Houttuynia cordata has a long history of use in indigenous systems of medicine as an antiseptic, febrifuge, diuretic, and deobstruant. It is frequently used in many traditional medicines for its antimicrobial, antiviral, and antiinflammatory properties. [1][2][3][4] H. cordata contains of methyl nonyl ketone, caryophyllene, bornyl acetate, a-pinene, b-pinene, limonene, and other components. These components have antibacterial properties against the Gram-positive bacteria Staphylococcus aureus and Sarcina ureae. 5) In experimental studies, H. cordata exhibited antibacterial activity, antileukemic activity, antiinflammatory activity, anaphylactic reaction and mast cell activation, and modulated nitric oxide (NO) production. [6][7][8][9][10] However, to date, studies to understand the other antibacterial effects, including the intracellularly replicating pathogens of these plants, are lacking.The mammalian immune response is divided broadly into the innate and adaptive responses. Innate immune responses of mammals involve the first line of defense against invading microorganisms, including the release of antimicrobial peptides at epithelial surfaces, phagocytosis, and intracellular killing of microorganisms by phagocytes and the activation of the complement cascade. In contrast, the adaptive immune response is antigen specific and modified by previous antigen exposure. 11) In the innate immune response, the reactive oxygen intermediates (ROIs) such as superoxide and reactive nitrogen intermediates (RNIs) such as NO have a key role in intracellular killing of microorganisms within phagocytes. 12)Several studies reported that RNIs are important for controlling Salmonella multiplication within macrophages. 13,14)Salmonellosis is a major bacterial zoonosis that causes a variety of disease syndromes, from self-limiting enteritis to fatal infection in animals and food-borne infection and typhoid fever in humans.15) The etiologic agents of salmonellosis are Salmonella sp. characterized by motile, Gram-negative, rod-shaped bacteria and facultative intracellular pathogens that can multiply within professional and nonprofessional phagocytes. Recently, the emergence of multidrugresistant strains of Salmonella sp. has caused more serious problems in public health.16) Multidrug resistance is a worldwide problem that does not recognize international borders and can indiscriminately affect the treatment and prevention of various diseases.To kill intracellular bacteria including Salmonella sp., Brucella sp., Listeria sp., Shigella sp., etc., much effort is needed to develop antibiotics, determine treatment duration, and resolve other issues.In this study, we examined the antibacterial effects, and macrophage activation of H. cordata water extract (HCWE) such as morphologic changes, NO production, phagocytic activity, and effects against the Salmonella enterica serovar Typhimurium in vitro and in vivo. Salmonellosis is a major bacterial zoonosis that causes a variety of disease syndromes, from self-limiting enteritis to fatal infec...

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Ginsenoside Rg3, a single ginseng saponin, is known to be a major anti-platelet component of protopanaxadiol that is isolated from Korean red ginseng. In this study, we investigated whether dihydroginsenoside Rg3, a stable chemical derivative of ginsenoside Rg3, also demonstrated anti-platelet activity. Dihydroginsenoside Rg3 inhibited thrombin-induced platelet aggregation in a concentration-dependent manner with an IC50 (concentration producing 50% inhibition) of 18.8 +/- 0.4 microM. Ginsenoside Rg3 inhibited platelet aggregation which was induced by thrombin (0.1 U mL(-1)) with an IC50 of 40.2 +/- 0.9 microM. We next determined whether dihydroginsenoside Rg3 affected different types of ligand-induced platelet aggregation. We found that dihydroginsenoside Rg3 inhibited collagen-induced platelet aggregation with an IC50 of 20.0 +/- 0.9 microM. To elucidate the inhibitory mechanism of dihydroginsenoside Rg3 on aggregation, we analysed its downstream signalling pathway. It was interesting to note that dihydroginsenoside Rg3 elevated cyclic AMP production in resting platelets, but did not affect cyclic GMP production. In addition, we found that dihydroginsenoside Rg3 potently suppressed phosphorylation of extracellular signal-regulated kinase 2 (ERK2), which was stimulated by collagen (2.5 microg mL(-1)), but not of p38 mitogen-activated protein kinase. Taken together, our results indicate that dihydroginsenoside Rg3 potently inhibited platelet aggregation via the modulation of downstream signalling components such as cAMP and ERK2.

