Flavonoids and Related Members of the Aromatic Polyketide Group in Human Health and Disease: Do They Really Work?

Abstract

Some aromatic polyketides such as dietary flavonoids have gained reputation as miraculous molecules with preeminent beneficial effects on human health, for example, as antioxidants. However, there is little conclusive evidence that dietary flavonoids provide significant leads for developing more effective drugs, as the majority appears to be of negligible medicinal importance. Some aromatic polyketides of limited distribution have shown more interesting medicinal properties and additional research should be focused on them. Combretastatins, analogues of phenoxodiol, hepatoactive kavalactones, and silymarin are showing a considerable promise in the advanced phases of clinical trials for the treatment of various pathologies. If their limitations such as adverse side effects, poor water solubility, and oral inactivity are successfully eliminated, they might be prime candidates for the development of more effective and in some case safer drugs. This review highlights some of the newer compounds, where they are in the new drug pipeline and how researchers are searching for additional likely candidates.

Multi-Therapeutic Potential of Naringenin (4′,5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms

“…Various research groups have reported the hepatoprotective potential of naringenin [ 11 , 96 , 97 , 98 , 99 , 100 , 101 ], which is attributed to its potential in neutralizing the ROS via increased expression and activation of antioxidant enzymes [ 102 , 103 ] and the ability to amend gamma-glutamylcysteine synthetase (GGT) enzyme activity, which is involved in the GSH synthesis pathway [ 104 , 105 , 106 ]. Reportedly, pre-treatment with naringenin causes a decline in levels of AST and ALT, while antioxidant parameters, viz GPx, SOD, CAT, and GSH, have shown a significant increase [ 101 , 107 ]. The groups of rats intoxicated with CCl4 have shown repression of caspase-3 and -9 levels [ 108 ].…”

Anticancer Activities of Marine-Derived Phenolic Compounds and Their Derivatives

“…Flavonoids 30-34 (Figure 3) are characterized as a class of polyphenols with polyhydroxylated 2-phenylchromen-4-one backbone [149]. Except the simplest, penimethavone A (30), all the other members of this group 31-34 are monoglycosylated with glucose or galactose.…”

From Foods to Chemotherapeutics: The Antioxidant Potential of Dietary Phytochemicals

“…However, despite their potential as a source of therapeutic drugs, only a few isolated flavonoids have, thus far, shown promise, since many of them have significant drawbacks due to their poor bioavailability, low water solubility, rapid metabolism and excretion, or possible adverse effects. Although silymarin, a flavonoid from Silybum marianum known for protecting the liver of people who ingested Amanita phalloides has been approved in an injectable form, other phenolics such as resveratrol and curcumin have shown clinically inconsistent results [155]. Epigallocatechin gallate (EGCG), for example, exhibits many anti-cancer capabilities, such as: acting as an antioxidant and an antiinflammatory; attenuating the NFκB pathway and, thus, its target genes that are involved in tumorigenesis; inhibiting angiogenesis and metastasis; and inducing apoptosis [156].…”