ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia ficus-indica (L.) Mill is frequently observed in the Moroccan traditional medicinal system, where these approaches are employed to mitigate the onset of diabetes and the subsequent complications it may entail. AIM OF THE STUDY: The aim of this research was to examine the effectiveness of Opuntia ficus-indica seed oil in preventing diabetic complications. Specifically, the study assessed its ability to counteract glycation at various stages, protected red blood cells from the harmful effects of glycated albumin, and inhibited pancreatic lipase digestive enzymes to understand its potential antihyperglycemic properties. Additionally, the study aimed to identify the chemical components responsible for these effects, evaluate antioxidant and anti-inflammatory properties, and conduct computational investigations such as molecular docking. MATERIALS AND METHODS: The assessement of Opuntia ficus-indica seed oil antiglycation properties involved co-incubating the extract oil with a bovine serum albumin-glucose glycation model. The study investigated various stages of glycation, incorporating fructosamine (inceptive stage), protein carbonyls (intermediate stage), and AGEs (late stage). Additionally, measurement of ß-amyloid aggregation of albumin was performed using Congo red, which is specific to amyloid structures. Additionally, the evaluation of oil's safeguarding effect on erythrocytes against toxicity induced by glycated albumin included the measurement of erythrocyte hemolysis, lipid peroxidation, reduced glutathione. The fatty acid of Opuntia ficus-indica seed oil were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The in vitro evaluation of antihyperglycemic activity involved the use of pancreatic lipase enzyme, while the assessement of antioxidant capability was carried out through the utilization of the ABTS and FRAP methods. The in vitro assessement of the denaturation of albumin activity was also conducted. In conjunction with the experimental outcomes, computational investigations were undertaken, specifically employing ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. Furthermore, molecular docking was utilized to predict antioxidant and antiglycation mechanisms based on protein targets. RESULTS: In vitro glycation assays, Opuntia ficus-indica seed oil displayed targeted inhibitory effects at multiple distinct stages. Within erythrocytes, in addition to mitigating hemolysis and lipid peroxidation induced by glycated albumin. GC-MS investigation revealed a richness of fatty acids and the most abundant compounds are Linoleic acid (36.59%), Palmitic acid (20.84%) and Oleic acid (19.33%) respectively. The findings of antioxidant ability showed a remarkable activity on FRAP and ABTS radicals. This oil showed a pronounced inhibitory impact (p < 0.001) on pancreatic lipase enzyme. It also exerted a notibale inhibition of albumin denaturation, in vitro. CONCLUSION: The identified results were supported by the abundant compounds of fatty acids unveiled through GC-MS analysis, along with the computational investigation and molecular docking.
Subject(s)
Antioxidants , Erythrocytes , Fatty Acids , Gas Chromatography-Mass Spectrometry , Molecular Docking Simulation , Opuntia , Oxidative Stress , Plant Oils , Seeds , Opuntia/chemistry , Erythrocytes/drug effects , Erythrocytes/metabolism , Oxidative Stress/drug effects , Seeds/chemistry , Fatty Acids/chemistry , Morocco , Antioxidants/pharmacology , Antioxidants/chemistry , Plant Oils/pharmacology , Plant Oils/chemistry , Gas Chromatography-Mass Spectrometry/methods , Glycation End Products, Advanced/metabolism , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Lipase/antagonists & inhibitors , Lipase/metabolism , Glycosylation/drug effects , Glycated Serum Albumin , Humans , Serum Albumin, Bovine , Serum Albumin/metabolismABSTRACT
BACKGROUND: Diabetes mellitus is a widespread metabolic disorder affecting global populations. Lavandula stoechas from Moroccan traditional medicine is used for its potential anti-diabetic effects. OBJECTIVE: This study aims to evaluate the antihyperglycemic impact of the aqueous extract of L. stoechas (AqLs) and explore its mechanisms. METHODS: The study employed a glucose tolerance test (OGTT) on normal and diabetic Wistar rats, administering AqLs at 150 mg/kg. In vitro, AqLs was tested against α-glucosidase and α-amylase activities, confirmed in vivo using normal and Allx-diabetic rats. The extract's impact on intestinal d-glucose absorption was assessed using the jejunum segment perfusion technique at 250 mg/kg in situ. Albino mice were used to assess toxicity. RESULTS: AqLs significantly reduced postprandial hyperglycemia (P < 0.001) due to glucose overload. It inhibited pancreatic α-amylase (IC50: 0.485 mg/mL) and intestinal α-glucosidase (IC50: 168 µg/mL) in vitro. Oral AqLs at 150 mg/kg reduced hyperglycemia induced by sucrose and starch in normal and diabetic rats. It also lowered (P < 0.001) intestinal glucose absorption in situ at 250 mg/kg. Oral acute toxicity tests on Albino mice indicated no adverse effects at different doses. CONCLUSION: to summarize, L. stoechas has evident antihyperglycemic effects attributed to inhibiting intestinal glucose absorption and key monosaccharide digestion enzymes like α-amylase and α-glucosidase.
ABSTRACT
Cannabis is considered (Cannabis sativa L.) a sacred herb in many countries and is vastly employed in traditional medicine to remedy numerous diseases, such as diabetes. This research investigates the chemical composition of the aqueous extracts from Cannabis sativa L. seeds. Furthermore, the impact of these extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase enzymes is evaluated, as well as their antihyperglycemic effect. Analysis of the chemical composition of the aqueous extract was conducted using high-performance liquid chromatography with a photodiode array detector (HPLC-DAD). In contrast, the ethanol, hexanic, dichloromethane, and aqueous extract compositions have been established. Additionally, the inhibitory effects of ethanolic, dichloromethane, and aqueous extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase activities were evaluated in vitro and in vivo. The results of HPLC analysis indicate that the most abundant phenolic compound in the aqueous cannabis seed extract is 3-hydroxycinnamic acid, followed by 4-hydroxybenzoic acid and rutin acid. Moreover, administration of ethanolic and aqueous extracts at a dose of 150 mg/Kg significantly suppressed postprandial hyperglycemia compared to the control group; the ethanolic, dichloromethane, and aqueous extracts significantly inhibit pancreatic α-amylase and lipase, and intestinal α-glucosidase in vitro. The pancreatic α-amylase test exhibited an inhibition with IC50 values of 16.36 ± 1.24 µg/mL, 19.33 ± 1.40 µg/mL, 23.53 ± 1.70 µg/mL, and 17.06 ± 9.91 µg/mL for EAq, EDm, EET, and EHx, respectively. EET has the highest inhibitory capacity for intestinal α-glucosidase activity, with an IC50 of 32.23 ± 3.26 µg/mL. The extracts inhibit porcine pancreatic lipase activity, demonstrating their potential as lipase inhibitors. Specifically, at a concentration of 1 mg/mL, the highest inhibition rate (77%) was observed for EDm. To confirm these results, the inhibitory effect of these extracts on enzymes was tested in vivo. The oral intake of aqueous extract markedly reduced starch- and sucrose-induced hyperglycemia in healthy rats. Administration of the ethanolic extract at a specific dose of 150 mg/kg significantly reduced postprandial glycemia compared with the control group. It is, therefore, undeniable that cannabis extracts represent a promising option as a potentially effective treatment for type 2 diabetes.