ABSTRACT
Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1-2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1-7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4-7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.
Subject(s)
Arginase/antagonists & inhibitors , Cyperus/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Animals , Aorta, Thoracic/drug effects , Arthritis, Experimental/drug therapy , Arthritis, Experimental/physiopathology , Benzofurans/chemistry , Benzofurans/isolation & purification , Benzofurans/pharmacology , Calamus , Cattle , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Enzyme Inhibitors/isolation & purification , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , In Vitro Techniques , Magnetic Resonance Spectroscopy , Male , Methanol , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Rats , Resveratrol/chemistry , Resveratrol/isolation & purification , Resveratrol/pharmacology , Stilbenes/chemistry , Stilbenes/isolation & purification , Stilbenes/pharmacology , Vasodilator Agents/chemistry , Vasodilator Agents/isolation & purification , Vasodilator Agents/pharmacologyABSTRACT
OBJECTIVES: We aimed to isolate and identify bioactive molecules from Morus alba (Moraceae) leaves having arginase inhibitory activity towards the combat of clinical outcomes related to endothelial dysfunction. METHOD: Extraction and isolation were carried out by successive macerations, prepurification by using a Solid Phase Extraction (SPE) and separation using preparative PLC. The structures of the isolated components were established and confirmed by spectroscopic analyses, including the ESI-HRMS and NMR spectroscopic investigations. Biological evaluation was performed by using an in vitro assay with liver bovine purified arginase and by an ex vivo aortic ring study. KEY FINDINGS: We demonstrated that a phenolic extract from the leaves of M. alba possesses mammalian arginase inhibitory capacities. Investigation of the chemical constituents of its leaves results in the isolation and identification of ten compounds investigated in vitro for their arginase inhibitory capacities. Four compounds showed significant inhibition of arginase, with percentage inhibition ranging from 54% to 83% at 100 µm. In isolated rat aortic rings incubated with NO synthase inhibitor, Luteolin-7-diglucoside compound (2) was able to increase acetylcholine-induced relaxation. CONCLUSIONS: These results demonstrated the attractive ability of M. alba to be a potential source for the discovery of new active products on vascular system.
Subject(s)
Arginase/antagonists & inhibitors , Flavonoids/pharmacology , Morus/chemistry , Plant Extracts/pharmacology , Animals , Aorta/drug effects , Aorta/metabolism , Cattle , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Flavonoids/isolation & purification , Liver/enzymology , Male , Phenols/isolation & purification , Phenols/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Viticultural residues from commercial viticultural activities represent a potentially important source of bioactive stilbenes such as resveratrol. The main aim of the present study was therefore to isolate, identify and perform biological assays against amyloid-ß peptide aggregation of original stilbenes from Vitis vinifera shoots. RESULTS: A new resveratrol oligomer, (Z)-cis-miyabenol C (3), was isolated from Vitis vinifera grapevine shoots together with two newly reported oligostilbenes from Vitis vinifera shoots, vitisinol C (1) and (E)-cis-miyabenol C (2), and six known compounds: piceatannol, resveratrol, (E)-ε-viniferin (trans-ε-viniferin), ω-viniferin, vitisinol C and (E)-miyabenol C. The structures of these resveratrol derivatives were established on the basis of detailed spectroscopic analysis including nuclear magnetic resonance experiments. All the newly reported compounds were tested for their anti-aggregative activity against amyloid-ß fibril formation. Vitisinol C was found to exert a significant activity against amyloid-ß aggregation. CONCLUSION: Vitis vinifera grapevine shoots are potentially interesting as a source of new bioactive stilbenes, such as vitisinol C.