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.

Aim In this study, we examined the anti‐inflammatory effect of fermented brown rice and rice bran with Aspergillus oryzae (FBRA) on acute and chronic inflammation mouse models. Methods As an acute inflammation model, we used a 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced ear edema model. As a chronic inflammation model, we used an imiquimod (IMQ)‐induced psoriasis model and ragweed pollen‐induced allergic rhinitis model. We also investigated the effect of FBRA on the expression of inflammatory mediators in skin biopsies from the imiquimod‐induced psoriasis model. Results The mice fed the 10% FBRA‐containing diet showed lower‐level inflammation among the three different experimental models. In the IMQ‐induced psoriasis model, mRNA expressions of IL‐17A, IL‐1β and COX‐2 were significantly inhibited in the skin tissue of mice fed 10% FBRA diet. Conclusion Our data suggest the potential benefit of FBRA as a functional food to prevent excessive inflammation.

Background Morus alba L. bark has been widely used in traditional medicine for treating several inflammatory diseases, such as hypertension, diabetes mellitus and coughing; however, the molecular mechanisms underlying its anti-inflammatory effects are not well understood. Methods We examined the effects of an extract of Morus alba L. bark (MabE) on Toll-like receptor (TLR) ligand-induced activation of RAW264.7 macrophages using a luciferase reporter assay and immunoassays. For the in vivo experiment, we used an imiquimod-induced ear edema model to examine the anti-inflammatory effects of MabE. Results MabE inhibited the TLR ligand-induced activation of NF-κB in RAW264.7 cells without affecting their viability. Consistent with the inhibition of NF-κB activation, MabE also inhibited the production of IL-6 and IL-1β from TLR ligand-treated RAW264.7 cells. In vivo MabE treatment inhibited the ear swelling of IMQ-treated mice, in addition to the mRNA expression of IL-17A, IL-1β and COX-2. The increases in splenic γδT cells in IMQ-treated mice and the production of IL-17A from splenocytes were significantly inhibited by MabE treatment. Conclusion Our study suggests that the anti-inflammatory effects of MabE on the activation of the macrophage cell line RAW246.7 by TLRs and IMQ-induced ear edema are through the inhibition of NF-κB activation and IL-17A-producing γδT cells, respectively.