Anti-inflammatory effects of a traditional Korean medicine: Ojayeonjonghwan.

OBJECTIVE: To study the anti-inflammatory properties of OJ. CONTEXT: Ojayeonjonghwan (OJ) is a traditional Korean prescription, which has been widely used for the treatment of prostatitis. However, no scientific study has been performed of the anti-inflammatory effects of OJ. MATERIALS AND METHODS: Peritoneal macrophages were isolated 3-4 days after injecting a C57BL/6J mouse with thioglycollate. They were then treated with OJ water extract (0.01, 0.1, and 1 mg/mL) for 1 h and stimulated with lipopolysaccharide (LPS) for different times. Nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and proinflammatory cytokine levels were determined by NO assay, Western blotting, RT-PCR and ELISA. RESULTS: NO generation and iNOS induction were increased in the LPS-activated mouse peritoneal macrophages. However, NO generation and iNOS induction by LPS were suppressed by treatment with OJ for the first time. The IC50 value of OJ with respect to NO production was 0.09 mg/mL. OJ did not influence LPS-stimulated COX-2 induction, but did significantly decrease LPS-stimulated secretions and mRNA expressions of tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Inhibition rates of TNF-α, IL-6, and IL-1ß at an OJ concentration of 1 mg/mL were 77%, 88%, and 50%, respectively. OJ also suppressed the LPS-induced nuclear translocation of NF-κB. High-performance liquid chromatography showed schizandrin and gomisin A are major components of OJ. CONCLUSIONS: OJ reduces inflammatory response, and this probably explains its positive impact on the prostatitis associated inflammation.

Ameliorative effect of atractylenolide III in the mast cell proliferation induced by TSLP.

Atractylenolide III (ATL-III) is an active compound of Atractylodes lancea, which has been widely used for the treatment of cancer. Cancer is closely connected with inflammation, and many anti-inflammatory agents are also used to treat cancer. We investigated the influence of ATL-III on thymic stromal lymphopoietin (TSLP)-induced inflammatory reactions. Pretreatment with ATL-III suppressed murine double minute 2 levels and promoted p53 levels in TSLP-treated human mast cell, HMC-1 cells. Mast cell proliferation increased by TSLP or IL-3 stimulation was significantly decreased by ATL-III pretreatment. Interleukin (IL)-13 and phosphorylated signal transducer and activator of transcription 3, 5, and 6 levels in TSLP-treated HMC-1 cells were also decreased by ATL-III pretreatment. In addition, ATL-III decreased the TSLP-induced production of proinflammatory cytokines (IL-6, IL-1ß, tumor necrosis factor-α, and IL-8). ATL-III decreased the levels of Bcl2 and procaspase-3 and increased caspase-3 activation and cleaved PARP levels. Furthermore, ATL-III decreased TSLP-induced mast cell proliferation and the production of inflammatory cytokine by LAD2 cells. Taken together, these findings suggest that ATL-III plays a useful role as an anti-inflammatory agent and should be viewed as a potential anti-cancer agent.

Antidepressant effect of Stillen.

Stillen has been used to treat patients with gastric mucosal ulcers and has an anti-inflammatory effect. It is well-known that neuro-inflammatory reactions are related to depression. Here we evaluated the antidepressant-like effect of Stillen on mice subjected to the forced swimming test (FST). Stillen and eupatilin (a major component of Stillen) significantly decreased immobility times compared with the FST control group. In the Stillen-administered group, increased levels of 5-hydroxytryptamine (serotonin) and brain-derived neurotrophic factor protein were observed in the hippocampus. Nissl bodies also increased in the hippocampus neuronal cytoplasm of the Stillen-administered group. Stillen decreased levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (at the mRNA and protein levels) in the hippocampus and serum, compared with the control group. In addition, the mRNA expression of estrogen receptor-ß increased after Stillen administration in the hippocampus. These findings suggest that Stillen should be viewed as a candidate antidepressant.

A natural dye, Niram improves atopic dermatitis through down-regulation of TSLP.

