29 ± 0.17% respectively compared to the controls above. The CD69 expression assay at the above doses showed that all the compounds have minimal stimulation. The present study supports the observed immunomodulatory property of the Eastern Nigeria mistletoe and thus confirms the efficacy of this plant in mitigating against wide array of disease conditions orchestrated by immunodeficiency.
Keywords:Abbreviations: LPS, lipopolysaccharides   Con A, concanavalin A   DMSO, dimethylsulphoxide   CSFE, carboxyfluorescein diacetate succinimidyl ester
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