| First Author | Mei L | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 19370 |
| PubMed ID | 31852965 | Mgi Jnum | J:297788 |
| Mgi Id | MGI:6479266 | Doi | 10.1038/s41598-019-55980-4 |
| Citation | Mei L, et al. (2019) Paeonol attenuates inflammation by targeting HMGB1 through upregulating miR-339-5p. Sci Rep 9(1):19370 |
| abstractText | Sepsis is a life-threatening disease caused by infection. Inflammation is a key pathogenic process in sepsis. Paeonol, an active ingredient in moutan cortex (a Chinese herb), has many pharmacological activities, such as anti-inflammatory and antitumour actions. Previous studies have indicated that paeonol inhibits the expression of HMGB1 and the transcriptional activity of NF-kappaB. However, its underlying mechanism is still unknown. In this study, microarray assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results confirmed that paeonol could significantly up-regulate the expression of miR-339-5p in RAW264.7 cells stimulated by LPS. Dual-luciferase assays indicated that miR-339-5p interacted with the 3' untranslated region (3'-UTR) of HMGB1. Western blot, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) analyses indicated that miR-339-5p mimic and siHMGB1 both negatively regulated the expression and secretion of inflammatory cytokines (e.g., HMGB1, IL-1beta and TNF-alpha) in LPS-induced RAW264.7 cells. Studies have confirmed that IKK-beta is targeted by miR-339-5p, and we further found that paeonol could inhibit IKK-beta expression. Positive mutual feedback between HMGB1 and IKK-beta was observed when we silenced HMGB1 or IKK-beta. These results indicated that paeonol could attenuate the inflammation mediated by HMGB1 and IKK-beta by upregulating miR-339-5p expression. In addition, we constructed CLP model mice by cecal ligation and puncture. Paeonol was used to intervene to investigate its anti-inflammatory effect in vivo. The results showed that paeonol could improve the survival rate of sepsis mice and protect the kidney of sepsis mice. |
