Neuroprotective effects of flavonoids: endoplasmic reticulum as the target.

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.

Endoplasmic reticulum as a target in cardiovascular diseases: Is there a role for flavonoids?

Flavonoids are found in natural health products and plant-based foods. The flavonoid molecules contain a 15-carbon skeleton with the particular structural construction of subclasses. The most flavonoid's critical subclasses with improved health properties are the catechins or flavonols (e.g., epigallocatechin 3-gallate from green tea), the flavones (e.g., apigenin from celery), the flavanones (e.g., naringenin from citrus), the flavanols (e.g., quercetin glycosides from berries, onion, and apples), the isoflavones (e.g., genistein from soya beans) and the anthocyanins (e.g., cyanidin-3-O-glucoside from berries). Scientific data conclusively demonstrates that frequent intake of efficient amounts of dietary flavonoids decreases chronic inflammation and the chance of oxidative stress expressing the pathogenesis of human diseases like cardiovascular diseases (CVDs). The endoplasmic reticulum (ER) is a critical organelle that plays a role in protein folding, post-transcriptional conversion, and transportation, which plays a critical part in maintaining cell homeostasis. Various stimuli can lead to the creation of unfolded or misfolded proteins in the endoplasmic reticulum and then arise in endoplasmic reticulum stress. Constant endoplasmic reticulum stress triggers unfolded protein response (UPR), which ultimately causes apoptosis. Research has shown that endoplasmic reticulum stress plays a critical part in the pathogenesis of several cardiovascular diseases, including diabetic cardiomyopathy, ischemic heart disease, heart failure, aortic aneurysm, and hypertension. Endoplasmic reticulum stress could be one of the crucial points in treating multiple cardiovascular diseases. In this review, we summarized findings on flavonoids' effects on the endoplasmic reticulum and their role in the prevention and treatment of cardiovascular diseases.