Antiproliferative and Anti-Inflammatory Effects of the Polyphenols Phloretin and Balsacone C in a Coculture of T Cells and Psoriatic Keratinocytes.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Phloretin*/pharmacology ; Psoriasis*/drug therapy ; Psoriasis*/metabolism ; Psoriasis*/pathology ; Keratinocytes*/drug effects ; Keratinocytes*/metabolism ; Anti-Inflammatory Agents*/pharmacology ; Cell Proliferation*/drug effects ; T-Lymphocytes*/drug effects ; T-Lymphocytes*/metabolism ; T-Lymphocytes*/immunology ; Coculture Techniques* ; Cytokines*/metabolism; Humans ; Polyphenols/pharmacology ; Methotrexate/pharmacology ; Cells, Cultured

Plaque psoriasis is a chronic inflammatory skin disease causing red inflamed lesions covered by scales. Leukocytes, including dendritic cells and T cells, participate in the inflammation of the skin by producing multiple cytokines, thus contributing to the hyperproliferation of keratinocytes. Lack of effectiveness and toxic side effects are the main concerns with conventional treatments, and research involving new antipsoriatic molecules is essential. In this study, the anti-inflammatory and antiproliferative effects of two natural polyphenols, phloretin and balsacone C, were investigated using the coculture of T cells and psoriatic keratinocytes. Phloretin exerted antiproliferative activity by regulating the expression of antigen Ki67 and proliferating cell nuclear antigen (PCNA). These effects were comparable to those of methotrexate, a reference treatment for moderate to severe psoriasis. With balsacone C, the expression of Ki67 was also reduced. Additionally, phloretin decreased the levels of multiple pro-inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1α (MIP-1α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-α). The increased interleukin-2 (IL-2) levels with phloretin and methotrexate also represented anti-inflammatory activity. Balsacone C and methotrexate decreased the levels of IL-1α and IL-1β, but methotrexate exerted a higher reduction. In summary, the anti-inflammatory effects of phloretin were more pronounced than those of methotrexate and balsacone C. In addition, the expression of lymphocyte common antigen (CD45) was more similar to that of the healthy condition after using phloretin or methotrexate. Finally, phloretin stood out from the other compounds and appears promising for psoriasis treatment.

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165822 Canada CAPMC CIHR

Keywords: anti-inflammatory activity; antiproliferative activity; balsacone; phloretin; polyphenols; psoriasis

S5J5OE47MK (Phloretin)
0 (Anti-Inflammatory Agents)
0 (Cytokines)
0 (Polyphenols)
YL5FZ2Y5U1 (Methotrexate)

Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240620

20240620

PMC11171971

10.3390/ijms25115639

38891824