Antiallergic action of Magnolia officinalis on immediate hypersensitivity reaction

We studied the effect of aqueous extract of Magnolia officinalis bark (Magnoliaceae) (MOAE) on the immediate hypersensitivity reaction. MOAE (0.01 to 1 g/kg) dose-dependently inhibited compound 48/80 induced systemic anaphylaxis in rats. MOAE (0.1 and 1 g/kg) also significantly inhibited local immunoglobulin E (IgE)-mediated passive cutaneous anaphylactic reaction. When MOAE was pretreated at concentrations ranging from 0.01 to 1 g/kg, the levels of plasma histamine were reduced in a dose-dependent manner. MOAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-dinitrophenyl (DNP) IgE. The level of cyclic AMP (cAMP) in RPMC, when MOAE was added, significantly increased compared with that of the normal control. Moreover, MOAE (0.01 to 1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that MOAE inhibits immediate hypersensitivity reaction in vivo and in vitro.     

Stylopine from<Emphasis Type="Italic">Chelidonium majus</Emphasis> inhibits LPS-Induced inflammatory mediators in RAW 264.7 cells

Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE2 production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Chelidonium majus.     

Controlled release of<Emphasis Type="Italic">Bordetella bronchiseptica</Emphasis> dermonecrotoxin (BBD) vaccine from BBD-loaded chitosan microspheres<Emphasis Type="Italic">In Vitro</Emphasis>

Chitosan microspheres were prepared by ionic gelation process with sodium sulfate for nasal vaccine delivery. Bordetella Bronchiseptica Dermonecrotoxin (BBD) as a major virulence factor of a causative agent of atrophic rhinitis (AR) was loaded to the chitosan microspheres for vaccination. Morphology of BBD-loaded chitosan microspheres was observed as spherical shapes. The average particle sizes of the BBD-loaded chitosan microspheres were about 2.69 microm. More BBD was released with an increase of molecular weight of chitosan and with an increase of medium pH in vitro due to weaker intermolecular interaction between chitosan and BBD. Tumor necrosis factor-alpha (TNFalpha) and nitric oxide (NO) from RAW264.7 cells stimulated with BBD-loaded chitosan microspheres were gradually secreted, suggesting that released BBD from chitosan microspheres had immune stimulating activity of AR vaccine.     

银杏内酯B对慢性炎症血管生成的抑制作用

目的研究银杏内酯B对慢性炎症血管生成的作用及部分作用机制。方法比色法测定小鼠慢性肉芽肿气囊模型血管生成指数，组织形态学方法检测气囊病理变化；放射免疫方法测定白介素-1β(IL-1β)含量；L929生物测定法测定肿瘤坏死因子(TNF-α)含量；RT-PCR法检测IL-1β和TNF-α mRNA的表达。结果银杏内酯B可显著抑制模型小鼠的血管指数，与病理观察结果相符；银杏内酯B可显著抑制模型小鼠血清中IL-1和TNF-α的分泌；能显著抑制PMA诱导的U937细胞IL-1β和TNF-α的分泌及其mRNA的表达。结论银杏内酯B能抑制小鼠慢性炎症性血管生成模型的血管生成，能抑制促血管生成细胞因子IL-1β和TNF-α的转录及表达，这可能是其抑制慢性炎症血管生成的机制之一。     

Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to 60Co

Aim of the study

The present study was designed to investigate the molecular weight (MW), chemical composition and effect of polysaccharide (CS-PS), from the fruiting bodies of cultured Cordyceps sinensis, on immune function and anti-oxidation activity of BALB/c mice exposed to ⁶⁰Co.

Materials and methods

The MW of CS-PS was determined by gel-filtration. The chemical composition of CS-PS was tested by using gas chromatography–mass spectrophotometer (GC–MS). Mice were administered CS-PS with doses of 50, 100 or 200 mg/kg body weight, then exposed to ⁶⁰Co. The normal control group and irradiated control group were also used. Four days later, lymphocyte proliferation, activity of macrophage phagocytosis, delayed type hypersensitivity (DTH), concentration of malondialdehyde (MDA), total-superoxide dismutase (SOD) enzyme activity, and cytokine expression in serum from the mice were tested.

