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)
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.
📖 Papers frequently viewed together
13 Authors (Hang Lei, ..., Qinglin Yang)
16 Citations
17 Authors (Qin Xu, ..., Hui Li)
6 Citations
6 Authors (Sae-Kwang Ku, ..., Jong-Sup Bae)
45 Citations
#1Shangwen Pan (HUST: Huazhong University of Science and Technology)H-Index: 7
#2Yan Wu (HUST: Huazhong University of Science and Technology)H-Index: 20
Last. You Shang (HUST: Huazhong University of Science and Technology)H-Index: 20
view all 13 authors...
Sepsis is a life-threatening state of organ dysfunction caused by infection and which can induce severe neurological disorders that lead to neuroinflammation and cognitive impairment. Inflammation has been reported to cause neuronal apoptosis in sepsis, which can finally lead to cognitive impairment. Previous studies have suggested that BML-111 can exhibit anti-inflammatory and proresolution activities. Additionally, silent information regulator 1 (SIRT1) can inhibit the NF-κB signaling pathway ...
15 CitationsSource
#1Xia Liu (Guangzhou University of Chinese Medicine)H-Index: 4
#2Qin Xu (Guangzhou University of Chinese Medicine)H-Index: 5
Last. Hui Li (Guangzhou University of Chinese Medicine)H-Index: 17
view all 15 authors...
Abstract High-mobility group box 1 (HMGB1) is a highly conserved DNA-binding nuclear protein that facilitates gene transcription and the DNA repair response. However, HMGB1 may be released by necrotic cells as well as activated monocytes and macrophages following stimulation with lipopolysaccharide (LPS), interleukin-1β (IL-1β), or tumor necrosis factor-α (TNF-α). Extracellular HMGB1 plays a critical role in the pathogenesis of acute lung injury (ALI) through activating the nuclear transcription...
15 CitationsSource
#1Jamie G. Hijmans (CU: University of Colorado Boulder)H-Index: 8
#2Kyle J. Diehl (CU: University of Colorado Boulder)H-Index: 8
Last. Christopher A. DeSouza (CU: University of Colorado Boulder)H-Index: 52
view all 8 authors...
BACKGROUND: Increased cardiovascular disease risk and prevalence associated with overweight and obesity is due, in part, to heightened inflammatory burden. The mechanisms underlying adiposity-related amplification of inflammation are not fully understood. Alterations in regulators of inflammatory processes such as microRNAs (miRs), however, are thought to play a pivotal role. OBJECTIVE: The aim of this study was to determine the influence of overweight and obesity, independent of other cardiovas...
21 CitationsSource
#1Laura Bouchareychas (UCSF: University of California, San Francisco)H-Index: 4
#2Robert L. Raffai (UCSF: University of California, San Francisco)H-Index: 25
Apolipoprotein (apo) E stands out among plasma apolipoproteins through its unprecedented ability to protect against atherosclerosis. Although best recognized for its ability to mediate plasma lipoprotein clearance in the liver and protect against macrophage foam cell formation, our recent understanding of the influence that apoE can exert to control atherosclerosis has significantly widened. Among apoE’s newfound athero-protective properties include an ability to control exaggerated hematopoiesi...
17 CitationsSource
#1Ulf Andersson (Karolinska University Hospital)H-Index: 80
#2Huan Yang (The Feinstein Institute for Medical Research)H-Index: 68
Last. Helena Erlandsson Harris (Karolinska University Hospital)H-Index: 38
view all 3 authors...
ABSTRACTIntroduction: High-mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that promotes inflammation when released extracellularly after cellular activation, stress, damage or death. HMGB1 operates as one of the most intriguing molecules in inflammatory disorders via recently elucidated signal and molecular transport mechanisms. Treatments based on antagonists specifically targeting extracellular HMGB1 have generated encouraging results in a wide number of experimental models of in...
98 CitationsSource
#1Yonghao Feng (Fudan University)H-Index: 7
#2Long Chen (Fudan University)H-Index: 6
Last. Xiaohong Shi (Fudan University)H-Index: 8
view all 6 authors...
