Activity of Bioactive Natural Compounds as Potential Agonists of GLP1R

The general objective of the present project is to confirm the activity of non-peptide compounds from bioactive natural sources, concretely jubenine, which will be a GLP1R agonists for their potential therapeutic usefulness for the treatment of obesity. The objective of the present trial was the determination of the effectiveness for weight loss, through a preclinical trial, of those compounds with the greatest potential, which according to our previous data, is jubenin. The design of the present study is a double-blind, randomized, placebo-controlled, crossover pilot trial conducted on healthy men and women volunteers. Individuals will be randomized to receive placebo, one of a range of jubenine doses, and a nopal extract for 7 days, where participants will be maintained on a precisely controlled diet along the different interventions. Each subject will receive three standardized meals daily with 30% of calories from fat. On the intervention days, meals will be distributed at breakfast, lunch and dinner, along with one of the indicated doses according to their randomization. Meals were distributed at 08:30, 13:30 and 20:00, trying to adjust to the patients\' habits. A nurse will be present during the distribution of meals to ensure the intake of the compound. All treatments will be delivered on green capsules, size 0, made with hard gelatin (head and body) (provided by Guinama Ltd, Valencia, Spain). These capsules are capable of disintegrating in less than 15 minutes and meet the requirements of the European Pharmacopoeia and USP. Capsucel (microcrystalline cellulose, Guinama Ltd, Valencia, Spain), will be employed as excipient in all treatments. Jubenine will be extracted from prickly pears following standard chemistry procedures. Jubenine, a prickly pear extract, with a 50% of jubanine content, will be obtained from Metapharmaceuticals (Metapharmaceuticals Ltd, Barcelona, Spain). The treatments will be made by two researchers, who will not be present at the time of administration. These researchers will also carry out the randomization, according to a Latin Square procedure, to ensure that all participants followed all the interventions. Randomization will be performed by a member of the research group with Excel software, with a visual basic Macro developed to this end. Each study will comprise an initial screening visit one week prior to the start of the study, with a 1-day run-in period, 7-day treatment period and a 1-day post-treatment follow-up visit. The initial evaluation will be carried out by a physician, where a complete physical examination will be performed. This will allow us to exclude the presence of any disease or disorder in the participants, so all volunteers took part in the study. The main endpoint of the effectiveness of the study will be changes in hunger/satiety sensations, determined by a visual analogic scale. Secondary endpoints will be clinical signs, and tolerability (gastrointestinal adverse effects), and clinical laboratory parameters, in particular, cholesterol, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and triglycerides.