PMID- 31767544 OWN - NLM STAT- MEDLINE DCOM- 20201021 LR - 20201021 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 78 DP - 2020 Jan TI - Schisandrin A protects against lipopolysaccharide-induced mastitis through activating Nrf2 signaling pathway and inducing autophagy. PG - 105983 LID - S1567-5769(19)31824-7 [pii] LID - 10.1016/j.intimp.2019.105983 [doi] AB - Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Schisandra chinensis (Turcz.) Baill., has anti-oxidant and anti-inflammatory effects, but the effect on masitits has not been studied. Therefore, we investigated the effect of Sch A in cell and mouse models of lipopolysaccharide (LPS)-induced mastitis. Studies in vivo showed that Sch A reduced LPS-induced mammary injury and the production of pro-inflammatory mediators. Sch A also decreased the levels of pro-inflammatory mediators and activated nuclear factor-E2 associated factor 2 (Nrf2) signaling pathway in mouse mammary epithelial cells (mMECs). The Nrf2 inhibitor partially abrogated the downregulation of Sch A on LPS-induced inflammatory response. In addition, LPS stimulation suppressed autophagy, while both Sch A and the autophagy inducer rapamycin activated autophagy in mMECs, which down-regulated inflammatory response. Sch A also restrained LPS-induced phosphorylation of mammalian target of rapamycin (mTOR) and activated AMP-activated protein kinase (AMPK) and unc-51 like kinase 1 (ULK1). In summary, these results suggest that Sch A exerts protective effects in LPS-induced mastitis models by activating Nrf2 signaling pathway and inducing autophagy and the autophagy is initiated by suppressing mTOR signaling pathway and activating AMPK-ULK1 signaling pathway. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Xu, Dianwen AU - Xu D AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Liu, Juxiong AU - Liu J AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Ma, He AU - Ma H AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Guo, Wenjin AU - Guo W AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Wang, Jiaxin AU - Wang J AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Kan, Xingchi AU - Kan X AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Li, Yanwei AU - Li Y AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Gong, Qian AU - Gong Q AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Cao, Yu AU - Cao Y AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Cheng, Ji AU - Cheng J AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. FAU - Fu, Shoupeng AU - Fu S AD - College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China. Electronic address: fushoupeng@jlu.edu.cn. LA - eng PT - Journal Article DEP - 20191122 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cyclooctanes) RN - 0 (IL1B protein, mouse) RN - 0 (Interleukin-1beta) RN - 0 (Lignans) RN - 0 (Lipopolysaccharides) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Polycyclic Compounds) RN - 0 (Tumor Necrosis Factor-alpha) RN - 74XQL5DO3S (schizandrin A) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/*therapeutic use MH - Autophagy/*drug effects MH - Cells, Cultured MH - Cyclooctanes/pharmacology/*therapeutic use MH - Epithelial Cells/drug effects/metabolism MH - Female MH - Interleukin-1beta/genetics MH - Lignans/pharmacology/*therapeutic use MH - Lipopolysaccharides MH - Mammary Glands, Animal/drug effects MH - Mastitis/chemically induced/*drug therapy/metabolism/pathology MH - Mice, Inbred C57BL MH - NF-E2-Related Factor 2/*metabolism MH - Peroxidase/metabolism MH - Polycyclic Compounds/pharmacology/*therapeutic use MH - Signal Transduction/drug effects MH - Tumor Necrosis Factor-alpha/genetics OTO - NOTNLM OT - AMPK-ULK1 OT - Autophagy OT - Mastitis OT - Nrf2 OT - Schisandrin A OT - mTOR EDAT- 2019/11/27 06:00 MHDA- 2020/10/22 06:00 CRDT- 2019/11/27 06:00 PHST- 2019/08/16 00:00 [received] PHST- 2019/10/11 00:00 [revised] PHST- 2019/10/14 00:00 [accepted] PHST- 2019/11/27 06:00 [pubmed] PHST- 2020/10/22 06:00 [medline] PHST- 2019/11/27 06:00 [entrez] AID - S1567-5769(19)31824-7 [pii] AID - 10.1016/j.intimp.2019.105983 [doi] PST - ppublish SO - Int Immunopharmacol. 2020 Jan;78:105983. doi: 10.1016/j.intimp.2019.105983. Epub 2019 Nov 22.