Dihydroquercetin Activates AMPK/Nrf2/HO-1 Signaling in Macrophages and Attenuates Inflammation in LPS-Induced Endotoxemic Mice
Copyright © 2020 Lei, Chai, Lin, Chen, Zhao, Xiong, Zhuang and Fan..
Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-oxidant effects. Oxidative stress plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation during endotoxemia. Whether and how DHQ regulates inflammatory responses in endotoxemia remains elusive. Here we show DHQ pretreatment effectively reduced the Ten-day mortality in bacterial endotoxin lipopolyssacharide (LPS)-challenged mice, suppressing LPS-induced inflammatory responses reflected by impaired production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the serum of mice. In Raw 264.7 cells, DHQ pretreatment significantly inhibited the transcriptional upregulation of TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10) and toll-like receptor 4 (TLR-4) after LPS stimulation. Additionally, knockdown of heme oxygenase-1 (HO-1), one of the most important DHQ induced antioxidant genes, cancelled the inhibition of DHQ treatment on LPS induced TNF-α, IFN-γ production. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and AMP-activated protein kinase (AMPK) phosphorylation were both enhanced by DHQ in Raw 264.7 cells, indicating a DHQ induced AMPK/Nrf2/HO-1 signal axis. In conclusion, DHQ pretreatment could protect mice against the inflammation and mortality associated with endotoxemia.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Frontiers in pharmacology - 11(2020) vom: 15., Seite 662 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lei, Liming [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
AMP-activated protein kinase |
|---|
| Anmerkungen: |
Date Revised 28.09.2020 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3389/fphar.2020.00662 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM310881293 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM310881293 | ||
| 003 | DE-627 | ||
| 005 | 20231225141044.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fphar.2020.00662 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1036.xml |
| 035 | |a (DE-627)NLM310881293 | ||
| 035 | |a (NLM)32508636 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lei, Liming |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dihydroquercetin Activates AMPK/Nrf2/HO-1 Signaling in Macrophages and Attenuates Inflammation in LPS-Induced Endotoxemic Mice |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 28.09.2020 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2020 Lei, Chai, Lin, Chen, Zhao, Xiong, Zhuang and Fan. | ||
| 520 | |a Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-oxidant effects. Oxidative stress plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation during endotoxemia. Whether and how DHQ regulates inflammatory responses in endotoxemia remains elusive. Here we show DHQ pretreatment effectively reduced the Ten-day mortality in bacterial endotoxin lipopolyssacharide (LPS)-challenged mice, suppressing LPS-induced inflammatory responses reflected by impaired production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the serum of mice. In Raw 264.7 cells, DHQ pretreatment significantly inhibited the transcriptional upregulation of TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10) and toll-like receptor 4 (TLR-4) after LPS stimulation. Additionally, knockdown of heme oxygenase-1 (HO-1), one of the most important DHQ induced antioxidant genes, cancelled the inhibition of DHQ treatment on LPS induced TNF-α, IFN-γ production. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and AMP-activated protein kinase (AMPK) phosphorylation were both enhanced by DHQ in Raw 264.7 cells, indicating a DHQ induced AMPK/Nrf2/HO-1 signal axis. In conclusion, DHQ pretreatment could protect mice against the inflammation and mortality associated with endotoxemia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AMP-activated protein kinase | |
| 650 | 4 | |a anti-inflammation | |
| 650 | 4 | |a dihydroquercetin | |
| 650 | 4 | |a endotoxemia | |
| 650 | 4 | |a heme oxygenase-1 | |
| 650 | 4 | |a nuclear factor erythroid 2-related factor 2 | |
| 700 | 1 | |a Chai, Yunfei |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Haoming |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chunbo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Mingyi |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Weiping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xiaoping |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in pharmacology |d 2010 |g 11(2020) vom: 15., Seite 662 |w (DE-627)NLM208568891 |x 1663-9812 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2020 |g day:15 |g pages:662 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fphar.2020.00662 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2020 |b 15 |h 662 | ||