miRNA-203b-3p Induces Acute and Chronic Pruritus through 5-HTR2B and TRPV4.

Growing evidence indicates that transient receptor potential (TRP) channels contribute to different forms of pruritus. However, the endogenous mediators that cause itch through transient receptor potential channels signaling are poorly understood. In this study, we show that genetic deletion or pharmacological antagonism of TRPV4 attenuated itch in a mouse model of psoriasis induced by topical application of imiquimod. Human psoriatic lesions showed increased expression of several microRNAs, including the miR-203b-3p, which induced a calcium ion response in rodent dorsal root ganglion neurons and scratching behavior in mice through 5-HTR2B activation and the protein kinase C‒dependent phosphorylation of TRPV4. Computer simulation revealed that the miR-203b-3p core sequence (GUUAAGAA) that causes 5-HTR2B/TRPV4-dependent itch targets the extracellular side of 5-HTR2B by interacting with a portion of the receptor pocket consistent with its activation. Overall, we reveal the unconventional pathophysiological role of an extracellular microRNA that can behave as an itch promoter through 5-HTR2B and TRPV4.

Curcumin nanoparticles potentiate therapeutic effectiveness of acitrein in moderate-to-severe psoriasis patients and control serum cholesterol levels.

OBJECTIVES: In this study, nanoparticles of curcumin were developed and orally administered to moderate-to-severe psoriasis (Psoriasis Area Severity Index values, PASI > 10) patients, in a placebo controlled, double blind, randomised clinical trial to evaluate the effectiveness. METHODS: Diverse binary systems of curcumin and hydrophilic polymers were investigated to optimise solubility and stability in terms of curcumin residual content and size of the crystals. Nanocrystals of curcumin stabilised with PVP (1 : 0.5, w/w), were characterised using X-ray diffraction, differential scanning calorimetry, TEM analyses and stability studies. The formulation was evaluated with a parallel artificial membrane permeability assay to predict the passive intestinal absorption. The first group of patients was treated orally with acitretin (0.4 mg/kg per day) plus nanocurcumin (3 g/day), the second group with acitretin, for 12 weeks. KEY FINDINGS: Curcumin nanoparticles were homogeneous and stable systems. Curcumin permeability was significantly enhanced when compared with aqueous saturated solution of curcumin. The reduction in PASI was significantly higher in patients treated with curcumin (P < 0.0001) and cholesterol serum levels remained unchanged in patients treated with acitretin plus nanocurcumin. CONCLUSIONS: Curcumin nanoparticles represent an effective adjuvant therapy in moderate-to-severe psoriasis patients treated with oral acitretin, improving their lipid serum profile.

Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris.

Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22.