Therapeutic effects of Artemisia scoparia Waldst. et Kitaib in a murine model of atopic dermatitis.

BACKGROUND: Artemisia scoparia Waldst. et Kitaib (AS) (Oriental wormwood, known as Bissuk in Korea) is a plant used in cosmetic and pharmaceutical treatments. However, the effect of AS on atopic dermatitis (AD) has not been described. AIM: To examine the inhibitory effect of AS on AD using a murine model. METHODS: We applied either AS, the butanol-extracted fraction of AS (Bu-OH) or 3,5-dicaffeoyl-epi-quinic acid (DEQA, a major component of Bu-OH) topically for 3 weeks to 2,4-dinitrofluorobenzene (DNFB)-induced skin lesions in BALB/c mice. RESULTS: AS, Bu-OH and DEQA suppressed the clinical symptoms of DNFB-induced skin lesions and he associated scratching behaviour. Numbers of inflammatory cells infiltrating skin lesions were significantly reduced by AS or Bu-OH application but not by DEQA. In addition, AS significantly suppressed serum levels of histamine and IgE, while Bu-OH significantly suppressed serum levels of histamine, IgE, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4 and IL-6, and DEQA significantly suppressed serum levels of histamine, IgE, TSLP and IL-4 in DNFB-induced AD mice. In skin lesions, AS and Bu-OH significantly reduced inflammatory cytokines, whereas DEQA did not. AS, Bu-OH and DEQA all significantly suppressed caspase-1 activities. CONCLUSIONS: These results demonstrate the anti-AD effects of AS, Bu-OH and DEQA, and suggest that all three have therapeutic potential.

Theanine is a candidate amino acid for pharmacological stabilization of mast cells.

The increasing occurrences of allergic disorders may be attributed to exposure to environmental factors that contribute to the pathogenesis of allergy. The health benefits of green tea have been widely reported but are largely unsubstantiated. Theanine is the major amino acid present in green tea. In this study, we investigated the role of theanine in both IgE- and non- IgE-induced allergic response. Theanine inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated passive cutaneous anaphylaxis was inhibited by the oral administration or pharmaceutical acupuncture of theanine. Histamine release from mast cells was decreased with the treatment of theanine. Theanine also repressed phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced TNF-α, IL-1ß, IL-6, and IL-8 secretion by suppressing NF-κB activation. Furthermore, theanine suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. The current study demonstrates for the first time that theanine might possess mast cell-stabilizing capabilities.

Anti-inflammatory effect of jeongshintang through suppression of p38 activation in human astrocytoma, U373MG cells.

Jeongshintang (JST) is a Korean herbal prescription, which has been successfully used for cerebral diseases. However, the anti-inflammatory effect of JST on Alzheimer's disease (AD) is still not fully understood. In this study, we investigated the effects of JST in attenuating the inflammatory response induced by interleukin (IL)-1beta plus beta-amyloid [1-42] fragment (A beta) in the human astrocyte cell line, U373MG. The production of IL-6, IL-8, and prostaglandin (PG)E2 was significantly increased by IL-1beta plus A beta (1-42) in a time-dependent manner (P < 0.05). JST significantly inhibited the IL-1beta plus A beta (1-42)-induced IL-6, IL-8, and PGE2 production at 24 h (P < 0.05). Maximal inhibition rate of IL-6, IL-8, and PGE2 production by JST was about 54.40%, 56.01%, and 44.06% respectively. JST (0.01-1 mg/ml) also attenuated the expression of cyclooxygenase (COX)-2 and activation of p38 MAPK induced by IL-1beta and A beta (1-42). These results demonstrated that JST has an anti-inflammatory effect, which might explain its beneficial effect in the treatment of various neurodegenerative diseases such as AD.

Daeganghwal-tang inhibits the stem cell factor-induced migration and inflammatory cytokines secretion in mast cells.

