Naphthoquinone derivatives as P-glycoprotein inducers in inflammatory bowel disease: 2D monolayers, 3D spheroids, and in vivo models
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Nuha Mahmoud
- Mohamed-Elamir F Hegazy
- Walaa Wadie
- Mohamed Elbadawi
- Edmond Fleischer
- Anette Klinger
- Gerhard Bringmann
- Mohamed T Khayyal
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000802223600003&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phrs.2022.106233
- eISSN
- 1096-1186
- Externe Identifier
- Clarivate Analytics Document Solution ID: 1P7ZK
- PubMed Identifier: 35462013
- ISSN
- 1043-6618
- Zeitschrift
- PHARMACOLOGICAL RESEARCH
- Schlüsselwörter
- Autophagy
- Intestinal inflammation
- Microtubules
- Naphthoquinone derivatives
- NLRP3 inflammasome
- IBD animal model
- Artikelnummer
- ARTN 106233
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Naphthoquinone derivatives as P-glycoprotein inducers in inflammatory bowel disease: 2D monolayers, 3D spheroids, and <i>in vivo</i> models
- Sub types
- Article
- Ausgabe der Zeitschrift
- 179
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Nuha Mahmoud
- Mohamed-Elamir F Hegazy
- Walaa Wadie
- Mohamed Elbadawi
- Edmond Fleischer
- Anette Klinger
- Gerhard Bringmann
- Mohamed T Khayyal
- Thomas Efferth
- DOI
- 10.1016/j.phrs.2022.106233
- ISSN
- 1043-6618
- Zeitschrift
- Pharmacological Research
- Sprache
- en
- Artikelnummer
- 106233
- Paginierung
- 106233 - 106233
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phrs.2022.106233
- Datum der Datenerfassung
- 2023
- Titel
- Naphthoquinone derivatives as P-glycoprotein inducers in inflammatory bowel disease: 2D monolayers, 3D spheroids, and in vivo models
- Ausgabe der Zeitschrift
- 179
Data source: Crossref
- Abstract
- Inflammatory bowel disease (IBD) represents a chronic inflammation of the gastrointestinal tract characterized by an overreaction of immune responses and damage at the intestinal mucosal barrier. P-glycoprotein (P-gp) plays a key role to protect the intestinal barrier from xenobiotic accumulation and suppressing excessive immune responses. Therefore, induction/activation of P-gp function could serve as a novel therapeutic target to treat IBD. This study aimed to evaluate the potential therapeutic values of naphthoquinone derivatives (NQ-1 - NQ-8) as P-gp modulators to counterbalance intestinal inflammation. The data indicate that NQ-2, NQ-3, and NQ-4 act as P-gp inducers/activators and are recognized as substrates for P-gp. The three derivatives possess anti-inflammatory effects mediated by suppression of NF-κB and HDAC6 activity in Caco2 monolayer cells. Besides, they reversed LPS-induced intestinal barrier dysfunction by enhancing the expression of P-gp and ZO-1 tight junction proteins in a Caco-2 spheroid model. NQ-2, NQ-3, and NQ-4 showed a robust inhibitory effect on IL-1β maturation in LPS-primed THP-1 cells. This effect may contribute to alleviate the inflammatory cascades associated with IBD. Distinctively, NQ-2 and NQ-3 exerted anti-NLRP3 inflammasome activity evidenced by the inhibition of CASP-1 activity and the promotion of autophagy. Both compounds induced disruptions of the microtubule network in transfected U2OS-GFP-α-tubulin cells. Treatment with NQ-2 remarkably attenuated dextran sulfate sodium (DSS)-induced colitis in rats by suppressing changes in colon length, colon mass index, and intestinal histopathology scores. Thus, 1,4-naphthoquinone derivatives such as NQ-2 may provide potential therapeutic anti-inflammatory effects for IBD patients and for other NLRP3-associated inflammatory diseases.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
- Autoren
- Nuha Mahmoud
- Mohamed-Elamir F Hegazy
- Walaa Wadie
- Mohamed Elbadawi
- Edmond Fleischer
- Anette Klinger
- Gerhard Bringmann
- Mohamed T Khayyal
- Thomas Efferth
- DOI
- 10.1016/j.phrs.2022.106233
