The Mixture of Natural Products SH003 Exerts Anti-Melanoma Effects through the Modulation of PD-L1 in B16F10 Cells.

Melanoma is the most invasive and lethal skin cancer. Recently, PD-1/PD-L1 pathway modulation has been applied to cancer therapy due to its remarkable clinical efficacy. SH003, a mixture of natural products derived from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, and formononetin (FMN), an active constituent of SH003, exhibit anti-cancer and anti-oxidant properties. However, few studies have reported on the anti-melanoma activities of SH003 and FMN. This work aimed to elucidate the anti-melanoma effects of SH003 and FMN through the PD-1/PD-L1 pathway, using B16F10 cells and CTLL-2 cells. Results showed that SH003 and FMN reduced melanin content and tyrosinase activity induced by α-MSH. Moreover, SH003 and FMN suppressed B16F10 growth and arrested cells at the G2/M phase. SH003 and FMN also led to cell apoptosis with increases in PARP and caspase-3 activation. The pro-apoptotic effects were further enhanced when combined with cisplatin. In addition, SH003 and FMN reversed the increased PD-L1 and STAT1 phosphorylation levels induced by cisplatin in the presence of IFN-γ. SH003 and FMN also enhanced the cytotoxicity of CTLL-2 cells against B16F10 cells. Therefore, the mixture of natural products SH003 demonstrates therapeutic potential in cancer treatment by exerting anti-melanoma effects through the PD-1/PD-L1 pathway.

A mixture of Panax ginseng and Scrophularia buergeriana improves immune function in an immunosuppressed murine model.

BACKGROUND: Immunomodulatory drugs are currently used for immunosuppressed individuals, but adverse side effects have been reported. Although Panax ginseng and Scrophularia buergeriana are known to have respective pharmacological properties, the potential of a mixture of Panax ginseng and Scrophularia buergeriana (Isam-Tang, IST) as an immunomodulatory drug has not yet been studied. PURPOSE: The present study was designed to assess the immunomodulatory activity of IST and p-coumaric acid (pCA), an active compound of IST, in the immune system. METHODS: The levels of immunostimulatory cytokines, nitrite, inducible nitric oxide synthase (iNOS), NF-kB activation, and proliferation were examined in RAW264.7 cells, primary splenocytes and splenic NK cells isolated from normal mouse spleen, and in cyclophosphamide-induced immunosuppressed mice using ELISA, quantitative real-time PCR, Western blotting, and immunofluorescence staining. RESULTS: IST or pCA treatment increased the production of immunostimulatory cytokines and nitrite and the expression of iNOS in RAW264.7 cells and splenocytes. IST or pCA also induced NF-κB signaling activation and promoted the phagocytic activity of RAW264.7 cells. In addition, the splenocyte proliferation and splenic NK activity were enhanced by IST or pCA. IST or pCA increased the levels of immunostimulatory cytokines in immunosuppressed mice and ameliorated splenic tissue damage. CONCLUSION: These findings suggest that IST supplementation may be used to enhance immune function.

The immune-enhancing effects of a mixture of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) or its active constituent nodakenin.

ETHNOPHARMACOLOGICAL RELEVANCE: A mixture (SH003) of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) has beneficial effects against several carcinomas. There have been few reports on an immune-enhancing activity of SH003 and its active constituent nodakenin. AIM OF THE STUDY: This study aimed at identifying the immune-enhancing effect of SH003 and nodakenin. MATERIALS AND METHODS: The immune-enhancing effect was evaluated using RAW264.7 macrophages, mouse primary splenocytes, and a cyclophosphamide (CP)-induced immunosuppression murine model. RESULTS: The results show that SH003 or nodakenin stimulated the production levels of granulocyte colony-stimulating factor, IL-12, IL-2, IL-6, TNF-α, and nitric oxide (NO) and the expression levels of iNOS in RAW264.7 macrophages. SH003 or nodakenin also enhanced NF-κB p65 activation in RAW264.7 macrophages. SH003 or nodakenin stimulated the production levels of IFN-γ, IL-12, IL-2, TNF-α, and NO and the expression levels of iNOS in splenocytes. SH003 or nodakenin increased the splenic lymphocyte proliferation and splenic NK cell activity. In addition, SH003 or nodakenin increased the levels of IFN-γ, IL-12, IL-2, IL-6, and TNF-α in the serum and spleen of CP-treated mice, alleviating CP-induced immunosuppression. CONCLUSION: Taken together, the results of this study show that SH003 improved immunosuppression through the activation of macrophages, splenocytes, and NK cells. These findings suggest that SH003 could be applied as a potential immunostimulatory agent for a variety of diseases caused or exacerbated by immunodeficiency.

