Flavonoid pathways models

Figure 21.3 Models of R2R3-MYB, bHLH, and WDR transcriptional control of different branches of the flavonoid pathway. (Adapted from Quattrocchio et al., [2006] and Lepiniec et al., [2006].)...

Koes, R., Verweij, W., and Quattrocchio, R, Flavonoids a colorful model for the regulation and evolution of biochemical pathways. Trends Plant Sci. 10, 236, 2005. Chandler, S., Commercialization of genetically modified ornamental plants, J. Plant Biotechnol. 5, 69, 2003. 

The best evidences are studies from preclinical animal models [86, 87, 105], or knockout animals lacking appropriate anti-oxidative pathways [106]. For example, Balb/c mice administered a variety of anti-oxidants in their chow were protected from acetaminophen hepatotoxicity [107]. Rats fed with the anti-oxidant melatonin were protected from cholesterol mediated oxidative liver damage [108]. The best clinical evidence that oxidative stress is a key player in a variety of liver injury diseases is the beneficial application of silymarin in these disease indications [109]. Silymarin is a polyphenolic plant fiavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin maria-num that has antioxidative, antilipid peroxidative, antifibrotic and anti-inflammatory effects [109, 110]. 

To fully understand the actual mechanism of action of dietary flavonoids either as antioxidants, modulators of cell signalling, or inflammatory pathways, it is important to detect and identify their metabolites in vivo as well as to study the consequences of interaction of these circulating metabolites with cells. Animal models and human studies should also be conducted to identify the in vivo mechanism of action of dietary flavonoids. Results of such studies are crucial in the evaluation of their potential as cardiovascular protective agents and may eventually lead to specific advice regarding intake of foods and beverages rich in flavonoids and attempts to alter and enhance flavonoid content of a range of foods. 

The basic structural model of flavanones is the 2-phenylbenzopiran-4-one skeleton [6], The flavanones are compounds of great interest due to the fact that they are a compulsory step in the metabolic pathway of the other flavonoids. Their metabolic precursors are the chalcones, and the flavones, the dihydroflavonols, and the isoflavones are biosynthesised from the flavanones. 

Sortinl affects the vacuolar trafficking of both proteins and flavonoids, indicating that flavonoid transport to the vacuole could share the same membrane-mediated pathway as vacuolar proteins. But this does not rule out the possibility that one of the trafficking defects is direct, whereas the other one is indirect. The fact that Sortinl mimics BSO to produce an oxidized cell environment to affect ABC transporter activity supports a model that a transporter-mediated flavonoid transport defect induces miss-trafficking of other vacuolar contents such as the proteins. On the other hand, mutants defective in flavonoid metabolism, such as tt4, show hypersensitivity to Sortinl and have altered vacuolar morphology... 

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