Luffa cylindrica suppresses development of Dermatophagoides farinae-induced atopic dermatitis-like skin lesions in Nc/Nga mice

Abstract

Context: The fruit pulp of Luffa cylindrica Roemer (Cucurbitaceae) (LC) has been used to induce hemostasis, resolve phlegm and clear fever in traditional Korean medicine. However, the efficacy of LC has not been examined in atopic dermatitis (AD).

Objective: A 70% ethanol extract of LC was evaluated to determine anti-inflammation and anti-AD effects in vitro and in vivo.

Materials and methods: The inhibitory effects of LC on the production of PGE₂ and histamine were respectively measured in lipopolysaccharide-treated (1?μg/mL) RAW264.7 macrophages and phorbol-12 myristate 13-acetate (50?nM) and A23187 (1?µM)-stimulated HMC-1 mast cells. The production of AD-related chemokines (RANTES, TARC, and MDC) were evaluated in IFN-γ and TNF-α-stimulated (10?ng/mL, each) HaCaT keratinocytes. LC (10?mg/mouse/d) was topically applied to the dorsal skin and ears of Dermatophagoides farina (Pyroglyphidae)-sensitized Nc/Nga mice for 4?weeks.

Results: The IC₅₀ values of LC on PGE₂ and histamine production were 16.89 and 139.9?μg/mL, individually. The production of TARC and RANTES were inhibited 20% and 12% by LC (50?μg/mL) in HaCaT cells, respectively (p?<?0.05). In sensitized-NC/Nga mice, the plasma levels of IgE and histamine were suppressed 36% and 41% by LC, respectively (p?<?0.05). LC also reduced hemorrhage, hypertrophy, and hyperkeratosis of the epidermis and infiltration of mast cells in the dorsal skin and ear.

Discussion and conclusion: LC can inhibit AD-like skin lesions and reduce the generation of IgE via inhibition of the inflammatory responses. LC has potential as a therapeutic agent to treat allergic diseases, including AD.     

DA-9601 suppresses 2, 4-dinitrochlorobenzene and dust mite extract-induced atopic dermatitis-like skin lesions

DA-9601 (Stillen?) is a novel anti-peptic formulation prepared from the ethanol extracts of Artemisia asiatica possessing anti-oxidative, anti-allergic and anti-inflammatory activities. However, their effect on atopic dermatitis (AD) has not been studied yet. In this study, we report that topical application of DA-9601 suppressed house dust mite extract (Dermatophagoides farinae extract, DFE) and 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in BALB/c mice model. We established atopic dermatitis model in BALB/c mice by repeated local exposure of DFE/DNCB to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like lesions. DA-9601 reduced AD-like skin lesions based on ear thickness and histopathological analysis, and serum IgE levels. DA-9601 inhibited mast cell infiltration into the ear and elevation of serum histamine in AD model. In addition, DA-9601 suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-31, and TNF-α in the ears. Taken together, our results showed that topical application of DA-9601 exerts beneficial effects in animal model of AD, suggesting that DA-9601 might be a candidate for the treatment of AD.     

Inhibitory effect of galangin on atopic dermatitis-like skin lesions

Galangin is a member of the flavonol class of flavonoids having anti-inflammatory and anti-oxidative potential. Previously we reported the inhibitory effect of galangin on the mast cell-mediated allergic inflammation. For incremental research, we investigated the effects of galangin on atopic dermatitis (AD)-like skin lesions and underlying mechanisms of action. We established an atopic dermatitis model in BALB/c mice by repeated local exposure of house dust mite (Dermatophagoides farinae) extract (DFE) and 2,4-dinitrochlorobenzene (DNCB) to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like skin lesions. Topical application of galangin reduced AD symptoms based on ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. Galangin inhibited mast cell infiltration into the ear and serum histamine level. Galangin suppressed DFE/DNCB-induced expression of interleukin (IL)-4, IL-5, IL-13, IL-31, IL-32, and interferon (IFN)-γ in the ear tissue. To define the underlying mechanisms of action, tumor necrosis factor-α/IFN-γ-activated human keratinocytes (HaCaT) model was used. Galangin significantly inhibited the expression of cytokines and chemokine by the down-regulation of nuclear factor-κB and mitogen-activated protein kinases in HaCaT cells. Taken together, the results demonstrate that galangin inhibited AD-like symptoms, suggesting that galangin might be a candidate for the treatment of AD.     

mAgK114 suppresses lymphocyte infiltration into epidermis in the picryl chloride-induced atopic dermatitis-like skin lesions of NC/Nga mice

