The role of polyphenols in modulating mitophagy: Implications for therapeutic interventions.

This review rigorously assesses the burgeoning research into the role of polyphenols in modulating mitophagy, an essential cellular mechanism for the targeted removal of impaired mitochondria. These natural compounds, known for their low toxicity, are underscored for their potential in therapeutic strategies against a diverse array of diseases, such as neurodegenerative, cardiovascular, and musculoskeletal disorders. The analysis penetrates deeply into the molecular mechanisms whereby polyphenols promote mitophagy, particularly by influencing crucial signaling pathways and transcriptional regulators, including the phosphatase and tensin homolog (PTEN) induced putative kinase 1 (PINK1)/parkin and forkhead box O3 (FOXO3a) pathways. Noteworthy discoveries include the neuroprotective properties of resveratrol and curcumin, which affect both autophagic pathways and mitochondrial dynamics, and the pioneering integration of polyphenols with other natural substances to amplify therapeutic effectiveness. Furthermore, the review confronts the issue of polyphenol bioavailability and emphasizes the imperative for clinical trials to corroborate their therapeutic viability. By delivering an exhaustive synthesis of contemporary insights and recent advancements in polyphenol and mitophagy research, this review endeavors to catalyze additional research and foster the creation of innovative therapeutic modalities that exploit the distinctive attributes of polyphenols to manage and prevent disease.

Flavonoids as therapeutic agents for epilepsy: unveiling anti-inflammatory and antioxidant pathways for novel treatments.

Epilepsy, a chronic neurological disorder affecting millions globally, is often exacerbated by neuroinflammation and oxidative stress. Existing antiepileptic drugs primarily manage symptoms, leaving the disease's progression largely unaddressed. Flavonoids, ubiquitous plant metabolites with potent anti-inflammatory and antioxidant properties, show promise in epilepsy treatment. Unlike conventional therapies, they target multiple pathophysiological processes simultaneously, offering a comprehensive approach to this complex neurological disorder. This review explores the dual role of flavonoids in mitigating neuroinflammation and reducing oxidative stress through various molecular pathways. By inhibiting key inflammatory mediators and pathways such as NF-κB, MAPK, JNK, and JAK, flavonoids offer neuronal protection. They enhance the body's natural antioxidant defenses by modulating enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase. Moreover, flavonoids influence crucial antioxidant response pathways like PI3K/AKT, Nrf2, JNK, and PKA. Despite their therapeutic promise, the low bioavailability of flavonoids poses a considerable challenge. However, cutting-edge strategies, including nanotechnology and chemical modifications, are underway to improve their bioavailability and therapeutic efficacy. These advancements support the potential of flavonoids as a valuable addition to epilepsy treatment strategies.

Therapeutic potential of resveratrol through ferroptosis modulation: insights and future directions in disease therapeutics.

Resveratrol, a naturally occurring polyphenolic compound, has captivated the scientific community with its promising therapeutic potential across a spectrum of diseases. This review explores the complex role of resveratrol in modulating ferroptosis, a newly identified form of programmed cell death, and its potential implications for managing cardiovascular and cerebrovascular disorders, cancer, and other conditions. Ferroptosis is intricately linked to the pathogenesis of diverse diseases, with resveratrol exerting multifaceted effects on this process. It mitigates ferroptosis by modulating lipid peroxidation, iron accumulation, and engaging with specific cellular receptors, thereby manifesting profound therapeutic benefits in cardiovascular and cerebrovascular conditions, as well as oncological settings. Moreover, resveratrol's capacity to either suppress or induce ferroptosis through the modulation of signaling pathways, including Sirt1 and Nrf2, unveils novel therapeutic avenues. Despite resveratrol's limited bioavailability, advancements in molecular modification and drug delivery optimization have amplified its clinical utility. Future investigations are poised to unravel the comprehensive mechanisms underpinning resveratrol's action and expand its therapeutic repertoire. We hope this review could furnish a detailed and novel insight into the exploration of resveratrol in the regulation of ferroptosis and its therapeutic prospects.