ABSTRACT
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.
Subject(s)
Cornus , Dermatitis , Psoriasis , Humans , Inflammasomes/metabolism , Imiquimod/adverse effects , HEK293 Cells , Psoriasis/chemically induced , Psoriasis/drug therapy , Inflammation , Plant Extracts/adverse effects , Seeds/metabolism , Caspases , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Interleukin-1beta/metabolism , Caspase 1/metabolism , DNA-Binding Proteins/metabolismABSTRACT
In the past, plastic microbeads (MBs) were added to personal healthcare products to improve the cleaning and exfoliating effects, but these have been withdrawn owing to their non-degradable nature and contribution to the pollution of marine environment, especially that caused by the adsorption of persistent organic pollutants (POPs) on MBs. Therefore, natural biodegradable alternatives are being developed, but these often do not exhibit sufficient performance to replace non-degradable MBs. In this study, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB-4HB), a biodegradable aliphatic polyester, was used to prepare MBs via melt-electrospraying. We carried out the rheological characterization of P3HB-4HB with respect to melting temperature, and the melt-electrospray process was optimized to prepare MBs having sizes similar to those of commercially available MBs. Furthermore, the adsorption properties of the P3HB-4HB MBs for POPs were investigated. Unlike commercial MBs, the P3HB-4HB MBs adsorbed significantly fewer contaminants owing to their smooth and regular surfaces. Finally, a cleansing product containing P3HB-4HB MBs was prepared to evaluate their cleaning ability, and we found that the MB-based product could remove dirt and contaminants that were not easily removed by water alone. Thus, the biodegradable P3HB-4HB MBs have great potential for use as sustainable additives for cosmetic products for skin exfoliation.