BACKGROUND: We have previously shown that when mouse AgK114 (mAgK114, a glycosylphosphatidylinositol anchored membrane-associated protein) is applied to the wound area, the inflammatory responses in the early recovery phase of damaged tissue are enhanced and wound closure is accelerated. This suggests that mAgK114 has an important effect on skin wound repairing. MATERIALS AND METHODS: Whether mAgK114 supresses the development, in NC/Nga mice, of atopic dermatitis (AD)-like skin lesions induced by repeated application of 2,4,6-trinitrochlorobenzene (picryl chloride, PiCl) was examined under specific pathogen-free conditions. RESULTS: Histopathologically, the application of mAgK114-ointment to the PiCl-treated NC/Nga mice remarkably suppressed severe lymphocytic infiltration into the epidermis, although total skin severity scores, histological changes in hypertrophy, erosion and infiltration of inflammatory cells into the corium and subcutaneous tissues were comparable between the mAgK114-treated group of mice and the control group. CONCLUSION: Our results suggest that mAgK114 would be beneficial for the treatment of atopic dermatitis by suppressing severe lymphocytic infiltration into the epidermis.     

Oral administration of royal jelly inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice

We have shown previously that in addition to IL-4, IL-5 and IL-10, antigen-specific interferon-gamma (IFN-gamma) production by spleen cells from ovalbumin (OVA)/Alum-immunized mice is inhibited by the administration of royal jelly (RJ). Since it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis (AD), we have examined whether RJ suppresses the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PiCl) under specific pathogen-free (SPF) conditions. Oral administration of RJ to the PiCl-treated NC/Nga mice inhibited the development of AD-like skin lesions in these mice as exemplified by the significant decrease in the total skin severity scores and the decrease in hypertrophy, hyperkeratosis, and infiltration of the epidermis and corium by inflammatory cells. IFN-gamma production by spleen cells from PiCl-treated NC/Nga mice in response to TNP-KLH was partially but significantly inhibited by the oral administration of RJ, while IFN-gamma production by Con A-stimulated spleen cells was not affected. Since inducible nitric oxide (NO) synthase (iNOS)-derived NO has been suggested as an important immunoregulatory mediator in inflammatory autoimmune diseases, we have also examined the expression of iNOS in the dorsal skin lesions of PiCl-treated NC/Nga mice. Interestingly, the expression of iNOS was significantly increased in the skin lesions of RJ-administered mice compared with those of control PBS-administered mice. Thus, our results suggest that RJ suppresses the development of AD-like skin lesions in PiCl-treated NC/Nga mice, possibly by a combination of down-regulating TNP-specific IFN-gamma production and up-regulating iNOS expression.     

Therapeutic application of human leukocyte antigen-G1 improves atopic dermatitis-like skin lesions in mice

Human leukocyte antigen (HLA)-G is an immune checkpoint molecule that plays critical roles in immune response and in triggering inhibitory signaling to immune cells such as T cells, natural killer cells, and antigen-presenting cells. Thus, the application of HLA-G can be considered for treating immune response-related inflammatory disorders. We have previously reported that treatment with HLA-G1 and HLA-G2 ameliorates the joint swelling associated with collagen-induced arthritis of DBA/1 mice, an animal model for rheumatoid arthritis. In this study, we further investigated the effects of HLA-G1 on atopic dermatitis (AD), the most common inflammatory skin disorder. AD-like lesions were induced with the extract of the house dust mite Dermatophagoides farinae in NC/Nga mice. Continuous administration of HLA-G1 ameliorated the AD-like skin lesions in the mice. Furthermore, production of immunoglobulin E, interleukin (IL)-13, and IL-17A was significantly reduced in HLA-G1-treated mice, suggesting a Th2/Th17-mediated immune-inhibitory function of HLA-G1 in vivo. Our studies shed light on novel therapeutic strategies with recombinant HLA-G proteins for immune reaction-mediated chronic inflammatory disorders.     

