Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

The biochemistry and medical significance of the flavonoids.

The formalin test in mice is a valid and reliable model of nociception and is sensitive for various classes of analgesic drugs. The noxious stimulus is an injection of dilute formalin (1% in saline) under the skin of the dorsal surface of the right hindpaw. The response is the amount of time the animals spend licking the injected paw. Two distinct periods of high licking activity can be identified, an early phase lasting the first 5 min and a late phase lasting from 20 to 30 min after the injection of formalin. In order to elucidate the involvement of inflammatory processes in the two phases, we tested different classes of drugs in the two phases independently. Morphine, codeine, nefopam, and orphenadrine, as examples of centrally acting analgesics, were antinociceptive in both phases. In contrast, the non-steroid anti-inflammatory drugs indomethacin and naproxen and the steroids dexamethasone and hydrocortisone inhibited only the late phase, while acetylsalicylic acid (ASA) and paracetamol were antinociceptive in both phases. The results demonstrate that the two phases in the formalin test may have different nociceptive mechanisms. It is suggested that the early phase is due to a direct effect on nociceptors and that prostaglandins do not play an important role during this phase. The late phase seems to be an inflammatory response with inflammatory pain that can be inhibited by anti-inflammatory drugs. ASA and paracetamol seem to have actions independent of their inhibition of prostaglandin synthesis and they also have effects on non-inflammatory pain.

The formalin test in mice: dissociation between inflammatory and non-inflammatory pain

https://www.amjmed.com/article/0002-9343(91)90279-7/pdf

Reactive oxygen species in living systems: source, biochemistry, and role in human disease.

Publisher Summary This chapter discusses the radical-scavenging efficiencies of flavonoids as antioxidants To test whether a certain substance acts as radical scavenger, the clearest evidence comes from the determination of reaction rate constants with a set of different specifically produced radicals In the tests discussed in the chapter, hydroxyl, azide, superoxide, linoleic acid peroxyl, tert-butoxyl, and sulfite radicals are used The spectral observation of radical reactions with flavonoids is assisted by the strong absorption characteristics of both the parent compounds and their respective aroxyl radicals Owing to the low solubility of flavonoids, conditions for pseudo-first order reactions with radical species can rarely be achieved for flavonoid aglycones Therefore, kinetic modeling calculations are employed The radical chemistry of flavonoids not only is of interest from a kinetic or mechanistic point of view but also offers considerable insight into structural relationships of highly evolved plant components First, the consistently high rate constants for attack by different types of radicals demonstrate the effective radicals scavenging capabilities of most flavonoids Second, owing to extensive electron delocalization as a prerequisite for radical stabilization, multiple mesomeric structures exist for aroxyl radical species of flavonoids

Flavonoids as antioxidants: determination of radical-scavenging efficiencies.

Oxidation of polyunsaturated fatty acids and lipids through thiyl and sulfonyl radicals: reaction kinetics, and influence of oxygen and structure of thiyl radicals.

Eine Hemmung der Cyclooxygenase-Reaktion bei der Prostaglandinbildung des Rattennierenmarks in vitro ist durch verschiedene Flavonoide mit o-Dihydroxystrukturen moglich. Diese Flavonoide mit einer Brenzcatechin-Anordnung im Molekul besitzen ausgepragte Radikalfangereigenschaften fur Peroxid-Anion-Radikale. Dagegen konnen einige Flavonoide und Phenolderivate, die starke O2−•-Radikalfanger sind, die Prostaglandinsynthetase aber auch aktivieren oder unbeeinflust lassen. Eine Korrelation zwischen den Radikalfangereigenschaften und der Beeinflussung des Cyclooxygenase-Enzyms besteht folglich bei den untersuchten Verbindungen nicht.



Prostaglandin Synthetase Inhibition by Flavonoids and Phenolic Compounds in Relation to their O2−•-Scavenging Properties



Several flavonoids containing an o-dihydroxy function inhibit the cyclo-oxygenase reaction during prostaglandin formation in the renal medulla of the rat. These flavonoids are strong scavengers for peroxide anion radicals. On the other hand, some flavonoids and phenolic compounds with strong O2−•-scavenging properties either stimulate the prostaglandin synthetase or have no effects. Thus, the radical scavenging properties of the compounds studied do not correlate with their influences on the cyclo-oxygenase activity.

[Prostaglandin synthetase inhibition by flavonoids and phenolic compounds in relation to their O2--scavenging properties (author's transl)].

Thiyl radical attack on polyunsaturated fatty acids: a possible route to lipid peroxidation.

Inhibitory actions of desacetylation products of phenacetin and paracetamol on prostaglandin synthetases in neuronal and glial cell lines and rat renal medulla

Inhibition of prostaglandin synthetases derived from neuronal and glial cells and rat renal medulla by ortho-, meta- and para-substituted aminophenolic compounds

Franz v. Bruchhausen

Papers

Oxidation of polyunsaturated fatty acids and lipids through thiyl and sulfonyl radicals: reaction kinetics, and influence of oxygen and structure of thiyl radicals.

[Prostaglandin synthetase inhibition by flavonoids and phenolic compounds in relation to their O2--scavenging properties (author's transl)].

Thiyl radical attack on polyunsaturated fatty acids: a possible route to lipid peroxidation.

Inhibitory actions of desacetylation products of phenacetin and paracetamol on prostaglandin synthetases in neuronal and glial cell lines and rat renal medulla

Inhibition of prostaglandin synthetases derived from neuronal and glial cells and rat renal medulla by ortho-, meta- and para-substituted aminophenolic compounds