Inhibitory effects of Paeonia suffruticosa on allergic reactions by inhibiting the NF-kappaB/I kappaB-alpha signaling pathway and phosphorylation of ERK in an animal model and human mast cells.

The root cortex of Paeonia suffruticosa Andrews (PSA), also known as Moutan Cortex, is known to have anti-allergic and anti-inflammatory properties. This study investigates the effect and mechanism of PSA by in vivo and in vitro methods. Treatings the root cortex from PSA with up to 0.4 mg/ml of an ethanol extract showed no cytotoxicity in human mast cells. The ethanol extract of PSA (200 mg/kg) significantly inhibited the passive cutaneous anaphylaxis reaction in vivo, and suppressed the release of histamine from rat peritoneal mast cells induced by compound 48/80. It was also found that PSA decreased the expressions of TNF-alpha and IL-6 in PMA- and A23187-stimulated HMC-1 cells. The results show the inactivation of I kappaB-alpha and NF-kappaB, as well as suppression of the phosphorylation of extracellular signal-regulated kinase (ERK). Our findings therefore suggest that PSA could be promising for anti-allergic inflammation by inhibiting the NF-kappaB/I kappaB-alpha signaling pathway and the phosphorylation of ERK.

Early antiallergic inflammatory effects of Rhus verniciflua Stokes on human mast cells.

Rhus verniciflua Stokes (RVS) is a traditional medicine used in Korea, Japan and China to treat various diseases including catharsis, diaphoretic gastritis and stomach cancer. However, the effects of RVS on allergic inflammatory diseases are unknown to date. This study showed the antiallergic inflammatory effects of RVS on human mast cells (HMC-1) which were stimulated by phorbol myristate acetate (PMA) and calcium ionophore A23187. RVS inhibited the expressions of TNF-alpha, IL-6 and IL-8 that were stimulated by treatment with both PMA and A23187. Among the mitogen-activated protein kinases (MAPKs), extracts of RVS suppressed the phosphorylation of ERK and p38, whereas RVS increased the phosphorylation of JNK in HMC-1. Consistent with the regulation of MAPKs, it was found that RVS inhibited the nuclear translocation of nuclear factor (NF)-kappaB via inhibition of the phosphorylation of IkappaB-alpha, which are important processes in controlling inflammatory responses. Taken together, these results suggest that RVS modulates the expressions of signal molecules related to allergic inflammatory responses mainly through the ERK signaling pathway, suggesting that RVS could be used as a treatment for mast cell-derived allergic inflammatory diseases.

Sophora flavescens Aiton inhibits the production of pro-inflammatory cytokines through inhibition of the NF kappaB/IkappaB signal pathway in human mast cell line (HMC-1).

The dried roots of Sophora flavescens Aiton (SFA) has been used in traditional medicine for treatment of inflammation, gastrointestinal hemorrhage, diarrhea, and asthma. In the present study, we investigated the effect of SFA on the inflammatory allergic reaction using human mast cell-1 (HMC-1). SFA (200mg/kg) inhibited the mast cell-mediated passive cutaneous anaphylaxis reaction in vivo and the release of histamine from rat peritoneal mast cells by compound 48/80. In addition, the expression levels of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-6, and IL-8 were also decreased by SFA treatment. In molecular mechanism level, this study showed that SFA inhibited the nuclear translocation of nuclear factor (NF) kappaB through inhibition of the phosphorylation and degradation of IkappaB-alpha, which is an inhibitor of NF kappaB. Moreover, SFA suppressed PMA plus A23187-induced phosphorylation of the mitogen-activated protein kinase p38 and c-jun N-terminal kinase. The inhibited induction of NF kappaB promoter by SFA was determined using luciferase activity. These results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

Inhibition of the PI3K-Akt/PKB survival pathway enhanced an ethanol extract of Rhus verniciflua Stokes-induced apoptosis via a mitochondrial pathway in AGS gastric cancer cell lines.

