5-demethylnobiletin and Psoriasis

Psoriasis is an inflammatory skin disease accompanied with chronic papulosquamous lesions and multiple comorbidities that considerably affect patients' quality of life. In order to develop an enhanced therapeutic strategy for psoriasis, 5-demethylnobiletin (5-DN), a kind of polymethoxyflavones (PMFs) with high anti-inflammatory activity, was delivered in vitro and in vivo by the nanocarrier of mesoporous silica nanoparticles (MSNs) both in the human keratinocytes HaCaT cell line and the mouse model with psoriasis-like lesions. The drug-loaded nanocarrier system (MSNs@5-DN) significantly improved the biocompatibility and bioavailability of 5-DN. Investigations at cell biological, histopathological, and molecular levels revealed the pharmacological mechanism of the drug delivery system, including the inhibition of inflammatory responses by downregulating the proinflammatory cytokine levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). The upregulation of anti‑inflammatory cytokine of transforming growth factor-β1 (TGF-β1) and microRNA-17-5p, a critical regulator of the PTEN/AKT pathway, was also observed. The psoriasis-like lesions were markedly ameliorated in the mouse models treated with MSNs@5-DN. The designed drug-loading system shows an enhanced therapeutic outcome for psoriasis-like lesion compared with free 5-DN. This study revealed the synergistic effect of functionalized MSNs loaded with PMFs on the clinical treatment of human psoriasis.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Humans; Hydrogen-Ion Concentration; Mice; MicroRNAs; Nanoparticles; Porosity; Psoriasis; Quality of Life; Reactive Oxygen Species; Silicon Dioxide

Psoriasis is a chronic and benign proliferative skin disease. Flavonoids in chenpi (aged tangerine peel) from tangerine ( Citrus reticulate Blanco), such as nobiletin (Nob), tangeretin, and 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (5-HPMF), possess anti-inflammation and regulation of immune activity among others. In this study, psoriasis-like skin lesions were induced by 12- O-tetradecanoylphorbol-13-acetate (TPA), and the preventive effect of Nob and 5-HPMF on psoriasis-like skin lesions was evaluated. Results showed that skin lesions were dramatically reduced by Nob and 5-HPMF. Levels of cytokines, including interleukin (IL)-1β, IL-17, IL-4, IL-6, tumor necrosis factor-α, and interferon-γ, were also reduced after Nob and 5-HPMF treatment. The expression levels of p-ERK1/2 and p-p38 mitogen-activated protein kinase (MAPK) in the TPA group were 5.3, 4.8, and 5.7 but downregulated to 2.7, 2.9, and 2.3 in the Nob group and 2.4, 2.7, and 1.2 in the 5-HPMF group, respectively ( p ≤ 0.05). The expression of transcription factors Ki-67 and proliferating cell nuclear antigen (PCNA) and the differentiation of CD4

Topics: Animals; CD4-Positive T-Lymphocytes; Citrus; Female; Flavones; Fruit; Gene Expression; Ki-67 Antigen; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Proliferating Cell Nuclear Antigen; Psoriasis; Signal Transduction; Tetradecanoylphorbol Acetate