• Natural Product Sciences
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• 제22권4호
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• pp.275-281
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• 2016

Perilla frutescens was empirically used for controlling airway inflammatory diseases in folk medicine. We investigated whether caffeic acid, myristicin and rosemarinic acid derived from Perilla frutescens significantly affect the gene expression and production of mucin from airway epithelial cells. Confluent NCI-H292 cells were pretreated with caffeic acid, myristicin or rosemarinic acid for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The MUC5AC mucin gene expression and production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, we examined whether caffeic acid, myristicin or rosemarinic acid affects MUC5AC mucin production indued by epidermal growth factor (EGF) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), the other two stimulators of production of airway mucin. The results were as follows: (1) Caffeic acid, myristicin and rosemarinic acid inhibited the gene expression and production of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively; (2) Among the three compounds derived from Perilla frutescens, only rosemarinic acid inhibited the production of MUC5AC mucin induced by EGF or $TNF-{\alpha}$, the other two stimulators of production of airway mucin. These results suggest that rosemarinic acid derived from Perilla frutescens can regulate the production and gene expression of mucin, by directly acting on airway epithelial cells and, at least in part, explains the traditional use of Perilla frutescens as remedies for diverse inflammatory pulmonary diseases.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.128-128
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• 2018

Nypa fruticans wurmb (NF) has been used as traditional medicinal food in Asian countries. Especially, NF has been used for conventional medicine to treat inflammatory periodontal diseases. Previous studies have been shown that NF has large amount of useful constituents such as phenolic acids, polyphenols and flavonoids. Also, NF is known as having medicinal effects such as anti-oxidant, anti-inflammatory and cholesterol-lowering effects. NF has recently been attracted to use complementary medicinal food on inflammatory diseases in Korea. However, there are no obvious effects in inflammatory and metabolic diseases also mechanisms has been studied yet. The purpose of this study was to investigate the anti-inflammatory effects of NF and steamed-NF (SNF), which recently has been used as health food, using Human keratinocyte cell line (HaCaT) and Human mast cell line (HMC-1). The cytotoxicities of NF and SNF were measured by using MTT assays in HaCaT cells and HMC-1 cell. To evaluate anti-inflammatory effects of NF and SNF, HaCaT cells were stimulated with tumor necrosis factor $(TNF)-{\alpha}$ and Interferon $(IFN)-{\gamma}$. Also, HMC-1 cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and A23187 calcium ionophore (A23187) to induce allergic inflammation. Inflammatory cytokine were measured by enzyme-linked immunosorbent assay (ELISA). In this result, the extract of NF and SNF (0.01 - 1mg/ml) did not show cytotoxicity in HaCaT cells and HMC-1 cells. In addition, the NF and SNF suppressed the production of interleukin (IL)-6 and IL-8 in HaCaT cells at highest concentration. Furthermore, the treatment of SNF significantly inhibited the secretion level of IL-8 in PMA plus A23187-stimulated HMC-1 cells compared with NF treatment group. These results suggest that the extract of NF and SNF may serve as a potential therapy for skin inflammatory diseases.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.210-217
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• 2015

Background: Adenophora triphylla var. japonica is empirically used for controlling airway inflammatory diseases in folk medicine. We evaluated the gene expression and production of mucin from airway epithelial cells in response to lupenone, lupeol and taraxerol derived from Adenophora triphylla var. japonica. Methods: Confluent NCI-H292 cells were pretreated with lupenone, lupeol or taraxerol for 30 minutes and then stimulated with tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) for 24 hours. The MUC5AC mucin gene expression and production were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Additionally, we examined whether lupenone, lupeol or taraxerol affects MUC5AC mucin production induced by epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA), the other 2 stimulators of airway mucin production. Results: Lupenone, lupeol, and taraxerol inhibited the gene expression and production of MUC5AC mucin induced by TNF-${\alpha}$ from NCI-H292 cells, respectively. The 3 compounds inhibited the EGF or PMA-induced production of MUC5AC mucin in NCI-H292 cells. Conclusion: These results indicated that lupenone, lupeol and taraxerol derived from Adenophora triphylla var. japonica regulates the production and gene expression of mucin, by directly acting on airway epithelial cells. In addition, the results partly explain the mechanism of of Adenophora triphylla var. japonica as a traditional remedy for diverse inflammatory pulmonary diseases.

