• Biomolecules & Therapeutics
• /
• v.28 no.5
• /
• pp.456-464
• /
• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.34 no.7
• /
• pp.953-958
• /
• 2005

This study was conducted to investigate the effect of beverage (beverage HC and beverage PG) using herbs on antimicrobial activity, proliferation of hepatic cancer cell (Hep3B) lines and sarcoma 180 (S-180) and antiallergy, respectively. Beverage PG showed higher antimicrobial activity than beverage HC against Staphylococcus aureus and Pseudomonas aeruginosa. Beverage HC and PG showed the tumor suppressive effect in mice injected with S-180 cells. The growth-inhibitoy ratio against tumor cells were $66\%\;for\;10\%$ beverage HC, $61\%\;for\;10\%$ beverage PG. In an anti-cancer test using Hep3B cells, beverage PG showed higher anti-proliferating effect than beverage HC. Beverage PG showed growth-inhibitory effect of $69.2\%\;at\;100\%$ beverage PG. Beverage PG inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80. In conclusion, these results suggest that beverage using herbs have an antimicrobial activity, anti-proliferating effect against Hep3B cell and S-180 tumor and will be beneficial in treatment of allergic reaction.

• Journal of Life Science
• /
• v.31 no.4
• /
• pp.418-424
• /
• 2021

Skin inflammation (dermatitis) is caused by varying skin damage due to ultraviolet radiation and microbial infection. Currently prescribed drugs for dermatitis include anti-histamine and steroid drug classes that soothe inflammation. However, incorrect or prolonged use of steroids can cause weakening of skin barriers as well as osteoporosis. Therefore, treating dermatitis with a drug that has minimal side effects is important. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are cholesterol-lowering drugs that have been widely treated for hyperlipidemia and cardiovascular diseases. Interestingly, recent studies have shown the anti-inflammatory effects of statins in both experimental and clinical models for of osteoarthritis. This study investigated the possible anti-inflammatory effects of atorvastatin and fluvastatin in human keratinocytes (HaCaT cells), which are crucial components of skin barriers. Stimulation of HaCaT cells with IL-1β increased the expression of the COX2 protein, a major player of inflammatory responses. However, this induction of the COX2 protein was downregulated by pretreatments with atorvastatin and fluvastatin. Treatment with IL-1ß-induced the upregulation of other inflammatory genes (such as iNOS and MMP-1) and these expressions were similarly lowered by these two statin drug treatments. Taken together, these results indicated that atorvastatin and fluvastatin can reduce IL-1β-induced inflammatory responses in HaCaT cells. In conclusion, the findings suggest that atorvastatin and fluvastatin can be potential modulators for ameliorating skin inflammation.

• Journal of Life Science
• /
• v.21 no.10
• /
• pp.1364-1369
• /
• 2011

Mast cells, the central effector cells involved in the allergic response, release histamine, arachidonic acid, and proinflammatory cytokines. We investigated the effect of the ethyl acetate fraction (EA), derived from Korean rice wine lees, on RBL-2H3 cell degranulation and passive cutaneous anaphylaxis in an animal model. The EA fraction suppressed the release of beta-hexosaminidase, a marker of degranulation, and the mRNA expression of interleukin-3 (IL-3) and IL-13. EA also successfully suppressed the passive cutaneous anaphylaxis (PCA) reaction in mice in a dose-dependent manner. These results suggest that EA can inhibit mast cell degranulation through the inhibition of IL-3 and IL-13 mRNA expression, and that EA may potentially serve as an anti-allergic agent.

• Journal of Life Science
• /
• v.25 no.9
• /
• pp.1000-1006
• /
• 2015

α-Asarone is the main component of Acorus gramineus, which is a widely used oriental traditional medicine. A. gramineus is known to have a variety of medicinal effects, such as anti-gastric ulcer, antiallergy and antioxidant activity. It is also known to inhibit the release of histamine. However, the mechanism of its action remains unclear in humans. In this study, the effects of α-asarone on matrix metalloproteinase (MMP) and its antioxidant effect in a cell-free system were examined in HT1080 cells. In an MTT assay, the effect of α-asarone on cell viability showed no cytotoxicity below 16 μM. In an antioxidant assay, α-asarone increased reducing power in a dose-dependent manner but not the scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In addition, α-asarone exhibited the protective effect against DNA oxidation induced by hydroxyl radicals produced by the Fenton reaction. Furthermore, in a gelatin disk assay, α-asarone enhanced collagenase activity. It also increased the activities of MMP-2 and MMP-9 stimulated by phorbol 12-myristate 13-acetate (PMA) in a gelatin zymography. On the other hand, the activity of MMP-9 stimulated by phenazine methosulfate (PMS) but not that of MMP-2 was increased in the presence of α-asarone. These findings suggest that α-asarone could be a candidate for the prevention and treatment of pathological diseases related to oxidative stress and MMPs.