Effect of Lactobacillus acidophilus strain L-55 on the development of atopic dermatitis-like skin lesions in NC/Nga mice

In this study, we examined whether Lactobacillus acidophilus strain L-55 (strain L-55) suppresses the development of atopic dermatitis (AD)-like skin lesions induced by repeated application of 2,4,6-trinitrochlorobenzene (TNCB) in sensitized NC/Nga mice. The effect of strain L-55 was assessed by measuring clinical symptoms, ear swelling, scratching behavior and serum levels of total IgE. Strain L-55 was administered orally once a day: Strain L-55 at doses of 1 and 10 mg cells/mouse inhibited the development of AD-like skin lesions in dermatitis scores for the back. The increase of dermatitis score and ear swelling was also inhibited by strain L-55. In addition, strain L-55 also caused an inhibition of histological changes induced by repeated application of TNCB. Scratching behavior observed in the back and ear was inhibited by strain L-55. Furthermore elevated serum IgE levels observed by TNCB were also decreased by strain L-55. These results indicate that the inhibition of strain L-55 on AD-like lesions induced by repeated application of TNCB in sensitized NC/Nga mice occurred via a decrease in the serum total IgE level.     

Oral administration of ginsenoside Rh1 inhibits the development of atopic dermatitis-like skin lesions induced by oxazolone in hairless mice

In the present study, we examined the inhibitive effect of ginsenoside Rh1 on oxazolone-induced atopic dermatitis-like skin lesions in hairless mice. Oral administration of ginsenoside Rh1 improved clinical symptoms, and it was confirmed by histophathological analysis. In ginsenoside Rh1 (20mg/kg) group, ear swellings and ear weights were significantly lower than the control group. Moreover, elevation of IL-6 and total IgE levels in serum were suppressed by ginsenoside Rh1 (20mg/kg). In addition, ginsenoside Rh1 (20mg/kg) significantly increased mRNA expression of IFNγ and Foxp3, and slightly decreased IL-4 expression in draining lymph nodes. The results suggest that ginsenoside Rh1 can alleviate inflammatory symptoms in atopic dermatitis (AD) by reduction of IgE and IL-6 levels in peripheral blood, increase of Foxp3 expression in draining lymph nodes and suppression of inflammation in skin regions. Indeed, ginsenoside Rh1 exhibited therapeutic possibility in immune disorders.     

Topical application of aloperine improves 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice

Aloperine has been shown to inhibit 2,4-dinitrofluorobenzene (DNFB) induced allergic contact dermatitis in BALB/c mice. In the present study, we further investigated the effect of aloperine on DNFB-induced atopic dermatitis-like skin lesions in NC/Nga mice. NC/Nga mice elicited atopic dermatitis-like skin lesions after the topical application of DNFB. Aloperine treatment significantly inhibited dermatitis index and ear thickness in DNFB-treated NC/Nga mice in a dose-dependent manner. Eosinophils, mast cells infiltration into the ears and plasma level of immunoglobulin (Ig) E were also suppressed by aloperine treatment. Finally, cytokine (interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-13, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) productions in ear biopsies homogenates were significantly elevated after DNFB challenge. Topical application of aloperine increased the immunosuppressive cytokine IL-10 level, while it reduced other cytokines production in a dose-dependent manner. Taken together, these data suggest that aloperine may be one of the effective therapeutic agents for the treatment of atopic dermatitis.     

Drug-loaded PLGA-mPEG microparticles as treatment for atopic dermatitis-like skin lesions in BALB/c mice model

Abstract

This study evaluated the feasibility of mizolastine-loaded microparticles as therapy for atopic dermatitis. Microparticles have been researched for decades as a controlled-release drug delivery system, but seldom been used as treatment for skin disease. In this research, we induced dermatitis in BALB/c mice model by repeated topical application of dinitrofluorobenzene and compared the mizolastine microparticles injection and daily mizolastine injection treatment. The results showed that the mizolastine microparticles treatments significantly inhibited ear thickness and dermatitis index in dermatitis model compared with the dermatitis mice without treatment, showing a similar curative effect compared with daily mizolastine injection treatment, and the improvement continued for several days. Inflammatory cells infiltration into the ears and the plasma level of immunoglobulin E were also suppressed by mizolastine microparticles according to the histopathology analysis. In conclusion, the results suggested that drug-loaded microparticles could be a proper candidate for the treatment of skin diseases.     

