Amelioration of TPA-induced skin inflammation by the leaf extract of Vernonia amygdalina involves ERK/STAT3 (Ser727) signaling inhibition
Copyright © 2022 Elsevier GmbH. All rights reserved..
BACKGROUND: Uncontrolled inflammation causes health problems. Extracellular signal-regulated kinase (ERK) phosphorylates signal transducer and activator of transcription 3 (STAT3) at Ser727, resulting in inflammation. The leaf of Vernonia amygdalina (VA) is a medicinal herb for managing inflammation-associated diseases. Oral administration or topical application of VA leaf extract exerts anti-inflammatory effects in rat models. However, the anti-inflammatory mechanisms of the herb are not fully understood.
PURPOSE: In this study, we aimed to investigate the involvement of ERK/STAT3 (Ser727) signaling in the anti-inflammatory effects of an ethanolic extract of VA leaves.
STUDY DESIGN AND METHODS: Extracts of VA leaves were prepared with different concentrations of ethanol. A LPS-stimulated RAW264.7 cell model was used for in vitro assays, and a TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model was employed for in vivo assays. The 95% ethanol extract of VA leaves (VAE) exerted the strongest inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages; thus it was selected for use in this study. Hematoxylin and eosin (H&E) staining was used to examine pathological conditions of mouse ear tissues. Griess reagent was employed to examine NO generation in cell cultures. Immunoblotting and ELISA were used to examine protein levels, and RT-qPCR was employed to examine mRNA levels.
RESULTS: Topical application of VAE ameliorated mouse ear edema induced by TPA. VAE suppressed the phosphorylation of ERK (Thr202/Tyr204) and STAT3 (Ser727); and decreased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in the mouse ear tissues and in LPS-stimulated RAW 264.7 cells. VAE also inhibited NO production, and lowered mRNA levels of IL-6, IL-1β and TNF-α in the macrophages.
CONCLUSIONS: VAE ameliorates TPA-induced mouse ear edema. Suppression of ERK/STAT3 (Ser727) signaling is involved in VAE's anti-inflammatory effects. These novel data provide further pharmacological justifications for the medicinal use of VA in treating inflammation-associated diseases, and lay the groundwork for developing VAE into a new anti-inflammatory agent.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:102 |
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| Enthalten in: |
Phytomedicine : international journal of phytotherapy and phytopharmacology - 102(2022) vom: 20. Juli, Seite 154194 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Jia-Ying [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.06.2022 Date Revised 15.06.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.phymed.2022.154194 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM341822523 |
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| 100 | 1 | |a Wu, Jia-Ying |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Amelioration of TPA-induced skin inflammation by the leaf extract of Vernonia amygdalina involves ERK/STAT3 (Ser727) signaling inhibition |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 14.06.2022 | ||
| 500 | |a Date Revised 15.06.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier GmbH. All rights reserved. | ||
| 520 | |a BACKGROUND: Uncontrolled inflammation causes health problems. Extracellular signal-regulated kinase (ERK) phosphorylates signal transducer and activator of transcription 3 (STAT3) at Ser727, resulting in inflammation. The leaf of Vernonia amygdalina (VA) is a medicinal herb for managing inflammation-associated diseases. Oral administration or topical application of VA leaf extract exerts anti-inflammatory effects in rat models. However, the anti-inflammatory mechanisms of the herb are not fully understood | ||
| 520 | |a PURPOSE: In this study, we aimed to investigate the involvement of ERK/STAT3 (Ser727) signaling in the anti-inflammatory effects of an ethanolic extract of VA leaves | ||
| 520 | |a STUDY DESIGN AND METHODS: Extracts of VA leaves were prepared with different concentrations of ethanol. A LPS-stimulated RAW264.7 cell model was used for in vitro assays, and a TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model was employed for in vivo assays. The 95% ethanol extract of VA leaves (VAE) exerted the strongest inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages; thus it was selected for use in this study. Hematoxylin and eosin (H&E) staining was used to examine pathological conditions of mouse ear tissues. Griess reagent was employed to examine NO generation in cell cultures. Immunoblotting and ELISA were used to examine protein levels, and RT-qPCR was employed to examine mRNA levels | ||
| 520 | |a RESULTS: Topical application of VAE ameliorated mouse ear edema induced by TPA. VAE suppressed the phosphorylation of ERK (Thr202/Tyr204) and STAT3 (Ser727); and decreased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in the mouse ear tissues and in LPS-stimulated RAW 264.7 cells. VAE also inhibited NO production, and lowered mRNA levels of IL-6, IL-1β and TNF-α in the macrophages | ||
| 520 | |a CONCLUSIONS: VAE ameliorates TPA-induced mouse ear edema. Suppression of ERK/STAT3 (Ser727) signaling is involved in VAE's anti-inflammatory effects. These novel data provide further pharmacological justifications for the medicinal use of VA in treating inflammation-associated diseases, and lay the groundwork for developing VAE into a new anti-inflammatory agent | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute inflammation | |
| 650 | 4 | |a COX-2, cyclooxygenase-2 | |
| 650 | 4 | |a ERK | |
| 650 | 4 | |a ERK, extracellular signal-regulated kinase | |
| 650 | 4 | |a IL, interleukin | |
| 650 | 4 | |a MAPK, mitogen-activated protein kinase | |
| 650 | 4 | |a NO, nitric oxide | |
| 650 | 4 | |a STAT3 | |
| 650 | 4 | |a STAT3, signal transducer and activator of transcription 3 | |
| 650 | 4 | |a TNF-α, tumor necrosis factor-α | |
| 650 | 4 | |a TPA | |
| 650 | 4 | |a VA, Vernonia amygdalina Del. | |
| 650 | 4 | |a VAE, the 95% ethanol extract of VA leaves | |
| 650 | 4 | |a Vernonia amygdalina | |
| 650 | 4 | |a iNOS, inducible nitric oxide synthase | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Plant Extracts |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a STAT3 Transcription Factor |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
| 650 | 7 | |a 31C4KY9ESH |2 NLM | |
| 650 | 7 | |a Ethanol |2 NLM | |
| 650 | 7 | |a 3K9958V90M |2 NLM | |
| 650 | 7 | |a Nitric Oxide Synthase Type II |2 NLM | |
| 650 | 7 | |a EC 1.14.13.39 |2 NLM | |
| 650 | 7 | |a Extracellular Signal-Regulated MAP Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 700 | 1 | |a Xie, Jian-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ying-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Xiu-Qiong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Rui-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Yu-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shuo |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hai-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Chun |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhi-Ling |e verfasserin |4 aut | |
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