Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation.

The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1ß induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1ß induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases.

Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272 and MG4577 Modulate Allergic Inflammatory Response in RAW 264.7 and RBL-2H3 cells.

Allergic inflammation refers to a hyperimmune reaction that causes hypersensitivity responses such as hives, itchiness, runny nose, and cough due to specific allergens. Allergic diseases are known to be influenced by the diversity and distribution of intestinal microbiota, and Lactobacill is known to relieve allergic symptoms by modulating cytokines secreted by T helper type 1 (Th1)/Th2 cells. This study was designed to investigate the effects of Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272, MG4577, and MG4657 on levels of pro-inflammatory cytokines and proteins associated with allergic symptoms in RAW 264.7 macrophages, and RBL-2H3 mast cells, as well as their probiotic properties. MG4247, MG4272, and MG4577 significantly reduced tumor necrosis factor-α and interleukin (IL)-6 levels in LPS-induced RAW 264.7 macrophages, and markedly decreased IL-4, IL-5, and IL-13 levels and STAT6 phosphorylation in DNP-IgE/HSA sensitized RBL-2H3 mast cells. Furthermore, MG4247, MG4272, and MG4577 tolerated the acidic condition with pepsin and basic condition with bile salt, and showed a high adhesion rate (≥ 73.9%). In safety evaluation, MG4247, MG4272, and MG4577 showed no hemolytic or bile salt hydrolase activity and no cytotoxicity to HT-29 cells (≥ 96.7%). Hence, MG4272, MG4272, and MG4577 can be used as candidate probiotic strains to relieve cytokines associated with allergic inflammation.