Hydroxytyrosol as a multitarget pharmacological agent for oxidative, inflammatory and metabolic disorders

Hydroxytyrosol (HTY), a phenolic compound mainly found in olive oil, has garnered significant interest in recent years due to its diverse pharmacological properties influenced by specific metabolic pathways. This review provides an in-depth analysis of the current research on HTY, with a specific focus on elucidating the key signaling pathways that underlie its antioxidant, anti-inflammatory, antidiabetic, anticancer, antiatherosclerotic, and wound healing properties. The key signaling pathways investigated include the nuclear factor erthriod 2 related factor 2 (Nrf2) activation cascade which leads to the upregulation of phase 2 detoxification genes heme oxygenase (HO1), superoxide dismutase and catalase (CAT), inhibition of the inflammatory signaling pathway of nuclear kappa B (NF-κB), modulation of PI3K/Akt/mTOR pathways in cancer cells and activation of the adenosine monophosphate activated protein kinase (AMPK) for metabolic regulation. Furthermore, HTY’s iron chelation ability not only inhibits ferroptosis cell death but also influences miRNA expression profiles, regulating various downstream targets and impacting crucial cellular processes. This review highlights the interconnected therapeutic potential of biochemical networks in addressing a spectrum of health issues, including cardiovascular diseases, neurological disorders, metabolic dysfunction, and cancer. Despite existing preclinical and clinical evidence indicating that HTY possesses pathway-specific mechanisms, further investigation is required to comprehensively elucidate its interactions with multiple targets, validate its efficacy in specific disease contexts, and ensure its safe and effective application in clinical environments. To make a significant impact on human health and well-being, it is crucial to focus on addressing the identified research gaps in validating biochemical pathways and translating research findings into clinical applications.