Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action.

Mohamed Bouhrim,Abdelkhaleq Legssyer,Hamza Mechchate,Hassane Mekhfi,Amal A Alotaibi,Mohammed Al-Zharani,Salima Boutahiri,Mohamed Bnouham,Hamada Imtara,Mohammed Aziz,Bruno Eto,Abderrahim Ziyyat,Hayat Ouassou,Nour Elhouda Daoudi,Bernard Gressier

doi:10.3390/molecules26061677

Abstract

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO’s effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.

Highlights

Diabetes mellitus is chronic metabolic trouble marked by a high blood sugar level due to abnormal insulin synthesis or action [1,2]
Hypoglycemic Test in Non-Diabetic Rats. The results of this test showed that the administration of Opuntia dillenii seed oil (ODSO) at a dose of 2 mL/kg did not produce a risk of hypoglycemia on the basal blood D-glucose level of nondiabetic rats
The change in blood sugar during the six h after ODSO administration was not significant compared to the control group

Summary

Introduction

Diabetes mellitus is chronic metabolic trouble marked by a high blood sugar level due to abnormal insulin synthesis or action [1,2]. Postprandial hyperglycemia is involved in plasmatic and cellular proteins glycation, which take part in the development of diabetes complications [7,8,9] In this regard, diabetes mellitus (DM) management requires accurate postprandial glycemic control through decreasing the glucose absorption [10]. Up to 1500 species belong to the Opuntia genus, and they are distributed in several regions in the world, like the Mediterranean countries, Europe, and sub-Saharan Africa [22] The majority of these species are characterized by the production of edible and aromatic fruits [23]. This Opuntia plant spreads wildly in arid and semi-arid regions, where there is a high use and low demand for water to increase the production of Cactus, as highlighted by the Food and Agriculture Organization [24]

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