Topical hesperidin improves epidermal permeability barrier function and epidermal differentiation in normal murine skin.

Orange peel extract appears to exhibit beneficial effects on skin whitening, inflammation, UVB protection, as well as keratinocyte proliferation. In the present study, we determine whether topical hesperidin influences epidermal permeability barrier function and its underlying mechanisms. Hairless mice were treated topically with 2% hesperidin or 70% ethanol alone twice daily for 6 days. At the end of treatment, basal transepidermal water loss (TEWL) was measured 2 and 4 h post barrier disruption. Epidermal proliferation and differentiation were evaluated by immunohistochemical staining and Western blot analysis. Additionally, lamellar body density and secretion were assessed by electron microscopy. Although there were no significant differences in basal barrier function, in comparison with control animals, topical hesperidin significantly accelerated barrier recovery at both 2 and 4 h after acute barrier abrogation. Enhanced barrier function in hesperidin-treated skin correlated with stimulation of both epidermal proliferation and differentiation, as well as enhanced lamellar body secretion. These results indicate that topical hesperidin enhances epidermal permeability barrier homeostasis at least in part due to stimulation of epidermal proliferation, differentiation, as well as lamellar body secretion.

Topical herbal extract (Huangdang mixture) exhibits both preventive and therapeutic effects in murine acute irritant contact dermatitis.

BACKGROUND: Contact dermatitises, including allergic contact dermatitis and irritant contact dermatitis, are among the most common skin disorders in humans. Chinese herbal medicines (CHM) have been used in treating contact dermatitises for centuries. Systemic administration of CHM, including ingredients in huangdang mixture containing Chinese angelica, radix Paeonlae rubra, cat nut, and phelloden dron, rhizoma alismatis, rhizoma smilacis glabrae, and rhizome of swordlike, improves allergic contact dermatitis induced by l-fluoro-2,4-dinitrobenzene. Whether topical applications of these herbal extracts display preventive and/or therapeutic effects on contact dermatitis, thereby avoiding the potential side effects of systemic CHM, remains largely unknown. AIMS: To determine whether this topical CHM extract exerts preventive and/or therapeutic effects, we assessed its efficacy in both allergic contact dermatitis and irritant contact dermatitis murine models. MATERIALS AND METHODS: Allergic contact dermatitis and irritant contact dermatitis murine models were established by topical oxazolone and a phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA), respectively. Ear thickness was assessed in both dermatitis models. RESULTS: Our results demonstrate that this topical CHM extract exhibits both therapeutic and preventive effects in acute irritant contact dermatitis but no demonstrable efficacy in murine allergic contact dermatitis. CONCLUSION: These results suggest that this topical CHM extract could provide an alternative regimen for the prevention and treatment of irritant contact dermatitis.

A topical Chinese herbal mixture improves epidermal permeability barrier function in normal murine skin.

Chinese herbal medicine (CHM) has been shown to have beneficial effects for both skin disorders with barrier abnormality and as skin care ingredients. Yet, how CHM exerts their benefits is unclear. As most, if not all, inflammatory dermatoses are accompanied by abnormal permeability barrier function, we assessed the effects of topical CHM extracts on epidermal permeability barrier function and their potential mechanisms. Topical CHM accelerated barrier recovery following acute barrier disruption. Epidermal lipid content and mRNA expression of fatty acid and ceramide synthetic enzymes increased following topical CHM treatment in addition to mRNA levels for the epidermal glucosylceramide transport protein, ATP-binding cassette A12. Likewise, CHM extract increased mRNA expression of antimicrobial peptides both in vivo and in vitro. These results demonstrate that the topical CHM extract enhances epidermal permeability barrier function, suggesting that topical CHM could provide an alternative regimen for the prevention/treatment of inflammatory dermatoses accompanied by barrier abnormalities.

The role of CD44 in cutaneous inflammation.

