D-Pinitol Ameliorates Imiquimod-Induced PsoriasisLike Skin Inflammation in a Mouse Model via the NF-κB Pathway.

Ma J ，Feng S ，Ai D ，Liu Y ，Yang X ... -  《-》

Quercetin ameliorates imiquimod-induced psoriasis-like skin inflammation in mice via the NF-κB pathway.

Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series of studies have shown that it has been shown to exhibit several biological properties, including anti-inflammatory, anti-oxidant, cardio-protective, vasodilatory, liver-protective and anti-cancer activities. However, so far the possible therapeutic effect of QC on psoriasis has not been reported. The present study was undertaken to evaluate the potential beneficial effect of QC in psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, and to further elucidate its underlying mechanisms of action. Effects of QC on PASI scores, back temperature, histopathological changes, oxidative/anti-oxidative indexes, pro-inflammatory cytokines and NF-κB pathway in IMQ-induced mice were investigated. Our results showed that QC could significantly reduce the PASI scores, decrease the temperature of the psoriasis-like lesions, and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC effectively attenuated levels of TNF-α, IL-6 and IL-17 in serum, increased activities of GSH, CAT and SOD, and decreased the accumulation of MDA in skin tissue induced by IMQ in mice. The mechanism may be associated with the down-regulation of NF-κB, IKKα, NIK and RelB expression and up-regulation of TRAF3, which were critically involved in the non-canonical NF-κB pathway. In conclusion, our present study demonstrated that QC had appreciable anti-psoriasis effects in IMQ-induced mice, and the underlying mechanism may involve the improvement of antioxidant and anti-inflammatory status and inhibition on the activation of the NF-κB signaling. Hence, QC, a naturally occurring flavone with potent anti-psoriatic effects, has the potential for further development as a candidate for psoriasis treatment.

Chen H ，Lu C ，Liu H ，Wang M ，Zhao H ，Yan Y ，Han L ... -  《-》

Ginsenoside Rg1 abolish imiquimod-induced psoriasis-like dermatitis in BALB/c mice via downregulating NF-κB signaling pathway.

This animal experiment was framed to evaluate the beneficial effect of ginsenoside Rg1 (GRg1) against imiquimod (IMQ)-induced psoriasis-like dermatitis model to reveal the underpinning mechanism. Fifty healthy BALB/c mice were divided into five groups as control, GRg1, IMQ induced, oral treatment of GRg1 (50 mg/kg), or dexamethasone (DXM; 10 mg/kg) in IMQ-induced mice. Treatment with GRg1 or DXM significantly mitigates (p < .01) psoriasis area severity index (PASI) score, skin thickness, lipid peroxidation, and inflammatory markers (IL-23, 22, 17A, 1β, and TNF-α). Moreover, administration of GRg1 or DXM considerably reversed the morphological changes induced by IMQ with improved (p < .01) antioxidant activity (SOD, CAT). In addition, a marked downregulation (p < .01) of protein expressions of pIκB and NF-κB p65 (NF-κB signaling pathway) were noted in GRg1 group. Collectively, GRg1 or DXM treatment significantly abolishes IMQ-induced psoriasis-like dermatitis by lowering PASI score, inflammation through downregulating NF-κB signaling pathway. PRACTICAL APPLICATIONS: This is the very first study to explore the efficacy of ginsenoside Rg1 (GRg1) against IMQ-induced psoriasis in the mice model to reveal the underpinning mechanism. The results clearly showed that GRg1 potent anti-psoriasis activity by lowering PASI score, inflammation through downregulating NF-κB signaling pathway. Hence, this study helps in the development of novel nutraceutical/functional food against psoriasis and thus could improve the quality of life in psoriasis patients. However, further clinical trials are needed to justify the above results before developing a commercial functional food using GRg1 against psoriasis.

Shi Q ，He Q ，Chen W ，Long J ，Zhang B ... -  《-》

Cimifugin ameliorates imiquimod-induced psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway.

