5,7-Dihydroxychromone is a natural antioxidant extracted from plants, such as peanut shell. It acts as an Nrf2/ARE signal activator [1]; or a PPARγ agonist [2].
NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signal has an important effect on the induction of antioxidant gene expression, the activation of Nrf2 can neutralize oxidative stress. Under normal state, Nrf2 is localized in the cytoplasm, antioxidant agents induce nuclear translocation of Nrf2 and subsequently make the Nrf2/ARE complex mediate the induction of antioxidant enzyme genes.
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family;
PPAR isoforms (α, β/δ, and γ) are key regulators of glucose absorption, lipid metabolism, proliferation, and cellular differentiation. PPARγ agonists are commonly used as insulin sensitizers for the treatment of type 2 diabetes mellitus.
In vitro: 5,7-Dihydroxychromone (DHC) (0.4–10 μM) was found to protect against neuronal cell death and the ROS generation in a dose-dependent manner in 6-OHDA-induced SH-SY5Y cells. DHC (0.08–10 μM) also dose-dependently increased the induction of nuclear Nrf2, which has a binding affinity to ARE and activates ARE-driven phase II antioxidant enzymes; NQO1, HO-1, and GCLc[1]. Daphniphyllum macropodum fruit extract (DME) administration in vivo and its major component 5,7-dihydroxychromone (1, 5, and 10 μg/mL) treatment in vitro dose dependently increased the mRNA expressions of PPARγ and LXRα in 3T3-L1 cells, 5,7-dihydroxychromone (1 μg/mL ) also potently increased adipocyte differentiation, suggesting that it functions as a PPARγ agonist and has anti-diabetic properties[2]. 5,7-dihydroxychromone also demonstrated significant activity against HIV replication in H9 lymphocyte cells[3].

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