Naju Jjok (Polygonum tinctorium Lour.) has been known to treat skin diseases in traditional Korean medicine. A natural textile dye, Niram made from Naju Jjok has traditionally been used to dye clothes. Thymic stromal lymphopoietin (TSLP) plays an important role in the development of atopic dermatitis (AD). Thus, we investigated that Niram might ameliorate AD through regulation of TSLP. Niram significantly inhibited the levels of TSLP through blockade of caspase-1/receptor-interacting protein 2 pathway in stimulated mast cells. Further, Niram ameliorated clinical symptoms in AD mouse. Niram significantly inhibited the infiltration of inflammatory cells in lesional skin. The levels of TSLP, caspase-1, IL-4, and IL-6 were inhibited in lesional skin applied topically with Niram. Niram significantly inhibited the serum levels of IgE and histamine in AD mouse. Finally, Niram significantly inhibited the levels of TSLP in polyriboinosinic polyribocytidylic acid-stimulated human keratinocyte HaCaT cells. These results establish Niram as a functional dye embracing the aspects of not only a traditional use but also a pharmacological effect.

The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin as a novel allergic rhinitis-control agent.

AIMS: The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin (OMC) is a novel secondary metabolite extracted from Corydalis heterocarpa, which has long been used as a folk medicine for various inflammatory diseases in Korea. We examined the effect of OMC on allergic rhinitis (AR). MAIN METHODS: We assessed the therapeutic effects and regulatory mechanisms of OMC on the phorbol 12-myristate 13-acetate plus A23187-stimulated mast cell line, HMC-1 cells and ovalbumin (OVA)-induced AR models. KEY FINDINGS: OMC significantly decreased the releases of histamine and tryptase from stimulated HMC-1 cells. The degranulation process, characterized by morphological extension of the filopodia on the surface and membrane ruffling, was strongly induced in the stimulated-HMC-1 cell, however OMC suppressed the morphological changes in stimulated-HMC-1 cells. OMC reduced the production and mRNA expression of inflammatory cytokines. These inhibitory actions by OMC were dependent on the regulation of mitogen-activated protein kinases, nuclear factor-κB, and caspapase-1 signaling pathways. In the AR animal model, the increased rub scores and AR biomarkers (histamine and IgE) in ovalbumin (OVA)-sensitized mice were significantly reduced by the administration of OMC. Furthermore, eosinophils and mast cell infiltrations in nasal mucosa tissue were also blocked through the regulation of macrophage-inflammatory protein and intercellular adhesion molecule-1 levels. SIGNIFICANCE: OMC showed the possibility to regulate AR in activated mast cells and OVA-induced AR models. Hence, we suggest that OMC is a powerful and feasible new agent to suppress AR.

Genuine traditional Korean medicine, Naju Jjok (Chung-Dae, Polygonum tinctorium) improves 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesional skin.

PURPOSE: Naju Jjok (NJJ, Polygonum tinctorium) is a clear heat and release toxin medicinal. It has been used to treat various inflammatory diseases and as a dye in clothing in traditional Korean medicine. However, the effect of NJJ on atopic dermatitis (AD) has not been elucidated. Therefore, we examined whether NJJ would have an inhibitory effect on AD using the mimic AD murine model and in vitro model. METHODS: We treated NJJ on 2,4-dinitrofluorobenzene (DNFB)-induced AD-like skin lesions in NC/Nga mice, phorbol myristate acetate/calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells, and anti-CD3/anti-CD28-stimulated splenocytes. Histological analysis, ELISA, PCR, and Western blot analysis were performed. RESULTS: The oral administration with NJJ suppressed the total clinical severity in DNFB-induced AD-like lesional skin. NJJ significantly suppressed the levels of inflammatory mRNA and protein in AD-like lesional skin. NJJ significantly suppressed the levels of IgE and interleukin-4 in the serum of DNFB-induced AD mice. The expression of mast cells-derived caspase-1 was suppressed by NJJ in AD-like lesional skin. In addition, topical application with NJJ improved clinical symptoms in DNFB-induced AD mice. The topical application with NJJ significantly suppressed the levels of IgE and histamine in the serum of DNFB-induced AD mice. NJJ suppressed the production and mRNA expression of TSLP by blockade of caspase-1 signal pathway in the activated HMC-1 cells. Furthermore, NJJ significantly decreased the production of tumor necrosis factor-α from the stimulated splenocytes. CONCLUSIONS: In conclusion, these results propose curative potential of natural dye, NJJ by showing the scientific evidence on anti-AD effect of NJJ which has been used traditionally.