Regulatory effects of chrysophanol, a bioactive compound of AST2017-01 in a mouse model of 2,4-dinitrofluorobenzene-induced atopic dermatitis.

The aim of this study is to determine whether AST2017-01 which consists of Rumex crispus and Cordyceps militaris would improve atopic dermatitis (AD). We analyzed anti-AD effects of AST2017-01 and chrysophanol, a bioactive compound of AST2017-01, using a 2,4-dinitrofluorobenzene-induced AD murine model. AST2017-01 and chrysophanol relieved clinical severity in AD-like skin lesions and significantly decreased scratching behavior. The thickness of epidermis and infiltration of inflammatory cells in AD-like skin lesions were reduced by AST2017-01 or chrysophanol. AST2017-01 and chrysophanol significantly suppressed the levels of histamine, immunoglobulin E, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-6, and tumor necrosis factor-α in serum of AD mice. The protein levels of TSLP, intercellular adhesion molecule-1, and macrophage inflammatory protein 2 were significantly inhibited in the skin lesions. The mRNA expressions of TSLP, thymus and activation-regulated chemokine/CCL17, and C-C chemokine receptor 3 were inhibited in the skin lesions by AST2017-01 or chrysophanol. In addition, AST2017-01 and chrysophanol significantly suppressed the expressions and activities of caspase-1 in the skin lesions. Taken together, these results suggest that AST2017-01 has beneficial effects on AD and may be used as a health functional food in AD.

Improvement effects of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich on postmenopausal symptoms of ovariectomized mice.

BACKGROUND: Menopausal hot flushes occur frequently in postmenopausal women. In the present study, we investigated a regulatory effect of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich (PCE17), an extract of flowers of Pueraria thomsonii Benth. (PE), an extract of peels of Citrus unshiu Markovich (CE), a mixture of tectorigenin 7-O-xylosylglucoside, tectoridin, and tectorigenin (Tec, the active compounds of PE), and hesperidin (Hes, an active compound of CE) on menopausal hot flushes. METHODS: We examined the anti-hot flushes properties of PCE17, PE, CE, Tec, or Hes using a mouse model of ovariectomy-induced hot flushes. RESULTS: The ovariectomy-induced rise in the tail skin temperature was significantly prevented by PCE17, PE, CE, Tec, or Hes. PCE17, PE, CE, Tec, or Hes significantly enhanced 5-HT levels and attenuated RANKL levels in the hypothalamus of ovariectomized (OVX) mice. Treatment with PCE17, PE, CE, Tec, or Hes significantly enhanced the levels of estrogen receptor (ER)-ß, 5-HT1A, 5-HT2A, and tryptophan hydroxylase mRNA expression in the hypothalamus of OVX mice. PCE17, PE, or CE decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, but did not increase estrogen levels in the serum of OVX mice. Tec or Hes decreased FSH or LH levels and increased estrogen levels. Treatment with PCE17, PE, CE, or Tec ameliorated vaginal atrophy in OVX mice. Finally, PCE17, PE, CE, Tec, or Hes significantly increased norepinephrine and dopamine levels in the hypothalamus of OVX mice. CONCLUSION: Thus, these results imply that PCE17 has protective effects against hot flushes.

The new therapeutic herbal drug HM0601 and its bioactive compound rutin exert potent antiproliferative activities in mast cells.

HM0601 consists of Allium hookeri and Lycium chinense fruit and contains a lot of rutin. Here, we ascertained whether HM0601 and its major compound rutin reduce proliferation of human mast cell line, HMC-1, under thymic stromal lymphopoietin (TSLP) stimulation. Therapeutic rutin or HM0601 treatment considerably reduced proliferation of mast cells without exposing activated HMC-1 cells to any cytotoxicity. Reduced levels of mouse double minute 2 and phosphorylated signal transducers and activators of transcription 6 were accompanied by treatment with rutin or HM0601. In TSLP-stimulated cells, rutin or HM0601 treatment significantly impaired levels of interleukin (IL)-13 and Bcl2 expression. Notably, rutin or HM0601 treatment returned Bax and phosphorylated p53 protein levels and caspase-3 activities impaired by TSLP. In addition, levels of inflammatory cytokine were considerably reduced by treatment with rutin or HM0601 on TSLP-stimulated cells. In conclusion, these results indicate that HM0601 can be used as a new therapeutic herbal drug for prevention and therapeutic intervention of allergic inflammatory diseases.