Inhibitory effects of Saururus chinensis (LOUR.) BAILL on the development of atopic dermatitis-like skin lesions in NC/Nga mice

The present study was performed to examine whether the leaves of Saururus chinensis (LOUR.) BAILL (SC), an herb used for the management of various skin diseases including atopic dermatitis (AD) in Eastern countries, inhibited the development of AD-like skin lesions in NC/Nga mice which was induced by repeated application of picryl chloride (PiCl). The efficacy of SC was judged by measurement of skin severity, itching behavior, histological study, serum IgE levels, IL-4 and IFN-gamma in lymph nodes. Oral administration of SC extract to the PiCl-treated NC/Nga mice for 8 weeks (5 d per week) inhibited significantly the development of AD-like skin lesions macroscopically. Histologically, SC inhibited dermatitis changes like hypertrophy, hyperkeratosis, and infiltration of inflammatory cells into epidermis and dermis. The itching behavior and serum IgE level decreased significantly after SC administration. SC administration enhanced IFN-gamma mRNA expression but did not have an effect on IL-4 mRNA expression. These results suggest that SC could inhibit the development of AD-like skin lesions in NC/Nga mice possibly through modulating the Th1/Th2 imbalance by the promoting of Th1 cell response. Thus, SC may be an alternative substance for the management of AD patients.     

Topical effects of roflumilast on 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice

Phosphodiesterase-4 (PDE-4) inhibitors have a wide range of anti-inflammatory and immunomodulatory activities. Here we examined the effects of roflumilast, a well-known PDE-4 inhibitor, on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like lesions. Roflumilast inhibited DNCB-stimulated IL-1alpha secretion in HaCaT cells, and reduced ear thickness and lymph node weights in BALB/c mice sensitized with DNCB. Topical application of roflumilast to DNCB-induced atopic dermatitis-like skin lesions of NC/Nga mice ameliorated intensity scores and dorsal skin thickness, in parallel with reduced tissue IL-1beta levels and epidermal hyperplasia. On the other hand, no effect on IgE and IL-4 was observed upon roflumilast treatment. Taken together, roflumilast showed beneficial effects against DNCB-induced atopic dermatitis.     

Mechanism underlying the effect of combined therapy using glucosamine and low-dose cyclosporine A on the development of atopic dermatitis-like skin lesions in NC/Nga mice

Combination therapy is often used in the treatment of atopic dermatitis (AD) to improve clinical efficacy or to spare the dose of each drug. Cyclosporine A (CsA) is a calcineurin inhibitor that was developed for the treatment of AD. Glucosamine (Glu) is a potent immunosuppressant that inhibits Th2-mediated immunity. We previously reported that Glu has an ameliorative effect on the development of the pathology in NC/Nga mice. The aims of our study were to investigate the therapeutic efficacy of combination of Glu and low-dose CsA in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with Glu (500 mg/kg) alone, low-dose CsA (2, 5, and 10 mg/kg) or in combination. The clinical scores were reduced significantly by the combination treatment with Glu and low-dose CsA. The suppression of dermatitis by combined therapy was accompanied by decrease in the plasma level of IgE and in the splenic level of IL-4, IL-5, IL-13, TARC and eotaxin. Histological analysis of the skin also revealed that combination treatment significantly reduced the inflammatory cellular infiltrate, including mast cells and eosinophils. Particularly, immunological evaluation reveals an increase of CD4⁺CD25⁺ Treg cells in the combined treatment. The induction of TSLP, which leads to systemic Th2 response, was reduced in the skin on combination treatment. The protein expression of filaggrin and involucrin was recovered by combination treatment in the skin lesions, whereas the protein expression of keratin-10 and keratin-14 decreased in the combination treatment. Collectively, our findings suggest that combination treatment of Glu and low-dose CsA leads to the therapeutic effects in Df-induced AD-like skin lesion in NC/Nga mice through inhibition of IgE, inflammatory cellular infiltrate, and recovery of skin barrier function via a mechanism that may inhibition of Th2-mediated immune responses, in part, increment of CD4⁺CD25⁺ Treg cells. These results suggest that this combined immunosuppressive treatment may provide important implications for the design of therapeutic strategies aimed at AD treatment.     

Effects of topically applied Korean red ginseng and its genuine constituents on atopic dermatitis-like skin lesions in NC/Nga mice

