Bioactivity of Flavonoids

COMT-catalyzed reactions with flavonoids do not yield metabolites with increased polarity or water solubility, but these methylated products may be important bioactive forms. Information on age-related changes in COMT is limited. Lee et al.85 and Stramentinoli et al.86 found COMT activity in rats was enhanced with age. In contrast, mRNA expression of COMT was 1.3-fold lower in 26- than 3-mo-old male C3H/a mice.87 Given the potential bioactivation of flavonoids by COMT, characterizing age-related changes in this enzyme is warranted. 

More recently, studies begin to emphasize the bioactivities of flavonoids through modulating several cellular signaling pathways involved in cell apoptosis, proliferation, survival, and inflammatory responses. 

V. WHAT ARE THE POTENTIAL MECHANISMS AND TARGETS FOR THE BIOACTIVITY OF FLAVONOIDS ... 

Phytochemicals or phytonutrients are bioactive substances that can be found in foods derived from plants and are not essential for life the human body is not able to produce them. Recently, some of their characteristics, mainly their antioxidant capacity, have given rise to research related to their protective properties on health and the mechanisms of action involved. Flavonoids are a diverse group of phenolic phytochemicals (Fig. 6.1) that are natural pigments. One function of flavonoids is to protect plants from oxidative stress, such as ultraviolet rays, environmental pollution, and chemical substances. Other relevant biological roles of these pigments are discussed in other chapters of this book. 

Finally, it should also be considered that flavonoid-rich foods contain a great diversity of compounds with bioactive properties (for e.g., carotenoids, other phenolics, fiber, and minerals), and multiple interactions occur among all of them. There is also great diversity in the ingestion, absorption, and metabolism of these compounds in different populations, and all of these circumstances could camouflage any effect of flavonoids on disease prevention or treatment. 

Seo, E.-K. et ak. Bioactive prenylated flavonoids from the stem bark of Artocarpus kemando. Arch. Pharm. Res., 26, 124, 2003. 

The isolation of flavonoids from the methanol extract of G. uralensis was carried out under non-basic conditions, because some flavonoids isomerize under basic conditions, e.g. racemization of flavanones and isoflavanones, ring-open reaction of flavanones etc. Bioactive fractions were separated by some chromatographic methods and each step was monitored with anti-H. pylori activity with the paper disk method. Eighteen compounds were isolated from these bioactive fractions and... 

There is growing evidence from human feeding studies that the absorption and bioavailability and thus bioactivity of phenolic compounds and flavonoids are very much dependent on the nature of their chemical structure. Their chemical classification and dietary occurrence is briefly discussed in the following section. 

Kris-Etherton PM, Lefevre M, Beecher GR, Gross MD, Keen CL, Etherton TD. 2004. Bioactive compounds in nutrition and health-research methodologies for establishing biological function The antioxidant and anti-inflammatory effects of flavonoids on atherosclerosis. Ann Rev Nutr 24 511-538. 

Spencer JP, Abd-el-Mohsen, Rice-Evans MC. 2004. Cellular uptake and metabolism of flavonoids and their metabolites Implications for their bioactivity. Arch Biochem Biophys 423 148-161. 

In plants, biosynthesis and exudation of allelochemicals follows developmental, diurnal, and abiotic/biotic stress-dependent dynamics. Compounds from 14 different chemical classes have been linked to allelopathic interactions, including several simple phenolic acids (e.g., benzoic and hydroxycinnamic acids) and flavonoids [Rice, 1984 Macias et al., 2007]. The existence of several soil biophysical processes that can reduce the effective concentration and bioactivity of these compounds casts doubts on their actual relevance in allelopathic interactions [Olofsdotter et al., 2002]. However, there are well-documented examples of phenylpropanoid-mediated incompatible interactions among plants. Several Gramineae mediate allelopathic interactions by means of... 

Rice-Evans C, Miller NJ. 1996. Antioxidant activities of flavonoids as bioactive components of foods. Biochem Soc Transac 24 790-795. 

RICE-EVANS, C.A., MILLER, N.J., Antioxidant activity of flavonoids as bioactive compounds. Biochem. Soc. Trans., 1996, 24, 790-794. 

Anthocyanins are a class of flavonoids separated from proanthocyani-dins. Anthocyanins have been known to be highly protective and therapeutic against especially age-related diseases such as hypertension, cardiac infraction and cerebral infarction. Additionally, because the colors of anthocyanins could help to ease psychic and physical troubles or tiredness, the anthocyanins could not only relax us, but also the colors themselves could prevent and remedy many diseases, especially, age-related diseases such as hypertension, heart failure, stroke and diabetes. Generally, anthocyanins have antioxidant properties, which could protect and enhance our body systems with bioactive abilities such as the immuno-, anticancer-, antimicrobial potencies and others. 

Flavonoids represent one class of bioactive compounds that may have multiple beneficial effects on several chronic diseases [3-4]. Cocoa represents an example of a potentially rich dietary source of flavonoids. High concentrations of flavonoids are present in certain cocoas, predominately as the flavanol monomers (-)-epicatechin (epicatechin) and (+)-catechin (catechin), and as oligomers of these monomeric base units which are known as the procyanidins (Figure 1) [5]. Other potential rich dietary sources of flavonoids include tea, wine, grape juice, apples, onions and certain nuts. 

As part of the series Topics in Heterocyclic chemistry, this volume titled Bioactive Heterocycles II presents comprehensive and up-to-date reviews on selected topics concerning mainly the usefulness for human health of flavonoids and related compounds, Sophora flavonoids and their functions in Sophora species (Leguminosae), the relationship of biological activity with the diverse structures of heterocycles by quantum chemical calculation, advances in bioactive mesoionic heterocycles, and the spectroscopic properties and application of bioactive phenothiazines including also benzo[a]phenothiazines. 

Rice-Evans C, Spencer JP, Schroeter H, Rechner AR. Bioavailability of flavonoids and potential bioactive forms in vivo. Drug Metabol Drug Interact 2000 17(1-4) 291-310. 

Biflavonoids comprise a group of the flavonoid family that possesses a variety of structures, and biological activities of high relevance, sueh as anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antinociceptive, antioxidant, vasodilator, anticlotting, among others, regardless of the bioactivity of each monomer unit. The chemistry of biflavonoids is very important in many fields of research, especially because these compormds are structurally different bioactive molecules with potential for biomedical application. 

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