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Anthocyanins from the petals of  Hibiscus syriacus  L. (PS) possess anti-inflammatory, antioxidant, and antimelanogenic activities. However, it remains unclear whether PS inhibit the NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation and assembly. This study is aimed at investigating whether PS downregulate NLRP3-mediated inflammasome by inhibiting nuclear factor- κ B (NF- κ B) and endoplasmic reticulum (ER) stress. BV2 microglia cells were treated with PS in the presence of lipopolysaccharide and adenosine triphosphate (LPS/ATP), and the NLRP3-related signaling pathway was investigated. In this study, we found that LPS/ATP treatment activated the NLRP3 inflammasome, which resulted in the release of interleukin-1 β  (IL-1 β ) and IL-18. Meanwhile, PS reduced LPS/ATP-mediated NLRP3 inflammasome at 12 h by inhibiting ER stress-mediated Ca 2+  accumulation and subsequent mitochondrial reactive oxygen species (mtROS) production, which, in turn, decreased IL-1 β  and IL-18 release. Furthermore, PS inhibited the NLRP3 inflammasome 1 h after LPS/ATP treatment by suppressing the NF- κ B pathway, which downregulated Ca 2+  accumulation and mtROS production. These data showed that PS negatively regulated activation of the NLRP3 inflammasome in a time-different manner by inhibiting the NF- κ B signaling pathway in the early stage and the ER stress response in the late stage. The pathways shared Ca 2+  accumulation-mediated mtROS production, which was significantly inhibited in the presence of PS. In conclusion, our results suggested that PS has potential as a supplement against NLRP3 inflammasome-related inflammatory disorders; nevertheless, further studies are needed to determine the effect of PS in the noncanonical NLRP3 inflammasome pathways and pathological conditions in vivo.

oxidative medicine and cellular longevity

Anthocyanins from Hibiscus syriacus L. Inhibit NLRP3 Inflammasome in BV2 Microglia Cells by Alleviating NF-κB- and ER Stress-Induced Ca2+ Accumulation and Mitochondrial ROS Production