Anti-proliferative and anti-inflammatory effects of the application of baclofen cream, a GABAB receptor agonist, on skin inflammation in mice
Copyright © 2023 Elsevier B.V. All rights reserved..
Previous studies have demonstrated the role of γ-aminobutyric acid type B (GABAB) receptors in skin-related conditions and pain. However, most studies have focused on the main effects of GABAB on the central nervous system. Therefore, this study has aimed to determine the potential topical anti-inflammatory and anti-proliferative effects of baclofen cream in an inflammatory skin disease model. The effects of the baclofen cream were evaluated using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears. Histological and immunohistochemical evaluations were performed using an ear oedema assay. The effect of baclofen on keratinocyte proliferation was assessed in PAM212, the murine keratinocyte cell line. The results demonstrate that a single topical application of 5% baclofen, 7.5% baclofen, and 1% dexamethasone each inhibited acute TPA-induced ear oedema (58.94 ± 6.14%, 47.73 ± 11.26%, and 87.33 ± 4.59%, respectively). These results were confirmed by histological analysis. In the chronic model, baclofen (5%) and dexamethasone (1%) each inhibited ear oedema and the maximum inhibitory effect was reached at the end of the experiment (9th day of TPA application) with a percentage inhibition of 54.60 ± 6.15% for baclofen and 71.68 ± 3.45% for dexamethasone, when compared to the vehicle. These results were confirmed by histological analysis. Baclofen and dexamethasone also reduced proliferating cell nuclear antigen expression by 62.01 ± 6.65% and 70.42 ± 6.11%, respectively. However, baclofen did not inhibit keratinocyte proliferation in PAM212 cells. In conclusion, these results demonstrate that baclofen exhibits notable topical antiproliferative and anti-inflammatory properties and could be a potential therapeutic alternative for treating inflammatory and proliferative skin diseases.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:955 |
|---|---|
| Enthalten in: |
European journal of pharmacology - 955(2023) vom: 15. Sept., Seite 175910 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
de Souza Oliveira, Vitor Hélio [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.08.2023 Date Revised 14.08.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ejphar.2023.175910 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359793509 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359793509 | ||
| 003 | DE-627 | ||
| 005 | 20231226081633.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejphar.2023.175910 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1199.xml |
| 035 | |a (DE-627)NLM359793509 | ||
| 035 | |a (NLM)37479017 | ||
| 035 | |a (PII)S0014-2999(23)00422-3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a de Souza Oliveira, Vitor Hélio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Anti-proliferative and anti-inflammatory effects of the application of baclofen cream, a GABAB receptor agonist, on skin inflammation in mice |
| 264 | 1 | |c 2023 | |
| 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 14.08.2023 | ||
| 500 | |a Date Revised 14.08.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a Previous studies have demonstrated the role of γ-aminobutyric acid type B (GABAB) receptors in skin-related conditions and pain. However, most studies have focused on the main effects of GABAB on the central nervous system. Therefore, this study has aimed to determine the potential topical anti-inflammatory and anti-proliferative effects of baclofen cream in an inflammatory skin disease model. The effects of the baclofen cream were evaluated using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears. Histological and immunohistochemical evaluations were performed using an ear oedema assay. The effect of baclofen on keratinocyte proliferation was assessed in PAM212, the murine keratinocyte cell line. The results demonstrate that a single topical application of 5% baclofen, 7.5% baclofen, and 1% dexamethasone each inhibited acute TPA-induced ear oedema (58.94 ± 6.14%, 47.73 ± 11.26%, and 87.33 ± 4.59%, respectively). These results were confirmed by histological analysis. In the chronic model, baclofen (5%) and dexamethasone (1%) each inhibited ear oedema and the maximum inhibitory effect was reached at the end of the experiment (9th day of TPA application) with a percentage inhibition of 54.60 ± 6.15% for baclofen and 71.68 ± 3.45% for dexamethasone, when compared to the vehicle. These results were confirmed by histological analysis. Baclofen and dexamethasone also reduced proliferating cell nuclear antigen expression by 62.01 ± 6.65% and 70.42 ± 6.11%, respectively. However, baclofen did not inhibit keratinocyte proliferation in PAM212 cells. In conclusion, these results demonstrate that baclofen exhibits notable topical antiproliferative and anti-inflammatory properties and could be a potential therapeutic alternative for treating inflammatory and proliferative skin diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Keratinocyte proliferation | |
| 650 | 4 | |a Psoriasis | |
| 650 | 4 | |a Skin disease | |
| 650 | 4 | |a Topical baclofen | |
| 650 | 7 | |a Baclofen |2 NLM | |
| 650 | 7 | |a H789N3FKE8 |2 NLM | |
| 650 | 7 | |a GABA-B Receptor Agonists |2 NLM | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 650 | 7 | |a Tetradecanoylphorbol Acetate |2 NLM | |
| 650 | 7 | |a NI40JAQ945 |2 NLM | |
| 700 | 1 | |a Amorim, Mayara Alves |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira, Janiana Raiza Jentsch Matias |e verfasserin |4 aut | |
| 700 | 1 | |a Soley, Bruna Silva |e verfasserin |4 aut | |
| 700 | 1 | |a Rocha, Fernanda Grillo |e verfasserin |4 aut | |
| 700 | 1 | |a de Mello Bandenburg, Margareth |e verfasserin |4 aut | |
| 700 | 1 | |a Lejeune, Vanessa Bordenowsky Pereira |e verfasserin |4 aut | |
| 700 | 1 | |a de Lima Silva, Alvaro Henrique Bernardo |e verfasserin |4 aut | |
| 700 | 1 | |a Witherden, Deborah A |e verfasserin |4 aut | |
| 700 | 1 | |a Havran, Wendy L |e verfasserin |4 aut | |
| 700 | 1 | |a Zanoveli, Janaina Menezes |e verfasserin |4 aut | |
| 700 | 1 | |a Cabrini, Daniela Almeida |e verfasserin |4 aut | |
| 700 | 1 | |a Calixto, João Batista |e verfasserin |4 aut | |
| 700 | 1 | |a Otuki, Michel Fleith |e verfasserin |4 aut | |
| 700 | 1 | |a André, Eunice |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of pharmacology |d 1967 |g 955(2023) vom: 15. Sept., Seite 175910 |w (DE-627)NLM000029769 |x 1879-0712 |7 nnns |
| 773 | 1 | 8 | |g volume:955 |g year:2023 |g day:15 |g month:09 |g pages:175910 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejphar.2023.175910 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 955 |j 2023 |b 15 |c 09 |h 175910 | ||