Traditional Oriental medicinal prescription, Daeganghwal-tang (DGHT) has been used for the treatment of rheumatoid arthritis (RA) in Korea. However, its effect in experimental models remains unknown. Recent reports suggest that in patients with RA, synovial mast cells increase in number and show signs of activation and inflammatory cytokines secretion. Our results show that stem cell factor (SCF) is a potent chemotactic factor for the mast cells in vitro. The chemotactic response to SCF was blocked by DGHT. When DGHT (1mg/ml) was added, the secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 was inhibited by 60.1, 81.8, 72.5%, respectively in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated HMC-1 cells. In addition, the expression of TNF-alpha mRNA in HMC-1 cells was inhibited by DGHT (1mg/ml). These findings indicate that DGHT inhibits SCF-induced migration and PMA plus calcium ionophore-stimulated inflammatory cytokines secretion in mast cells.

Contribution of the Na-K-Cl cotransporter on GABA(A) receptor-mediated presynaptic depolarization in excitatory nerve terminals.

GABA(A) receptor-mediated responses manifest as either hyperpolarization or depolarization according to the intracellular Cl(-) concentration ([Cl(-)](i)). Here, we report a novel functional interaction between the Na-K-Cl cotransporter (NKCC) and GABA(A) receptor actions on glutamatergic presynaptic nerve terminals projecting to ventromedial hypothalamic (VMH) neurons. The activation of presynaptic GABA(A) receptors depolarizes the presynaptic nerve terminals and facilitates spontaneous glutamate release by activating TTX-sensitive Na(+) channels and high-threshold Ca(2+) channels. This depolarizing action of GABA was caused by an outwardly directed Cl(-) driving force for GABA(A) receptors; that is, the [Cl(-)](i) of glutamatergic nerve terminals was higher than that predicted for a passive distribution. The higher [Cl(-)](i) was generated by bumetanide-sensitive NKCCs and was responsible for the GABA-induced presynaptic depolarization. Thus, GABA(A) receptor-mediated modulation of spontaneous glutamatergic transmission may contribute to the development and regulation of VMH function as well as to the excitability of VMH neurons themselves.

Kunbi-Boshin-Hangam-Tang stimulates nitic oxide production through activation of nuclear factor-kappaB.

The objective of the currently study was to determine the effect of Kunbi-Boshin-Hangam-Tang (KBH-Tang) on the production of nitric oxide (NO). Stimulation of RAW 264.7 cells with KBH-Tang after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in increased NO synthesis. KBH-Tang partially increased NO synthesis by itself. When KBH-Tang was used in combination with rIFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) protein. NO production was inhibited by NG-monomethyl-L-arginine (NGMMA). Furthermore, activation of nuclear factor (NF)-kappaB was increased by KBH-Tang. These results suggest that KBH-Tang may stimulate the NO production through the activation of the NF-kappaB.

Inhibition of immunologic and nonimmunologic stimulation-mediated anaphylactic reactions by water extract of white eggplant (Solanum melongena).

We investigated the effect of water extract of Solanum melongena(SMWE) on immunologic and nonimmunologic stimulation-mediated anaphylactic reactions. Nonimmunologic anaphylactic reaction was induced by compound 48/80 injection. Oral administration of SMWE (1 g kg(-1)) completely inhibited compound 48/80-induced anaphylactic reaction. Immunologic anaphylactic reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. Oral administration of SMWE (0.01--1 g kg(-1)) significantly inhibited passive cutaneous anaphylactic reaction activated by anti-DNP IgE to between 83.10 +/- 1.67% and 70.17 +/- 2.17%. SMWE (0.01--1 mg ml(-1)) also inhibited histamine release activated by compound 48/80 to between 93 +/- 2.65 and 70 +/- 1.50%. Moreover, SMWE (0.01--1 mg ml(-1)) had a significant inhibitory effect on IgE-induced tumor necrosis factor (TNF)-alpha secretion from rat peritoneal mast cells. These results indicate that SMWE inhibits immunologic and nonimmunologic stimulation-mediated anaphylactic reactions and TNF-alpha secretion from mast cells.

Inhibitory effects of mast cell-mediated allergic reactions by cell cultured Siberian Ginseng.

