Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic Dermatitis
Atopic dermatitis (AD) is a chronic inflammatory skin disease with rising prevalence, marked by eczematous lesions, itching, and a weakened skin barrier often tied to filaggrin gene mutations. This breakdown allows allergen and microbe entry, with thymic stromal lymphopoietin (TSLP) playing a crucia...
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2024-11-01
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| author | Muhammad Suleman Chiara Moltrasio Paola Maura Tricarico Angelo Valerio Marzano Sergio Crovella |
| author_facet | Muhammad Suleman Chiara Moltrasio Paola Maura Tricarico Angelo Valerio Marzano Sergio Crovella |
| author_sort | Muhammad Suleman |
| collection | DOAJ |
| description | Atopic dermatitis (AD) is a chronic inflammatory skin disease with rising prevalence, marked by eczematous lesions, itching, and a weakened skin barrier often tied to filaggrin gene mutations. This breakdown allows allergen and microbe entry, with thymic stromal lymphopoietin (TSLP) playing a crucial role by activating immune pathways that amplify the allergic response. TSLP’s central role in AD pathogenesis makes it a promising therapeutic target. Consequently, in this study, we used the virtual drug screening, molecular dynamics simulation, and binding free energies calculation approaches to explore the African Natural Product Database against the TSLP protein. The molecular screening identified four compounds with high docking scores, namely SA_0090 (−7.37), EA_0131 (−7.10), NA_0018 (−7.03), and WA_0006 (−6.99 kcal/mol). Furthermore, the KD analysis showed a strong binding affinity of these compounds with TSLP, with values of −5.36, −5.36, −5.34, and −5.32 kcal/mol, respectively. Moreover, the strong binding affinity of these compounds was further validated by molecular dynamic simulation analysis, which revealed that the WA_0006-TSLP is the most stable complex with the lowest average RMSD. However, the total binding free energies were −40.5602, −41.0967, −27.3293, and −51.3496 kcal/mol, respectively, showing the strong interaction between the selected compounds and TSLP. Likewise, these compounds showed excellent pharmacokinetics characteristics. In conclusion, this integrative approach provides a foundation for the development of safe and effective treatments for AD, potentially offering relief to millions of patients worldwide. |
| format | Article |
| id | doaj-art-f6697d6702cc4b8e872d2440a814ed5b |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-f6697d6702cc4b8e872d2440a814ed5b2024-12-27T14:13:41ZengMDPI AGBiomolecules2218-273X2024-11-011412152110.3390/biom14121521Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic DermatitisMuhammad Suleman0Chiara Moltrasio1Paola Maura Tricarico2Angelo Valerio Marzano3Sergio Crovella4Laboratory of Animal Research Center (LARC), Qatar University, Doha 2713, QatarDermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Pediatrics, Institute for Maternal and Child Health—IRCCS Burlo Garofolo, 34137 Trieste, ItalyDermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyLaboratory of Animal Research Center (LARC), Qatar University, Doha 2713, QatarAtopic dermatitis (AD) is a chronic inflammatory skin disease with rising prevalence, marked by eczematous lesions, itching, and a weakened skin barrier often tied to filaggrin gene mutations. This breakdown allows allergen and microbe entry, with thymic stromal lymphopoietin (TSLP) playing a crucial role by activating immune pathways that amplify the allergic response. TSLP’s central role in AD pathogenesis makes it a promising therapeutic target. Consequently, in this study, we used the virtual drug screening, molecular dynamics simulation, and binding free energies calculation approaches to explore the African Natural Product Database against the TSLP protein. The molecular screening identified four compounds with high docking scores, namely SA_0090 (−7.37), EA_0131 (−7.10), NA_0018 (−7.03), and WA_0006 (−6.99 kcal/mol). Furthermore, the KD analysis showed a strong binding affinity of these compounds with TSLP, with values of −5.36, −5.36, −5.34, and −5.32 kcal/mol, respectively. Moreover, the strong binding affinity of these compounds was further validated by molecular dynamic simulation analysis, which revealed that the WA_0006-TSLP is the most stable complex with the lowest average RMSD. However, the total binding free energies were −40.5602, −41.0967, −27.3293, and −51.3496 kcal/mol, respectively, showing the strong interaction between the selected compounds and TSLP. Likewise, these compounds showed excellent pharmacokinetics characteristics. In conclusion, this integrative approach provides a foundation for the development of safe and effective treatments for AD, potentially offering relief to millions of patients worldwide.https://www.mdpi.com/2218-273X/14/12/1521atopic dermatitisTSLPmolecular dockingMD simulationbinding free energies |
| spellingShingle | Muhammad Suleman Chiara Moltrasio Paola Maura Tricarico Angelo Valerio Marzano Sergio Crovella Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic Dermatitis Biomolecules atopic dermatitis TSLP molecular docking MD simulation binding free energies |
| title | Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic Dermatitis |
| title_full | Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic Dermatitis |
| title_fullStr | Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic Dermatitis |
| title_full_unstemmed | Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic Dermatitis |
| title_short | Natural Compounds Targeting Thymic Stromal Lymphopoietin (TSLP): A Promising Therapeutic Strategy for Atopic Dermatitis |
| title_sort | natural compounds targeting thymic stromal lymphopoietin tslp a promising therapeutic strategy for atopic dermatitis |
| topic | atopic dermatitis TSLP molecular docking MD simulation binding free energies |
| url | https://www.mdpi.com/2218-273X/14/12/1521 |
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