Kaempferol attenuates imiquimod-induced psoriatic skin inflammation in a mouse model

Abstract

Psoriasis is an immune-mediated inflammatory skin disease that mainly affects the skin barrier. Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, long-term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti-inflammatory, anti-oxidant and anti-cancerous properties. However, it is unknown whether kaempferol is also anti-psoriatic. Here we established an imiquimod (IMQ)-induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesions and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis-like skin lesions induced by topical administration of IMQ. Kaempferol reduced CD3 + T cell infiltration and gene expression of major proinflammatory cytokines, including interleukin (IL)-6, IL-17A and tumor necrosis factor (TNF)-α, in the psoriatic skin lesion. It also down-regulated proinflammatory nuclear factor kappa B (NF-κB) signaling in the skin. The therapeutic effects were associated with a significant increase in CD4 + forkhead box protein 3 (FoxP3) + regulatory T cell (T reg ) frequency in the spleen and lymph nodes as well as FoxP3-positive staining in the skin lesion. Conversely, depletion of CD4 + CD25 + T regs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL-17A + CD4 + T cells in the spleen and lymph nodes of IMQ-induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future.

Potential Mechanism of Tibetan Medicine Dali in the Treatment of Respiratory Diseases via Network Pharmacology

“…Isorhamnetin inhibited the activity of myeloperoxidase (MPO), the levels of TNF-α and IL-6, to abolish in ammation and support the mRNA expression of proin ammatory mediators (30). Kaempferol reduced the in ltration of CD3 + T cell and gene expression of major pro-in ammatory cytokines including IL-6, IL-17A and TNF-α, at the same time, it also reduced the signal of regulated pro-in ammatory NF-κB (31). Avicularin prevented the activation of MEK/NF-κB pathway, inhibited in ammatory response, prevented cell viability, and induced TNF-α treatment of apoptosis of human RA synovial cells (32).…”

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“…Among all the active ingredients, the top 4 were quercetin, luteolin, kaempferol, and wogonin in terms of Degree. Previous preclinical studies have confirmed that all of them could delay the progression of psoriasis and relieve symptoms in multiple animal models [32][33][34]. Among all the targets, the top three were PTGS2, MAPK14, and NOS3 in terms of Degree, and all of them have been demonstrated to play important roles in the pathogenesis of psoriasis, such as inflammatory infiltration, abnormal differentiation of keratinocytes, and oxidative stress injury [35,36].…”

Flavonoids Present in Propolis in the Battle against Photoaging and Psoriasis

“…Psoriasis is characterized by the presence of epidermal hyperproliferation, abnormal keratinocyte differentiation, angiogenesis with blood vessel dilatation, and excess of Th1 and Th17 inflammation in the skin of the affected area. Psoriasis affects 2–3% of the global population [ 8 , 39 , 115 , 116 , 117 ].…”

“…Similarly, kaempferol at a 6 or 12 μM concentration suppressed T cell proliferation, although this concentration was not cytotoxic in T cells. Interestingly, it inhibited the phosphorylation of p70S6K downstream of the mTOR signaling [ 117 ]. Moreover, these same authors mention that oral treatment with kaempferol (50 or 100 mg/kg) reduced the severity of psoriatic-like lesions induced by imiquimod cream and that PASI reduction was closely related to CD4 + CD25 + Treg cells.…”