Potential protective mechanisms exerted by nutraceuticals in degenerative pathologies: focus on osteoarthritis and heart failure.

With the rise in life expectancy and the prevalence of chronic degenerative conditions, research efforts have intensified, focusing on age-related diseases. Osteoarthritis (OA) and heart failure (HF), both prevalent in the aging population, significantly impact the quality of life, necessitating long-term management. This thesis explores molecular mechanisms underlying OA and HF, aiming to contribute to therapeutic strategies. The investigation begins by exploring the potential therapeutic impact of olive-derived compounds, hydroxytyrosol (HT), and oleuropein (OE), in mitigating lipopolysaccharide (LPS)-induced oxidative stress and the expression of inflammation gene markers correlated with OA. Concurrently, the study elucidates the involvement of the Notch--1 pathway and MAPKs (p38 and JNK) in the inflammatory response to LPS, providing an understanding of their role in OA pathogenesis. The examination extends to the assessment of protein aggregates in LPS-treated chondrocytes and their distribution within OA cartilage, shedding light on a novel aspect of OA pathology. In the context of HF, the study establishes a 3D cardiac model derived from induced pluripotent stem cells (iPSCs), demonstrating its ability to recapitulate features of HF after exposure to endothelin-1 (ET-1). The exploration of microRNA expression profiles post ET-1 treatment identifies a characteristic signature that includes miR-129-5p as significantly up-regulated, emphasizing its potential role in the hypertrophic response. The investigation further extends to assess the impact of nutraceuticals, including epigallocatechin gallate (EGCG), spermidine (SPD), OE, and quercetin (QUE), in mitigating protein aggregate accumulation in ET-1-treated cardiac organoids. The thesis underscores the shared molecular aspects between OA and HF, such as inflammation, oxidative stress, and ECM alterations. The research contributes to understanding these diseases, opening avenues for integrated management strategies and identifying potential therapeutic targets.