Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

Abstract

Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z,13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E,12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R*-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14–3.73 μM) and elastase release (IC50 1.26–4.57 μM) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187- and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E,12Z-octadecadienoic acid, IC50 92.4 and 49.7 μM, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.

Qualitative and Quantitative Analysis of Ukrainian Iris Species: A Fresh Look on Their Antioxidant Content and Biological Activities

“…A methylthiazole tetrazolium (MTT) assay [ 79 ] was used to measure the possible toxic effects of the samples on RBL-2H3 cells and the experiment was performed as previously described [ 80 ]. β -Hexosaminidase activity assay was used to determine the degree of A23187-induced [ 81 , 82 ] and antigen-induced [ 83 ] degranulation in RBL-2H3 cells as previously described. The details of the assays are presented in the Supplementary Materials section .…”

Epigenetic Manipulation Induces the Production of Coumarin‐Type Secondary Metabolite from Arthrobotrys foliicola

“…The mucosal mast cell‐derived rat basophilic leukemia cells (RBL‐2H3, Bioresource Collection and Research Center) were cultured in DMEM medium (containing 10 % FBS and 100 μg/mL streptomycin with 100 U/mL penicillin). The potential cytotoxic effects of the samples on RBL‐2H3 cells were determined by methylthiazol tetrazolium (MTT) assay as described previously . Tested samples were considered as nontoxic towards RBL‐2H3 cells (viability over 80 %, n=3).…”

“…The degree of A23187‐induced degranulation in RBL‐2H3 cells was evaluated by a β‐hexosaminidase release assay as described previously . RBL‐2H3 cells were seeded in 96‐well plate (2×10 4 cells/well) and treated with the samples for 20 h. The cells were stimulated by A23187 (1 μM), a calcium ionophore, for 1 h. Dexamethasone (10 nM) was used as the positive control.…”

“…RBL‐2H3 cells were seeded in 96‐well plate (2×10 4 cells/well) and treated with the samples for 20 h. The cells were stimulated by A23187 (1 μM), a calcium ionophore, for 1 h. Dexamethasone (10 nM) was used as the positive control. The amount of β‐hexosaminidase was detected by using the method that utilizes p ‐nitrophenyl‐ N ‐acetyl‐d‐glucosaminide ( p ‐NAG) as a substrate for β‐hexosaminidase according to the method described before . Tested samples showed insignificant inhibition of degranulation (below 20 %, n=3).…”

Study of the anti-allergic and anti-inflammatory activity of Brachychiton rupestris and Brachychiton discolor leaves (Malvaceae) using in vitro models

“…A23187-induced degranulation in RBL-2H3 cells was evaluated by a β -hexosaminidase activity assay as previously reported employing certain modifications [ 45 , 46 ]. RBL-2H3 cells were seeded into 96-wells plate using a density of 2 × 10 4 cells/well and were incubated at 37 °C for 5 h in 5% CO 2 .…”