Cimifugin is an important component of chromones in the dry roots of Saposhikovia divaricata for treating inflammatory diseases. However, the possible effect of cimifugin in psoriasis needs further investigation. This current work was designed to evaluate the effects of cimifugin in psoriasis in vivo and in vitro, and unravel the underlying molecular mechanism. Here, we used imiquimod (IMQ) or tumor necrosis factor (TNF)-α to induce a psoriasis-like model in mice or keratinocytes. Obviously, the results showed that cimifugin reduced epidermal hyperplasia, psoriasis area severity index (PASI) scores, ear thickness and histological psoriasiform lesions in IMQ-induced mice. The decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and the accumulation of malondialdehyde (MDA) in skin tissues by IMQ were attenuated by cimifugin. Furthermore, it was observed that cimifugin effectively reversed IMQ-induced up-regulation of proinflammatory cytokines, including TNF-α, IL-6, IL-1β, IL-17A, and IL-22. Mechanically, we noticed that cimifugin inhibited IMQ-activated phosphorylation of NF-κB (IκB and p65) and MAPK (JNK, ERK, and p38) signaling pathways. Similar alterations for oxidative stress and inflammation parameters were also detected in TNF-α-treated HaCaT cells. In addition, cimifugin-induced down-regulation of ICAM-1 were observed in TNF-α-treated cells. Altogether, our findings suggest that cimifugin protects against oxidative stress and inflammation in psoriasis-like pathogenesis by inactivating NF-κB/MAPK signaling pathway, which may develop a novel and effective drug for the therapy of psoriasis.

Liu A ，Zhao W ，Zhang B ，Tu Y ，Wang Q ，Li J ... -  《-》

Tryptanthrin ameliorates imiquimod-induced psoriasis in mice by suppressing inflammation and oxidative stress via NF-κB/MAPK/Nrf2 pathways.

Nowadays, approximately 3% of the world's population suffers from psoriasis, an inflammatory dermatosis with high recurrence. Tryptanthrin (TRYP) is a natural alkaloid that possesses anti-inflammatory activities on multiple diseases. The present study aimed to unravel whether TRYP could relieve psoriasis and how it works. Imiquimod (IMQ)-induced psoriatic mouse models were administered saline (model), TRYP (25 and 100 mg/kg), or methotrexate (MTX, 1 mg/kg) and considered as the positive control. TNF-α-induced keratinocytes (HaCaT cells) with TRYP (0, 10, 20 and 50 nM) were used for in vitro verification. Psoriasis area severity index (PASI) and spleen index were evaluated. Th17 cell infiltration in both spleens and lymph nodes was detected by flow cytometry. The expression levels of inflammatory cytokines, glutathione (GSH), malondialdehyde (MDA) and catalase (CAT), as well as superoxide dismutase (SOD), were examined by ELISA, while the NF-κB/MAPK/Nrf2 pathways-related proteins were determined by western blot. TRYP significantly attenuated psoriatic skin lesions, increased GSH, SOD, and CAT levels, reduced spleen index, accumulation of MDA, the abundance of Th17 cells in both the spleen and lymph nodes, and secretion of inflammatory cytokines in IMQ-induced psoriatic mouse models. Mechanically, TRYP suppressed IMQ-activated NF-κB (IκB and p65), MAPK (JNK, ERK1/2, and p38), and activated Nrf2 signaling pathways. Similar alterations for inflammation and oxidative stress parameters and NF-κB/MAPK/Nrf2 pathways were also observed in TNF-α-treated HaCaT cells upon TRYP treatment. Our findings suggested TRYP is effective in protecting against inflammation and oxidative stress in psoriasis-like pathogenesis by modulating the NF-κB/MAPK/Nrf2 pathways.

Xiong Y ，Wang J ，Wang S ，Li H ，Zhou X ... -  《-》