PMID- 33242555 OWN - NLM STAT- MEDLINE DCOM- 20210114 LR - 20210114 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 410 DP - 2021 Jan 1 TI - Andrographolide inhibits IL-1beta release in bone marrow-derived macrophages and monocyte infiltration in mouse knee joints induced by monosodium urate. PG - 115341 LID - S0041-008X(20)30463-4 [pii] LID - 10.1016/j.taap.2020.115341 [doi] AB - Andrographolide (AND) is the major diterpenoid in A. paniculata with wide clinical application and has been shown to be a potent anti-inflammatory agent. Gout is the leading inflammatory disease of the joints, and the deposition of urate in the articular cavity attracts immune cells that release inflammatory cytokines. Monosodium urate (MSU) is known to be one of the activators of the NLRP3 (NLR family pyrin domain containing 3) inflammasome. After activation, the NLRP3 inflammasome releases interleukin-1beta (IL-1beta), which causes the development of many inflammatory diseases. The aim of the present study was to investigate whether AND attenuates the release of IL-1beta mediated by the NLRP3 inflammasome. The effects of AND were studied in bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS) and MSU and in mice with MSU-induced joint inflammation. AND suppressed MSU phagocytosis dose-dependently and markedly inhibited LPS- and MSU-induced IL-1beta release in BMDMs. Moreover, AND pretreatment inhibited the LPS-induced NLRP3 inflammasome priming stage by inhibiting the IKK/NFkappaB signaling pathway, which resulted in decreased protein expression of NLRP3 and proIL-1beta. AND induced HO-1 protein expression in a dose-dependent manner and attenuated MSU-induced ROS generation. Silencing HO-1 mitigated AND inhibition of LPS/MSU-induced IL-1beta release in J774A.1 cells. In addition, AND decreased MSU-mediated ASC binding to NLRP3. Oral administration of AND attenuated MSU-induced monocyte infiltration in mouse knee joints. These results suggest that the working mechanisms by which AND down-regulates MSU-induced joint inflammation might be via HO-1 induction and attenuation of ROS-mediated NLRP3 inflammasome assembly and subsequent IL-1beta release. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Lo, Chia-Wen AU - Lo CW AD - Department of Nutrition, China Medical University, Taichung, Taiwan. FAU - Lii, Chong-Kuei AU - Lii CK AD - Department of Nutrition, China Medical University, Taichung, Taiwan; Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan. FAU - Hong, Jian-Jhe AU - Hong JJ AD - Department of Nutrition, China Medical University, Taichung, Taiwan. FAU - Chuang, Wei-Ting AU - Chuang WT AD - Department of Nutrition, China Medical University, Taichung, Taiwan. FAU - Yang, Ya-Chen AU - Yang YC AD - Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan. FAU - Huang, Chin-Shiu AU - Huang CS AD - Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan. FAU - Chen, Haw-Wen AU - Chen HW AD - Department of Nutrition, China Medical University, Taichung, Taiwan. Electronic address: chenhw@mail.cmu.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201124 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Diterpenes) RN - 0 (IL1B protein, mouse) RN - 0 (Interleukin-1beta) RN - 268B43MJ25 (Uric Acid) RN - 410105JHGR (andrographolide) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Antioxidants/toxicity MH - Cell Line MH - Cells, Cultured MH - Diterpenes/*pharmacology MH - Humans MH - Interleukin-1beta/*antagonists & inhibitors/metabolism MH - Knee Joint/*drug effects/metabolism/pathology MH - Macrophages/*drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/*drug effects/metabolism MH - Uric Acid/*toxicity OTO - NOTNLM OT - Andrographolide (AND) OT - Bone marrow-derived macrophages (BMDMs) OT - Gout OT - Interleukin 1beta (IL-1beta) OT - Monosodium urate (MSU) OT - NLR family pyrin domain containing 3 (NLRP3) inflammasome EDAT- 2020/11/27 06:00 MHDA- 2021/01/15 06:00 CRDT- 2020/11/26 20:08 PHST- 2020/08/03 00:00 [received] PHST- 2020/11/12 00:00 [revised] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/11/27 06:00 [pubmed] PHST- 2021/01/15 06:00 [medline] PHST- 2020/11/26 20:08 [entrez] AID - S0041-008X(20)30463-4 [pii] AID - 10.1016/j.taap.2020.115341 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2021 Jan 1;410:115341. doi: 10.1016/j.taap.2020.115341. Epub 2020 Nov 24.