Rhus verniciflua Stokes (RVS) has been used in traditional Eastern Asia medicine for the treatment of gastritis and stomach cancer, although the mechanism for its biological activity remains to be elucidated. We previously established that an ethanol extract of RVS-induced G(1)-cell cycle arrest via accumulation of p27(Kip1) controlled by Skp2 reduction and apoptosis in AGS human gastric cancer cells. Here, we showed that an ethanol extract of RVS-induced apoptosis via caspase-9 activation (mitochondrial death pathway) is mediated by the loss of mitochondrial membrane potential (MMP, Deltapsi(m)) and the release of cytochrome C from the mitochondrial intermembrane space. In addition, an ethanol extract of RVS inactivated PI3K-Akt/PKB kinase in a time-dependent manner. Moreover, combined treatment of an ethanol extract of RVS and LY294002 (a PI3K inhibitor) markedly increased apoptosis compared to treatment with an ethanol extract of RVS alone. The role of PI3K-Akt/PKB in this process was confirmed by constitutive expression of inactive mutants of this kinase in AGS cells. Finally, siRNA-mediated knockdown of Akt/PKB expression resulted in a significant reduction in AGS cell proliferation. Taken together, these results suggest that an ethanol extract of RVS induces apoptosis via a mitochondrial death pathway in human gastric cancer cells, but not in normal cells, and inhibition of the PI3K-Akt/PKB pathway enhanced the mitochondrial death pathway.

Protective effect of a phenolic-rich fraction from Schisandra chinensis against H2O2-induced apoptosis in SH-SY5Y cells.

We have investigated the neuroprotective effects of a phenolic-rich fraction (PRF) on the hydrogen peroxide (H(2)O(2))-induced apoptosis of cultured SH-SY5Y cells. The PRF was obtained from the 80% ethanol extract of the fruits of Schisandra chinensis by Sepabeads SP-850 column chromatography. Cell viability assays revealed that pretreating SH-SY5Y cells with PRF (10-200 mugmL(-1)) resulted in significant dose-dependent protection against H(2)O(2)-induced cell death. The protective effect of PRF against H(2)O(2)-induced apoptosis was assessed by flow cytometric analysis of DNA contents using propidium iodide (PI) staining. Pre-incubation of cells with PRF at different concentrations for 24 h partially protected apoptosis by H(2)O(2) (150 muM). Moreover, cells treated with PRF reduced H(2)O(2)-induced caspase-3 activation and poly (ADP-ribose) polymerase cleavage and exerted an apparent suppressive effect on oxidative stress induced by reactive oxygen species (ROS). We concluded that PRF may be useful in the treatment and prevention of neurodegenerative diseases associated with elevated ROS levels.

Phenolic-rich fraction from Rhus verniciflua Stokes (RVS) suppress inflammatory response via NF-kappaB and JNK pathway in lipopolysaccharide-induced RAW 264.7 macrophages.

The effects of phenolic-rich fraction (PRF) from Rhus verniciflua Stokes (Anacardiaceae) on the activities of cellular signaling molecules that mediate inflammatory responses in LPS-induced RAW 264.7 macrophages were investigated. At various concentrations of PRF significantly inhibited NO, PGE(2) and TNF-alpha production in LPS-induced RAW 264.7 macrophage cells. The PRF also significantly inhibited iNOS and COX-2 protein expression in LPS-induced RAW 264.7 macrophage in a concentration-dependent manner. Transcription factor NF-kappaB plays a key role for the inducible expression of genes mediating proinflammatory effects and here, we show that PRF can inhibit the induction of NF-kappaB activity. The PRF effectively inhibited the iNOS and COX-2 protein expression through suppression of phospho-JNK1/2 activation. Study using PDA HPLC has found that the PRF contains several low molecular compounds (i.e. p-coumaric acid, fustin, kaempferol-3-O-glucoside, sulfuretin, butein, kaempferol). Our results indicate that the anti-inflammatory properties of PRF might result from the inhibition of pro-inflammatory mediators (e.g., NO, PGE(2) and TNF-alpha) by suppression of such signaling pathways as NF-kappaB and JNK1/2.

Inhibition of cell cycle progression via p27Kip1 upregulation and apoptosis induction by an ethanol extract of Rhus verniciflua Stokes in AGS gastric cancer cells.