• Journal of Life Science
• /
• v.22 no.5
• /
• pp.595-599
• /
• 2012

Allergic response is associated with mast cells, through the release of arachidonic acid, proinflammatory cytokines, and histamine. We investigated the effect of Platycodon grandiflorum including platycodin D (PG-Platycodin D) on allergic responses in an animal model and on mast cell degranulation. PG-Platycodin D suppressed the release of ${\beta}$-hexosaminidase, a type of marker associated with degranulation. PG-Platycodin D efficiently inhibited the passive cutaneous anaphylaxis (PCA) reaction in ICR mice. In addition, molecular analysis demonstrated that PG-Platycodin D inhibited mRNA expression of both IL-3. These results suggest that PG-Platycodin D can inhibit mast cell degranulation through the inhibition of IL-3 mRNA expression, and that PG-Platycodin D may potentially serve as an anti-allergic agent.

• The Journal of Pediatrics of Korean Medicine
• /
• v.25 no.1
• /
• pp.1-27
• /
• 2011

Objectives: The purpose of this study is to investigate the effects of Yijungtang(YJT) on atopic dermatitis in an in-vitro and in-vivo experiment using a RBL-2H3 mast cells and a NC/Nga atopic dermatitis mouse. Methods: In-vitro experiment, IL-4, IL-13 mRNA expression were evaluated by a real-time PCR, IL-4, IL-13 production by ELISA and transcription factor as GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-kB by western blotting. In-vivo experiment, clinical skin score we evaluated by, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mouse, cytokine level, total number of cell, Immunohistochemical staining and Histological features of auxiliary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue in NC/Nga mouse. Results: YJT decreased IL-4, IL-13 mRNA expression, IL-4, IL-13 production and prominently decreased the expression of mast cell specific transcription factors including GATA-2, NF-AT2, c-Fos and NF-kB. YJT oral administration reduced the levels of skin severity scores. It also decreased the level of inflammatory cytokines such as IL-5, IL-13, histamine and IgE in the serum. It elevated IFN-gamma level in the spleenocyte culture supernatant but decreased. $CD3e^+$, $CD19^+$, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $CD11b^+Gr-1^+$, $CCR3^+$ in the PBMCs, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $B220^+CD23^+$ in the ALN, $CD4^+$, $CD3e^+CD69^+$ in the ALN and $CD4^+$, $CD11b^+Gr-1^+$ in the dorsal skin. Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mice were much improved by YJT oral administration. Conclusions: The anti-allergic activities of YJT may be mediated by down-regulation of Th2 cytokines, such as IL-4 and IL-13, through the regulation GATA-2, NF-AT2 and NF-kB transcription factors in mast cells. YJT would be regulate molecular mediators and immune cells which are functionally associated with atopic dermatitis induced in NC/Nga mice, and may play an important role in recovering AD symptoms.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.15 no.2
• /
• pp.252-260
• /
• 2002

