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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Main Authors: Ivanka K. Koycheva, Liliya V. Mihaylova, Monika N. Todorova, Zhivka P. Balcheva-Sivenova, Kalina Alipieva, Claudio Ferrante, Giustino Orlando, Milen I. Georgiev
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/26/22/7014
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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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