Hye-Sun Lim

Traditional herbal formula Jakyakgamcho-tang (Paeonia lactiflora and Glycyrrhiza uralensis) impairs inflammatory chemokine production by inhibiting activation of STAT1 and NF-κB in HaCaT cells

A traditional herbal formula Jakyakgamcho-tang (JYGCT; Paeonia lactiflora and Glycyrrhiza uralensis) has been used for treatment of backache, muscle pain, acute abdominal pain, neuralgia, bronchial asthma, and painful peripheral neuropathy in Oriental medicine. We report on our experiments using the HaCaT human keratinocyte cell line showing that a traditional herbal formula JYGCT has inhibitory effects on inflammatory responses in skin. Stimulation with tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) caused a significant increase in the production of the following chemokines: thymus- and activation-regulated chemokine (TARC)/CCL17; macrophage-derived chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTES)/CCL5; and interleukin-8 (IL-8) in HaCaT cells. By contrast, treatment with JYGCT extract significantly reduced the production of TARC, MDC, RANTES, and IL-8, but caused no cytotoxicity, compared with TNF-α and IFN-γ-treated control cells. Consistently, JYGCT extract downregulated the mRNA expression of TARC, MDC, RANTES, and IL-8 induced by TNF-α and IFN-γ in a dose-dependent manner. In addition, TNF-α and IFN-γ markedly increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and the nuclear translocation of nuclear factor kappa B (NF-κB) in HaCaT cells. By contrast, TNF-α and IFN-γ-induced activation of STAT1 and NF-κB activation was inhibited by JYGCT treatment in a dose-dependent manner. Our data indicate that JYGCT attenuates TNF-α and IFN-γ-mediated chemokine production by targeting the STAT1 and NF-κB signalling in keratinocytes. Our findings suggest that JYGCT has potential as a therapeutic drug candidate for the treatment of inflammatory skin diseases.

Protective effects of the traditional herbal formula oryeongsan water extract on ethanol-induced acute gastric mucosal injury in rats.

This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5 mL/kg. OSWE (100 and 200 mg/kg) was administered to rats 2 h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Gastric mucosal injuries were evaluated by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were observed at doses up to 2000 mg/kg/day. Administration of OSWE reduced the damage by conditioning the gastric mucosa against ethanol-induced acute gastric injury, which included hemorrhage, hyperemia, and loss of epithelial cells. The level of MDA was reduced in OSWE-treated groups compared with the ethanol-induced group. Moreover, the level of GSH and the activity of antioxidant enzymes were significantly increased in the OSWE-treated groups. Our findings suggest that OSWE has a protective effect on the gastric mucosa against ethanol-induced acute gastric injury via the upregulation of antioxidant enzymes.

Alantolactone from Saussurea lappa Exerts Antiinflammatory Effects by Inhibiting Chemokine Production and STAT1 Phosphorylation in TNF‐α and IFN‐γ‐induced in HaCaT cells

Skin inflammation is the most common condition seen in dermatology practice and can be caused by various allergic reactions and certain toxins or chemicals. In the present study, we investigated the antiinflammatory effects of Saussurea lappa, a medicinal herb, and its marker compounds alantolactone, caryophyllene, costic acid, costunolide, and dehydrocostuslactone in the HaCaT human keratinocyte cell line. HaCaT cells were stimulated with tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ), and treated with S. lappa or each of five marker compounds. Chemokine production and expression were analyzed by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction, respectively. Phosphorylation of signal transducer and activator of transcription (STAT) 1 was determined by immunoblotting. Stimulation with TNF‐α and IFN‐γ significantly increased the production of the following chemokines: thymus‐regulated and activation‐regulated chemokine (TARC): regulated on activation, normal T‐cell expressed and secreted (RANTES): macrophage‐derived chemokine (MDC): and interleukin‐8 (IL‐8). By contrast, S. lappa and the five marker compounds significantly reduced the production of these chemokines by TNF‐α and IFN‐γ‐treated cells. S. lappa and alantolactone suppressed the TNF‐α and IFN‐γ‐stimulated increase in the phosphorylation of STAT1. Our results demonstrate that alantolactone from S. lappa suppresses TNF‐α and IFN‐γ‐induced production of RANTES and IL‐8 by blocking STAT1 phosphorylation in HaCaT cells. Copyright

