Characterization of the biological effects of natural compounds against inflammation, metabolic syndrome and cancer

Identifier:  TDX:2638

Handle: https://hdl.handle.net/20.500.11797/TDX2638

Authors:  Tomás Hernández, Sara

Abstract:
Natural products (NPs) have been used for the treatment and prevention of many diseases and illnesses since early human history. The main goal of this doctoral thesis is the characterization of bioactive natural compounds that could be used for the prevention or treatment of some major significant diseases, such as metabolic syndrome, neurodegenerative diseases and cancer. These medical conditions constitute an important health problem worldwide since they are included in the world leading causes of death. Since numerous studies have shown that the chronic inflammation process is directly involved in the onset of metabolic syndrome and neurodegenerative diseases we aimed to identify NP that could mitigate this harmful persistent inflammation state. In that sense, we investigated if the natural compound o-oresllinaldehyde might modulate the inflammatory response by acting as IKK-2 inhibitor. Our results confirm that o-orsellinaldehyde possesses strong anti-inflammatory properties suggesting that it may be a potential preventive or therapeutic candidate for the treatment of pathologies that deal with chronic inflammation such as metabolic syndrome and neurodegenerative diseases. Then, we examined the anti-diabetic effects of another natural compound kwon as 2,4,6-Trimethoxybenzophenone. Concretely, we analyzed the effect of this novel selective PPARγ modulator (SPPARγM) on the Cdk5-mediated phosphorylation of PPARγ as well as its influence on adipogenesis. Our data demonstrated that 2,4,6-Trimethoxybenzophenone would retain the benefits of improving insulin resistance since its able to inhibit Cdk5-meditated PPARγ phosphorylation at ser273, but minimizes the common side effects of existent drugs, such as adipogenesis, by alleviating PPARγ agonistic activity. The last part of this thesis aimed to clarify the combined effect of the two natural compounds, Quercetin and Resveratrol, on the autophagic process in HepG2 cancer cells, concluding that resveratrol potently counteracts quercetin starvation-induced autophagy and sensitizes HepG2 cancer cells to apoptosis.