Topical apigenin improves epidermal permeability barrier homoeostasis in normal murine skin by divergent mechanisms

Abstract

The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, Chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In the present study, we first determined whether topical apigenin positively influences permeability barrier homeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice-daily for 9 days. At the end of treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homeostasis after tape stripping, though basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were up-regulated by apigenin. Finally, both CAMP and mBD3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels, and impaired antimicrobial defenses, such as atopic dermatitis.

Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis

“…Because reduced exposure to the benefits of suberythemogenic UV-B has been proposed as a key factor in the recent, urban resurgence of AD [45], it would seem prudent to recommend moderate amounts of exposure to ambient UV-B as a part of the management plan for AD patients. Finally, not only PPAR activators [46], but also several bioflavonoid ingredients, such as hesperidin and apigenin [47], have been shown to boost filaggrin production, and could therefore prove useful in those AD patients who do not exhibit double-allele mutation in Filaggrin gene expression.…”

Herbal medicines that benefit epidermal permeability barrier function

“…9 Whereas topical applications of 0.1% apigenin, an ingredient from chrysanthemum, twice daily for 9 days induced a significant acceleration in barrier recovery only 4 hours after barrier disruption, and a reduction in SC hydration in normal murine skin. 10 Moreover, topical application of herbal extracts to barrier damaged skin also accelerated barrier recovery. 11e13 These results indicate that the influences of topical herbal medicines on permeability homeostasis vary with the ingredient.…”

“…Likewise, hesperidin increased epidermal filaggrin and loricrin expression, and keratinocyte proliferation in a murine model 8 while topical apigenin only unregulated epidermal filaggrin and its mRNA expression. 10 Moreover, studies indicate that hesperidin increased PPARg and its mRNA expression in NALM-6 cells and human preadipocytes. Our prior study showed that activation of PPARg upregulated epidermal differentiation, resulting in improvement of barrier function.…”

“…1 Our prior studies showed that topical applications of herbal extract increased epidermal lipid content 6 and the expression of mRNA for lipid synthetic enzymes. 8,10 Topical applications of either 1% ursolic acid or 1% oleanolic acid for 3 days significantly increased epidermal ceramide content. 12 Ishikawa et al 13 reported that both macrocarpal A and extract of Eucalyptus globulus increased ceramide production and expression of mRNA for ceramide synthetic enzyme.…”

Therapeutics and Other Interventions

“…These studies need to be replicated. The candidates include sericin-rich diets (animal study) [ 35 ]; apigenin, an active constituent in chrysanthemum (in vitro study) [ 36 ]; interferon-γ (in vitro study) [ 21 ]; hyaluronic acid; and bacterial antimicrobial peptide plantaricin A (in vitro study) [ 37 ]. Urea, a well-known humectant, also possesses fi laggrin upregulatory effects and may prove more versatile than previously assumed [ 38 ].…”