Ginseng (the root of Panax ginseng C.A. Meyer, family Araliaceae) possesses various biological activities, including anti-inflammatory and anti-tumor actions. However, their topical effect on atopic dermatitis (AD) has not been studied yet. The aim of this study was to examine the therapeutic effects of topical Korean red ginseng saponin fraction (KRGS) and its genuine constituents on AD-like skin lesions in an AD mouse model. The therapeutic effect of topical KRGS and ginsenosides in 2-chloro-1,3,5-trinitrobenzene (TNCB)-treated NC/Nga mice was assessed by measuring the skin severity scores, ear thickness, histological changes of lesional skin including mast cell count, tissue tumor necrosis factor (TNF)-α, interleukin (IL)-4, and interferon (IFN)-γ mRNA expression, and total serum IgE. Topical administration of 0.1% KRGS, 0.1% Rh2 and 0.1% Rh2+0.1% Rg3 significantly reduced the clinical skin severity scores, ear thickness and mast cell infiltration in the TNCB-induced AD-like skin lesions. Topical application of KRGS and its constituents significantly reduced TNCB-induced increase in ear TNF-α and IL-4 mRNA expression, but not IFN-γ mRNA expression. There was little change of serum total IgE level by topical KRGS and its constituents. In this study, topical KRGS and ginsenosides Rh2 and Rg3 were found to exert an anti-inflammatory effect in vivo and proved to be beneficial in an animal model of AD. Our results suggest that KRGS and its ginsenosides Rh2 and Rg3 have potential as a topical agent for the treatment of AD.     

Epigallocatechin-3-gallate improves Dermatophagoides pteronissinus extract-induced atopic dermatitis-like skin lesions in NC/Nga mice by suppressing macrophage migration inhibitory factor

Epigallocatechin-3-gallate (EGCG) has been shown to exert anti-inflammatory effects on the inflammatory skin conditions. However, little is known about its effect on atopic dermatitis (AD). We first attempted to assess the anti-inflammatory effect of topical application of EGCG in vivo AD model using NC/Nga mice and to determine whether EGCG exerts the anti-inflammatory effect by inhibiting macrophage migration inhibitory factor (MIF) and other cytokines that are related to immune dysregulation in the pathogenesis of AD. Murine AD-like skin lesions were made by painting Dermatophagoides pteronissinus extract (DPE). The effects of EGCG treatment were assessed by total clinical severity score and ear thickness, and by histological grading. In addition, the mRNA and protein expression of the cytokines including MIF were measured by real-time RT-PCR and immunohistochemistry. The serum levels of MIF and IgE were measured by ELISA. In the AD mouse model, EGCG significantly reduced the total clinical severity score and ear thickness (p<0.05). The histological grading was also markedly improved. The mRNA expression of MIF, TNF-alpha, IFN-gamma, IL-2 and IL-12 p40, but not of IL-4, IL-5 and IL-13 in the lesions was significantly reduced by EGCG (p<0.05). On the immunohistochemistry, EGCG also markedly diminished the expression of MIF, TNF-alpha and IFN-gamma. The serum MIF and IgE production was significantly reduced by EGCG (p<0.05). These results demonstrate that topical application of EGCG may improve the AD-like skin lesions by suppressing MIF and T helper 1 cytokines. Taken together, it is suggested that EGCG may be a potential therapeutic modality for AD.     

Inhibitory effect of chitosan-containing lotion on scratching response of hairless mice with atopic dermatitis-like dry skin

In this study, using a special diet-induced mouse model of atopic dermatitis, we tested the effect of chitosan-containing lotion (CL) on itch-related scratching associated with barrier-disrupted dry skin. HR-1 hairless mice fed a special diet exhibited apparent dry skin symptoms characterized by decreased skin hydration and increased transepidermal water loss. In the special diet-fed mice, scratching behavior was markedly enhanced for 60 min after oral administration of ethanol. When CL was applied once immediately after ethanol administration, the enhanced scratching response was significantly suppressed, but this effect was abolished within 30-40 min; when applied twice immediately and at 30 min, CL almost completely blocked scratching throughout 60 min. Comparison of CL and the chitosan-free vehicle showed that CL inhibited scratching more strongly and persistently than the vehicle, which transiently suppressed scratching only for 10 min after application. Although the decreased skin hydration was improved even by the vehicle, the increased transepidermal water loss was resolved only by CL. Skin surface temperature was much more reduced in CL-treated mice than in vehicle-treated mice. Collectively, CL has an antipruritic effect, which could be partly explained by recovery of skin barrier function and cooling of the skin.     

