Is chemo-preventive effect of Apium leptophyllum (Pers.) caused only by anti-oxidative property of flavonoids?

Sir,

I read with great enthusiasm the article by of Sahoo et al.[1] entitled “Chemo-preventive potential of Apium leptophyllum against DMBA induced skin carcinogenesis model by modulatory influence on.” In the study, flavonoids of Marsh Parsley showed a strong protective effect against induced carcinogenesis. Due to the advances of molecular sciences, in isolation and structure elucidation techniques of various natural products, it will be interesting to determine specific bioactive compounds obtained from the flavonoid fraction of this plant. However, it is not clear, what is the real molecular basis for the observed protective effect, and which bioactive compounds produced this effect. Currently, several different molecular targets of flavonoids are discussed.[2] Medicinal chemists and pharmacologists have studied mainly the anti-oxidative properties of flavonoids, and their metabolites, but flavonoids may exert effects in cells through the influence of anti-apoptotic and pro-proliferative signaling pathways. During DMBA-induced carcinogenesis, protective effect can also be caused by suppression of kinase signaling cascades such as mitogen-activated protein kinases/extracellular signal–regulated kinase, phosphoinositide 3-kinase/Akt, or inhibit induced activation of epidermal growth factor receptor-related pathway [Figure 1].[234] It can be a critical step in this carcinogenicity. However, these proliferative cascades are activated by DMBA irritation, and thus prevention of their activation by flavonoids might play an additive role in suppression of induced carcinogenesis.[56]

Figure 1

The simplified proposal of alternative action of flavonoids through suppression of pro-proliferative and anti-apoptotic kinase signaling cascades in early phase of induced carcinogenesis

Blocking of these pathways leads to a reduction of expression of some proliferative and anti-apoptotic factors and has been shown that these signaling pathways have a key role in the early phases of carcinogenesis.[6] Consequently, compounds from the flavonoid fraction of A. leptophyllum should be isolated, structurally characterized, and screened for their bioactivity in cell cultures and murine models. Whether, a part of the chemo-protective effect is not caused by the suppression of kinases related signaling pathway responsible for the cell growth and survival should be evaluated.