Cyclodextrin⁻Drug Inclusion Complexes: In Vivo and In Vitro Approaches.

This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies.

Evidence of insulin-dependent signalling mechanisms produced by Citrus sinensis (L.) Osbeck fruit peel in an insulin resistant diabetic animal model.

Citrus sinensis (L.) Osbeck is extensively cultivated worldwide and one of the most consumed fruits in the world. We evaluated the therapeutic properties of the methanol extract from Citrus sinensis fruit peel (CSMe) in high-fat diet-fed streptozotocin-induced insulin-resistant diabetic rats. Body weight, food intake, and water consumption were analysed. Biochemical and molecular biologic indices, and the expression of insulin receptor-induced signalling molecules were assessed to identify possible mechanisms. In addition, we conducted histology of pancreatic and adipose tissues. UHPLC-MS/MS analysis showed the presence of 17 dietary phenolics at substantial concentrations. High-fat diet-fed streptozotocin-induced diabetic rats administered CSMe (50 and 100 mg/kg) had reduced fasting blood glucose (56.1% and 55.7%, respectively) and plasma insulin levels (22.9% and 32.7%, respectively) compared with untreated diabetic control rats. CSMe reversed the biochemical abnormalities in diabetic rats, showed cytoprotective activity, and increased the intensity of the positive immunoreactions for insulin in pancreatic islets. CSMe treatment increased the expression of PPARγ in the adipose tissue and signalling molecules GLUT4 and insulin receptor. Our data suggest that CSMe could optimize glucose uptake of adipose tissues through the insulin-dependent signalling cascade mechanism and it should be investigated in the management of individuals with type 2 diabetes mellitus.