Unveiling the Therapeutic Potential of Sarcopoterium spinosum Fruits: A Comprehensive Exploration from Chemical Characterization to Cellular Models of Health Challenges

The search for new bioactive compounds is of increasing interest, and it seems that despite new technical and scientific progress, most of the active ingredients have been known for centuries. Indeed, plants are an inexhaustible source of bioactive compounds that have been used since ancient times in both folk medicines and as preservatives of food. Medicinal plants have always been of interest for many kinds of industries because of their multiple applications for their antioxidant, antibacterial and cytoprotective properties. Plants, and plant-derived secondary metabolites may be applied in the management of a broad spectrum of metabolic dysfunction including obesity, fatty liver, cardiovascular disease. Metabolic diseases encompass a broad category of disorders characterized by disruptions of the body's metabolic homeostasis. These conditions impact on many metabolic pathways, such as glucose and lipid metabolism, with severe consequences for human health. Many phytochemicals being found in plants may exhibit diverse properties that can modulate metabolic pathways, enhance insulin sensitivity, and regulate lipid metabolism. Among them, Sarcopoterium spinosum has emerged as a noteworthy medicinal plant with the potential to address metabolic diseases. Indigenous to the Mediterranean region and the Middle East, this botanical species boasts a rich history in traditional medicine. Recent research has spotlighted its anti-diabetic properties, particularly in the context of its root extracts exhibiting the capacity to regulate blood glucose levels and enhance insulin sensitivity. A flourishing interest has emerged regarding its role as a natural remedy for metabolic disorders, contributing to the expanding array of medicinal plants with the potential to promote metabolic equilibrium and overall well-being. Notably, ongoing investigations have predominantly focused on the roots rather than the fruits of S. spinosum. In the context of this exploration, my PhD thesis aims to study different extracts derived from S. spinosum fruits, examining their bioactive compounds and their promising potential in ameliorating health and metabolic diseases. Three extracts were prepared from S. spinosum fruits, employing water, boiling water, and ethanol as extraction solvents. The ethanol extract, being distinguished by its superior radical scavenging potential, was selected for a detailed examination of the polyphenolic profile and the investigation of the potential beneficial effects. Two relevant cellular models were employed in this study: the rat hepatoma cell line (FaO) to mimic a cell model of hepatic steatosis, and the human endothelial cell line (HECV) to mimic a dysfunctional endothelium. The findings unveiled a rich profile of bioactive compounds for the ethanol extract, highlighting its abundance in ellagitannins, flavonoids, and terpenoids. Notably, this comprehensive chemical composition corresponded with the extract's demonstrated lipid-lowering, antioxidant, anti-inflammatory, and cytoprotective properties. In the final step of our investigation, our focus shifted to the design and develop a cellular model of insulin resistance utilizing the human hepatoma cell line HepG2. Employing hyperinsulinemia and fat accumulation as inducers, we successfully elicited the insulin resistance in vitro and this model will be tested using the S. spinosum extracts. In conclusion, the outcome of this PhD thesis shows that S. spinosum fruits could be a source of many bioactive compounds and the extracts represent a promising candidate to develop nutraceuticals or dietary supplements to treat/prevent obesity-related metabolic diseases.