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.

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.

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.

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.

SoSoSo or its active ingredient chrysophanol regulates production of inflammatory cytokines & adipokine in both macrophages & adipocytes.

BACKGROUND & OBJECTIVES: Obesity is now considered as a major risk factor for the development of fatty liver diseases, cardiovascular diseases, and atherosclerosis. SoSoSo is a newly developed dietary supplement made of seven medicinal herbs. This study was aimed at examining the anti-obesity effect of SoSoSo or its active ingredient chrysophanol on the production of inflammatory cytokines and adipokine in macrophyage cell line RAW264 and 3T3-L1 adipocytes. METHODS: No release was measured as a form of nitrite by Griess method. The production of inflammatory cytokines and adipokine were measured with the ELISA method. The m-RNA expression of each cytokine and adipokine were measured using RT-PCR. The nuclear proteins for NF-κB were analyzed with western blotting. RESULTS: SoSoSo or chrysophanol significantly inhibited the nitric oxide production in lipopolysaccharide-stimulated RAW264 cells as well as in RAW264 cells-conditioned medium (CM)-treated 3T3-L1 cells. The production of interleukin (IL)-6 and tumour necrosis factor (TNF)-α were inhibited by SoSoSo or chrysophanol. In addition, SoSoSo or chrysophanol inhibited the activation of nuclear factor-κB in RAW264 cells. SoSoSo or chrysophanol inhibited the productions of IL-6, TNF-α, and monocyte chemoattractant protein-1 as well as the reduction of adiponectin production in CM-treated 3T3-L1 cells. INTERPRETATION & CONCLUSIONS: These results suggest a potential of SoSoSo or chrysophanol as a source of anti-inflammatory agent for obesity. Further in vivo studies would be required to confirm these findings.

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.

Anti-fatigue effect of Zizania caudiflora (Turczaninow) Nakai.

The purpose of the present study was to investigate the anti-fatigue effect of Zizania caudiflora (Turczaninow) Nakai (ZC) and hydrolyzed ZC by malted barley (HZC) through a forced swimming test (FST) in mice. After the first measurement of immobility times, the mice were divided into control, fluoxetine, ZC, and HZC groups to match the swimming times in each group. The immobility times in the FST of the control as well as the fluoxetine, ZC, and HZC-administered groups after administration for three days were 135.3 ± 3.3,66.8 ± 3.9,120.2 ± 2.7, and 123.2 ± 2.9 sec, respectively. The immobility times in the FST of the ZC and HZC-administered groups for 14 days were significantly decreased in comparison with the control group (p < 0.01). In addition, the immobility times of ZC and HZC-administered groups for 14 days in the tail-suspension test were also significantly decreased in comparison with the control group (p < 0.05). The plasma levels of albumin, glucose, and total protein were significantly increased and creatine phosphokinase was significantly decreased in the ZC and HZC-administered groups compared to the control group. However, the levels of lactate dehydrogenase and blood urea nitrogen in the ZC and HZC-administered groups did not represent a significant difference compared to the control group. In summary, these results suggest that ZC or HZC might be a candidate for an anti-fatigue agent.

The suppression of thymic stromal lymphopoietin expression by selenium.

Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis. Selenium (Se) has various effects such as antioxidant, antitumor, antiulcer, and anti-inflammatory effects. However, the effect of Se on the production of TSLP has not been clarified. Thus, we investigated how Se inhibits the production of TSLP in the human mast cell line, HMC-1 cells. Se suppressed the production and mRNA expression of TSLP in HMC-1 cells. The maximal inhibition rate of TSLP production by Se (10 µM) was 59.14 ± 1.10%. In addition, Se suppressed the nuclear factor-κB luciferase activity induced by phorbol myristate acetate plus A23187. In the activated HMC-1 cells, the activation of caspase-1 was increased; whereas the activation of caspase-1 was decreased by pretreatment with Se. These results suggest that Se can be used to treat inflammatory and atopic diseases through the suppression of TSLP.

Antiinflammatory effects of traditional Korean medicine, JinPi-tang and its active ingredient, hesperidin in HaCaT cells.

A traditional Korean medicine, JinPi-tang (JPT), has been used in dermatological therapeutics and cosmeceuticals including antiaging creams and moisturizers. However, it has not been clarified how JPT and its active ingredient, hesperidin (HES), regulates inflammatory reactions in HaCaT cells. Thus, the mechanisms of action of JPT and HES on inflammatory reactions were investigated for the first time in an experimental model. The antiinflammatory effects of JPT and HES in HaCaT cells were investigated by using an enzyme-linked immunosorbent assay and a reverse transcription-polymerase chain reaction as well as western blot analysis. JPT and HES inhibited the H(2)O(2)-induced interleukin-8 and tumor necrosis factor-α production as well as its mRNA expression. In addition, JPT and HES inhibited the activation of the nuclear factor-κB, the phosphorylation of IκBα and the p38 mitogen-activated protein kinase, as well as the activation of cyclooxygenase-2. The findings suggest that JPT and HES would be helpful in the treatment of UV radiation-induced inflammatory skin diseases.