Purpose: Recent evidence has shown the involvement of inflammation in the development of diabetic peripheral neuropathy (DPN). MicroRNA-146a (miR-146a) is closely involved in the inflammatory response. However, the role of miR-146a in the inflammatory reaction in DPN has not been clarified. This study was designed to explore the role of miR-146a in the regulation of inflammatory responses in DPN. Methods: Rats were randomly divided into three groups (n=6 per group): control group, type 2 diabete...
40 CitationsSource
#1Shiyu Zong (SHU: Shanghai University)H-Index: 4
#2Yiqiong Pu (SHU: Shanghai University)H-Index: 10
Last. Bing Wang (SHU: Shanghai University)H-Index: 13
view all 7 authors...
AbstractPaeonol, as the main phenolic compound isolated from the Chinese herbs, has been confirmed to present anti-inflammatory effects on ulcerative colitis (UC) in our previous study. However, its poor solubility has hindered its development of being a favourable pharmaceutical product in treating colon diseases. In this study, we prepared the colon-specific delivery system (Pae-SME-CSC) with paeonol-loaded self-microemulsion (Pae-SMEDDS), and evaluated its in vitro and in vivo properties, esp...
17 CitationsSource
#1Yun LiH-Index: 1
#1Yun Li (Chinese PLA General Hospital)H-Index: 6
Last. Liang An ChenH-Index: 2
view all 6 authors...
: Metastasis is a common event in cancer pathology, and represents the primary cause of cancer-associated mortality. Metastasis, which is the process in which cancer cells at the primary tumor site spread to a different location in the body and form a new tumor, is regulated by multiple factors and includes a number of steps and stages. In our previous study, it was demonstrated miR-339-5p inhibits cell migration and invasion in vitro and is associated with the tumor-node-metastasis stage and th...
10 CitationsSource
#1Ross D. Dolan (Glasgow Royal Infirmary)H-Index: 13
#2Jason Lim (Glasgow Royal Infirmary)H-Index: 1
Last. Donald C. McMillan (Glasgow Royal Infirmary)H-Index: 95
view all 5 authors...
Cancer remains a leading causes of death worldwide and an elevated systemic inflammatory response (SIR) is associated with reduced survival in patients with operable cancer. This review aims to examine the evidence for the role of systemic inflammation based prognostic scores in patients with operable cancers. A wide-ranging literature review using targeted medical subject headings for human studies in English was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. The ...
113 CitationsSource
#1Yi XuH-Index: 4
#2Jianyong ZhuH-Index: 4
Last. Yanyue TongH-Index: 4
view all 7 authors...
Paeonol (Pae) is the main active ingredient from the root bark of Paeonia moutan and the grass of Radix Cynanchi Paniculati. Numerous reports indicate that Pae effectively inhibits several types of cancer lines. In this study, we report that Pae hinders prostate cancer growth both in vivo and in vitro. Human prostate cancer lines DU145 and PC-3 were cultured in the presence of Pae. The xenograft tumor in mice was established by subcutaneous injection of DU145 cells. Cell growth was measured by M...
23 CitationsSource
Cited By8
#1Sze Chung Yuen (UM: University of Macau)H-Index: 2
#2Xiaonan Liang (UM: University of Macau)
Last. Siu-wai Leung (SZU: Shenzhen University)
view all 5 authors...
BACKGROUND Blood circulating microRNAs that are specific for Alzheimer's disease (AD) can be identified from differentially expressed microRNAs (DEmiRNAs). However, non-reproducible and inconsistent reports of DEmiRNAs hinder biomarker development. The most reliable DEmiRNAs can be identified by meta-analysis. To enrich the pool of DEmiRNAs for potential AD biomarkers, we used a machine learning method called adaptive boosting for miRNA disease association (ABMDA) to identify eligible candidates...
#1Zheng Zha (Capital Medical University)
#2Yan-Fang Gao (Capital Medical University)
Last. Lei Wang (Capital Medical University)H-Index: 21
view all 13 authors...
