Reassessing the role of phytochemicals in cancer chemoprevention

The chemopreventive effects of Curcumin against oxidative stress induced by Cadmium or H2O2are mediated by Nrf2/ARE signaling and protective autophagy in myeloid cells

“…In biology and medicine, hormesis denotes the adaptive response of cells and organisms to moderate, typically intermittent, stress (Calabrese et al, 2007, Calabrese et al, 2023. The low concentration of Cur employed in the present study is compatible with a hormetic dose that "directly" or "indirectly" can trigger an adaptive cellular response by acting on the Nrf2/Keap1 system (Calabrese et al, 2007, Russo et al, 2024. Our hypothesis is that the presence of Cur, even at low concentrations, induces a moderate cellular pro-oxidant response ( (Nimiya et al, 2016) and Figure 5), not sufficient to induce cellular damage but enough to activate protective autophagy and the antioxidant response dependent on p62 SQSTM1 /Nrf2/Keap1, as suggested by the increased expression of GSH HO and NQO1.…”

“…As far as we know, this study stands out as one of the few to demonstrate the biological activities of Cur at low micromolar concentration (Russo et al, 2024) evidencing that nutritional doses of the molecule can be associated with measurable chemopreventive effects measured by the capacity to establish crosstalk between autophagy and the Nrf2 system in cellular models resembling human peripheral myeloid cells (Tang et al, 2022, Wahyudi et al, 2022.…”

“…An intrinsic limitation of our study, as mentioned in the Introduction section, is represented by the low bioavailability of Cur, which is a very unstable molecule with rapid clearance (Table 2) and possesses toxical potential, resulting in its categorization as a pan-assay interference compound (PAIN) (Nelson et al, 2017), although the low concentrations employed in the present work strongly limits this eventuality. A thorough review of the literature found that there are very few double-blind human clinical trials that demonstrate the therapeutic effect of Cur (Trial NCT00365209) (Russo et al, 2024). Thus, it is crucial to ascertain that Cur possesses real therapeutic potential rather than being a mere "PAIN".…”

Modulatory Effects of Phytochemicals on Gut–Brain Axis: Therapeutic Implication

“…Phytochemicals, which are compounds derived from plants, have been the subject of extensive research over the past few decades [ [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] ]. These natural products, which encompass different classes of compounds ( Figure 1 ), have been demonstrated to exert regulatory effects on the GBA.…”