lator of G protein signaling (RGS) family members, such as RGS2, interact with G␣ subunits of heterotrimeric G proteins, accelerating the rate of GTP hydrolysis and attenuating the intracellular signaling triggered by the G protein-coupled receptor-ligand interaction. They are also reported to regulate G protein-effector interactions and form multiprotein signaling complexes. Ischemic stress-induced changes in RGS2 expression have been described in astrocytes, and these changes are associated with intracellular signaling cascades, suggesting that RGS2 upregulation may be an important mechanism by which astrocytes may regulate RGS2 function in response to physiological stress. However, information on the functional roles of stress-induced modulation of RGS2 protein expression in astrocyte function is limited. We report the role of ischemic stress in RGS2 protein expression in rat C6 astrocytoma cells and primary mouse astrocytes. A marked increase in RGS2 occurred after ischemic stress induced by chemicals (sodium azide and 2-deoxyglucose) or oxygen-glucose deprivation (OGD, real ischemia). RGS2 mRNA expression was markedly enhanced by 1 h of exposure to chemical ischemia or 6 h of OGD followed by 2 or 6 h of recovery, respectively. This enhanced expression in primary astrocytes and C6 cells was restored to baseline levels after 12 h of recovery from chemically induced ischemic stress or 4 -6 h of recovery from OGD. RGS2 protein was also significantly expressed at 12-24 h of recovery from ischemic insult. Ischemiainduced RGS2 upregulation was associated with enhanced apoptosis. It significantly increased annexin V-positive cells, cleaved caspase-3, and enhanced DNA ladder formation and cell cycle arrest. However, a small interfering RNA (siRNA)-mediated RGS2 knockdown reversed the apoptotic cell death associated with ischemia-induced RGS2 upregulation. Upregulated RGS2 was significantly inhibited by SB-203580, a p38 MAPK inhibitor. Rottlerin, a potent inhibitor of PKC␦, completely abrogated the increased RGS2 expression. We also examine whether ischemia-induced RGS2-mediated apoptosis is affected by siRNA-targeted endogenous PKC␦ downregulation or its phosphorylation. Although RGS2 upregulation was not affected, siRNA transfection significantly suppressed endogenous PKC␦ mRNA and protein expressions. Ischemia-induced PKC␦ phosphorylation and caspase-3 cleavage were dose dependently inhibited by PKC␦ knockdown, and this endogenous PKC␦ suppression reversed ischemia-induced annexin V-positive cells. This study suggests that ischemic stress increases RGS2 expression and that this condition contributes to enhanced apoptosis in C6 cells and primary astrocytes. The signaling it follows may involve PKC␦ and p38 MAPK pathways. stress; protein kinase C; p38 MAPK; gliocytoma ASTROCYTES, THE MOST ABUNDANT glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity (52). It has been reported that astrocytes play an important role in the metabolism of neurotransmitters and in ...

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Ginsenoside Rg3, a single ginseng saponin, is known to be a major anti-platelet component of protopanaxadiol that is isolated from Korean red ginseng. In this study, we investigated whether dihydroginsenoside Rg3, a stable chemical derivative of ginsenoside Rg3, also demonstrated anti-platelet activity. Dihydroginsenoside Rg3 inhibited thrombin-induced platelet aggregation in a concentration-dependent manner with an IC50 (concentration producing 50% inhibition) of 18.8 +/- 0.4 microM. Ginsenoside Rg3 inhibited platelet aggregation which was induced by thrombin (0.1 U mL(-1)) with an IC50 of 40.2 +/- 0.9 microM. We next determined whether dihydroginsenoside Rg3 affected different types of ligand-induced platelet aggregation. We found that dihydroginsenoside Rg3 inhibited collagen-induced platelet aggregation with an IC50 of 20.0 +/- 0.9 microM. To elucidate the inhibitory mechanism of dihydroginsenoside Rg3 on aggregation, we analysed its downstream signalling pathway. It was interesting to note that dihydroginsenoside Rg3 elevated cyclic AMP production in resting platelets, but did not affect cyclic GMP production. In addition, we found that dihydroginsenoside Rg3 potently suppressed phosphorylation of extracellular signal-regulated kinase 2 (ERK2), which was stimulated by collagen (2.5 microg mL(-1)), but not of p38 mitogen-activated protein kinase. Taken together, our results indicate that dihydroginsenoside Rg3 potently inhibited platelet aggregation via the modulation of downstream signalling components such as cAMP and ERK2.

Mushrooms have a long history of dietary benefits in Asia due to their health-promoting effects. Phellinus baumii, a wild mushroom, has been reported to have anti-platelet, anti-inflammatory, anti-obesity and free radical scavenging activities. However, its anti-rheumatoid arthritis (RA) property remains poorly understood. Hence, we investigated the protective effect of Phellinus baumii ethyl acetate extract (PBEAE) against bovine collagen type II induced arthritis (CIA) in DBA/1 mice. PBEAE (50 and 150 mg/kg) reduced the CIA score and leukocyte count in draining lymph nodes (DLNs) and inflamed joints. PBEAE also attenuated the expressions of CD3⁺ (T cells), CD19⁺ (B cells), CD4⁺ (T-helper), CD8⁺ (T-cytotoxic), MHC class II/CD11c⁺ (antigen-presenting cells), double positives (B220⁺/CD23⁺ and CD3⁺/CD69⁺: early lymphocyte activation markers) and CD4⁺/CD25⁺ (activated T-helper) leukocyte subpopulations in DLNs. Likewise, CD3⁺ and Gr-1⁺CD11b⁺ (neutrophil) counts in inflamed joints were also decreased. Furthermore, PBEAE reduced the serum levels of anti-collagen type immunoglobulin G, tumor necrosis factor-α and interleukin (IL)-1β and IL-6. Taken together, PBEAE impaired cellular recruitment to the inflamed joint and alleviated CIA, and thus could be considered as a potential agent against rheumatoid arthritis.