- eISSN
- 1096-1186
- Externe Identifier
- PubMed Identifier: 35462013
- Open access
- false
- ISSN
- 1043-6618
- Zeitschrift
- Pharmacological research
- Schlüsselwörter
- Colon
- Caco-2 Cells
- Animals
- Mice, Inbred C57BL
- Humans
- Mice
- Rats
- Colitis
- Inflammatory Bowel Diseases
- Disease Models, Animal
- Inflammation
- Naphthoquinones
- Lipopolysaccharides
- Dextran Sulfate
- Anti-Inflammatory Agents
- ATP Binding Cassette Transporter, Subfamily B
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Paginierung
- 106233
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum der Datenerfassung
- 2022
- Titel
- Naphthoquinone derivatives as P-glycoprotein inducers in inflammatory bowel disease: 2D monolayers, 3D spheroids, and in vivo models.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 179
Data source: Europe PubMed Central
- Abstract
- Inflammatory bowel disease (IBD) represents a chronic inflammation of the gastrointestinal tract characterized by an overreaction of immune responses and damage at the intestinal mucosal barrier. P-glycoprotein (P-gp) plays a key role to protect the intestinal barrier from xenobiotic accumulation and suppressing excessive immune responses. Therefore, induction/activation of P-gp function could serve as a novel therapeutic target to treat IBD. This study aimed to evaluate the potential therapeutic values of naphthoquinone derivatives (NQ-1 - NQ-8) as P-gp modulators to counterbalance intestinal inflammation. The data indicate that NQ-2, NQ-3, and NQ-4 act as P-gp inducers/activators and are recognized as substrates for P-gp. The three derivatives possess anti-inflammatory effects mediated by suppression of NF-κB and HDAC6 activity in Caco2 monolayer cells. Besides, they reversed LPS-induced intestinal barrier dysfunction by enhancing the expression of P-gp and ZO-1 tight junction proteins in a Caco-2 spheroid model. NQ-2, NQ-3, and NQ-4 showed a robust inhibitory effect on IL-1β maturation in LPS-primed THP-1 cells. This effect may contribute to alleviate the inflammatory cascades associated with IBD. Distinctively, NQ-2 and NQ-3 exerted anti-NLRP3 inflammasome activity evidenced by the inhibition of CASP-1 activity and the promotion of autophagy. Both compounds induced disruptions of the microtubule network in transfected U2OS-GFP-α-tubulin cells. Treatment with NQ-2 remarkably attenuated dextran sulfate sodium (DSS)-induced colitis in rats by suppressing changes in colon length, colon mass index, and intestinal histopathology scores. Thus, 1,4-naphthoquinone derivatives such as NQ-2 may provide potential therapeutic anti-inflammatory effects for IBD patients and for other NLRP3-associated inflammatory diseases.
- Date of acceptance
- 2022
- Autoren
- Nuha Mahmoud
- Mohamed-Elamir F Hegazy
- Walaa Wadie
- Mohamed Elbadawi
- Edmond Fleischer
- Anette Klinger
- Gerhard Bringmann
- Mohamed T Khayyal
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35462013
- DOI
- 10.1016/j.phrs.2022.106233
- eISSN
- 1096-1186
- Zeitschrift
- Pharmacol Res
- Schlüsselwörter
- Autophagy
- IBD animal model
- Intestinal inflammation
- Microtubules
- NLRP3 inflammasome
- Naphthoquinone derivatives
- ATP Binding Cassette Transporter, Subfamily B
- Animals
- Anti-Inflammatory Agents
- Caco-2 Cells
- Colitis
- Colon
- Dextran Sulfate
- Disease Models, Animal
- Humans
- Inflammation
- Inflammatory Bowel Diseases
- Lipopolysaccharides
- Mice
- Mice, Inbred C57BL
- Naphthoquinones
- Rats
- Sprache
- eng
- Country
- Netherlands
- Paginierung
- 106233
- PII
- S1043-6618(22)00178-5
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Naphthoquinone derivatives as P-glycoprotein inducers in inflammatory bowel disease: 2D monolayers, 3D spheroids, and in vivo models.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 179
Data source: PubMed
- Beziehungen:
- Property of