Penta-O-galloyl-ß-D-glucose from Paeonia lactiflora Pall. root extract enhances the expression of skin barrier genes via EGR3.

ETHNOPHARMACOLIGICAL RELEVANCE: Paeonia lactiflora Pall. has long been used to treat inflammatory skin diseases, such as psoriasis. AIM OF THE STUDY: The skin acts as a barrier and provides protection against various stresses by expressing skin barrier genes during keratinocyte differentiation. However, the effect of Paeonia lactiflora Pall. root extract on the expression of skin barrier genes has not been investigated. Here, we aimed to show that treatment of keratinocytes with Paeonia lactiflora Pall. root can upregulate genes related to keratinocyte differentiation. MATERIALS AND METHODS: To determine the effect Paeonia lactiflora Pall. root extract, RNA-Seq, gene ontology, and gene set enrichment analysis were performed. Reverse transcriptase quantitative polymerase chain reaction analysis was performed to confirm the increased expression of skin barrier genes. RESULTS: Treatment with Paeonia lactiflora Pall. root enhanced the expression of skin barrier genes, including the filaggrin, loricrin, and involucrin. Moreover, we found that penta-O-galloyl-ß-D-glucose (PGG), one of the ingredients in Paeonia lactiflora Pall. root, enhanced the expression of skin barrier genes, by upregulating the expression of the transcription factor EGR3. CONCLUSIONS: PGG and Paeonia lactiflora Pall. root extract have therapeutic potential for the treatment of diseases related to skin barrier disruption and can be used in cosmetics to enhance skin barrier function.

Evaluating hair growth promoting effects of candidate substance: A review of research methods.

Androgenetic alopecia (AGA) is the most common form of hair loss disorder. As the prevalence of AGA rises, the demand for AGA treatments is rising accordingly, prompting research to identify therapeutic candidates to treat AGA. Because AGA is caused by crosstalk among multiple hair follicle (HF) cell components, understanding the effects of candidate molecules on HF cells is essential to determining therapeutic candidates for treatment. To date, research has centered on HF dermal papilla and outer root sheath cells and has indicated that the hair growth effects of candidate substances may be mediated via alterations in several signaling pathways and signature genes in these HF cells. In more integrative evaluations, the HF unit is used as an ex vivo organ culture model to verify the effects of therapeutic candidates. Animal models have also been used to evaluate the effects of candidate substances. The main outcomes used to evaluate the effects of candidate substances are 1) changes in HF growth rates in vitro, 2) anagen induction capabilities, and 3) the effects of androgen modulation. This article reviews a series of methods used to evaluate the hair growth-promoting effects of candidate substances, providing an overview of cell assays, organs, and animal models used in AGA research in order to facilitate AGA research moving forward.

Effects of Emollient Containing Bee Venom on Atopic Dermatitis: A Double-Blinded, Randomized, Base-Controlled, Multicenter Study of 136 Patients.

BACKGROUND: Atopic dermatitis (AD) is a common, complex disease that follows a chronic relapsing course and significantly affects the quality of life of patients. Skin barrier dysfunction and inflammatory processes induce and aggravate this skin condition. Proper use of an emollient for hydration is a keystone of AD treatment. Bee venom is known to have anti-inflammatory effects and has been widely used in traditional medicine to treat various inflammatory disorders. OBJECTIVE: To find out the beneficial effect of an emollient containing bee venom in the treatment of patients with AD. METHODS: This study included 136 patients with AD who were randomized to receive either an emollient containing bee venom and silk-protein or a vehicle that was identical except for the bee venom for 4 weeks. The patients were instructed to apply the emollient twice daily on their entire body and not to use other medications, including topicals, during the course of the study. The eczema area and severity index (EASI) score, transepidermal water loss, and visual analogue scale (VAS) score of itching were evaluated at the first visit and after 2 and 4 weeks. The investigator global assessment was evaluated at 2 and 4 weeks after the application of emollient containing bee venom or vehicle. RESULTS: Patients applying emollient containing bee venom showed significantly lower EASI score and VAS value compared to patients applying emollient without bee venom. CONCLUSION: Emollient containing bee venom is a safe and effective option for patients with AD.