Botanical preparations are widely used by patient with cancer in Korea, Japan and China. Rhus verniciflua Stokes (RVS) has traditionally been used as a medicinal ingredient for the therapy of stomach and uterine cancer. In this study, we showed that exposure to an ethanol extract of RVS (50 microg/ml) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces G1-cell cycle arrest through the regulation of cyclins, the induction of p27Kip1, and decrease the CDK2 kinase activity. The upregulated p27Kip1 level is caused by protein stability increment by the reduction of Skp2, a key molecule related with p27Kip1 ubiquitination and degradation, and de novo protein synthesis. RVS extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces G1-cell cycle arrest via accumulation of p27Kip1 controlled by Skp2 reduction and apoptosis passing through an intrinsic pathway in human gastric cancer cells but not in normal cells, therefore we suggest that this extract could be a candidate medicine or compound for the development of novel class of anti-cancer drugs.

Atractylodes japonica Koidzumi inhibits the production of proinflammatory cytokines through inhibition of the NF-kappaB/IkappaB signal pathway in HMC-1 human mast cells.

The rhizome of Atractylodes japonica Koidzumi (AJK) has been used in traditional medicine for treatment of arthritis, bronchitis and respiratory infectious disease, whereas its effects on inflammatory reactions have not been unknown recently. In this study, the effects of AJK on allergic inflammation and its signaling were investigated in the induced human mast cells and animal model. This study showed that ethanol extract of AJK interestingly suppressed the production and mRNA expression of TNF-alpha, IL-6 and IL-8, as important inflammatory cytokines. Furthermore, AJK inhibited the nuclear translocation of nuclear factor (NF)-kappaB through inhibition of the phosphorylation of IB-kappa, which was additionally elucidated by NF-kappaB promoter-mediated luciferase activity. In addition, the phosphorylation of ERK was increased in pretreatment with AJK, whereas there was no change in JNK and p38 MAPK. However, AJK showed no effects on anti-DNP IgE-mediated in vivo PCA reaction and histamine release, as key events of mast cell-mediated immediate allergic reactions. These results suggest that AJK might be involved in not early-phase but transition to late-phase reactions of allergic inflammation and could modulate through other signal pathways. Taken together, AJK could be used as a treatment for mast cell mediated late-phase/chronic allergic inflammatory reactions.

Antihyperglycemic activity of herb extracts on streptozotocin-induced diabetic rats.

We investigated the effects of herb extracts, Rhus verniciflua, Agrimonia pilosa, Sophora japonica, and Paeonia suffruticosa, on the lowering of blood glucose levels and thiobarbituric acid reactive substances (TBARS) in streptozotocin (STZ)-induced diabetic rats. After 4 weeks, oral administration of Rhus verniciflua extract (50 mg/kg) exhibited a significant decrease in blood glucose levels in diabetic rats (P<0.05). Blood TBARS concentrations, the products of glucose oxidation in blood, were also lowered by Rhus verniciflua extract supplementation. In addition, Sophora japonica and Paeonia suffruticosa extracts significantly reduced TBARS levels versus diabetic controls. Serum concentrations of liver-function marker enzymes, GOT and GPT, were also restored by Rhus verniciflua (50 mg/kg) supplementation in diabetic rats.

Comparative proteomic analysis of Helicobacter pylori strains associated with iron deficiency anemia.

Helicobacter pylori is known to cause chronic gastritis, peptic ulcer, and gastric cancer, and has also been linked to iron deficiency anemia (IDA). To determine whether H. pylori clinical isolates correlate with the prevalence of H. pylori-associated IDA, we compared the proteomic profiles of H. pylori strains isolated from antral biopsy specimens of H. pylori-positive patients with or without IDA. Fifteen strains, including eight non-IDA and seven IDA strains, were cultured under iron-rich and iron-depleted conditions and then analyzed for protein expression profiles by 2-DE. The distances between two H. pylori strains were determined on the basis of similarities between their expression patterns of 189 protein spots, and a phylogenetic tree was constructed. The results revealed that the IDA strains formed a cluster separate from that of six non-IDA strains, with two non-IDA strains between the clusters. H. pylori strain 26695 was located in the non-IDA cluster. Protein spots displaying similar expression patterns were clustered, and 18 spots predominantly expressed in IDA strains were identified by MALDI-TOF analysis. These data indicate that the non-IDA and IDA strains can be distinguished by their protein expression profiles, suggesting that the polymorphism of H. pylori strains may be one of the factors determining the occurrence of H. pylori-associated IDA.