Results

The average molecular weight of CP-PS was 12 kD. The polysaccharide was composed of mannose, rhamnose, arabinose, xylose, glucose and galactose. Lymphocyte proliferation, the activity of macrophage phagocytosis, DTH and total-SOD enzyme activity in the CS-PS groups were significantly enhanced compared to the irradiated control group. Lipid peroxidation level was significantly reduced in the CS-PS groups compared to the irradiated control group. Levels of cytokine IL-4, IL-5 and IL-17 are also affected in the CS-PS groups compared to the irradiated control group.

Conclusions

CS-PS, a heteropolysaccharide, enhances immunity activity in mice treated by ionizing radiation, through reducing oxidative injury and modulating the secretion of cytokine IL-4, IL-5 and IL-17.     

The effect of slow acting antirheumatic drugs on the production of cytokines by human monocytes

The mode of action of slow acting antirheumatic drugs (SAARDs) is poorly understood. Interleukin (IL)-1α, IL-1β, IL-6 and tumour necrosis factor (TNF)α are pleiotropic cytokines produced predominantly by macrophages which have been implicated in the pathogenesis of rheumatoid arthritis. We have investigated the potential of the following drugs to modulate the production of those cytokines by purified human monocytes stimulated by either lipopolysaccharide (LPS) or cytokines in vitro: gold sodium thiomalate (GST), auranofin, hydroxychloroquine (HCQ),d-penicillamine (d-Pen), sulphasalazine and its metabolites, sulphapyridine and 5-aminosalicylic acid (5-ASA). Auranofin, HCQ and sulphasalazine, at therapeutically relevant concentrations, inhibited the production of all four cytokines in vitro. There were some differential effects suggesting that HCQ was less effective at inhibiting cell-associated IL-1 production compared with IL-1 release, and the reverse seemed to be the case for sulphasalazine which did not inhibit IL-1 secretion as effectively as cell-associated IL-1 production. Sulphasalazine was also less effective at inhibiting IL-6 production compared with the other three cytokines. GST had only a minor inhibitory effect (on IL-1β release) andd-Pen, sulphapyridine and 5-ASA did not inhibit cytokine production. Finally, low concentrations of gold compounds (GST and auranofin) stimulated IL-1 and IL-6 production directly and potentiated IL-1, IL-6 and TNFα production induced by LPS. These results suggest that some SAARDs may inhibit cytokine production as part of their antirheumatic effect and that the enhancement of cytokine production by low doses of gold may potentially exacerbate rheumatoid disease at the early stages of chrysotherapy.     

Eudesmin inhibits tumor necrosis factor-α production and T cell proliferation

Possible antiinflammatory effects of eudesmin were examined by assessing the effects on tumor necrosis factor (TNF)-alpha production and lymphocyte proliferation as well as cytotoxicity against murine and human macrophages. The compound significantly inhibited TNF-alpha production by lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 without displaying cytotoxicity suggesting that eudesmin may inhibit TNF-alpha production without any interference of normal cell function. It also significantly attenuated T cell proliferation stimulated by concanavalin A (Con A) in a dose-dependent manner.     

Protective effect of polysaccharides from Angelica sinensis on ulcerative colitis in rats

Ulcerative colitis (UC) involves the dysregulation of intestinal mucosal immunity and imbalance between the reactive oxygen species (ROS) and the endogenous anti-oxidants. While the protective effects of Angelica sinensis (AS) polysaccharides on neutrophil-dependent gastric mucosal damage have been reported, similar protective effects on UC are still uncertain. Hence our study aimed to investigate the effects of AS polysaccharides on rats with acute UC induced by 2,4-dinitrobenzene sulphonic acid (DNBS) evaluated after 24 h. Intrarectal injection of DNBS significantly reduced the glutathione (GSH) content, increased malondialdehyde concentration and raised the amount of apoptotic cells in colon tissues, which were related to oxidative stress and attenuated by AS polysaccharides pretreatment (5 mg/ml and 10 mg/ml). These findings suggest that oxidative stress and GSH depletion are highly associated with the pathological mechanism of UC, and the protective effects of AS polysaccharides are closely related to the prevention of oxidative stress, which may occur during neutrophil infiltration in the pathological process of UC.     