Pinellia ternata Breitenbach attenuates ovalbumin-induced allergic airway inflammation and mucus secretion in a murine model of asthma

Abstract Objective: Pinellia ternata is an important plant in traditional Chinese medicine. This study describes the anti-inflammatory effects of a water extract of P. ternata (PTE) in allergic airway inflammation in a model of asthma in mice. Materials and methods: BALB/c mice were sensitized with ovalbumin (OVA) and, upon an OVA aerosol challenge, developed airway eosinophilia, mucus hypersecretion, elevations in cytokine, chemokine, and immunoglobulin levels and overexpression of inducible nitric oxide (iNOS). Results: Intragastric administration of PTE significantly attenuated OVA-induced influx of total leukocytes, eosinophils, neutrophils, macrophages and lymphocytes into lungs, and attenuated levels of interleukin (IL)-4, IL-13 and tumor necrosis factor-α (TNF-α), in a dose-dependent manner. PTE also significantly reduced the plasma levels of total and OVA-specific immunoglobulin (Ig)E release into the airspace. Histological studies showed that PTE inhibited OVA-induced lung tissue eosinophilia and airway mucus production. Moreover, in whole lung tissue lysates, immunohistology showed that PTE markedly attenuated the OVA-induced increase in mucin 5AC and iNOS expression. Conclusions: These results indicate that PTE has protective effects against allergic airway inflammation.

Tiarellic acid attenuates airway hyperresponsiveness and inflammation in a murine model of allergic asthma.

Asthma is a persistent inflammatory disease characterized by airway obstruction and hyperresponsiveness in association with airway inflammation. In the current research, we studied the anti-inflammatory and anti-asthmatic effects of tiarellic acid (TA) isolated from Tiarella polyphylla, based on asthmatic parameters, such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness (AHR), reactive oxygen species (ROS) and mucus hypersecretion, in an ovalbumin (OVA)-sensitized/challenged mouse model. TA significantly inhibited increases in IgE, levels of ROS and T helper cytokines, such as interleukin (IL)-4, IL-5, TNF-α, and IL-13, in bronchoalveolar lavage fluid (BALF), and effectively suppressed airway hyperresponsiveness, eosinophilia, and mucus hypersecretion in the asthmatic mouse model. In addition, we found that administration of TA attenuated ovalbumin-induced increases in NF-κB activity in lungs. The efficacy of TA was comparable to that of montelukast, a currently available anti-asthmatic drug. Our results support the utility of TA as a herbal medicine for asthma treatment and may have application in the development of anti-inflammatory and anti-asthmatic drugs.

Effect of Alpinia katsumadai Hayata on House Dust Mite-Induced Atopic Dermatitis in NC/Nga Mice

We evaluated the effects of Alpinia katsumadai Hayata (AKH, Zingiberaceae) extract on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells, thymus- and-activation-regulated chemokine (TARC/CCL17) in HaCaT cells, and histamine level in HMC-1 cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for 4 weeks, and the protective effects of AKH was investigated by measuring the severity of the skin reaction on the back and ears, and plasma levels of immunoglobulin E (IgE) and histamine. AKH extract suppressed the production of NO and PGE2 in RAW 264.7 cells, TARC in HaCaT cells, and histamine in HMC-1 cells in a dose-dependent manner. In in vivo experiments, the severity of dermatitis, including erythema/hemorrhage, edema, erosion and scaling, and plasma levels of IgE, and histamine were lower in NC/Nga mice with atopic dermatitis, treated with AKH extract than in untreated mice. AKH extract reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration on the skin of the back and ear. These results suggest that AKH inhibits the development of house dust mite-induced atopic dermatitis in NC/Nga mice.