Introduction Urticaria is widely spread disease. About 15-20 $\%$ of population has experienced at least once in a life time. The etiology of urticaria is uncertain till now, and the affcting factors are various chemical material, physical factors, alcohol, fever, exercise, and hormone, etc. The symptoms of urticaria are small or large wheal-erythema reaction and itching or tingling sense. Cause there is no probe to detect the urticaria clearly, the treatment of urticaria is symptomatic. And mostly urticaria can be chronic and very hard to treat it fundamentally. Nowadays, many trials to treat the urticaria in oriental medical way show good curability. In this paper I'd like to report the treatment rate and degree of urticaria patients mostly using anti-histamine medication. Subjects From the outpatients who visited Korean Hospital of Kyunghee Kangnam during 2000-4 and 2002-1, the 36 chronic urticaria patients, at least more than 4 weeks from onset and 2weeks of treatment period, were chosen. Methods I evaluated the results of treatment with the following scale. Very Good: The all symptoms are clearly disappeared or one third of symptoms remain and sometimes eruption is appeared. Good: Half of the symptoms are improved but most of symptoms remain. No Change: No change appears before and after treatment. Worse: The degree and duration of eruption get worse than pre-treatment state. Results For Acupuncture treatment, I chose the several Acu points like Hapgok(합곡), Taichung(대충), Gokji(곡지), Yanggok(양곡), Yanggea(양계), and lmeup(족임읍), and usually lasted it 15 minutes. With the acupuncture treatment and herb medicine, 2-3 times a week, the patients whose treatment period was 2 to 4 weeks were 17(47.2$\%$), 4 to 8 weeks were 11(30.5$\%$), 8 to 12 weeks were 3(8.3$\%$), 12 to 16 weeks were 3(8.3$\%$), longer than 16 weeks were 2(5.5$\%$) Collecting the statistics of the frequency of prescripted herb medicine, Hyangsosan(향소산) was prescripted 21 times(58.3$\%$), Hyangsapyungwisan(향사평위산) was 15 times(41.6$\%$), Hwapisan(화피산) was 9 times(25$\%$), Yangwitang(양위탕) was 6 times(16.6$\%$), Bojungikkitang(보중익기탕가미) was 4 times(11.1$\%$), Yongdamsagantang (용담사간탕가미) was 4 times(11.1$\%$). The result of the treatments, evaluating with mentioned rate scale, was 11 cases(30.5$\%$) were Very Good degree, 19 cases(52.7$\%$) were Good , 6 cases(16.6$\%$) were No Change. No cases were Worse degree. Conclusion According to this research, we could say that chronic urticaria can be treated with Oriental medical methods. But more precise probes in both Oriental and Western medicine to diagnose the chronic urticaria should be established and we need to make standards for testing and diagnosing the chronic urticaria.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.36 no.5
• /
• pp.187-192
• /
• 2022

The purpose of this study is to examine the effect of herbal medicine complex (HMC) containing Camellia sinensis L., Duchoesna chrysantha, Houttuynia cordata Thunberg, Poncirus trifoliata Rafinesque on skin inflammation and atopic dermatitis. First, we examined the anti-inflammatory effect of HMC in TNF-α induced human keratinocytes (HaCaT cell). Real-time PCR and western blotting were performed to evaluate the expression of inflammatory cytokines (e.g., iNOS, COX-2, IL-6, IL-8) mRNA and protein. Four-weeks old male NC/Nga mice were treated with 1% 2,4-dinitrochlorobenzene (DNCB) solution and used as an atopic dermatitis mice model. And, HMC (200 mg/kg or 400 mg/kg) was administered directly into the stomach of mice for 4 weeks, and blood or serum analysis, tissue staining were performed after oral gavage. As a result HMC inhibited the mRNA expression of iNOS, COX-2, IL-6, and IL-8, which had been increased by TNF-α in HaCaT cells. In addition, the protein expression was also significantly suppressed in the same way as the mRNA expression results. The in vivo experiment results showed that, HMC administration reduced thickening of the epidermis and infiltration of eosinophil into the skin stratum basale compared to DNCB treatment. In addition, HMC administration significantly reduced the inflammatory cytokines (IL-4, IL-5, IL-6, and IL-13) production and immunocyte (white blood cell, lymphocyte, neutrophil, and eosinophil) count compared to DNCB treatment. Moreover, the serum IgE and histamine level was decreased by HMC administration. These results suggest that HMC can be used as effective herbal medicine extract for skin inflammation and atopic dermatitis. And this study may contribute to the development of the herbal medicine-based drug for the treatment of skin inflammation and atopic dermatitis.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.39 no.11
• /
• pp.1611-1618
• /
• 2010

This study was conducted to evaluate the effects of Eriobotrya japonica and Saurus chinensis extracts and their fermented extracts on immune parameters in BALB/c mice treated with 1% 2,4-dinitrochlorobenzene (DNCB). The groups were Eriobotrya japonica extract (BI), Saurus chinensis extract (SA), mixture with E. japonica extract and S. chinensis extract (FB) and fermented mixture with E. japonica extract and S. chinensis extract (FA) and distilled water treated control. The level of serum immunoglobulin (Ig) E was decreased in FA compared to control group, but significant difference was not observed (p<0.05). The histamine and contents in FA and control group were $1.47{\pm}0.20$ ng/mL and $1.90{\pm}0.04$ ng/mL, respectively (p<0.05). Ceramide contents were significantly increased in FA compared to BI, SA, FB and control group (p<0.05). These results suggest that FA supplementation in the DNCB treated BALB/c mice affect anti-allergic activities positively, and may be used as functional material for suppression of atopy dermatitis in food industry.