Parametric study of a dyeing wastewater treatment by modified sericite.

The aim of this study was to investigate color, suspended solids (SS), chemical oxygen demand (COD) and biological oxygen demand (BOD) removal using modified sericite with magnesium (Mg-Sericite) flocculants in dyeing wastewater. Mg-Sericite flocculants successfully removed >95% of color, SS. COD and BOD in dyeing wastewater at the following optimal conditions: Mg-Sericite dosage of 40 mg/L, pH of 11, Mg/Sericite ratio of 1.5, settling time of 20 min, mixing time of 10 min and mixing rate of 100 rpm. The bioflocculant, Mg-Sericite, can be a promising flocculants due to its high efficiency and low dose requirements in dyeing wastewater treatment. In addition, Mg-Sericite does not contaminate treated wastewater, which can be recycled to reduce not only the cost and the demand for water but also the extra operational costs for reusing wastewater.

Novel inhibitory effect of the antidiabetic drug voglibose on melanogenesis.

Overproduction of melanin can lead to medical disorders such as postinflammatory melanoderma and melasma. Therefore, developing antimelanogenic agents is important for both medical and cosmetic purposes. In this report, we demonstrated for the first time that the antidiabetic drug voglibose is a potent antimelanogenic agent. Voglibose is a representative antidiabetic drug possessing inhibitory activity towards human α-glucosidase; it blocked the proper N-glycan modification of tyrosinase, resulting in a dramatic reduction of the tyrosinase protein level by altering its stability and subsequently decreasing melanin production. Acarbose, another antihyperglycaemic drug that has a lower inhibitory effect on human intracellular α-glucosidase compared with voglibose, did not cause any changes in either the N-glycan modification of tyrosinase or the tyrosinase protein level, indicating that voglibose was the most efficient antimelanogenic agent among the widely used antihyperglycaemic agents. Considering that voglibose was originally selected from the valiolamine derivatives in a screen for an oral antidiabetic drug with a strong inhibitory activity towards intestinal α-glucosidase and low cell permeability, we propose an alternative strategy for screening compounds from valiolamine derivatives that show high inhibitory activity towards human intracellular α-glucosidases and high cell permeability, with the goal of obtaining antimelanogenic agents that are effective inside the cells.

Effects of orally administered Actinidia arguta (Hardy Kiwi) fruit extract on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice.

Atopic dermatitis (AD) is characterized by highly pruritic, chronic, relapsing inflammatory skin lesions. Furthermore, therapeutic choices are limited, especially in long-standing cases, despite its increasing prevalence. This study was performed to examine the clinical efficacy and the therapeutic mechanism underlying the effects of Actinidia arguta (hardy kiwi) fruit extract in an animal model of AD. To examine the effects of A. arguta extract on AD, 2-chloro-1,3,5-trinitrobenzene-treated NC/Nga mice were orally administered A. arguta extract (100 mg/kg/day), tacrolimus (1 mg/kg/day), or dexamethasone (3 mg/kg/day) for 8 weeks. Skin severity scores, epidermal thickening, mast cell infiltration and degranulation, total serum immunoglobulin (Ig) isotypes (IgE, IgG(1)), and cytokine (interleukin [IL]-4 and interferon [IFN]-gamma) and Toll-like receptor (TLR) (TLR-2, TLR-4, and TLR-9) expressions were examined in each of the study groups. Orally administered A. arguta extract significantly reduced clinical dermatitis severity, epidermal thickness, mast cell dermal infiltration and degranulation, and total levels of serum IgE and IgG(1). Furthermore, this suppression of total serum IgE and IgG(1) levels was accompanied by a decrease in IL-4 and an increase in IFN-gamma expression in skin and splenocytes. Interestingly, TLR-9 expression was increased by oral A. arguta extract. This study confirms that A. arguta extract has potential as a dietary therapeutic agent for the treatment of AD. Furthermore, our findings suggest that its clinical efficacy and mode of action against AD are associated with the modulation of biphasic T-helper (Th) 1/Th2 cytokines, with the inhibition of Th2-mediated IgE overproduction, and possibly with the up-regulation of TLR-9.