Interleukin-1β and tumor necrosis factor-α inhibit the release of [3H]-Noradrenaline from isolated human atrial appendages

In the present study, we have investigated the ability of human recombinant interleukin-1β (hIL-1β) and human recombinant tumor necrosis factor-α (hTNF-α) to modulate the stimulation-induced (S-I) outflow of [³H]-noradrenaline ([³H]-NA) from isolated superfused human atria. Pieces of human right atrial appendages were excised during routine cardiac surgery. Tissues were incubated with [³H]-NA (0.2 μmol/l) for 30 min at 37°C, then inserted in a Brandel suprafusion system where the radioactivity was washed for 75 min with a Krebs-Henseleit solution at a rate of 0.4 ml/min. Thereafter, the effluent was collected for the remainder of the protocol during which two trains of electrical stimulation (50 mA intensity, 5 Hz frequency, 60 s duration, 2 ms pulses) were delivered at 10 min and 45 min (short protocol) or 85 min (long protocol). The effect of drugs on the S-I outflow of [³H]-NA was determined by adding drugs 20 min (short protocol) or 60 min (long protocol) before the second stimulation. Experiments were carried out in the continuous presence of desipramine (1 μmol/l) to prevent neuronal NA reuptake. The results showed that in human atrium, hIL-1β (3 ng/ml) and hTNF-α (0.5 ng/ml) significantly inhibited the S-I release of [³H]-NA. The inhibitory effect of hIL-1β was blocked by human recombinant IL-1 receptor antagonist (50 ng/ml), and by the cyclooxygenase inhibitor, diclofenac (1 μmol/l), suggesting that hIL-1β inhibited NA release through the formation of prostaglandins. The ability of hIL-1β and hTNF-α to inhibit NA release suggest that mediators of the immune system produced locally may modulate the activity of the sympathetic nervous system in human atrial appendages. Received: 11 October 1996 / Accepted: 27 November 1996     

Inhibitory effect of Yunnan traditional medicines on hepatitis C viral polymerase

For the purpose of developing novel anti-hepatitis C virus (HCV) agents from natural resources, 93 Yunnan crude drugs were screened for their inhibitory effects on RNA-dependent RNA polymerase (RdRp) of HCV. Although 71 methanol extracts and 50 water extracts inhibited HCV-RdRp by more than 50% at a concentration of 50 g/ml, the majority of them contained a high percentage of tannins. However, methanol extracts of Plumbago zeylanica (branch), Maytenus fookerii (leaf) and Huashidancha (Y61, branch and leaf), and water extracts of Potentilla griffithii (whole plant) and Salvia yunnanensis (underground part), having IC₅₀ values of less than 10 g/ml, showed less than 10% tannin content. In addition, from a methanol extract of Tripterygium hypoglaucum (root bark), demethylzeylasteral was isolated as a strongly inhibitory substance against HCV-RdRp.     

Antipruritic effect of DA-5018, a capsaicin derivative, in mice

The antipruritic effect of DA-5018, a capsaicin derivative, was examined in mice. Male ICR mice were topically pretreated with Zostrix-HP (0.075% capsaicin cream), 0.1%, 0.3% DA-5018 cream or cream base (control) twice daily for 4 days. One hour after the last application, itch was induced either by compound 48/80 (50 microg, s.c.) or leukotriene B4 (0.03 nmol, i.d.) injection into the rostral back of the animals, and the number of scratches made by the animals at the injection site was counted for 60 min post-injection. DA-5018 cream (both 0.1 and 0.3%) significantly inhibited compound 48/80-induced scratching when compared with the cream base control (p<0.01), while Zostrix-HP showed minimal inhibition of the scratching behavior. In leukotriene B4-induced itch model, Zostrix-HP and 0.3% DA-5018 cream significantly inhibited the scratching during the first 10-min period (p<0.01). The results suggest that DA-5018 cream can be used as an antipruritic agent and warrant clinical evaluation.     

