Do Certain Flavonoid IMPS Have a Vital Function?

Abstract

Flavonoids are a vast group of metabolites that are essential for vascular plant physiology and, thus, occur ubiquitously in plant-based/-derived foods. The solitary designation of thousands of known flavonoids hides the fact that their metabolomes are structurally highly diverse, consist of disparate subgroups, yet undergo a certain degree of metabolic interconversion. Unsurprisingly, flavonoids have been an important theme in nutrition research. Already in the 1930s, it was discovered that the ability of synthetic Vitamin C to treat scurvy was inferior to that of plant extracts containing Vitamin C. Subsequent experimental evidence led to the proposal of Vitamin P (permeability) as an essential phytochemical nutrient. However, attempts to isolate and characterize Vitamin P gave confusing and sometimes irreproducible results, which today can be interpreted as rooted in the unrecognized (residual) complexity of the intervention materials. Over the years, primarily flavonoids (and some coumarins) were known as having Vitamin P-like activity. More recently, in a NAPRALERT meta-analysis, essentially all of these Vitamin P candidates were identified as IMPs (Invalid/Improbable/Interfering Metabolic Panaceas). While the historic inability to define a single compound and specific mode of action led to general skepticism about the Vitamin P proposition for “bioflavonoids,” the more logical conclusion is that several abundant and metabolically labile plant constituents fill this essential role in human nutrition at the interface of vitamins, cofactors, and micronutrients. Reviewing 100+ years of the multilingual Vitamin P and C literature provides the rationales for this conclusion and new perspectives for future research.

Identification of structural features of selected flavonoids responsible for neuroprotection using a Drosophila model of Parkinson’s disease

“…Numerous epidemiological studies have shown that a diet rich in flavonoids decreases the risk of developing neurodegenerative diseases, including PD (4,8,11,(14)(15)(16)36). Neuroprotective activity of several flavonoids has also been proven in numerous animal studies, however, the molecular mechanism of action of these compounds remains elusive (2,12). It also remains unknown whether all classes of flavonoids are characterized by similar neuroprotective activity.…”

“…A score of epidemiological studies strongly points to the fact that lifestyle modifications such as regular physical activity and/or following certain types of diet, such as the Mediterranean diet, have been linked to a lower risk of developing Alzheimer's (AD) or Parkinson's disease (PD) (3)(4)(5)(6)(7)(8)(9)(10)(11). Bioactive compounds, often referred to as specialized (or secondary) metabolites abundant in plant-rich diets, have been linked to beneficial and disease-preventive effects of dietary approaches (12). Polyphenols belong to a class of abundant specialized metabolites that have been often considered as majorly responsible for the beneficial effects of plant-based diets (2,12,13).…”

“…Bioactive compounds, often referred to as specialized (or secondary) metabolites abundant in plant-rich diets, have been linked to beneficial and disease-preventive effects of dietary approaches (12). Polyphenols belong to a class of abundant specialized metabolites that have been often considered as majorly responsible for the beneficial effects of plant-based diets (2,12,13).…”

“…Single compounds displaying pleiotropic effects, such as flavonoids, have been suggested to be more effective in the prevention or treatment of multifactorial diseases (2). Seigler et al proposed that flavonoids and coumarins may play an essential role in human nutrition, following the concept of vitamin P, proposed by Szent-Györgyi (12). Previous structure-activity relationship studies focused majorly on flavonoid antioxidant effects tested using in vitro assays (37,38).…”

“…Despite many years of research on flavonoids, none of the investigated compounds has been successfully registered as a drug (2, 12). This has led to the classification of these compounds as invalid/improbable metabolic panaceas (IMPs) lacking drug-like characteristics, such as an exquisitely specific interaction with a definable receptor (2, 12, 33). Additionally, flavonoids have been often classified as pan-assay interference compounds (PAINs) due to their ability to interact with numerous targets in in vitro assays (34).…”