A novel role for the TRPV1 channel in UV-induced matrix metalloproteinase (MMP)-1 expression in HaCaT cells.

Transient receptor potential vanilloid type 1 (TRPV1) is a molecular sensor for detecting adverse stimuli, such as capsaicin, heat, and acid. TRPV1 has been localized in keratinocytes and is suggested to be a mediator of heat-induced matrix metalloproteinase-1 (MMP-1). With regard to the multimodal activation of TRPV1, we hypothesize that TRPV1 might also mediate UV-induced MMP-1 in keratinocytes. In HaCaT, a human keratinocyte cell line, we initially confirmed capsaicin-induced membrane current and Ca(2+) influx. UV irradiation induced slow and persistent calcium influx and increased membrane current, which was inhibited by TRPV1 inhibitors (capsazepine and ruthenium red). The UV-induced MMP-1 expression in HaCaT was also decreased by TRPV1 inhibitors and was facilitated by capsaicin. Knock-down of TRPV1 using siRNA transfection also decreased MMP-1 expression, as well as UV-induced Ca(2+) influx in HaCaT. UV failed to induce MMP-1 expression in HaCaT cells cultured in Ca(2+)-free media. Both the UV-induced increase in [Ca(2+)](i) and MMP-1 were suppressed by Gö6976 (a calcium-dependent PKC inhibitor), but not by rottlerin (a calcium-independent PKC inhibitor). In addition to a plausible role of TRPV1 in UV-induced MMP-1 expression, we showed that UV increased TRPV1 expression in both HaCaT cells and human skin in vivo. From these results, we suggest that UV-induced MMP-1 expression might be mediated in part by PKC-dependent activation of TRPV1 and subsequent Ca(2+)-influx in human keratinocytes. J. Cell. Physiol. 219: 766-775, 2009. (c) 2009 Wiley-Liss, Inc.

Suppression of spontaneous dermatitis in NC/Nga murine model by PG102 isolated from Actinidia arguta.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, which requires safe and effective pharmacological therapy. We previously found that two preparations from Actinidia arguta, PG102T, and PG102E, could modulate Th1/Th2 pathways and suppress IgE biosynthesis. This study was performed to assess the therapeutic effects of PG102T and PG102E on the development of dermatitis in NC/Nga mice, characterized by the spontaneous onset of AD along with an elevated level of IgE under conventional conditions. PG102T or PG102E administration significantly reduced dermatitis severity as well as scratching tendency in conventional mice. The suppression of dermatitis by PG102 was accompanied by a decrease in the plasma level of IgE, IgG1, and IL-4 and also by an increase in that of IgG2a and IL-12. The splenic level of IL-4, IL-5, and IL-10 was downregulated, whereas that of IFN-gamma and IL-12 was increased. The number of eosinophils and the expression of eotaxin and thymus and activation-regulated chemokine were decreased by PG102T or PG102E. Histological findings also indicated that the thickening of epidermis/dermis and the dermal infiltration of inflammatory cells including mast cells were greatly inhibited. These data suggest that PG102 may be effective therapeutic agents for the treatment of AD.

The effect of tiarellic acid on the expressions of matrix metalloproteinase-1 and type 1 procollagen in ultraviolet irradiated cultured human skin fibroblasts.