Development of numerous nerve fibers in the epidermis of hairless mice with atopic dermatitis-like pruritic skin inflammation

Itching is the most important symptom in atopic dermatitis because the persistent scratching in response to itching aggravates the disease. However, the etiologic mechanisms of itching in atopic dermatitis remain uncertain. HR-1 hairless mice fed a special diet, HR-AD, develop atopic dermatitis-like symptoms with prolonged scratching episodes. The purpose of this study was to examine whether skin nerve fiber changes were involved in the prolonged scratching seen in this mouse model. On day 56 after the start of feeding, prolonged scratching, as well as atopic dermatitis-like skin changes, were clearly observed in HR-AD-fed mice, while no abnormal changes were observed in mice fed a normal diet. Immunohistochemical analyses of the skin using antibody to protein gene product 9.5 showed the development of numerous immunoreactive nerve fibers in the epidermis of HR-AD-fed mice. Furthermore, after cessation of HR-AD feeding, the reduction in intraepidermal nerve fibers coincided with decreased scratching. Neither the prolongation of scratching nor the increase in intraepidermal nerve fibers was affected by dexamethasone treatment. Thus, the increased number of intraepidermal nerve fibers could be involved in the aggravation of itch-related scratching observed in this model.     

Topical application of a novel ceramide derivative, K6PC-9, inhibits dust mite extract-induced atopic dermatitis-like skin lesions in NC/Nga mice

Atopic dermatitis (AD) is a chronic inflammatory skin disease. K6PC-9 (N-Ethanol-2-hexyl-3-oxo-decanamide) is a novel synthetic ceramide derivative of PC-9S (N-Ethanol-2-mirystyl-3-oxo-stearamide), which was known to be effective in atopic and psoriatic patients. To investigate the immunomodulatory activity of K6PC-9, we examined the effect of K6PC-9 on T lymphocyte and macrophage function and the effect of topical application of K6PC-9 on skin inflammation and AD-like skin lesions in mouse models. K6PC-9 had no effect on concanavalin A-induced proliferation, interleukin (IL)-2 secretion and IL-4 secretion in mouse splenocytes. In contrast, lipopolysaccharide-induced nitrite generation was potently suppressed by K6PC-9 in mouse peritoneal macrophages. In mouse model of skin inflammation, K6PC-9 inhibited phorbol ester-induced increase in ear thickness and expression of tumor necrosis factor-alpha in the ear of BALB/c mice. Topical application of K6PC-9 also suppressed mite extract-induced AD-like skin lesions in NC/Nga mice. Increase in ear thickness was significantly inhibited by K6PC-9 in this model. K6PC-9 also blocked the infiltration of mast cells and neutrophils into the ear. Further study demonstrated that the mRNA expression of tumor necrosis factor-alpha and adhesion molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, was also suppressed by K6PC-9 in the ear of mite extract-treated NC/Nga mice. Taken together, the results presented in this report show that K6PC-9 has an anti-inflammatory potential and exerts beneficial effects in an animal model of AD, indicating that K6PC-9 might be used as a topical agent for the treatment of AD.     

桔梗的化学成分和抗肿瘤活性研究进展

桔梗作为一种药食两用的植物,具有显著的镇咳祛痰、抗肿瘤、抗氧化及降血糖等作用。迄今为止,从桔梗中共分离得到55种皂苷类化合物,三萜皂苷是其主要的活性成分。本文对近年来桔梗的化学成分研究进展进行了总结,并从诱导肿瘤细胞凋亡、增强机体免疫功能、抑制端粒酶活性、抑制肿瘤细胞浸润与转移以及阻滞细胞周期等方面,对国内外桔梗抗肿瘤活性的研究进展进行了阐述。     

Effect of bakumijiogan, an herbal formula in traditional Chinese medicine, on atopic dermatitis-like skin lesions induced by mite antigen in NC/Jic mice

We evaluated the effectiveness of bakumijiogan (BJG), an herbal formula in traditional Chinese medicine used to treat atopic dermatitis (AD), using a NC/Jic mouse model of AD. AD symptoms were induced by repeated injections of Dermatophagoides farinae antigen (Df-antigen) into the ear auricle at 2- to 3-d intervals for 16 d. Ear thickness dramatically increased up to 16 d after the first injection of Df-antigen. Daily oral administration of BJG from 7 d before to 16 d after the first injection significantly reduced ear swelling. Serum concentrations of total immunoglobulin (Ig)E and Df-antigen-specific IgG1 were augmented when assayed 17 d after the first injection of Df-antigen, and these increases were slightly suppressed by BJG administration. Serum interferon (IFN)-gamma and lesional IFN-gamma mRNA levels were significantly higher, whereas lesional IL-1alpha and tumor necrosis factor-alpha mRNA levels were lower in BJG-treated mice than those in control mice. These results suggest that BJG suppressed AD-like symptoms by correcting the Th1/Th2 imbalance skewed toward Th2. Evaluation of herbal constituents in BJG revealed that the combination of two herbal ingredients, ophiopogon tuber and schisandra fruit, mainly contributed to the effects of BJG.