Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes
Psoriasis is a chronic inflammatory skin condition characterized by abnormal keratinocyte proliferation and differentiation that is accompanied with dysregulated immune response and abnormal vascularization. Devil’s claw (<i>Harpagophytum procumbens</i> (Burch.) DC. ex Meisn.) tubers ext...
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2021-11-01
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author | Ivanka K. Koycheva Liliya V. Mihaylova Monika N. Todorova Zhivka P. Balcheva-Sivenova Kalina Alipieva Claudio Ferrante Giustino Orlando Milen I. Georgiev |
author_facet | Ivanka K. Koycheva Liliya V. Mihaylova Monika N. Todorova Zhivka P. Balcheva-Sivenova Kalina Alipieva Claudio Ferrante Giustino Orlando Milen I. Georgiev |
author_sort | Ivanka K. Koycheva |
collection | DOAJ |
description | Psoriasis is a chronic inflammatory skin condition characterized by abnormal keratinocyte proliferation and differentiation that is accompanied with dysregulated immune response and abnormal vascularization. Devil’s claw (<i>Harpagophytum procumbens</i> (Burch.) DC. ex Meisn.) tubers extract has been used both systemically and topically for treatment of chronic inflammatory diseases such as arthritis, osteoporosis, inflammatory bowel disease, among others. However, its potential mechanisms of action against psoriasis remains poorly investigated. The human keratinocyte HaCaT cell line is a well-accepted in vitro model system for inflammatory skin disorders such as psoriasis. The present study involved an exploration of the effect of biotechnologically produced <i>H. procumbens</i> (HP) cell suspension extract and pure phenylethanoid glycosides verbascoside (VER) and leucosceptoside A (LEU) in interferon (IFN)-γ/interleukin (IL)-17A/IL-22-stimulated HaCaT cells as a model of psoriasis-like inflammation. Changes in key inflammatory signaling pathways related to psoriasis development were detected by reverse transcription polymerase chain reaction and western blotting. Treatment with LEU, but not VER and HP extract improved psoriasis-related inflammation via suppression of the PI3K/AKT signaling in IFN-γ/IL-17A/IL-22-stimulated HaCaT cells. Our results suggest that LEU may exhibit therapeutic potential against psoriasis by regulating keratinocyte differentiation through inhibition of the PI3K/AKT pathway. |
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spelling | doaj.art-99b65710ec314300a165d3fbc4a597822023-11-23T00:37:15ZengMDPI AGMolecules1420-30492021-11-012622701410.3390/molecules26227014Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in KeratinocytesIvanka K. Koycheva0Liliya V. Mihaylova1Monika N. Todorova2Zhivka P. Balcheva-Sivenova3Kalina Alipieva4Claudio Ferrante5Giustino Orlando6Milen I. Georgiev7Department Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, BulgariaDepartment Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, BulgariaDepartment Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, BulgariaDepartment Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaDepartment of Pharmacy, G. d’Annunzio University, 66100 Chieti, ItalyDepartment of Pharmacy, G. d’Annunzio University, 66100 Chieti, ItalyDepartment Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, BulgariaPsoriasis is a chronic inflammatory skin condition characterized by abnormal keratinocyte proliferation and differentiation that is accompanied with dysregulated immune response and abnormal vascularization. Devil’s claw (<i>Harpagophytum procumbens</i> (Burch.) DC. ex Meisn.) tubers extract has been used both systemically and topically for treatment of chronic inflammatory diseases such as arthritis, osteoporosis, inflammatory bowel disease, among others. However, its potential mechanisms of action against psoriasis remains poorly investigated. The human keratinocyte HaCaT cell line is a well-accepted in vitro model system for inflammatory skin disorders such as psoriasis. The present study involved an exploration of the effect of biotechnologically produced <i>H. procumbens</i> (HP) cell suspension extract and pure phenylethanoid glycosides verbascoside (VER) and leucosceptoside A (LEU) in interferon (IFN)-γ/interleukin (IL)-17A/IL-22-stimulated HaCaT cells as a model of psoriasis-like inflammation. Changes in key inflammatory signaling pathways related to psoriasis development were detected by reverse transcription polymerase chain reaction and western blotting. Treatment with LEU, but not VER and HP extract improved psoriasis-related inflammation via suppression of the PI3K/AKT signaling in IFN-γ/IL-17A/IL-22-stimulated HaCaT cells. Our results suggest that LEU may exhibit therapeutic potential against psoriasis by regulating keratinocyte differentiation through inhibition of the PI3K/AKT pathway.https://www.mdpi.com/1420-3049/26/22/7014psoriasiskeratinocytesinflammationverbascosideleucosceptoside Adevil’s claw |
spellingShingle | Ivanka K. Koycheva Liliya V. Mihaylova Monika N. Todorova Zhivka P. Balcheva-Sivenova Kalina Alipieva Claudio Ferrante Giustino Orlando Milen I. Georgiev Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes Molecules psoriasis keratinocytes inflammation verbascoside leucosceptoside A devil’s claw |
title | Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes |
title_full | Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes |
title_fullStr | Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes |
title_full_unstemmed | Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes |
title_short | Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes |
title_sort | leucosceptoside a from devil s claw modulates psoriasis like inflammation via suppression of the pi3k akt signaling pathway in keratinocytes |
topic | psoriasis keratinocytes inflammation verbascoside leucosceptoside A devil’s claw |
url | https://www.mdpi.com/1420-3049/26/22/7014 |
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