Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo/Yap signalling pathway
Context: Emodin is a compound in Rheum undulatum Linne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects.Objective: Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism.Materials and methods: We used the hepatocyte stimulated by arachidonic acid (AA) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 ∼ 30 μM) for 1 h before AA + iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP.Results: In vitro, emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 μM (EC50 > 3 μM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 μM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway. In vivo, the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage.Conclusion: Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:58 |
|---|---|
| Enthalten in: |
Pharmaceutical biology - 58(2020), 1 vom: 21. Dez., Seite 333-341 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lee, Eun Hye [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 03.02.2021 Date Revised 04.12.2021 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1080/13880209.2020.1750658 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM308915895 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM308915895 | ||
| 003 | DE-627 | ||
| 005 | 20231225132752.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/13880209.2020.1750658 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1029.xml |
| 035 | |a (DE-627)NLM308915895 | ||
| 035 | |a (NLM)32306810 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lee, Eun Hye |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo/Yap signalling pathway |
| 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 Completed 03.02.2021 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Context: Emodin is a compound in Rheum undulatum Linne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects.Objective: Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism.Materials and methods: We used the hepatocyte stimulated by arachidonic acid (AA) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 ∼ 30 μM) for 1 h before AA + iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP.Results: In vitro, emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 μM (EC50 > 3 μM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 μM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway. In vivo, the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage.Conclusion: Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AMP-activated protein kinase | |
| 650 | 4 | |a Yes-associated protein 1 | |
| 650 | 4 | |a liver kinase B1 | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 650 | 7 | |a Eicosanoic Acids |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a YAP-Signaling Proteins |2 NLM | |
| 650 | 7 | |a Yap1 protein, mouse |2 NLM | |
| 650 | 7 | |a Acetaminophen |2 NLM | |
| 650 | 7 | |a 362O9ITL9D |2 NLM | |
| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a AMP-Activated Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.31 |2 NLM | |
| 650 | 7 | |a Emodin |2 NLM | |
| 650 | 7 | |a KA46RNI6HN |2 NLM | |
| 650 | 7 | |a arachidic acid |2 NLM | |
| 650 | 7 | |a PQB8MJD4RB |2 NLM | |
| 700 | 1 | |a Baek, Su Youn |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Ji Young |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Young Woo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmaceutical biology |d 1997 |g 58(2020), 1 vom: 21. Dez., Seite 333-341 |w (DE-627)NLM097504416 |x 1744-5116 |7 nnns |
| 773 | 1 | 8 | |g volume:58 |g year:2020 |g number:1 |g day:21 |g month:12 |g pages:333-341 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/13880209.2020.1750658 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 58 |j 2020 |e 1 |b 21 |c 12 |h 333-341 | ||