CD44 is a transmembrane glycoprotein expressed in various tissues including the skin. Previous studies indicated that CD44 is required for epidermal permeability barrier homeostasis and keratinocyte differentiation. Yet, while some studies have demonstrated that CD44 is critical for the development of inflammation, others have shown that CD44 is not essential for the development of cutaneous inflammation. In this study, we evaluated the changes in epidermal CD44 expression in a variety of skin inflammatory models and determined whether CD44 is required for the development of cutaneous inflammation. Inflammatory responses were compared in CD44 KO versus wild-type mice in acute models of irritant and allergic contact dermatitis, as well as in a subacute allergic contact dermatitis induced by repeated hapten treatment. Inflammatory responses were assessed by measuring ear thickness and epidermal hyperplasia in haematoxylin & eosin-stained sections. Our results demonstrate that: (i) epidermal CD44 expression increases in both acute and subacute cutaneous inflammatory models; and (ii) acute disruption of the epidermal permeability barrier function increases epidermal CD44 expression. Whereas inflammatory responses did not differ between CD44 KO and wild-type mice in acute models of irritant and allergic contact dermatitis, both inflammatory responses and epidermal hyperplasia increased in CD44 KO mice following repeated hapten challenges. These results show first, that permeability barrier disruption and inflammation stimulate epidermal CD44 expression, and second, that CD44 modulates epidermal proliferation and inflammatory responses in a subacute murine allergic contact dermatitis model.

Chinese herbal medicine (Tuhuai extract) exhibits topical anti-proliferative and anti-inflammatory activity in murine disease models.

While psoriasis is one of the most common skin disorders in humans, effective, safe and inexpensive treatments are still largely unavailable. Chinese herbal medicine (CHM) has been used for centuries for treating psoriasis and several reports claim that systemic administration of one such CHM, Tuhuai, mainly composed of flos sophorae, smilax glabra roxb and licorice, is effective in psoriasis. However, the mechanisms by which this CHM improves psoriasis are not yet clear. Two universal features of psoriasis are epidermal hyperplasia and inflammation. Moreover, drugs that specifically inhibit epidermal hyperplasia and/or inflammation are widely used to treat psoriasis. Here, we investigated whether topical applications of Tuhuai extract exhibit anti-proliferative and anti-inflammatory activities in two murine models of inflammatory dermatoses. To assess Tuhuai's potential anti-proliferative effect, we disrupted epidermal barrier function twice-daily for 4 days in normal hairless mice followed by topical applications of either 1% Tuhuai extract or Vehicle to both flanks immediately after each barrier perturbation. Changes in epidermal proliferation and apoptosis were evaluated by immunohistochemistry and TUNEL staining. To assess the anti-inflammatory effects of Tuhuai, both irritant (phorbol ester) and acute allergic contact dermatitis (oxazolone) models were used. Whereas topical Tuhuai extract did not alter epidermal proliferation or induce irritation in normal skin, it both reduced epidermal hyperplasia in the epidermal hyperproliferative model, and reduced inflammation in both irritant and allergic contact dermatitis models. As topical Tuhuai extract exhibits anti-proliferative and anti-inflammatory properties in a variety of human models of inflammatory dermatoses, Tuhuai could provide an effective, relatively safe and inexpensive therapeutic alternative for the treatment of inflammatory dermatoses, including psoriasis.

Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges.

Atopic dermatitis (AD) is a chronic dermatosis bearing clinical, histological, and immunologic similarities to chronic allergic contact dermatitis (ACD). AD shows a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels, a permeability barrier abnormality, and Staphylococcus aureus colonization. Repeated hapten challenges reportedly produce a Th2-like hypersensitivity reaction (Th2-like HR). Here, 9-10 challenges with oxazolone (Ox) to hairless mice also produced a chronic Th2-like HR. Permeability barrier function and expression of differentiation proteins, filaggrin, loricrin, and involucrin, became abnormal. CRTH-positive Th2-dominant inflammatory infiltrate, with increased IL-4 expression, and a large increase in serum IgE levels were observed. The barrier abnormality was associated with decreased stratum corneum (SC) ceramide content and impaired lamellar body secretion, resulting in abnormal lamellar membranes, as in human AD. Furthermore, as in human AD, epidermal serine protease activity in SC increased and expression of two lamellar body-derived antimicrobial peptides, CRAMP and mBD3, declined after Ox challenges, paralleling the decrease of their human homologues in AD. Thus, multiple Ox challenges to normal murine skin produce a chronic Th2-like HR, with multiple features of human AD. Because of its reproducibility, predictability, and low cost, this model could prove useful for evaluating both pathogenic mechanisms and potential therapies for AD.