PMID- 36419253 OWN - NLM STAT- MEDLINE DCOM- 20230131 LR - 20230202 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) VI - 51 IP - 1 DP - 2023 TI - Andrographolide Inhibits Lipotoxicity-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages. PG - 129-147 LID - 10.1142/S0192415X23500088 [doi] AB - Andrographolide is the major bioactive component of the herb Andrographis paniculata and is a potent anti-inflammatory agent. Obesity leads to an excess of free fatty acids, particularly palmitic acid (PA), in the circulation. Obesity also causes the deposition of ectopic fat in nonadipose tissues, which leads to lipotoxicity, a condition closely associated with inflammation. Here, we investigated whether andrographolide could inhibit PA-induced inflammation by activating autophagy, activating the antioxidant defense system, and blocking the activation of the NLRP3 inflammasome. Bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and then activated with PA. LPS/PA treatment increased both the mRNA expression of NLRP3 and IL-1[Formula: see text] and the release of IL-1[Formula: see text] in BMDMs. Andrographolide inhibited the LPS/PA-induced protein expression of caspase-1 and the release of IL-1[Formula: see text]. Furthermore, andrographolide attenuated LPS/PA-induced mtROS generation by first promoting autophagic flux and catalase activity, and ultimately inhibiting activation of the NLRP3 inflammasome. Our results suggest that the mechanisms by which andrographolide downregulates LPS/PA-induced IL-1[Formula: see text] release in BMDMs involve promoting autophagic flux and catalase activity. Andrographolide may thus be a candidate to prevent obesity- and lipotoxicity-driven chronic inflammatory disease. FAU - Yen, Chih-Ching AU - Yen CC AD - Department of Respiratory Therapy, China Medical University, Taichung, Taiwan. AD - Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Lii, Chong-Kuei AU - Lii CK AD - Department of Nutrition, China Medical University, Taichung, Taiwan. AD - Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan. FAU - Chen, Chih-Chieh AU - Chen CC AD - Department of Nutrition, China Medical University, Taichung, Taiwan. FAU - Li, Chien-Chun AU - Li CC AD - Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Tseng, Meng-Hsien AU - Tseng MH AD - Department of Nutrition, China Medical University, Taichung, Taiwan. FAU - Lo, Chia-Wen AU - Lo CW AD - Department of Nutrition, China Medical University, Taichung, Taiwan. FAU - Liu, Kai-Li AU - Liu KL AD - Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Yang, Ya-Chen AU - Yang YC 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. LA - eng PT - Journal Article DEP - 20221125 PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 410105JHGR (andrographolide) RN - 0 (Lipopolysaccharides) RN - EC 1.11.1.6 (Catalase) RN - 0 (Antioxidants) RN - 0 (Interleukin-1) RN - 0 (Nlrp3 protein, mouse) SB - IM MH - Animals MH - Mice MH - *Inflammasomes/metabolism MH - *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism MH - Lipopolysaccharides/adverse effects MH - Catalase/metabolism MH - Macrophages/metabolism MH - Inflammation/metabolism MH - Antioxidants/metabolism MH - Interleukin-1/metabolism MH - Mice, Inbred C57BL OTO - NOTNLM OT - Andrographolide (AND) OT - Autophagy OT - Bone Marrow-Derived Macrophages (BMDMs) OT - NLRP3 Inflammasome OT - Palmitic Acid (PA) EDAT- 2022/11/25 06:00 MHDA- 2023/02/01 06:00 CRDT- 2022/11/24 00:52 PHST- 2022/11/25 06:00 [pubmed] PHST- 2023/02/01 06:00 [medline] PHST- 2022/11/24 00:52 [entrez] AID - 10.1142/S0192415X23500088 [doi] PST - ppublish SO - Am J Chin Med. 2023;51(1):129-147. doi: 10.1142/S0192415X23500088. Epub 2022 Nov 25.