PMID- 34571975 OWN - NLM STAT- MEDLINE DCOM- 20211119 LR - 20211119 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 10 IP - 9 DP - 2021 Sep 6 TI - Sinapic Acid Controls Inflammation by Suppressing NLRP3 Inflammasome Activation. LID - 10.3390/cells10092327 [doi] LID - 2327 AB - A natural phenolic acid compound, sinapic acid (SA), is a cinnamic acid derivative that contains 3,5-dimethoxyl and 4-hydroxyl substitutions in the phenyl ring of cinnamic acid. SA is present in various orally edible natural herbs and cereals and is reported to have antioxidant, antitumor, anti-inflammatory, antibacterial, and neuroprotective activities. Although the anti-inflammatory function of SA has been reported, the effect of SA on the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome has not been explored. In the present study, to elucidate the anti-inflammatory mechanism of SA, we examined whether SA modulates the NLRP3 inflammasome. We found that SA blocked caspase-1 activation and IL-1beta secretion by inhibiting NLRP3 inflammasome activation in bone marrow-derived macrophages (BMDMs). Apoptosis-associated speck-like protein containing CARD (ASC) pyroptosome formation was consistently blocked by SA treatment. SA specifically inhibited NLRP3 activation but not the NLRC4 or AIM2 inflammasomes. In addition, SA had no significant effect on the priming phase of the NLRP3 inflammasome, such as pro-IL-1beta and NLRP3 inflammasome expression levels. Moreover, we found that SA attenuated IL-1beta secretion in LPS-induced systemic inflammation in mice and reduced lethality from endotoxic shock. Our findings suggest that the natural compound SA has potential therapeutic value for the suppression of NLRP3 inflammasome-associated inflammatory diseases. FAU - Lee, Eun Hye AU - Lee EH AD - Department of Molecular Bioscience, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Korea. FAU - Shin, Jin Hak AU - Shin JH AD - Department of Molecular Bioscience, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Korea. FAU - Kim, Seon Sook AU - Kim SS AD - Department of Molecular Bioscience, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Korea. FAU - Seo, Su Ryeon AU - Seo SR AUID- ORCID: 0000-0002-4830-4965 AD - Department of Molecular Bioscience, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Korea. LA - eng GR - 2018R1A2B6006286/National Research Foundation of Korea/ GR - 2021R1A2C1008170/National Research Foundation of Korea/ GR - 2019/Kangwon National University/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210906 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Coumaric Acids) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 68A28V6010 (sinapinic acid) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Apoptosis/drug effects MH - Caspase 1/metabolism MH - Cells, Cultured MH - Coumaric Acids/*pharmacology MH - Inflammasomes/*drug effects/metabolism MH - Inflammation/*drug therapy/*metabolism MH - Interleukin-1beta/metabolism MH - Lipopolysaccharides/pharmacology MH - Macrophages/drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism MH - RAW 264.7 Cells PMC - PMC8470482 OTO - NOTNLM OT - NLRP3 inflammasome OT - bone marrow-derived macrophages OT - inflammation OT - natural compound OT - sinapic acid COIS- The authors declare that there are no conflict of interest. EDAT- 2021/09/29 06:00 MHDA- 2021/11/20 06:00 PMCR- 2021/09/06 CRDT- 2021/09/28 01:04 PHST- 2021/08/06 00:00 [received] PHST- 2021/08/31 00:00 [revised] PHST- 2021/09/03 00:00 [accepted] PHST- 2021/09/28 01:04 [entrez] PHST- 2021/09/29 06:00 [pubmed] PHST- 2021/11/20 06:00 [medline] PHST- 2021/09/06 00:00 [pmc-release] AID - cells10092327 [pii] AID - cells-10-02327 [pii] AID - 10.3390/cells10092327 [doi] PST - epublish SO - Cells. 2021 Sep 6;10(9):2327. doi: 10.3390/cells10092327.