Paeonol attenuates inflammation by targeting HMGB1 through upregulating miR-339-5p

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.

Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome

“…The extracellular release of HMGB1 is induced when cells are stimulated, and HMGB1 is considered an important new target for treating various inflammatory diseases, including brain injury and cancer (Sun and Chao, 2005;Das et al, 2021). Some other studies revealed that Paeonol reduces sepsis by promoting the miR-339-5p expression to repress the HMGB1 and IKK-β-mediated inflammation (Mei et al, 2019). During the process of IDD, HMGB1 is significantly upregulated in the intervertebral disc (IVD) and promotes the expression of inflammatory cytokines such as prostaglandin E2 (PGE2), TNF-α, IL-6, and IL-8 and matrix metalloproteinases (MMPs) (Rajan et al, 2013;Fang and Jiang, 2016).…”

Bu Shen Yi Sui Capsule Alleviates Neuroinflammation and Demyelination by Promoting Microglia toward M2 Polarization, Which Correlates with Changes in miR‐124 and miR‐155 in Experimental Autoimmune Encephalomyelitis

“…Growing evidence has confirmed that herbs in traditional Chinese medicine (TCM) are effective in treating neurodegenerative diseases of the CNS, including Alzheimer's disease (AD) [21,22], amyotrophic lateral sclerosis (ALS) [23], and MS. Previous studies have shown that numerous prescriptions and herbal extracts of TCM have protective effects against diseases by modulating various miRs [24][25][26][27]. Thus, it is reasonable to explore new therapeutic strategies based on TCM to treat MS. Bu Shen Yi Sui capsule (BSYS) was modified from the Liu Wei Di Huang pill, a well-known traditional Chinese formula, which has been used for 10 years in MS clinical treatment at Tiantan Hospital (Beijing, China).…”

Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer’s disease by meta-analysis and adaptive boosting ensemble learning

“…MiR-339-5p is upregulated to alleviate neuroinflammation by inhibiting HMGB1 [ 106 ]. HMGB1 encodes high mobility group box 1 to produce proinflammatory cytokines by binding to receptors for advanced glycation end products (RAGE) [ 107 ] and inhibiting IKK-β and IKK-γ, which are key elements of NF-κB signaling [ 108 ].…”