Extracellular signal-regulated kinase induces phosphorylation of IκBα in <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-infected gastric epithelial AGS cells

In Helicobacter pylori (H. pylori)-induced gastric ulceration, NF-κB regulates the expression of inflammatory genes. NF-κB is activated by phsophorylation of its endogenous inhibitor, IκBα. The possible involvement of mitogenactivated protein kinase (MAPK) on NF-κB activation has been suggested in various cells. Present study aims to investigate whether H. pylori in a Korean isolate induces phosphorylation of IkBα and whether H. pylori-induced phosphorylation of IkBα is mediated by MAPK in gastric epithelial AGS cells. AGS cells were treated with MAPK inhibitors (U0126 for extracellular signal-regulated kinase, SB203580 for p38 kinase, SP600125 for c-Jun NH2-terminal protein kinases) and stimulated with H. pylori. As a result, H. pylori increased phospho-specific IκBα accompanied with the decrease in control IκBα. H. pylori-induced phosphorylation of IκBα was inhibited by treatment of U0126, but not by SB203580 or SP600125. In conclusion, extracellular signal-regulated kinase induces phosphorylation of IκBα in H. pylori-infected AGS cells. Received 4 August 2006; accepted 21 August 2006     

Anti-allergic components from the peels ofCitrus unshiu

In a bioassay-guided search for anti-allergic compounds from higher plants of Korea, polymethoxyflavones, 3',4',5,6,7,8-hexamethoxyflavone (1), 5-hydroxy-3',4',6,7,8-pentamethoxyflavone (II) and 3',4',5,7,8,-pentamethoxyflavone (III) have been isolated from the immature peels of Citrus unshiu. Structures of these compounds were elucidated on the basis of spectroscopic techniques. Compounds I and II inhibited dose-dependently histamine release from the rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE.     

Tissue factor inhibitory flavonoids from the fruits of Chaenomeles sinensis

Tissue factor (TF, tissue thromboplastin or coagulation factor III) accelerates the blood clotting, activating both the intrinsic and the extrinsic pathways to serve as a cofactor. In order to isolate TF inhibitors from the fruits of Chaenomeles sinensis, an activity-guided purification utilizing a bio-assay method of prothrombin time prolongation, was carried out to yield five active flavoniods such as hovetrichoside C (1) (IC50 = 14.0 microg), luteolin-7-O-beta-D-glucuronide (3) (IC50 = 31.9 microg), hyperin (4) (IC50 = 20.8 microg), avicularin (6) (IC50 = 54.8 microg) and quercitrin (10) (IC50 = 135.7 microg), along with other inactive compounds such as (+/-)-(2E,4E-O-beta-D-glucopyranosyl-4'-hydroxy-beta-ionylideneacetic acid ester (2), genistein-7-O-beta-D-glucopyranoside (5), luteolin-3'-methoxy-4'-O-beta-D-glucopyranoside (7), luteolin-7-O-beta-D-glucuronide methyl ester (8), tricetin-3'-methoxy-4'-O-beta-D-glucopyranoside (selagin-4'-O-beta-D-glucopyranoside) (9), (-)-epicatechin (11), luteolin-4'-O-beta-D-glucopyranoside (12) and apigenin-7-O-beta-D-glucuronide methyl ester (13). The structures of the isolated compounds were elucidated through spectral analysis. Among them, compounds 1 to 9,12 and 13 were isolated for the first time from the fruits of this plant and the compound 9 is a new flavonoid.     

Inhibitory effect of Psidium guajava water extract in the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice

Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disease associated with eczematous symptoms and IgE hyperproduction. Psidium guajava is an important food crop and medicinal plant with anti-oxidant, anti-inflammatory, and anti-allergic activities, supporting its traditional uses. Our previous studies have shown that P. guajava extract inhibits Th2 chemokine expression by suppressing the activation of NF-κB and STAT1 co-stimulated with TNF-α and INF-γ. In this study, we investigated the inhibitory effect of P. guajava water extract (PGW) on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in NC/Nga mice. Treatment of cream containing PGW onto DNCB-induced AD-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, levels of IgE, thymus and activation-regulated chemokine (TARC), TNF-α, and IL-4 in serum and ears. In contrast, PGW increased level of the immunosuppressive cytokine IL-10. Histological analyses demonstrated decreased thickening of the epidermis/dermis as well as dermal infiltration by inflammatory cells. These results suggest that cream containing PGW may be a potential therapeutic modality for AD and adjunctive agent to control pruritus in AD.     