Anti-inflammatory effects of Artemisia scoparia and its active constituent, 3,5-dicaffeoyl-epi-quinic acid against activated mast cells.

OBJECTIVES: Artemisia scoparia Waldst. et Kit. (AS) has been used to treat inflammation, urticaria and hepatitis. However, the scientific studies of AS and its active compound for inflammatory reactions in activated human mast cell line, HMC-1 cells have not yet been elucidated. MATERIALS AND METHODS: Here, we isolated 3,5-dicaffeoyl-epi-quinic acid (DEQA) from AS butanol fraction. The anti-inflammatory effect of AS and its new active compound, DEQA was examined in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced thymic stromal lymphopoietin (TSLP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 secretion and mRNA expression by ELISA and RT-PCR, respectively. Furthermore, mechanism related to anti-inflammatory was examined by Western blotting. RESULTS: We reported that AS and its new active compound, DEQA significantly reduced TSLP, TNF-α, IL-1ß and IL-6 production levels through the reduction of caspase-1 activity. The mRNA expression of these inflammatory cytokine was also reduced via blocking nuclear factor-κB nuclear translocation by AS and DEQA. In addition, AS significantly reduced phosphorylated-c-Jun N-terminal kinase level and DEQA significantly reduced both phosphorylated-c-Jun N-terminal kinase and -p38 mitogen-activated protein kinase levels. CONCLUSIONS: Therefore, these results indicated that AS and its active compound, DEQA may improve mast cell-mediated inflammatory diseases.

Schisandra chinensis and Its Main Constituent Schizandrin Attenuate Allergic Reactions by Down-Regulating Caspase-1 in Ovalbumin-Sensitized Mice.

Schisandra chinensis (SC) and its main constituent, schizandrin (SCH) exhibit anti-inflammatory and anti-allergic activities. Allergic and inflammatory reactions are aggravated via caspase-1 signaling pathway. However, the regulatory effects of SC and SCH on caspase-1 activation have not been clarified yet. In this study, we aimed to clarify the anti-allergic effects of SC and SCH using an ovalbumin (OVA)-sensitized mice and anti-CD3 and anti-CD28 antibodies-stimulated splenocytes. SC or SCH significantly inhibited the levels of immunoglobulin (Ig)E, IgG1, or interleukin (IL)-4 in serum of OVA-sensitized mice. SC or SCH significantly inhibited the levels of IL-6, tumor necrosis factor (TNF)-[Formula: see text], and IL-1[Formula: see text] in spleen of the OVA-sensitized mice. SC or SCH significantly suppressed the expression of caspase-1 and receptor-interacting protein (RIP)-2 in spleen of the OVA-sensitized mice. In activated splenocytes, SC or SCH significantly decreased the expression of caspase-1 and RIP-2 as well as the production of IL-6 and TNF-[Formula: see text]. We suggest that SC and SCH exert an anti-allergic effect by down-regulating caspase-1 signaling.

Hydrogen sulfide diminishes the levels of thymic stromal lymphopoietin in activated mast cells.

Bamboo salt (BS) is a Korean traditional type of salt and has been reported to have therapeutic effects on allergic inflammation. Thymic stromal lymphopoietin (TSLP) aggravates inflammation in the pathogenesis of allergic reactions, such as allergic rhinitis (AR). To confirm an active compound of BS, we investigated the effect of sulfur, a compound of BS, on the levels of TSLP in a human mast cell line, HMC-1 cells and a mouse model of AR using hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaSH). We treated NaSH or BS in HMC-1 cells and activated the HMC-1 cells with phorbol myristate acetate and calcium ionophore A23187 (PMACI). ELISA for the production measurement of TSLP, PCR for the mRNA expression measurement of TSLP, and western blot analysis for the expression measurement of upstream mediators were performed. Mice were treated with NaSH and sensitized with ovalbumin (OVA). The levels of TSLP were measured in serum and nasal mucosa tissue in an OVA-induced AR mouse model. NaSH or BS diminished the production and mRNA expression of TSLP as well as interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the PMACI-activated HMC-1 cells. NaSH or BS diminished the level of intracellular calcium in the PMACI-activated HMC-1 cells. NaSH or BS reduced the expression and activity of caspase-1 in the PMACI-activated HMC-1 cells. And NaSH or BS inhibited the expression of receptor interacting protein-2 and the phosphorylation of extracellular signal-regulated kinase in the PMACI-activated HMC-1 cells. The translocation of NF-κB into the nucleus as well as the phosphorylation and degradation of IκBα in the cytoplasm were diminished by NaSH or BS in the PMACI-activated HMC-1 cells. Furthermore, NaSH inhibited the production of TSLP, IL-6, and IL-8 in TNF-α-activated HMC-1 cells. Finally, the administration of NaSH showed a decrease in number of rubs on mice with OVA-induced AR. And the levels of immunoglobulin E and TSLP in the serum and the level of TSLP in the nasal mucosa tissue of the OVA-induced AR mice were reduced by NaSH. In conclusion, these findings show that H2S, as an active compound of BS is a potential agent to cure allergic inflammation.

