Anti-inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF-κB pathway

Accumulating evidence suggests that inflammation is linked to multiple pathological processes and induces cellular and molecular damage through the activation of inflammatory signaling pathways, including the NF-κB pathway. The aim of the present study was to identify natural anti-inflammatory products that can target NF-κB activity, in order to establish a novel therapeutic approach for inflammatory diseases. Using a 4T1 breast cancer cell line that expresses the firefly luciferase gene under the control of an NF-κB response element, 112 natural products were tested for their anti-inflammatory properties. Sohakuhi (Morus alba Linn. bark) extract was observed to strongly suppress NF-κB activity without affecting cell viability. To further examine the anti-inflammatory effect of Sohakuhi, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cellular damage of human HaCaT keratinocytes was evaluated. While TRAIL triggered the phosphorylation of the p65 subunit of NF-κB, leading to cellular damage in HaCaT cells, treatment with Sohakuhi extract protected HaCaT cells against TRAIL-induced cellular damage. Moreover, Sohakuhi treatment also upregulated the anti-apoptotic proteins Bcl-xL and Bcl-2. Importantly, through chemical fractionation of Sohakuhi extract, moracin O and P were confirmed to mediate its anti-inflammatory effects. Collectively, the present results indicated that Sohakuhi and moracin may represent potential candidates for the development of novel anti-inflammatory drugs.