A MULTIDISCIPLINARY APPROACH FOR THE STUDY OF ORIGANUM GENUS

THIS STUDY INVESTIGATES THE PHYTOCHEMICAL PROFILE AND BIOLOGICAL POTENTIAL OF SELECTED SPECIES OF THE GENUS ORIGANUM, WITH A FOCUS ON O. DICTAMNUS, O. MAJORANA, O. VULGARE, AND O. HERACLEOTICUM. THE WORK WAS STRUCTURED INTO THREE MAIN OBJECTIVES. FIRST, THE VOLATILE AND NON-VOLATILE FRACTIONS OF O. DICTAMNUS WERE EVALUATED. THE ESSENTIAL OIL WAS CHARACTERISED THROUGH GC–MS AND EVALUATED FOR ITS INHIBITORY EFFECTS ON KEY ENZYMES INVOLVED IN NEURODEGENERATIVE AND METABOLIC DISORDERS. KINETIC ANALYSES WERE PERFORMED TO CLARIFY THE MODE OF INHIBITION AND BY IN SILICO ANALYSIS, MOLECULAR DOCKING SUPPORTED THE IN VITRO RESULTS BY CLARIFYING THE INTERACTIONS OF THE MAIN CONSTITUENTS, IN PARTICULAR CARVACROL AND P-CYMENE, WITH THE ACTIVE SITES OF THE ENZYME. FOR THE NON-VOLATILE FRACTION, THREE EXTRACTION METHODS (MACERATION WITH 70% ETHANOL, MACERATION WITH 20% ETHANOL, AND PRESSURIZED LIQUID EXTRACTION (PLE) WITH 20% ETHANOL) WERE COMPARED IN TERMS OF EXTRACTION EFFICIENCY AND BIOLOGICAL ACTIVITY (ANTIOXIDANT AND ENZYMATIC ASSAYS). THE EXTRACT OBTAINED VIA PLE, WHICH SHOWED THE BEST OVERALL PERFORMANCE, WAS FURTHER ANALYZED BY LC-HRESIMS/MS TO CHARACTERIZE ITS METABOLIC PROFILE. THE SECOND OBJECTIVE CONSISTED OF AN INTERSPECIFIC COMPARISON OF ESSENTIAL OILS FROM O. MAJORANA, O. VULGARE, AND O. HERACLEOTICUM. THEIR CHEMICAL COMPOSITION WAS DETERMINED THROUGH GC–MS, AND THEIR ANTIOXIDANT PROPERTIES AND ENZYME INHIBITORY ACTIVITIES WERE ASSESSED ON TARGETS RELATED TO NEURODEGENERATIVE AND METABOLIC DISEASES. ENZYME KINETIC STUDIES WERE PERFORMED TO INVESTIGATE POTENTIAL DIFFERENCES IN THEIR MECHANISMS OF ACTION. THE THIRD OBJECTIVE FOCUSED ON AN INTRASPECIFIC COMPARISON OF O. HERACLEOTICUM COLLECTED FROM DIFFERENT ITALIAN REGIONS. EIGHT SAMPLES WERE ANALYSED FOR THE VOLATILE FRACTION, ALLOWING THE IDENTIFICATION OF CHEMICAL VARIABILITY THROUGH GC–MS AND MULTIVARIATE STATISTICAL ANALYSIS. SELECTED SAMPLES WERE TESTED FOR ACTIVITIES RELATED TO THE CENTRAL NERVOUS SYSTEM AND METABOLIC DISORDERS. FOR THE NON-VOLATILE FRACTION, SIX SAMPLES WERE EXTRACTED USING THE OPTIMIZED PLE METHOD AND EVALUATED FOR THEIR CHEMICAL FEATURES AND BIOLOGICAL PROPERTIES, PARTICULARLY REGARDING ENZYMES INVOLVED IN METABOLIC DYSFUNCTION. OVERALL, THE FINDINGS DEMONSTRATE CHEMICAL DIVERSITY AMONG ORIGANUM SPECIES AND HIGHLIGHT THEIR POTENTIAL AS SOURCES OF NATURAL INHIBITORS TARGETING ENZYMES IMPLICATED IN NEURODEGENERATIVE AND METABOLIC DISORDERS. THE STUDY SUPPORTS THE RELEVANCE OF ORIGANUM SPP. AS PROMISING CANDIDATES FOR NUTRACEUTICAL AND PHYTOTHERAPEUTIC APPLICATIONS