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Polygonatum polysaccharides inhibit keratinocyte proliferation and inflammation via JAK2/STAT3 pathway modulation in
Lanbing Deng1, Zhibo Yang2, Zhuxin Wang3
1Function Branch, the Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China.
Abstract:
Psoriasis is an immune-mediated inflammatory skin condition characterized by hyperproliferation of keratinocytes and inflammatory response leading to erythematous plaques covered with silvery scales. Despite existing therapies, there remains a critical need for effective treatments with fewer side effects, making the exploration of natural compounds like Polygonatum polysaccharides (PSP) highly relevant. Male Babl/c mice were induced with psoriasis-like skin lesions using Imiquimod (IMQ) and then treated with varying doses of PSP. Skin lesion appearance, Psoriasis Area and Severity Index (PASI) scores, and histological features were assessed. Additionally, human keratinocytes (HaCaT cells) were treated with PSP to evaluate its effects on cell viability, DNA synthesis, migration, and proliferation marker expression. The involvement of the JAK2/STAT3 pathway was investigated using a JAK2 activator, Coumermycin A1. In parallel, pharmacological inhibition of JAK2/STAT3 signaling using AG490 further confirmed pathway dependency. PSP significantly improved skin lesion appearance and reduced PASI scores in the murine model, comparable to the effects of Methotrexate (MTX). Histological analysis revealed that PSP reduced epidermal thickness and inflammatory cell infiltration. Additionally, PSP decreased the expression of proliferation markers such as Ki67 and Cyclin D1 in skin sections. In vitro, HaCaT cells treated with PSP showed reduced cell viability, DNA synthesis, and migration. PSP also downregulated the expression of proliferation markers, while promoted keratinocyte differentiation markers, and inhibited the activation of the JAK2/STAT3 pathway. The involvement of the JAK2/STAT3 pathway was further confirmed by reversing PSP's effects using a Coumermycin A1 and AG490. These findings suggest that PSP ameliorates psoriasis by modulating the JAK2/STAT3 pathway, reducing keratinocyte proliferation, and attenuating inflammation, highlighting its potential as a timely alternative or adjunctive treatment for psoriasis.
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