• Advances in Traditional Medicine
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• 제6권3호
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• pp.237-244
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• 2006

Samultang has been believed for prevention and remedy various blood diseases such as menstrual irregularity, anemia, and metrorrhagia. However, the mechanism that accounts for anti-inflammatory effects of the Samultang is still not fully understood. This study was designed to evaluate whether and how the Samultang could modulate the production of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 treated-human mast cell line, HMC-1. Samultang inhibited the production of tumor necrosis factor $(TNF)-\alpha$, interleukin (IL)-6, granulocyte macrophage colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in HMC-1. Maximal inhibition rate of $TNF-\alpha$, IL-6, GM-CSF, and VEGF by 0.1 mg/ml Samultang was about $70.73{\pm}3.0%,\;51.49{\pm}4.14%,\;54.03{\pm}2.09%$, and $47.95{\pm}7.86%$, respectively. Samultang partially blocked PMA plus A23187-induced cyclooxygenase (COX)-2 expression. In addition, Samultang inhibited activation of nuclear factor (NF)-kB, and extracellular signal-regulated kinase (ERK) activation. These results suggest that anti-inflammatory effect of Samulatng may be mediated by the suppression of cytokine production and COX-2 activation via down-regulation of NF-kB and ERK activation.

• 한방안이비인후피부과학회지
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• 제20권3호
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• pp.71-81
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• 2007

Objective : In this study, herbal medicine(GJE, Gardenia jasminoides Ellis; HCT, Houttuynia cordata Thunb.; CIL, Chrysanthemum indicum Linne; PMS,Paeonia moutan Sims, P. subfruticosa Makino; APL, Agrimonia pilosa Ledebour) were screened for their inhibitory activities against Tyrosinase and PMA plus A23187-induced $TNF-{\alpha}$, IL-6, IL-8 productions in HMC-1 cells to reveal their skin -whitening and anti-allergic effect. Method : To investigate Tyrosinase inhibition we treated Mushroom Tyrosinase(Fluka, 93898) $10{\mu}{\ell}$ and 7.5mM Tyrosine (Sigma, T3754) $20{\mu}{\ell}$ with 80% ethanol medicine extracts. Then we observed 96well micro plate extinction at 490nm. In the next experiment, to investigate Anti-allergic effect we blended cultured Human Mast Cells(HMC-1) with medicine extracts. We treated the blended solution with Phorbol 12-myristate 13-acetate(PMA) and A23187, then observed $TNF-{\alpha}$, IL-6, IL-8 by ELISA (enzyme-linked immunosorbent assay) at 450nm. Results : In inhibiting Tyrosinase the results are as follows. 1. We observed 22% inhibition of Mushroom Tyrosinase at $500{\mu}g/m{\ell}$ concentration of GJE extracts. 2. We also could observe that the decreased Mushroom Tyrosinase activities in HCT, CIL extracts. In inhibiing $TNF-{\alpha}$, IL-6, IL-8 productions in HMC-1 cells the results are as follows. 1. Of the extracts examined, HCT, PMS, APL extracts showed over 50% inhibitions of Cytokines at $200{\mu}g/m{\ell}$ concentration. 2. In particular, APL extracts showed the best inhibitory effect on Cytokine productions in a dose-dependent manner. Conclusion : These results suggest that GJE extracts contributes to the anti melanin activities and represent a potential source of whitening agent. Thus these herbal medicines suggest novel drugs on anti-allergic effects.

• 한방안이비인후피부과학회지
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• 제20권3호
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• pp.63-70
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• 2007

Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently hyperresponsive Th2 cells in the acute phase are reported as the important mechanisms. Cheonggisan(CGS) is used in oriental clinics for curing acute skin lesions of eczema, atopic dermatitis or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic mechanism of CGS on atopic dermatitis, so we observed Th2 cell differentiation in EL 4 cells and $NF-kB$ p65 activation in RAW 264.7 cells. Materials and Methods : EL 4 cells were induced the increase of IL-4 mRNA expression by phorbol-12-myristate-13-acetate(PMA) and 4-tert-Octylphenol(OP) and treated with CGS extract. RAW 264.7 cells were induced the increase of cyclooxygenase(COX)-2 mRNA expression by lipopolysaccharide(LPS) and treated with CGS extract. Results : The PMA and OP induced IL-4 mRNA expression was dose-dependantly decreased in CGS treated EL 4 cells. The LPS-induced COX-2 mRNA expression was dose-dependantly decreased in CGS treated RAW 264.7 cells. Conclusion : The results may suggest that the CGS inhibits Th2 cell differentiation in EL 4 cells and inhibits $NF-kB$ p65 activation in RAW 264.7 cells.

