Phytochemical and Biological Evaluations of Arum hygrophilum Boiss. (Araceae)

BACKGROUND: Arum hygrophilum is a traditional medicinal plant indigenous to Jordan. The present study explores its phytochemistry, antioxidative, antidiabesity, and antiproliferative potentialities. MATERIALS AND METHODS: Column chromatography and HPLC-MS analysis were used for its phytochemical evaluation. Using leaf crude water and ethanol extracts, the antioxidative capacities, their modulation of pancreatic β-cell proliferation, and insulin secretion as well as glucose diffusion and enzymatic bioassays were evaluated. RESULTS: Three flavonoids (luteolin, isoorientin, and vitexin) and β-sitosterol have been isolated and their structures determined. HPLC-MS analysis of the ethanol extract further revealed the presence of caffeic, ferulic, gallic, and rosmarinic acids and quercetine-3-O-rhamnoside. The ethanol extract exhibited DPPH and ABTS radical scavenging and antioxidative capacities. A. hygrophilum (1), vitexin (2), and rosmarinic acid (3) inhibited pancreatic lipase (PL) dose dependently with PL-IC(50) (µg/mL) values in an ascending order: (3); 51.28 ± 7.55 < (2); 260.9 ± 21.1 < (1); 1720 ± 10. Comparable to GLP-1-enhanced β-cell proliferation in 2-day treatment wells, a dose-dependent augmentation of BrdU incorporation was obtained with the A. hygrophilum aqueous extract (AE) (0.5 and 1 mg/mL, with respective 1.33- and 1.41-folds, P < 0.001). A. hygrophilum AE was identified as an inhibitor of α-amylase/α-glucosidase with IC(50) value of 30.5 ± 2.1 mg/mL but lacked antiproliferative effects in colorectal cancer cell lines (HT29, HCT116, and SW620) and insulinotropic effects in β-cell line MIN6. CONCLUSION: A. hygrophilum extracts inhibited gastrointestinal enzymes involved in carbohydrate and lipid digestion and absorption. SUMMARY: Phytochemical evaluation of Arum hygrophilum recovered flavonoids (luteolin, isoorientin and vitexin) and β-sitosterol. HPLC-MS analysis of its antioxidative ethanol extract further revealed the presence of caffeic-, ferulic-, gallic- and rosmarinic acids and quercetine-3-O-rhamnoside. A. hygrophilum inhibited α-amylase/α-glucosidase and pancreatic lipase dose-dependently. A. hygrophilum augmented β-cell proliferation dose dependently, but it lacked antiproliferative effects in colorectal cancer cell lines (HT29, HCT116, and SW620) and insulinotropic effects in β-cell line MIN6. Abbreviations used: ABTS: 2,2’-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid, AE: Aqueous Extract, ANOVA: Analysis Of Variance, AUC: Area Under Curve, BrdU: 5-Bromo-2’-Deoxyuridine, DPPH: 2,2-Diphenyl -1-Pycriylhydrazyl, ELISA: Enzyme Linked Immunosorbent Assay, GLP1: Glucagon Like Peptide 1, GSIS: Glucose Stimulated Insulin Secretion, HPLC-MS: High Performance Liquid Chromatography –Mass Spectrometry, IC50: 50% Inhibitory Concentration, KRH: Krebs/Ringer/Hepes, MTT: 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide, OGTT: Oral Glucose Tolerance Test, ORAC: Oxygen Radical Antioxidant Capacity, OSTT: Oral Starch Tolerance Test, PL: Pancreatic Lipase, SEM: Standard Error Of The Mean, SRB: Sulforhodamine B, TEAC: Trolox Equivalent Antioxidant Capacity, TLC: Thin Layer Chromatography