No abstract

Closed patch testing and the nitrocellulose-replica method are performed as useful clinical methods for the evaluation of human skin irritation by cosmetics and topical medicaments. Comparison of the sensitivity between microscopic scoring by nitrocellulose-replica method and visual scoring by closed patch test in the detection of skin irritation, however, has not been well studied with statistical analysis. Here, we evaluated human skin irritation by carboxylic acids, alcohols, esters and aldehydes, with different chain length (C8-C18), using both methods. The results of closed patch testing showed that, although the score of skin irritation for carboxylic acids (C8, C12), alcohols (C8) and aldehydes (C8), tested at a concentration of 0.5 m-2.0 m, significantly increased with increasing concentration of the test compounds, ester compounds scarcely caused any irritation on the surface of the skin occluded. In addition, an increase of carbon chain length in the test compounds made it impossible to detect skin irritation. In contrast, the nitrocellulose-replica method could evaluate skin reactions against very weak irritants that gave no macroscopic alterations on the skin surface in the closed patch test. However, the scoring system is somewhat subjective and should be improved to make the analysis more objective.

Partially myristoylated chitosan pyrrolidone carboxylate (PMCP) is a cationic amphiphilic chitosan derivative. Glabridin (Glab) from licorice root extracts is a hydrophobic antimelanogenic agent. Here we assessed the effects of cationic Glab-containing polymeric micelles derived from PMCP (Glab/PMCP-PM) on the ability of Glab to penetrate the skin and inhibit melanogenesis using a human skin model. The amount of Glab absorbed 24 h after the application of Glab/PMCP-PM was approximately four times higher than that of conventional oil-in-water micelles (control) prepared using Tween 60. Further, the release of IL-1α, a mediator of inflammation, was not detected. Treatment with Glab/PMCP-PM significantly increased the inhibition of melanogenesis compared with control. The inhibition of melanogenesis depends upon the enhanced ability of Glab to penetrate the skin, particularly the epidermis. Moreover, the inhibition of melanogenesis and the cationic potential of the Glab/PMCP-PM levels were increased by the cationic phospholipid copolymer. Therefore, Glab/PMCP-PM shows potential as an effective transdermal delivery system for treating skin hyperpigmentation.

Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on mesenchymal stem cell migration.

Investigation of partially myristoylated carboxymethyl chitosan, an amphoteric-amphiphilic chitosan derivative, as a new material for cosmetic and dermal application.