• 생약학회지
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• 제44권1호
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• pp.60-69
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• 2013

The worldwide prevalence and severity of allergic diseases including atopic and contact dermatitis has increased dramatically over the past decade, especially in developed countries. Mast cells are important effector cells in allergic reactions. The purpose of this study was undertaken to investigate the anti-allergic and anti-pruritic effects of Diospyros lotus leaf extract (DLE). DLE was prepared by extracting with distilled water. In the present study, we investigated the effect of DLE on the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\alpha}$) and histamine in rat peritoneal mast cells (RPMCs), and on the skin lesion, leukocyte infiltration and scratching behavior in mice. Phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 significantly increased TNF-${\alpha}$ and IL-$1{\beta}$ production compared with media control. However, TNF-${\alpha}$ and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by DLE in a dose-dependent manner. DLE also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, DLE administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine) in ICR mice. Furthermore, DLE inhibited the skin lesions, inflammatory and mast cells in hairless mice sensitized by 2,4-dinitrofluorobenzene (DNFB). DLE administration reduced the IL-4 and IgE production induced by DNFB sensitization in hairless mice. These results suggest that DLE has a potential use as a herb medicine for treatment against allergy and pruritus-related disease.

• 동의생리병리학회지
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• 제25권3호
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• pp.438-444
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• 2011

Dojuk-San is known to be effective for treating a urinary diseases and stomatitis. However, its effects on the bone marrow-derived mast cell(BMMC) mediated allergy and inflammation mechanism remain unknown. In this study, the biological effects of Dojuk-San ethanol extract(DJS) were evaluated while focusing on its effects on the allergic mediator in phorbol 12-myristate 13-acetate(PMA) plus calcium ionophore A23187(A23187)-stimulated BMMCs. An investigation was also conducted to determine its effects on the production of several allergic mediators including interleukin-6(IL-6), prostaglandin D2($PGD_2$), leukotrieneC4(LTC4) and ${\beta}$-Hexosaminidase(${\beta}$-Hex). The results revealed that DJS inhibited the PMA plus A23187 induced production of IL-6, PGD2, LTC4 and ${\beta}$-Hex. Taken together, these findings indicate that DJS has the potential using in the treatment of allergy.

• 동의생리병리학회지
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• 제25권3호
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• pp.503-509
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• 2011

Jakyaktang(芍藥湯; JYT) exhibits potent anti-inflammatory activity in widely intestinal disease, but its mechanism was undisclosed. To elucidate the molecular mechanisms of JYT on pharmacological and biochemical actions in inflammation, we examined the effect of JYT on pro-inflammatory mediators in phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell and lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether JYT inhibited pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in PMA plus A23187- induced HMC-1 cells and inflammatory madiators such as nitric oxide (NO), TNF-${\alpha}$, IL-6, iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that JYT inhibited LPS-induced NO, TNF-${\alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that JYT has inhibitory effects on mast cell-mediated and macropage-mediated inflammation.

• Molecules and Cells
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• 제39권4호
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• pp.322-329
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• 2016

Voltage-gated $Ca^{2+}$ ($Ca_V$) channels are dynamically modulated by Gprotein-coupled receptors (GPCR). The $M_1$ muscarinic receptor stimulation is known to enhance $Ca_V2.3$ channel gating through the activation of protein kinase C (PKC). Here, we found that $M_1$ receptors also inhibit $Ca_V2.3$ currents when the channels are fully activated by PKC. In whole-cell configuration, the application of phorbol 12-myristate 13-acetate (PMA), a PKC activator, potentiated $Ca_V2.3$ currents by ~two-fold. After the PMA-induced potentiation, stimulation of $M_1$ receptors decreased the $Ca_V2.3$ currents by $52{\pm}8%$. We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) is responsible for the muscarinic suppression of $Ca_V2.3$ currents by using two methods: the Danio rerio voltage-sensing phosphatase (Dr-VSP) system and the rapamycin-induced translocatable pseudojanin (PJ) system. First, dephosphorylation of $PI(4,5)P_2$ to phosphatidylinositol 4-phosphate (PI(4)P) by Dr-VSP significantly suppressed $Ca_V2.3$ currents, by $53{\pm}3%$. Next, dephosphorylation of both PI(4)P and $PI(4,5)P_2$ to PI by PJ translocation further decreased the current by up to $66{\pm}3%$. The results suggest that $Ca_V2.3$ currents are modulated by the $M_1$ receptor in a dual mode-that is, potentiation through the activation of PKC and suppression by the depletion of membrane $PI(4,5)P_2$. Our results also suggest that there is rapid turnover between PI(4)P and $PI(4,5)P_2$ in the plasma membrane.