ABSTRACT
This study employed the α-glucosidase inhibitory activity model as an anti-diabetic assay and implemented a bioactivity-guided isolation strategy to identify novel natural compounds with potential therapeutic properties. Hypericum sampsoniiwas investigated, leading to the isolation of two highly modified seco-polycyclic polyprenylated acylphloroglucinols (PPAPs) (1 and 2), eight phenolic derivatives (3-10), and four terpene derivatives (11-14). The structures of compounds 1 and 2, featuring an unprecedented octahydro-2H-chromen-2-one ring system, were fully characterized using extensive spectroscopic data and quantum chemistry calculations. Six compounds (1, 5-7, 9, and 14) exhibited potential inhibitory effects against α-glucosidase, with IC50 values ranging from 0.050 ± 0.0016 to 366.70 ± 11.08 μg·mL-1. Notably, compound 5 (0.050 ± 0.0016 μg·mL-1) was identified as the most potential α-glucosidase inhibitor, with an inhibitory effect about 6900 times stronger than the positive control, acarbose (IC50 = 346.63 ± 15.65 μg·mL-1). A docking study was conducted to predict molecular interactions between two compounds (1 and 5) and α-glucosidase, and the hypothetical biosynthetic pathways of the two unprecedented seco-PPAPs were proposed.
Subject(s)
Molecular Structure , Hypericum/chemistry , alpha-Glucosidases , Magnetic Resonance Spectroscopy , Glycoside Hydrolase Inhibitors/pharmacologyABSTRACT
Several species of the Myrcia genus have been used in folk medicine to treat diabetes. Therefore, the aim of this work was to investigate the inhibitory activity of α-glucosidase and pancreatic lipase in the crude extract (EBF) and in the ethyl acetate fraction (FFA) of Myrcia hatschbachii, as well as to identify isolated phenolic compounds and to evaluate the antioxidant property and preliminary in vitro toxicity against Artemia salina. EBF (IC50: 3.21 µg/mL) and FFA (IC50: 1.14 µg/mL) showed inhibitory activity superior to acarbose (IC50: 193.65 µg/mL). In addition, they showed inhibitory effects of pancreatic lipase (IC50: 556.58 µg/mL for EBF and 532.68 µg/mL for FFA), antioxidant potential, absence of preliminary toxicity and presence of gallic andellagic acids in FFA. The relevant results in the inhibition of α-glucosidase and pancreatic lipase motivate new studies for the development of herbal medicines that assist in the treatment of diabetic patients.
Varias especies del género Myrcia se han utilizado en la medicina popular para tratar la diabetes. Por lo tanto, el objetivo de este trabajo fue investigar la actividad inhibitoria de la α-glucosidasa y la lipasa pancreática en el extracto crudo (EBF) y en la fracción de acetato de etilo (FFA) de Myrcia hatschbachii, así como identificar compuestos fenólicos aislados y evaluar la propiedad antioxidante y toxicidad in vitro preliminar contra Artemia salina. EBF (IC50: 3.21 µg/mL) y FFA (IC50: 1.14 µg/mL) mostraron una actividad inhibitoria superior a la acarbosa (IC50: 193.65 µg/mL). Además, mostraron efectos inhibitorios de la lipasa pancreática (IC50: 556.58 µg/mL para EBF y 532.68 µg/mL para FFA), potencial antioxidante, ausencia de toxicidad preliminar y presencia de ácidos gálico y elágico en FFA. Los resultados relevantes en la inhibición de la α-glucosidasa y la lipasa pancreática motivan nuevos estudios para el desarrollo de medicamentos a base de hierbas que ayudan en el tratamiento de pacientes diabéticos.
Subject(s)
Plant Extracts/pharmacology , Myrtaceae/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Lipase/drug effects , Antioxidants/pharmacology , Pancreas/enzymology , Phenols/analysis , X-Ray Diffraction , In Vitro Techniques , Plant Extracts/toxicity , Plant Extracts/chemistry , Free Radical Scavengers , Complex Mixtures , Ellagic Acid , Gallic Acid , Antioxidants/chemistryABSTRACT
Euphorbia dioeca Kunth belongs to the Wanderers herb complex that is traditionally used for skin diseases and recently as antidiabetic. The methanol and aqueous extracts were evaluated for their in vitro alpha-glucosidase inhibitory activity and an oral starch tolerance test. These extracts showed an IC50 of 0.55 and 0.85 mg/mL, respectively. In diabetic Long Evans rats, the methanol and aqueous extracts reduced significantly the postprandial hyperglycemia peak in 15.2 percent and 12.8 percent, respectively. The alpha-glucosidase inhibitory activity is related with the presence of glycosides, phenolic compounds and flavonoids. Additionally, the safety parameters of both extracts were assessed by means of an acute toxicity test, being classified as innocuous. The traditional use of E. dioeca to control type 2 diabetes was confirmed, being an important source of alfa-glucosidase inhibitors.
Euphorbia dioeca Kunth, pertenece al complejo de plantas medicinales denominado Hierba de la Golondrina; el cual se utiliza para diversos padecimientos, destacando su uso como antidiabético. En dicho marco, se evaluó tanto la actividad inhibitoria de alfa-glucosidasa in vitro, como su desempeño en una prueba de tolerancia a una carga de almidón postprandial. Los extractos inhibieron la actividad de la alfa-glucosidasa con una CI50 de 0.55 y 0.85 mg/mL, respectivamente. Los extractos metanólico y acuoso disminuyeron significativamente el pico hiperglucémico postprandial en un 15.2 por ciento y un 12.8 por ciento, respectivamente, cuando se evaluó en ratas diabéticas. La actividad inhibitoria de alfa-glucosidasa, reflejada en ambas pruebas, está relacionada con la presencia de glicósidos, compuestos fenólicos y flavonoides. De manera adicional, ambos extractos fueron evaluados en una prueba de toxicidad aguda, siendo clasificados como inocuos. Se corroboró el uso tradicional de E. dioeca para el control de la diabetes tipo 2, siendo una importante fuente de compuestos inhibidores de alfa-glucosidasa.
Subject(s)
Animals , Mice , /drug therapy , Euphorbia/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Plant Extracts/pharmacology , Hyperglycemia/drug therapy , Mice, Inbred BALB CABSTRACT
In vitro study revealed that pancreatic lipase inhibitory activity of C. asiatica extract was significantly higher than rutin but lower than orlistat, an anti-obesity drug. α-Amylase inhibitory activities of C. asiatica extract and rutin were significantly lower than acarbose, an anti-diabetic drug. Inhibition of α-glucosidase activity by C. asiatica extract, rutin, and acarbose was not different. The in vivo study substantiated the in vitro results. C. asiatica extract (1000 and 2000 mg/4 mL/kg), rutin (1000 mg/4 mL/kg), and orlistat (45 mg/4 mL/kg) significantly decreased plasma glucose, triglyceride and total cholesterol levels in lipid emulsion-induced hyperlipidemic rats at 3 h. However, plasma aspartate aminotransferase and alanine aminotransferase levels did not show significant change. The present work further supports that the C. asiatica extract and its bioactive rutin may help managing hypolipidemic and hypoglycemic effects.