Icariin restrains NLRP3 inflammasome-mediated Th2 immune responses and ameliorates atopic dermatitis through modulating a novel lncRNA MALAT1/miR-124-3p axis.

CONTEXT: Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases. OBJECTIVE: The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development. MATERIALS AND METHODS: BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin. RESULTS: Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses. DISCUSSION AND CONCLUSIONS: The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.

[Clinical study of modified Yiyi Baijiang Decoction on psoriasis vulgaris due to dampness-heat accumulation].

The present study observed the clinical effect of modified Yiyi Baijiang Decoction on psoriasis vulgaris and explored its influence on growth factors and inflammatory factors in the serum and skin tissues. A total of 130 patients were randomly divided into control group and experimental group, with 65 cases in each group. The patients in the control group received Acitretin Capsules and Calcipotriol Ointment, and those in the experimental group received modified Yiyi Baijiang Decoction combined with external application for four weeks. The psoriasis area and severity index(PASI), blood vessel count in the superficial dermis(SDBVC), skin thickness(STK), and traditional Chinese medicine(TCM) symptoms were observed before and after treatment. The growth factors [epidermal growth factor(EGF), endothelial cell-specific molecule-1(ESM-1), fibroblast growth factor-23(FGF-23), and transforming growth factor-ß1(TGF-ß1)] and inflammatory factors [nuclear factor-κB(NF-κB), prealbumin(PA), CC chemokine ligand 20(CCL20), and procalcitonin(PCT)] in the serum and skin tissues were detected. The total effective rate was 98.5% in the experimental group, higher than that 83.1% in the control group(P<0.05). Compared with the control group after treatment, the experimental group showed decreased PASI, SDBVC, STK, TCM symptoms, ESM-1, FGF-23, TGF-ß1, NF-κB, CCL20, and PCT(P<0.05), and increased EGF and PA(P<0.05). The incidence of adverse events was 1.5% in the experimental group, lower than that 21.5% in the control group(P<0.05). The results showed that modified Yiyi Baijiang Decoction could effectively relieve skin lesions in patients with psoriasis vulgaris and improve the growth factors and inflammatory factors in the serum and skin lesions, with high safety.

Morinda officinalis extract exhibits protective effects against atopic dermatitis by regulating the MALAT1/miR-590-5p/CCR7 axis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a genetic predisposition, and the traditional Chinese medicine Morinda officinalis and its roots are characterized with anti-inflammatory effects and have been used for the treatment of various disease. However, it is still largely unknown whether Morinda officinalis extract (MOE) can be used for the treatment of AD. OBJECTIVES: In our study we aimed to determine whether MOE could ameliorate 2,4-dinitrochlorobenzene (DNCB)-induced AD and elucidate molecular mechanisms. METHODS: We established an AD mouse model by using DNCB. Skin pathological analysis and ELISA assay were used to detect the effect of MOE on the inflammation of AD model mouse skin and the expression changes of inflammatory factors, and further functional verification was performed in TNF-α/IFN-γ-induced HaCaT cells. RESULTS: Our in vivo experiments confirmed that MOE remarkably reduced DNCB-induced AD lesions and symptoms, such as epidermal and dermal thickness and mast cell infiltration and inflammatory cytokines secretion in the mice models. In addition, the underlying mechanisms by which MOE ameliorated AD had been uncovered, and we verified that MOE inhibited MALAT1 expression in AD, resulting in attenuated expression of C-C chemokine receptor type 7 (CCR7) regulated by MALAT1-sponge miR-590-5p in a competing endogenous RNA (ceRNA) mechanisms-dependent manner, thereby inhibiting TNF-α/IFN-γ-induced cellular proliferation and inflammation.