Glutamic acid ameliorates estrogen deficiency-induced menopausal-like symptoms in ovariectomized mice.

Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of γ-aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency-induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)-positive human osteoblast-like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER-ß messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal-regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER-ß mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells.

Taurine, a major amino acid of oyster, enhances linear bone growth in a mouse model of protein malnutrition.

Oysters (Oys) contain various beneficial components, such as, antioxidants and amino acids. However, the effects of Oys or taurine (Tau), a major amino acid in Oys on bone growth have not been determined. In the present study, we evaluated the effects of Oys or Tau on linear bone growth in a mouse model of protein malnutrition. To make the protein malnutrition in a mouse, we used a low protein diet. Growth plate thickness was increased by Oys or Tau. Bone volume/tissue volume, trabecular thickness, trabecular number, connection density, and total porosity were also improved by Oys or Tau. Oys or Tau increased insulin-like growth factor-1 (IGF-1) levels in serum, liver, and tibia-growth plate. Phosphorylations of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were increased by Oys and by Tau. These findings show that Oys or Tau may increase growth plate thickness by elevating IGF-1 levels and by promoting the phosphorylations of JAK2-STAT5, and suggest that Oys or Tau are growth-promoting substances of potential use in the food and pharmaceutical industries.

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.

Hyperoside regulates the level of thymic stromal lymphopoietin through intracellular calcium signalling.

Hyperoside (HYP) is the principle active component of Crataegus pinnatifida. Thymic stromal lymphopoietin (TSLP) plays a vital role in the pathogenesis of allergic reactions. Here, we investigated how HYP regulates the levels of TSLP in a human mast cell line, HMC-1 cells. We analyzed the levels of TSLP by treatment with HYP in phorbol myristate acetate plus calcium ionophore A23187-stimulated HMC-1 cells with ELISA and a polymerase chain reaction analysis. We also analyzed the pathway that HYP regulates TSLP by measuring the level of fluorescent intracellular calcium and using a Western blot analysis. HYP decreased the level of intracellular calcium in stimulated HMC-1 cells. It also significantly decreased the production and mRNA expression of TSLP in stimulated HMC-1 cells. It significantly decreased the levels of receptor-interacting protein 2 and active caspase-1 in stimulated HMC-1 cells. HYP significantly decreased the translocation of NF-κB into the nucleus and degradation of IκBα in the cytoplasm in stimulated HMC-1 cells. Furthermore, it significantly decreased the production and mRNA expression of interleukin-1ß and interleukin-6 in stimulated HMC-1 cells. Taken together, our findings establish HYP as a potential agent for the treatment of allergic reactions.

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.

Inhibitory effects of BiRyuChe-bang on mast cell-mediated allergic reactions and inflammatory cytokines production.

BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-κB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-α, IL-6, and IL-8 as well as the activation of NF-κB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF-α and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8-Cineole, Linalool, Linalyl acetate, α-Pinene, and α-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells.

Interleukin-32-induced thymic stromal lymphopoietin plays a critical role in macrophage differentiation through the activation of caspase-1 in vitro.

INTRODUCTION: Interleukin (IL)-32 is an inflammatory cytokine induced by Mycobacterium tuberculosis and Mycobacterium bovis in a variety of cell types and discovered in the synovial of patients with rheumatoid arthritis (RA). Thymic stromal lymphopoietin (TSLP) play several roles in the pathogenesis of RA. However, the role of IL-32 and TSLP in RA has not been elucidated. METHODS: We evaluated the specific mechanism of between IL-32 and TSLP in RA using human monocyte cell line, THP-1 cells. RESULTS: Here we documented for the first time that IL-32 highly increased TSLP production in THP-1 cells and human blood monocytes. TSLP expression was induced by IL-32 via activation of caspase-1 and nuclear factor-κB. TSLP produced by IL-32 increased differentiation of monocytes but depletion of TSLP prevented differentiation of monocytes into macrophage-like cells. Chondroprotective drugs such as chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT) decrease production of TSLP and activation of caspase-1 and nuclear factor-κB. In addition, CS and BT inhibited IL-32-induced monocytes differentiation. CONCLUSIONS: Taken together, IL-32 and TSLP are important cytokines involved in the development of RA. The effects of CS and BT were associated with the downregulation of TSLP and caspase-1 through negative regulation of IL-32 pathways in RA.

