Vildagliptin attenuates acetic acid-induced colitis in rats via targeting PI3K/Akt/NFκB, Nrf2 and CREB signaling pathways and the expression of lncRNA IFNG-AS1 and miR-146a
Copyright © 2020 Elsevier B.V. All rights reserved..
Inflammatory processes, including ulcerative colitis (UC), are associated with the increase in synthesis and release of pro-inflammatory cytokines. The release of these cytokines is regulated by phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NFκB) and cAMP response element-binding protein (CREB) signaling pathways as well as over expression of microRNA 146a (miR-146a) and long non-coding RNA interferon gamma antisense 1 (lncRNA IFNG-AS1). Vildagliptin (Vilda), a dipeptidyl peptidase IV (DPP-IV) inhibitor, has an anti-inflammatory, antioxidant and anti-apoptotic effects which were established in various models. However, its possible protective effect in UC has not been clarified. Hence, the current study aimed to explore the possible prophylactic effect of different doses of Vilda against acetic acid (AA)-induced colitis in rats. Forty-eight adult Wistar rats were divided into six groups: control, Vilda (10 mg/kg/day; p.o.), AA, AA + Vilda (5 mg/kg/day; p.o.), AA + Vilda (10 mg/kg/day; p.o.) and AA + sulfasalazine (Sulfa) (100 mg/kg/day; p.o.).Low- and high-dose Vilda showed significant improvement in the disease activity index (DAI) and macroscopic assessment markers. Vilda has markedly inhibited the expression of lncRNA IFNG-AS1 and miR-146a, as well as PI3K/Akt/NFκB pathway, while activated CREB and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, and this was reflected in alleviated oxidative stress, inflammation and apoptosis. Such outcomes were more prominent with the high-dose Vilda versus low-dose Vilda and Sulfa. Moreover, the histological examination showed almost intact histological features in Vilda-treated groups when compared to AA group treated with saline. In conclusion, Vilda can be regarded as a new promising therapeutic alternative against UC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:92 |
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| Enthalten in: |
International immunopharmacology - 92(2021) vom: 01. März, Seite 107354 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fouad, Marina R [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.06.2021 Date Revised 25.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2020.107354 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Vildagliptin attenuates acetic acid-induced colitis in rats via targeting PI3K/Akt/NFκB, Nrf2 and CREB signaling pathways and the expression of lncRNA IFNG-AS1 and miR-146a |
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| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a Inflammatory processes, including ulcerative colitis (UC), are associated with the increase in synthesis and release of pro-inflammatory cytokines. The release of these cytokines is regulated by phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NFκB) and cAMP response element-binding protein (CREB) signaling pathways as well as over expression of microRNA 146a (miR-146a) and long non-coding RNA interferon gamma antisense 1 (lncRNA IFNG-AS1). Vildagliptin (Vilda), a dipeptidyl peptidase IV (DPP-IV) inhibitor, has an anti-inflammatory, antioxidant and anti-apoptotic effects which were established in various models. However, its possible protective effect in UC has not been clarified. Hence, the current study aimed to explore the possible prophylactic effect of different doses of Vilda against acetic acid (AA)-induced colitis in rats. Forty-eight adult Wistar rats were divided into six groups: control, Vilda (10 mg/kg/day; p.o.), AA, AA + Vilda (5 mg/kg/day; p.o.), AA + Vilda (10 mg/kg/day; p.o.) and AA + sulfasalazine (Sulfa) (100 mg/kg/day; p.o.).Low- and high-dose Vilda showed significant improvement in the disease activity index (DAI) and macroscopic assessment markers. Vilda has markedly inhibited the expression of lncRNA IFNG-AS1 and miR-146a, as well as PI3K/Akt/NFκB pathway, while activated CREB and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, and this was reflected in alleviated oxidative stress, inflammation and apoptosis. Such outcomes were more prominent with the high-dose Vilda versus low-dose Vilda and Sulfa. Moreover, the histological examination showed almost intact histological features in Vilda-treated groups when compared to AA group treated with saline. In conclusion, Vilda can be regarded as a new promising therapeutic alternative against UC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a PI3K/Akt/CREB | |
| 650 | 4 | |a Ulcerative colitis | |
| 650 | 4 | |a Vildagliptin | |
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| 700 | 1 | |a Zaki, Hala F |e verfasserin |4 aut | |
| 700 | 1 | |a El-Sahar, Ayman E |e verfasserin |4 aut | |
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