The crude drug "Siberian Ginseng (SG)" has long been used in empirical Oriental medicine for the nonspecific enhancement of resistance in humans and animals. In this study, we investigated the effect of cell cultured SG by oral administration in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound 48/80-induced systemic allergy with doses of 10(-2) to 1 g/kg 1 h before oral administration. Of special note, SG inhibited systemic allergy with the dose of 1 g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by 51%. SG dose-dependently inhibited histamine release from rat peritoneal mast cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in antidinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition, SG inhibited anti-DNP IgE antibody-stimulated TNF-alpha protein expression in mast cells. Our studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases.

Inhibitory action of water soluble fraction of Terminalia chebula on systemic and local anaphylaxis.

We investigated the effects of the water soluble fraction of Terminalia chebula (Combretaceae) (WFTC) on systemic and local anaphylaxis. WFTC administered 1h before compound 48/80 injection inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.01-1.0 g/kg. When WFTC was administered 5 or 10 min after compound 48/80 injection, the mortality also decreased in a dose-dependent manner. Passive cutaneous anaphylaxis was inhibited by 63.5+/-7.8% by oral administration of WFTC (1.0 g/kg). When WFTC was pretreated at concentrations ranging from 0.005 to 1.0 g/kg, the serum histamine levels were reduced in a dose-dependent manner. WFTC (0.01-1.0 mg/ml) also significantly inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. However, WFTC (1.0 mg/ml) had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that WFTC may possess a strong antianaphylactic action.

Inhibition of heat shock-induced apoptosis by peppermint oil in astrocytes.

Exposure to environmental stresses and toxins is linked to the pathogenesis of neuropsychiatric disorders. Astrocytes, the most abundant glial-cell type in the brain, are considered to have physiological and pathological roles in neuronal activities. We have investigated whether peppermint oil inhibits heat shock-induced apoptosis of astrocytes. We found that peppermint oil inhibits the heat shock-induced apoptosis in both human astrocyte CCF-STTG1 cells and rat astrocytes. Pretreatment of the cells with peppermint oil inhibited the heat shock-induced DNA fragmentation and condensation of nuclear chromatin. Peppermint oil also inhibited the caspase-3 activation and poly-ADP-ribose polymerase fragmentation in CCF-STTG1 cells. These results suggest that peppermint oil may modulate the apoptosis of astrocytes via the activation of the caspase-3.

Effect of allergina on mast cell-mediated allergic reactions.

The herbal formulation ALLERGINA has been used against allergic inflammation disease for generations, and still occupies an important place in traditional medicine in Korea. In this study, we investigated the effect of ALLERGINA by oral administration in mast cell-mediated anaphylaxis responses. ALLERGINA dose-dependently inhibited compound 48/48-induced systemic anaphylaxis with doses of 10(-2) to 5 g/kg 1 h before orally administered. Of special note, ALLERGINA inhibited systemic anaphylaxis completely with doses of 1 g/kg and 5 g/kg. ALLERGINA (1 g/kg) also inhibited passive cutaneous anaphylaxis by 84%. ALLERGINA dose-dependently inhibited histamine release from rat peritoneal mast cells. When ALLERGINA (0.01 mg/ ml) was added, ALLERGINA inhibited the production of tumor necrosis factor-alpha and interleukin-6, 80% and 26%, respectively in anti-dinitrophenyl IgE antibody-stimulated mast cells. Our studies provide evidence that ALLERGINA may be beneficial in the treatment of allergic inflammation diseases.

Inhibition of tumor necrosis factor-alpha-induced apoptosis by Asparagus cochinchinensis in Hep G2 cells.

A human hepatoma cell line, Hep G2 cells, is a reliable system for the study of alcohol-induced hepatotoxicity. In this study, we investigated the effect of an aqueous extract of Asparagus cochinchinensis(MERRIL) (Liliaceae) roots (ACAE) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. ACAE (1-100 microg/ml) dose-dependently inhibited the EtOH-induced tumor necrosis factor-alpha (TNF-alpha) secretion. ACAE (1-100 microg/ml) also inhibited the EtOH and TNF-alpha-induced cytotoxicity. Furthermore, we found that ACAE inhibited the TNF-alpha-induced apoptosis of Hep G2 cells. These results suggest that ACAE may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.

Effect of Vitex rotundifolia on immediate-type allergic reaction.

