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

Abstract

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-κB (NF-κB) 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-1β (IL-1β) and IL-18. Meanwhile, PS reduced LPS/ATP-mediated NLRP3 inflammasome at 12 h by inhibiting ER stress-mediated Ca2+ accumulation and subsequent mitochondrial reactive oxygen species (mtROS) production, which, in turn, decreased IL-1β and IL-18 release. Furthermore, PS inhibited the NLRP3 inflammasome 1 h after LPS/ATP treatment by suppressing the NF-κB pathway, which downregulated Ca2+ 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-κB signaling pathway in the early stage and the ER stress response in the late stage. The pathways shared Ca2+ 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.

A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome

“…While the specific mechanism as well as whether the effects are present in microglial mitochondria isn't clear, Kastl et a., found that TNF-α treatment on Hepa1-6 (mouse) and Huh-7 (human) liver cell lines in vitro, depolarized mitochondrial membranes, decreased ATP production, and increased ROS release. Similar mitochondrial deficits have been described in BV2 cells treated with LPS, indicating that cytokines produced by TLR activation may directly signal changes in mitochondria function and efficiency (Voloboueva et al, 2013;Molagoda et al, 2021). As previously mentioned, transient cytokine levels increase in the brain with age, thus posing a greater risk to mitochondrial heath.…”

Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway

“…In turn, black rice, as well as its active compounds, anthocyanins, have been studied for their anti-inflammatory properties, especially with regard to the inhibition of the NLRP3 inflammasome pathway. Anthocyanins from Hibiscus syriacus L. inhibited LPS/ATPinduced NLRP3 inflammasome by inhibiting the NF-κB signaling pathway and leading to the inhibition of IL-1β and IL-18 release [60]. Another study found that, C3G from black rice possessed anti-inflammatory properties in lipopolysaccharide-induced RAW 264.7 cells and carrageenan-induced inflammation in air pouches in BALB/c mice through the suppression of the proinflammatory cytokines, TNF-α and IL-1β, mechanistically via regulating NF-κB and MAPK activation [50].…”

Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis

“…An increase in intracellular concentration of this ion in conjunction with reduced levels of potassium activates the inflammasome pathway and causes the release of IL-18 and IL-1β through plasma membrane-resident Ca 2+ channels as TRPV2, TRPM2, TRPM7, and P2X7R (86). In addition, this role is further confirmed by the fact that suppressing the outflow of calcium through membrane receptors and preventing its overload in the endoplasmic reticulum through nigericin, ATP, and alum [ 79 ], inflammasome activation and L-1β maturation are inhibited. Through the ASICs (acid-sensing ion channels), plasma membrane-resident Ca 2+ channels, calcium entry is allowed from the extracellular environment inside the cell [ 80 ].…”