Anti-allergic actions of the leaves ofCastanea crenata and isolation of an active component responsible for the inhibition of mast cell degranulation

The anti-allergic actions of the leaves of Castanea crenata (Fagaceae) were studied. The water extract demonstrated potent anti-allergic actions in in vivo and in vitro experiments. The oral or intraperitoneal administration of the extract (100 or 200 mg/kg) caused a significant inhibition of the 48 hr-PCA (up to 90%) and the vascular permeability induced by histamine or serotonin in rats (about 80%). The anaphylactic release of beta-hexosaminidase from RBL-2H3 cells was also significantly inhibited by the extract in a dose-dependent manner with an IC50 value of 230 microg/ml. The activity-guided fractionation of the extract, based on the determination of inhibitory effect upon the release of beta-hexosaminidase, led to the isolation of quercetin as an active principle responsible for the inhibition of degranulation.     

The effect of linarin on LPS-induced cytokine production and nitric oxide inhibition in murine macrophages cell line RAW264.7

The herb, Chrysanthemum zawadskii var, latilobum commomly known as Gu-Jul-Cho in Korea, used in traditional medicine to treat pneumonia, bronchitis, cough, common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. Linarin is the main active compound and the biological mechanisms of its activity are unclear. It is believed that effects of this herb may be exerted through the pluripotent effectors of linarin due to its ability to treat a variety of afflictions. In this study, the effects of linarin on the mouse macrophages cell line, RAW 264.7, were investigated. It was found that linarin could activate macrophages by producing cytokines. Monocytes and tissue macrophages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1) and the tumor necrosis factor (TNF). Recent studies have shown that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. TNF-alpha production by macrophages treated with linarin occured in a dose dependent manner. However, IL-1 production was largely unaffected by this natural product. This study demonstrated the ability of linarin to activate macrophages both directly and indirectly. Linarin also affect both cytokine production and nitric oxide inhibition, in addition to the expression of some surface molecules. Nitric oxide (NO), derived from L-argin-ine, is produced by two forms(constitutive and inducible) of nitric oxide synthase (NOS). The NO produced in large amounts by inducible NOS is known to be responsible for the vasodilation and hypotension observed in septic shock. Linarin was found to inhibit NO production in the LPS-activated RAW 264.7 cells. Linarin may be a useful candidate as a new drug for treating endotoxemia and the inflammation accompanied by NO overproduction. The linarin-treated total lymphocytes exhibited cytotoxicity in a dose dependent manner between 20 microg/ml and 40 microg/ml. These results suggest that linarin may function through macrophage activation.     

Inhibitory effects of an aqueous extract of <Emphasis Type="Italic">Cornus kousa</Emphasis> Burg. Leaves on TNF-α-induced chemokine expression and monocyte adhesion to human colonic epithelial cells

An aqueous extract of Cornus kousa Burg. leaves (ACK) that contained high amount of polyphenols showed significant antioxidant activity against diphenylpicrylhydrazyl (DPPH) radicals and TNF-α-generated reactive oxygen species. ACK at concentrations of 10 and 50 μg/mL significantly inhibited TNF-α-induced adhesion of U937 pre-monocytic cells to HT-29 colon epithelial cells in a concentrationdependent manner. The reduced adhesion by ACK correlated with the suppressed expressions of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, the major inflammatory bowel disease (IBD)-associated chemokines. Moreover, ACK significantly suppressed TNF-α-induced translocation of redox-sensitive nuclear factor (NF)-κB as well as degradation of cytosolic I-κBα. The effective concentrations of ACK were much lower than that of 5-aminosalicylic acid (3.06 mg/mL), which is an active metabolite of sulfasalazine, a well-known drug used in the treatment of IBD. The results indicate that ACK may provide a potential benefit for the prevention and treatment of inflammatory diseases such as IBD.