Effect of Resveratrol-Enriched Rice on Skin Inflammation and Pruritus in the NC/Nga Mouse Model of Atopic Dermatitis

Abstract

Resveratrol-enriched rice (RR) was developed using genetic engineering to combine the properties of resveratrol and rice. To evaluate the effect of RR on pruritic skin inflammation in atopic dermatitis (AD)-like skin lesions, we used dinitrochlorobenzene (DNCB)-induced NC/Nga mice and an in vitro 3D skin model. Normal rice (NR), resveratrol, and RR were topically applied to mice dorsal skin, following which the dermatitis index and scratching frequency were calculated. Histological examination was performed by hematoxylin and eosin and immunohistochemistry staining of IL-31 level. The level of immunoglobulin E (IgE) and IL-31 in the serum was determined by enzyme-linked immunosorbent assay (ELISA). The cytotoxicity of RR and the expression levels of pro-inflammatory cytokines were also determined in cultured human keratinocytes and a 3D skin model. RR significantly reduced scratching frequency, decreased the dermatitis severity and trans-epidermal water loss (TEWL) and improved skin hydration in DNCB-induced NC/Nga mice. RR also significantly decreased serum IL-31 and IgE levels and suppressed the production of IL-6 in human keratinocytes and the 3D skin model. Our study indicates that the synergistic effect of rice and resveratrol manifested by the topical application of RR can serve as a potential alternative therapy for chronic skin inflammatory diseases such as AD.

Role of Resveratrol in Regulating Cutaneous Functions

“…Keratinocytes were pretreated with 20 or 100 μM resveratrol for 16 hr, followed by removal of media, and then exposed to 800 μM cumen hydroperoxide for 8 hr ↑GSH expression ↓Apoptosis ↑NRF2 activation [99] Evidence-Based Complementary and Alternative Medicine 5 Mice BALB/c mouse ears were treated topically with 10 mM resveratrol 2 hr prior to DNFB challenge ↓Ear thickness ↓CD3-positive cells ↓ICAM-1, CCL2, and CXCL10 expression ↓Interferon regulatory factor 1 and phosphorylated STAT1 [113] Following induction of allergic contact dermatitis, NC/Nga mice were treated topically with 2.5% resveratrol or resveratrol-enriched rice extract twice weekly for 5 weeks ↓Epidermal thickness ↓Dermatitis score ↓Serum IgE ↓TEWL ↑Skin hydration ND [114] BALB/c mice were orally treated with resveratrol at a dose of 10 mg/kg body weight 1 hr prior to intravenous challenge with 200 μg dinitrophenylhuman serum albumin ↓IL-4 and TNF-α ↓CD11b-positive cells ↓Tyk2-STAT1 activation [116] Atopic dermatitis-like lesions were induced by topical applications of DNFB to the back of BALB/c mice for 5 weeks, followed by orally given resveratrol at a daily dose of 30 mg/kg body weight for 1 week ↓Dermatitis scores ↓Epidermal thickness ↓Cytokine mRNA ND [117] Atopic dermatitis-like lesions were induced by topical applications of dermatophagoides farinae to the back of NC/Nga mice for 2 weeks, followed by orally given resveratrol at a daily dose of 20 mg/kg body weight for 2 weeks ↓Dermatitis scores ↓Cytokine mRNA and protein ↓High mobility group box 1 expression [118] Psoriasis-like skin lesions were induced by topical applications of imiquimod to the back of BALB/c mice, which were orally given resveratrol at a daily dose of 400 mg/ kg body weight, for 7 days.…”

“…For example, incubation of keratinocytes with 50 μM resveratrol for 3 hr lowered the expression levels of mRNA for IL-6, IL-8, TNF-α, and macrophage inflammatory protein 1 (MIF-1) by over 50% [91]. While production of proinflammatory cytokines markedly increased in keratinocytes exposed to TNF-α, lipopolysaccharide, interferon c (IFN-c), and UV irradiation [91,102,[112][113][114], addition of 50 μM resveratrol 1 hr prior to lipopolysaccharide treatment dramatically decreased mRNA levels (>40% reduction) for MIF-1, IL-6, and cyclooxygenase 2 in comparison with keratinocytes treated with lipopolysaccharide alone [91]. Yet, resveratrol also dose-dependently stimulated IL-8 production in keratinocyte cultures [91], suggesting that resveratrol differentially regulates cytokine production.…”

“…Moreover, the therapeutic effects of topical resveratrol have also been demonstrated in an atopic dermatitis-like disease model. Kang et al showed that topical applications of either 2.5% resveratrol or resveratrol-enriched rice extract for five weeks markedly reduced dermatitis score and serum IgE levels in a dermatitis model induced by topical dinitrochlorobenzene [114]. Likewise, both intravenously and orally given resveratrol significantly alleviated dermatitis score and decreased cytokine expression [117,118].…”

Laminaria japonica Suppresses the Atopic Dermatitis-Like Responses in NC/Nga Mice and Inflamed HaCaT Keratinocytes via the Downregulation of STAT1

“…The severity of skin lesions was blindly graded every two weeks, for 4 weeks, according to the method reported by Kang et al [19]. The total severity index of dermatitis was defined as the sum of individual scores graded as follows: 0 (none), 1 (mild), 2 (moderate), and 3 (severe) for each of the five symptoms: erythema, itchiness/dryness, edema/hematoma, excoriation/erosion, and lichenification.…”

Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation

“…The immune response plays an important role in the host defense against harmful stimulants. However, excessive inflammatory reaction resulting from an impaired immune system can contribute to the development of various skin disorders such as allergic/irritant contact dermatitis, atopic dermatitis, and psoriasis [5,6]. These chronic recurring disorders are characterized by various clinical symptoms of edema and epidermal hyperproliferation [7,8].…”