1. Aldose Reductase Inhibitor Engeletin Suppresses Pelvic Inflammatory Disease by Blocking the Phospholipase C/Protein Kinase C-Dependent/NF-κB and MAPK Cascades.
- Author
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Wang C, La L, Feng H, Yang Q, Wu F, Wang C, Wu J, Hou L, Hou C, and Liu W
- Subjects
- Aldehyde Reductase genetics, Aldehyde Reductase immunology, Animals, Female, Humans, MAP Kinase Signaling System drug effects, Macrophages drug effects, Macrophages immunology, Mice, Pelvic Inflammatory Disease genetics, Pelvic Inflammatory Disease immunology, Protein Kinase C genetics, RAW 264.7 Cells, Rats, Rats, Sprague-Dawley, Transcription Factor RelA genetics, Type C Phospholipases genetics, Aldehyde Reductase antagonists & inhibitors, Anti-Inflammatory Agents administration & dosage, Enzyme Inhibitors administration & dosage, Flavonols administration & dosage, Glycosides administration & dosage, Pelvic Inflammatory Disease diet therapy, Protein Kinase C immunology, Transcription Factor RelA immunology, Type C Phospholipases immunology
- Abstract
Pelvic inflammatory disease (PID) is a common inflammation in the upper reproductive tract in women and may cause serious and costly consequences without effective treatment. Engeletin is a flavanonol glycoside and a naturally derived aldose reductase (AR) inhibitor that is widely distributed in vegetables, fruits, and plant-based foods. The present study investigated the anti-PID activity of engeletin in a mucilage-induced rat model of PID and LPS-stimulated RAW 264.7 macrophages. Engeletin significantly reduced inflammation and ameliorated the typical uterine pathological changes in PID rats. Engeletin also inhibited AR-dependent PLC/PKC/NF-κB and MAPK inflammatory pathways, as indicated by the suppression of the phosphorylation levels of PLC, PKC, p38, ERK, and JNK and the nuclear translocation of NF-κB p65. In vitro studies demonstrated that engeletin significantly inhibited inflammatory mediator expression and enhanced the phagocytic ability of LPS-induced RAW 264.7 macrophages. RNA interference of AR prevented the engeletin-induced inhibition of inflammatory mediators. Engeletin also inhibited AR-dependent PLC/PKC/NF-κB and MAPK inflammatory pathways, which was consistent with the in vivo results. These findings support engeletin as a potential agent for prevention or treatment of PID.
- Published
- 2020
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