Background. Bu Shen Yi Sui capsule (BSYS) is a traditional Chinese medicine prescription that has shown antineuroinflammatory and neuroprotective effects in treating multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). Microglia play an important role in neuroinflammation. The M1 phenotype of microglia is involved in the proinflammatory process of the disease, while the M2 phenotype plays an anti-inflammatory role. Promoting the polarization of microgl...
#1Junfa Yang (Anhui Medical University)H-Index: 5
#2Lei Xu (Anhui Medical University)
Last. Lei Zhang (Anhui Medical University)H-Index: 34
view all 12 authors...
Paeonol is a natural phenolic compound and isolated as an active ingredient from Moutan Cortex. Paeonol derivative-6 (DPF-6) is a derivative of paeonol improved in water solubility and bioavailability. Previous studies have reported that paeonol possesses a variety of pharmacological activities, such as antioxidant and anti-inflammatory properties. Moreover, we have previously verified that DPF-6 has anti-inflammatory effects. However, the role and fundamental mechanism of DPF-6 in acute liver i...
1 CitationsSource
#1Chen Qiu (Fourth Military Medical University)H-Index: 2
#2Liu-Di Yang (Fourth Military Medical University)
Last. Min Wang (Fourth Military Medical University)H-Index: 10
view all 9 authors...
The enhanced release of inflammatory cytokines mediated by high mobility group box1 (HMGB1) leads to pain sensation, and has been implicated in the etiology of inflammatory pain. Paeonol (PAE), a major active phenolic component in Cortex Moutan, provides neuroprotective efficacy via exerting anti-inflammatory effect. However, the role and mechanism of PAE in inflammatory pain remain to be fully clarified. In this study, we showed that PAE treatment significantly ameliorated mechanical and therma...
#1Feng Zhao (Soochow University (Suzhou))
#2Zhenye Guo (Shanxi Medical University)
Last. Zhonglai Qian (Soochow University (Suzhou))
view all 6 authors...
Intervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we aimed to probe the effect of Magnoflorine (MAG) on NP cell apoptosis mediated by "M1" polarized macrophages. THP-1 cells were treated with lipopolysaccharide (LPS) to induce "M1" polarized macrophages....
#1Junfeng Heng (Soochow University (Suzhou))H-Index: 1
#2Dingye WuH-Index: 1
Last. Yiming ZhaoH-Index: 1
view all 4 authors...
BACKGROUND Sepsis is an organ dysfunction characterized by systemic inflammatory response. Micro(mi)ribonucleic acids take part in the regulation of the inflammatory response in many conditions. However, the role and mechanism of miR-106a and anoctamin 1 (ANO1) in the inflammatory response in sepsis remain largely unknown. MATERIAL AND METHODS The serum samples were collected from 31 sepsis patients and healthy volunteers. Lipopolysaccharide (LPS)-treated RAW264.7 cells were used for the study i...
1 CitationsSource
#1Tian-Tian Fan (ZJNU: Zhejiang Chinese Medical University)H-Index: 1
#2Bao-Li Cheng (ZJU: Zhejiang University)H-Index: 1
Last. Fan Su (SDUTCM: Shandong University of Traditional Chinese Medicine)H-Index: 3
view all 5 authors...
Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance...
6 CitationsSource
#1Zhi Zhao (HUST: Huazhong University of Science and Technology)H-Index: 7
#2Zhizhi Hu (HUST: Huazhong University of Science and Technology)H-Index: 4
Last. Ying Yao (HUST: Huazhong University of Science and Technology)H-Index: 16
view all 4 authors...
Abstract High mobility group box 1 (HMGB1) is a highly conserved nucleoprotein involving in numerous biological processes, and well known to trigger immune responses as the damage-associated molecular pattern (DAMP) in the extracellular environment. The role of HMGB1 is distinct due to its multiple functions in different subcellular location. In the nucleus, HMGB1 acts as a chaperone to regulate DNA events including DNA replication, repair and nucleosome stability. While in the cytoplasm, it is ...
1 CitationsSource