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.

Baekjeolyusin-tang and its active component berberine block the release of collagen and proteoglycan from IL-1ß-stimulated rabbit cartilage and down-regulate matrix metalloproteinases in rabbit chondrocytes.

Osteoarthritis (OA) is a major degenerative disease affecting millions of individuals. The ability of articular cartilage to self-repair is limited due to a low tissue turnover rate and the avascular nature of the cartilage, making OA an irreversible disease. In Korea, however, many traditional Korean medical doctors have treated joint disease with a prescription of traditional Korean medicine, BaekJeolYuSin-tang (BYT). Thus, the chondroprotective effects of BYT and its active component, berberine (Ber) were investigated in an experimental model. Here it is shown that BYT or Ber significantly inhibited the expression of matrix metalloproteinase (MMP)-3 and a disintegrin and metalloproteinase with thrombospondin motifs-5 as well as increasing the expression of tissue inhibitors of metalloproteinase-1, aggrecan and collagen in rabbit articular chondrocytes (p < 0.05). BYT or Ber significantly inhibited the secretion and activity of MMP-3 (p < 0.05). In addition, BYT or Ber significantly inhibited the release of collagen and glycosaminoglycan into the culture media from rabbit articular cartilage explants (p < 0.05). The data suggest that BYT or Ber has a therapeutic potential for the treatment of cartilage damage in osteoarthritis.

Chungsim-Yeunja-Tang decreases the inflammatory response in peripheral blood mononuclear cells from patients with cerebral infarction through an NF-κB dependent mechanism.

BACKGROUND: Chungsim-Yeunja-Tang (CYT) has been used as a medicine for cerebral infarction (CI) patients in Korea. The objective of this study was to determine precisely the effect of CYT on CI patients using peripheral blood mononuclear cells (PBMCs). METHODS: For a clinical study, 47 CI patients were identified who had taken CYT (0.01 g/kg) 3 times a day after meals for 2 weeks by oral administration. For ex vivo experiments, peripheral blood mononuclear cells (PBMCs) were isolated from CI patients. We analyzed the effect of CYT and its main components on lipopolysaccharide (LPS)-induced cytokine production and mechanism on PBMCs of CI patients by using ELISA, western blot analysis, transcription factor enzyme-linked immunoassay, and caspase assay. RESULTS: Clinical signs of CI significantly disappeared about 2 weeks after oral administration of CYT to CI patients (P < 0.05). CYT and quercetin, an active compound of CYT, significantly inhibited LPS-induced interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production and expression in PBMCs. CYT and quercetin also inhibited LPS-induced nuclear translocation and DNA binding activities of nuclear factor-κB and degradation of IκBα. In addition, CYT and quercetin inhibited LPS-induced IL-32 expression and caspase-1 activation. CONCLUSION: These results suggest a mechanism that might explain the beneficial effect of CYT in treating CI patients. Taken together, our findings indicate that inhibition of IL-32 expression and caspase-1 activation may be a novel biomarker and potential therapeutic target in CI.

Libanoridin inhibits the mast cell-mediated allergic inflammatory reaction.

BACKGROUND AND AIM: Corydalis heterocarpa is a biennial herb in South Korea, with spikes of yellow flowers. It has been used for as a folk medicine to cure travail and spasm. However, studies on this herb and its secondary metabolites have rarely been reported. In the present study, we isolated secondary metabolite libanlibanoridin from Corydalis heterocarpa. We have also examined the effect of libanoridin on the inflammatory cytokines production in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore, A2318 stimulated human mast cell line, HMC-1. PMA plus A23187 significantly increased interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha production compared to media control (P < 0.05). RESULTS: We report that treatment with libanlibanoridin can inhibit PMA plus A23187-induced IL-1beta, IL-6, IL-8, and TNF-alpha production in a concentration-dependent manner with IC50 of 0.002, 1.38, 1.48, and 0.36 mug/ml, respectively. Maximal inhibition rates of IL-1beta, IL-6, IL-8, and TNF-alpha production by libanlibanoridin were about 117.5%, 86.22%, 86.41%, and 90.74%, respectively. libanoridin inhibits the mRNA expression of IL-1beta, IL-6, IL-8, and TNF-alpha. libanoridin also inhibits the expression of cyclooxygenase-2. CONCLUSION: These results indicate that libanlibanoridin may be helpful in regulating mast cell-mediated allergic inflammatory response.