Long term and repeated exposure of ultraviolet (UV) light, a harmful environmental stress, on the skin often induces chronic skin diseases such as skin cancer as well as photoaging (premature skin aging), and the mechanisms of these skin damages are closely associated with up-regulation of matrix metalloproteinases (MMPs) activities. Here we investigated the effect of tiarellic acid on the expressions of MMP-1 and type 1 procollagen in ultraviolet irradiation of cultured human skin fibroblasts. Tiarellic acid reduced the expression of MMP-1 and induced the expression of type 1- procollagen at the protein levels in a dose-dependent manner by ultraviolet irradiation. Taken together, our results suggest that tiarellic acid plays an important role in the reduction of MMP-1 and induction of type 1- procollagen by ultraviolet irradiation.

Erythrodiol-3-acetate, pentacyclic triterpenoid from Styrax japonica, expressions of matrix metalloproteinase-1,2 in cultured human skin fibroblasts.

Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of natural products. Ultraviolet irradiation is widely considered to be an environmental stress. Here we investigated the effect of erythrodiol-3-acetate on the expressions of MMP-1,2 in cultured human skin fibroblasts. Erythrodiol-3-acetate was isolated from the stems of Styrax japonica (Styracaceae). Erythrodiol-3-acetate reduced the expression of MMP-1 but not MMP-2, at the mRNA and protein levels in a dose-dependent manner by ultraviolet irradiation. Taken together, our results suggest that erythrodiol-3-acetate an important role in the reduction of MMP-1 induction by ultraviolet irradiation.

Modulation of collagen metabolism by the topical application of dehydroepiandrosterone to human skin.

Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEA-S) are the most abundantly produced human adrenal steroids to be reduced with age. DHEA may be related to the process of skin aging through the regulation and degradation of extracelluar matrix protein. In this study, we demonstrate that DHEA can increase procollagen synthesis and inhibit collagen degradation by decreasing matrix metalloproteinases (MMP)-1 synthesis and increasing tisuue inhibitor of matrix metalloprotease (TIMP-1) production in cultured dermal fibroblasts. DHEA was found to inhibit ultraviolet (UV)-induced MMP-1 production and the UV-induced decrease of procollagen synthesis, probably due to the inhibition of UV-induced AP-1 activity. DHEA (5%) in ethanol:olive oil (1:2) was topically applied to buttock skin of volunteers 12 times over 4 weeks, and was found to significantly increase the expression of procollagen alpha1(I) mRNA and protein in both aged and young skin. On the other hand, topical DHEA significantly decreased the basal expression of MMP-1 mRNA and protein, but increased the expression of TIMP-1 protein in aged skin. We also found that DHEA induced the expressions of transforming growth factor-beta1 and connective tissue growth factor mRNA in cultured fibroblasts and aged skin, which may play a role in the DHEA-induced changes of procollagen and MMP-1 expression. Our results suggest the possibility of using DHEA as an anti-skin aging agent.

Evaluation of the anti-inflammatory and atopic dermatitis-mitigating effects of BSASM, a multicompound preparation.

For effective management of atopic dermatitis (AD), it is important to introduce a therapeutic agent, which although having the fewest side effects, has the greatest anti-inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM, a mixture of several plant extracts. This study was designed to investigate the AD-mitigating effect of BSASM in patients, as well as its anti-inflammatory and immunomodulatory effects in an in vitro experiment. The anti-inflammatory effects of BSASM were evaluated by the level of production of proinflammatory cytokines. Clinical evaluation was also done using eczema area severity index (EASI) score in AD patients. BSASM inhibited LPS-induced activation of NF-kappaB promoter. In addition, LPS-induced an increase of IL-8, and the TNF-alpha production in THP-1 cells was also inhibited. These results suggest that BSASM has an anti-inflammatory activity. A clinical study in patients with AD showed that BSASM induced a reduction of EASI score, degree of pruritus, and TEWL on both the antecubital fossa and abdomen. Besides, BSASM had no irritative or allergic effects. Based on these results, we conclude that BSASM has anti-inflammatory and AD-mitigating effects.