Molecular mechanisms and translational therapeutic potential of plant-derived bioactives in metabolic and neurodegenerative disorders

Abstract

Metabolic disorders and neurodegenerative diseases have emerged as a set of interrelated disorders caused by inflammatory processes, oxidative stress, mitochondrial impairment and disruption of cellular signalling mechanisms. Metabolic disorders like obesity and type 2 diabetes, along with neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are characterized by common molecular mechanisms that include insulin resistance, neuroinflammation, dysregulation of energy metabolism and cellular damage. Natural bioactive compounds from plants have gained significant attention in scientific circles because of their potential to target several mechanisms at once. Phytochemicals like polyphenols, flavonoids, alkaloids, terpenoids and saponins exhibit antioxidant, anti-inflammatory, neuroprotective and metabolic activities. Bioactive compounds like curcumin, resveratrol, quercetin, epigallocatechin gallate and berberine modulate important signalling pathways like NF-?B, AMP-activated protein kinase (AMPK), PI3K/Akt, MAPK, Nrf2 and SIRT1. Nonetheless, even with promising experimental data, there are limitations associated with poor bioavailability, fast metabolism, unpredictable pharmacokinetics and lack of large-scale clinical studies. It is important to mention that some phytochemicals exhibit dose-dependent and context-dependent actions, which could suggest variations in efficacy depending on the condition being treated. There are novel approaches involving nanotechnology, bioenhancers, alteration of gut microbiota composition and precision nutrition approaches that have been proposed for solving these translational challenges. This review discusses the molecular mechanisms by which phytochemicals modulate metabolism, inflammation and neurodegeneration, but it also includes the existing limitations and contradictory results regarding these compounds.