Paeonol Attenuates Inflammation by Targeting HMGB1 Through Upregulating miR-339-5p

Published on Dec 18, 2019in Scientific Reports3.998
· DOI :10.1038/S41598-019-55980-4
Liyan Mei5
Estimated H-index: 5
(Guangzhou University of Chinese Medicine),
Meihong He1
Estimated H-index: 1
(Guangzhou University of Chinese Medicine)
+ 14 AuthorsHui Li17
Estimated H-index: 17
(Guangzhou University of Chinese Medicine)
Sources
Abstract
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-κB. 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-1β and TNF-α) in LPS-induced RAW264.7 cells. Studies have confirmed that IKK-β is targeted by miR-339-5p, and we further found that paeonol could inhibit IKK-β expression. Positive mutual feedback between HMGB1 and IKK-β was observed when we silenced HMGB1 or IKK-β. These results indicated that paeonol could attenuate the inflammation mediated by HMGB1 and IKK-β 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.
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