Pyeongwee-San extract (KMP6): a new anti-allergic effect.

OBJECTIVES: The prevalence of allergic diseases is increasing due to rapid industrialization and changes in lifestyle. Pyeongwee-San (KMP6) is a traditional Korean medicine that has been used as a basic prescription for digestive disorders. This study investigated the efficacy of KMP6 and its component hesperidin on experimental allergic models. METHODS: The anti-allergic effect of KMP6 was studied against a compound 48/80-induced systemic anaphylactic reaction and the ear swelling response. In addition, a human mast cell line (HMC-1) was used to analyze the activity of histidine decarboxylase. Passive cutaneous anaphylaxis (PCA) from immunoglobulin E (IgE) was used. KEY FINDINGS: KMP6 and hesperidin inhibited the compound 48/80-induced systemic anaphylactic reaction and the ear swelling response as well as histamine release, intracellular calcium levels and tryptase release from rat peritoneal mast cells. KMP6 inhibited histidine decarboxylase activity in stimulated HMC-1 cells and macrophages. In addition, KMP6 inhibited the PCA reaction induced by IgE as well as the levels of IgE, interleukin (IL)-4, IL-5, IL-6 and IL-13 in serum from mice. CONCLUSIONS: These results suggest that KMP6 may exert an anti-allergic effect through not only the inhibition of mast cell degranulation but also the inhibition of histamine synthesis.

Effect of Pyeongwee-San (KMP6) on 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice.

AIMS: Recently, some studies reported that digestive tract disease is closely associated with atopic dermatitis (AD). Pyeongwee-San (KMP6) is a Korean medicine, which has come onto the drugstore for the treatment of digestive tract disease. The aim of the present study was to examine whether KMP6 could suppress 2,4-dinitrofluorobenzene (DNFB)-induced AD-like skin lesions in NC/Nga mice. MAIN METHODS: Mice were sensitized with DNFB by applying to shaved dorsal skin. At that time, the drugs or saline were orally administrated to DNFB-applied mice. KEY FINDINGS: The administration of KMP6 or glycyrrhizic acid (GL), a major component of KMP6, inhibited the scratching number in DNFB-induced AD model. The mRNA expressions of interleukin (IL)-4, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and CCR3 were upregulated by DNFB sensitization, but the upregulated mRNA expressions were significantly reduced by the administration of KMP6 or GL. In addition, the levels of IgE, histamine, and IL-4 were significantly reduced by the administration of KMP6 or GL in serum of DNFB-induced AD model. However, the level of IFN-γ in serum was significantly increased by KMP6 or GL. KMP6 or GL also significantly inhibited the numbers of inflammatory cells, mast cells, and protein level of IL-4 in lesions of DNFB-induced AD model. Finally, KMP6 or GL significantly decreased the productions of IL-4, IFN-γ, and TNF-α in anti-CD3 plus anti-CD28 antibody-stimulated splenocytes. SIGNIFICANCE: KMP6 showed anti-atopic potential in this setting; hence we suggest it as a potential prospect for anti-atopic agent besides being just a medicine for the stomach and bowels.

Dokhwaljihwang-tang inhibits LPS-induced inflammatory cytokine production in peripheral blood mononuclear cells.

OBJECTIVES: Dokhwaljihwang-tang, one of the prescriptions in Four Constitution medicine, has been used to treat neurological disorders. This work was aimed to examine the effect of Dokhwaljihwang-tang on lipopolysaccharide-induced inflammatory cytokine production in peripheral blood mononuclear cells from the lesser yang subjects. METHODS: The inflammatory cytokines, interleukin 1 beta, interleukin 4 and tumor necrosis factor were measured using the ELISA. The interleukin 1 beta mRNA expression was evaluated with reverse transcriptase-polymerase chain reaction. The expression level of nuclear factor kappa B was examined by western blotting. RESULTS: Dokhwaljihwang-tang significantly inhibited interleukin 1 beta and interleukin 4 production (p<0.05). When Dokhwaljihwang-tang was pre-treated at the dose of 1 mg/ml, it not only decreased the interleukin 1 beta mRNA expression, but also inhibited the activation of nuclear factor kappa B. DISCUSSION: These results suggest the potential of Dokhwaljihwang-tang as a source of pharmaceutical acupuncture for neuronal inflammatory diseases.