Anti-inflammatory Actions of Herbal Formula Gyejibokryeong-Hwan Regulated by Inhibiting Chemokine Production and STAT1 Activation in HaCaT Cells

Gyejibokryeong-hwan (GJBRH; Keishi-bukuryo-gan in Japan and Guizhi Fuling Wan in China) is a traditional herbal formula comprising five medicinal herbs and is used to treat climacteric syndrome. GJBRH has been shown to exhibit biological activity against diabetes, diabetic nephropathy, atherosclerosis, ischemia, and cancer. However, there is no scientific evidence of its activities against skin inflammation, including atopic dermatitis. We used the HaCaT human keratinocyte cell line to investigate the effects of GJBRH on skin inflammation. No significant cytotoxicity was observed in cells treated with GJBRH up to a concentration of 1000 µg/mL. Exposure to the proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) significantly increased HaCaT cell production of the following chemokines: macrophage-derived chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTES)/CCL5; and interleukin-8 (IL-8). In contrast, GJBRH significantly reduced the production of MDC, RANTES, and IL-8 compared with control cells simulated with TNF-α and IFN-γ. Consistently, GJBRH suppressed the mRNA expression of MDC, RANTES, and IL-8 in TNF-α and IFN-γ-treated cells. Treatment with GJBRH markedly inhibited phosphorylation of signal transducer and activator of transcription 1 (STAT1) in HaCaT cells stimulated with TNF-α and IFN-γ. Our findings indicate that GJBRH impairs TNF-α and IFN-γ-mediated inflammatory chemokine production and STAT1 phosphorylation in keratinocytes. We suggest that GJBRH may be a potent therapeutic agent for inflammatory skin disorders.

Morus alba L. suppresses the development of atopic dermatitis induced by the house dust mite in NC/Nga mice

BackgroundMorus alba, a medicinal plant in Asia, has been used traditionally to treat diabetes mellitus and hypoglycemia. However, the effects of M. alba extract (MAE) on atopic dermatitis have not been verified scientifically. We investigated the effects of MAE on atopic dermatitis through in vitro and in vivo experiments.MethodsWe evaluated the effects of MAE on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7, as well as thymus and activation-regulated chemokine (TARC/CCL17) in HaCaT cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for four weeks, and the protective effects of MAE were investigated by measuring the severity of the skin reaction on the back and ears, the plasma levels of immunoglobulin E (IgE) and histamine, and histopathological changes in the skin on the back and ears.ResultsMAE suppressed the production of NO and PGE2 in RAW 264.7 cells, as well as TARC in HaCaT cells, in a dose-dependent manner. MAE treatment of NC/Nga mice reduced the severity of dermatitis and the plasma levels of IgE and histamine. MAE also reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration in the skin on the back and ears.ConclusionOur results suggest that MAE has potent inhibitory effects on atopic dermatitis-like lesion and may be a beneficial natural resource for the treatment of atopic dermatitis.

Quantitative Analysis of Psoralea corylifolia Linne and its Neuroprotective and Anti-Neuroinflammatory Effects in HT22 Hippocampal Cells and BV-2 Microglia

The seeds of Psoralea corylifolia L. (P. corylifolia), also known as “Bo-Gol-Zhee” in Korea, are used in a traditional herbal medicine for treating various skin diseases. In the present study, we performed quantitative analyses of the seven standard components of P. corylifolia: psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol, using high-performance liquid chromatography. We also investigated the neuroprotective and anti-neuroinflammation effects of P. corylifolia and its standard components in the hippocampal cell line HT22 and microglia cell line BV-2. A 70% ethanol extract of P. corylifolia was prepared and the seven standard components were separated using C-18 analytical columns by gradient solvents with acetonitrile and water, and ultraviolet detection at 215, 225 and 275 nm. The analytical method showed high linearity, with a correlation coefficient of ≥0.9999. The amounts of the standard components ranged from 0.74 to 11.71 mg/g. Among the components, bakuchiol (11.71 mg/g) was the most potent phytochemical component of P. corylifolia. Furthermore, we analyzed the inhibitory effects of the components from P. corylifolia to determine the bioactive compound needed to regulate neuronal cell changes. Angelicin, isobavachalcone, and bakuchiol suppressed lipopolysaccharide (LPS)-stimulated nitric oxide production in LPS-treated BV-2 microglia more significantly than did the other components. In HT22 hippocampal cells, neobavaisoflavone and bakuchiol had more potent inhibitory activity against hydrogen peroxide-induced cell death. Taken together of the quantification and efficacy analyses, bakuchiol appeared to be the most potent bioactive phytochemical component of P. corylifolia for the potential treatment of neurodegenerative diseases.

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.