Some studies have shown that flavonoids induce apoptosis of various tumour cells including K562cells. This effect has also been observed in other tumor cell lines from gastric, colon and lung carcinomas [19
]. In addition, flavonoids inhibited tumor growth through cell cycle arrest and induced apoptosis through a p53-dependent mechanism [20
Flavonoids may intervene at the different levels of lipid peroxidation process [21
]. They are able to directly capture radical species and thus interrupt the step of propagating radical [22
]. Moreover, being good chelating, they are capable to coordinate the free iron. Finally, flavonoids on the surface of the membranes are able to regenerate vitamin E, an essential antioxidant in the cell membranes protection [23
On the other hand, flavonoids are powerful antioxidants against free radicals because they act as “radical-scavengers”, the antioxidant capacity of a flavonoid is linked to its particular chemical structure. We believe that the presence of the double bond C2–C3 in conjugation with a 4-oxo in the I3-O
-Rob structure participates in the antioxidant potenty of the purified compound (I3- O
-Rob), as well as its original extract (EA extract). This hypothesis is in accordance with the results described by Rice-evans et al. [24
] and Van Acker et al. [25
], who reported that the antioxidant activity of quercetin (flavonoids with C2-C3 and C4 carbonyl function on cycle C) is greater than dihydroquercetin (flavonoids without double band C2-C3 but with C4 carbonyl function on cycle C). Rice-Evans et al. [24
] explained this property by the conjugation of rings A and B that allows the resonance of the aromatic ring, thus stabilizing the phenoxy radical.
The presence of 5-OH and 7-OH functions, together with carbonyl group may be involved in I3-O
-Rob antioxidant potenty as it has been advanced by Edenharder and Grünhage [26
], who reported that the hydroxylation of C5 and C7, together with carbonyl group in C4 meets the criteria of potent radical scavenger.
The antioxidant potenty of I3-O
-Rob can also be related to the presence of the OH group at C4 of ring B of the tested flavonoid. This hypothesis is supported by the studies of Mathiesen et al. [27
] that showed that C4 hydroxylated angolétine are more antioxidant than C4 O-methylated myrigalone.
Likewise, we believe that the presence of sugar moiety participates in antioxidant activity of I3-O
-Rob. This observation is in accordance with the results reported by Hayder et al. [28
] stipulating that glycosylated myricetin improves the antioxidant capacity of the corresponding aglycone.
EA extract exhibited a lower antioxidant capacity compared to its major constituent, I3-O-Rob. This could be explained by the presence, in the extract, of compounds with antagonistic effects and also that I3- O-Rob was diluted in the original EA extract.
Obviously, flavonoid antioxidant capacity is also linked to another structural element, which is the presence of methoxyl group on the ring B of I3-O
-Rob that could participate in the antioxidant potential of this molecule. Kawaii et al. [29
] reported that many flavonoids with methoxyl substitutions are considered potent anticancer flavonoids.
When treated with H2
, the predominant lesion in cell DNA is the strand breaks and base oxidation. Such damages can increase the risk of cancer development [30
]. The protective action of the tested compounds can be explained by their ability to penetrate through the cell membrane and to interrupt the radical chain induced by H2
, thus, allowing the prevention or reduction of free radical formation, which are responsible for cellular macromolecules damage.
Many studies reported the capacity of natural antioxidants in influencing disease progression. This property is closely related to their ability to reduce DNA damage, mutagenesis, carcinogenesis and inhibition of pathogenic bacterial growth [31
Indeed, flavonoids have been shown to be effective scavengers of reactive oxygen species (ROS), and it has been suggested that flavonoid anticancer activities greatly depend on their antioxidant and chelating properties [32
We deduce that the antigenotoxic activity can be ascribed not only to the antioxidant effect of these molecules but also to other additional mechanisms like DNA repair enzyme induction as it was evidenced by Hayder et al. [28
] who reported that, compared to myricetin alone, the antioxidant enzymes and DNA repair enzyme expression, are modulated in the presence of glycosylated myricetin, using a microarray system. In fact, Kooststra [34
] demonstrated that flavonoids should neutralize the free radicals that promote mutations, when generated near DNA. Flavonoids can also protect the DNA by directly interacting with the mutagen agents, as in the induced chromosomal aberration by bleomycin alluded by Heo et al. [35
]. Nevertheless, the inhibition of mutagenesis is often complex, acting through multiple mechanisms. Edenharder et al. [36
] demonstrated a dual role of flavonoids as far as they do not only inhibit membrane-bound cytochrome P-450-dependent monooxygenases, but also inhibit various soluble enzymatic factors, suggesting interactions with biological membranes and effects on expression and fixation of DNA damages.