Journal of Pharmacology and Therapeutic Research

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Editorial - Journal of Pharmacology and Therapeutic Research (2018) Volume 2, Issue 4

Flavonoids friends or foes.

Hanem M. Awad*

Regulatory Toxicology Lab, Centre of Excellence & Tanning Materials and Leather Technology Department, National research Centre, 12622, Dokki, Cairo, Egypt

*Corresponding Author:
Hanem M. Awad
Regulatory Toxicology Lab
Centre of Excellence & Tanning Materials and Leather Technology Department
National research Centre
12622, Dokki, Cairo, Egypt
E-mail: [email protected]

Accepted on October 09, 2018

Citation: Awad HM. Flavonoids friends or foes. J Pharmacol Ther Res 2018;2(4):4-6.

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Flavonoids, which are groups of plant bioactive compounds, are natural polyphenols and their corresponding glycosides are important constituents of fresh fruits, green vegetables, nuts, spices, seeds, tea, olive oil and red wine [1,2]. According to the chemical structures, flavonoids are classified into different subclasses including: flavonols, flavones, flavanones, flavanols, anthocyanins and isoflavones [3,4]. In plant, flavonoids are very important in protecting against oxidant damage, providing the color that attracts pollinators, and repels insects and microbes attacks. In human, flavonoids are having health benefits related to metabolic syndrome, the immune system, brain health, reducing risk of cardiovascular and photosensitivity diseases, neurodegenerative disorders, and ageing [1,2]. In addition, they are having antiviral and antibacterial properties, they also regulate gene expression and modulate some enzymatic actions [5].

In addition to their antioxidant activity, flavonoids may inhibit carcinogenesis by different mechanisms like: modulation of food-born carcinogens metabolism via inhibition and/or induction of phase I and II biotransformation enzymes; expression of various tumor-related genes including antioxidant protein genes or the tumor suppressor gene p53; abnormal proliferation suppression of early preneoplastic lesions, this suppression of cell proliferation may result from inhibition of different enzymes, including protein kinase C, tyrosine kinase, phosphatidylinositol 3-kinase [1,6-9].

Although, there is an increased interest in the use of flavonoids alone or in combination with other medicines, as food supplements and/or nutraceuticals, there is a possibility of flavonoid-drug interactions [10]. Some reported data indicated that some dietary flavonoids may have the potential to negatively interact with clinical drugs. In addition, flavonoids supplements toxicity may result from bacterial or fungal contamination or contamination with heavy metals, pesticides, and/or herbicides [11]. However, there is need for scientific support for the health benefits, identification of the active compound(s), and investigation of the possible toxicological concerns. According to Paracelsus paradigm (1493-1541), toxicity is a matter of dose; when daily consumption of these food supplements increases above a limited threshold, they may become toxic. Therefore, at higher food supplements doses, these flavonoids may become prooxidants including radicals formation instead of being radicals scavenging antioxidants [12,13].

Good antioxidant activity of these flavonoids is generally related to the presence of (1) a 3’,4’-dihydroxy (=catechol) moiety; (2) the C4=O keto group; (3) a 3-hydroxyl substituent; and (4) a C2=C3 double bond [2]. Surprisingly, the flavonoids structural requirements for good antioxidant activity are the same needed for prooxidant activity; especially the presence of a two hydroxyl groups in their B ring. Flavonoids with only one hydroxyl group in their B-rings, like apigenin and naringenin, their corresponding phenoxyl radicals have high one-electron oxidation potential [14-16]. This may be the reason behind their ability to increase formation of lipid peroxidation via enzymatic and/or chemical (auto)oxidation to their corresponding semiquinone radicals, which will be able to be scavenged by glutathione (GSH) [15-17].

In case of flavonoids which have two hydroxyl groups in their B rings, because their one-electron redox potentials are not high enough, instead, these flavonoids form two-electron oxidized quinine-metabolites [18,19]. They only oxidized to semiquinones and their corresponding isomeric quinone methides but they will not be able to co-oxidize the intracellular non enzymatic molecules like GSH [14]. Instead, they will be able to form electrophilic toxic quinine-metabolites by conjugation with GSH in addition to the possibility of alkylating intracellular macromolecules like DNA and proteins [15,18-21]. Taking quercetin as an example of flavonoids which contain catechol type B ring, its corresponding carcinogenicity, prooxidant toxicity and bacterial and mammalian mutagenicity have been related to its quinone/ quinone methide chemistry [1,21-41]. Therefore, the pro-oxidative toxicity of flavonoids containing catechol B rings is needed to be re-evaluated in order to confirm the risks and/or the benefits of these daily food ingredients.


Considering the high flavonoids intake as food additives and/or food supplements, and because the fact that the underlying mechanisms of action at the molecular level are still not fully understood and toxicity of flavonoids consumed in large doses remains unknown. For this reason, it is very important to more clearly understand the benefits, risks and related dosing and timing issues, in order to increase their benefits and to decrease to the lesser extent their risks. In addition, further clinical and epidemiological studies are greatly needed.