We investigated the effect of aqueous extract of Vitex rotundifolia (L.) (Verbenaceae) fruits (VRFE) on the immediate-type allergic reactions in vivo and in vitro. VRFE (10(-4)-1.0 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80. When VRFE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. VRFE (5x10(-1) and 1.0 g/kg) inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. VRFE (10(-3)-1.0 mg/ml) also dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 or anti-DNP IgE. Moreover, VRFE (10(-3) mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results suggest that VRFE may be beneficial in the regulation of immediate-type allergic reaction.

Regulatory effect of cytokine production in patients with cerebral infarction by Yulda-Hanso-Tang.

Yulda-Hanso-Tang (YH-Tang) is a prescription for the Taeumin cerebral infarction (CI) patients according to Sasang constitution philosophy. Taeumin patients with CI were treated with YH-Tang during the acute stage. Clinical signs of CI disappeared markedly in about 2 weeks after oral administration of YH-Tang in all patients. The mean interleukin (IL)-2 serum levels were lower in the patients with CI than in the normal groups, whereas the mean IL-4, IL-6 and IgE levels were significantly higher in the patients. There were no significant differences in interferon-gamma (IFN-gamma) levels between the groups. Serum IFN-gamma and IL-2 levels derived from T helper (Th)1 cells elevated significantly in the patients with CI by YH-Tang administration. Significant reduced serum levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with YH-Tang. During the period of YH-Tang administration, there were no other adverse effects. The data indicate that YH-Tang has a good CI treatment effect, and that its action may be due to regulation of cytokine production.

Suppression of immunoglobulin E-mediated anaphylactic reaction by Alpinia oxyphylla in rats.

We investigated the effect of Alpinia oxyphylla water extract (AOWE) on immunoglobulin E (IgE)-mediated anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody. AOWE dose-dependently suppressed passive cutaneous anaphylaxis (PCA) when intraperitoneally or orally administered. On the other hand, it showed weak suppressive activity when administered intravenously. AOWE dose-dependently suppressed anaphylactic histamine release from rat peritoneal mast cells (RPMC) activated by anti-DNP IgE antibody. However, AOWE had a significant augmenting effect on anti-DNP IgE antibody-induced tumor necrosis factor-alpha secretion from RPMC. These results indicated that AOWE may possess strong antianaphylactic action and also suggest that differential activity following administration routes may be caused by difference of bioavailability.

Inhibitory effect of interleukin-1alpha-induced apoptosis by Polygala tenuifolia in Hep G2 cells.

A human hepatoma cell line, Hep G2 cells are reliable for the study of alcohol-induced hepatotoxicity. In this study, we investigated the effect of an aqueous extract of Polygala tenuifolia WILLDENOW (Polygalaceae) roots (PTAE) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. PTAE (0.01-1 microg/ml) dose-dependently inhibited the EtOH-induced interleukin-1alpha (IL-1alpha) secretion. PTAE (0.01-1 microg/ml) also inhibited the EtOH- and IL-1alpha-induced cytotoxicity. Furthermore, we found that PTAE inhibited the IL-1alpha-induced apoptosis of Hep G2 cells. These results suggest that PTAE may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.

Aromatase inhibitors from Isodon excisus var. coreanus.

The diethyl ether extract of Isodon excisus var. coreanus exhibited significant inhibitory activity in aromatase assay. Bioactivity-guided fractionation of the extract led to the isolation of three active compounds: inflexin (ent-1alpha-hydroxy-3beta,6a-diacetoxykaur-16-en-11,15-dione ) (1), ursolic acid (2), and ursolic acid 3-O-acetate (3).

Aromatase and sulfatase inhibitors from Lepiota americana.

From an edible mushroom Lepiota americana Pk., (Agaricaceae), 2-aminophenoxazin-3-one that inhibited aromatase at IC50 = 5.7 microM and 3 beta-hydroxy-5,8-epidioxyergosta-6,22-diene that inhibited sulfatase at IC50 = 0.9 microM were isolated. Neither 2-aminophenoxazin-3-one was active against sulfatase nor was 3 beta-hydroxy-5,8-epidioxyergosta-6,22-diene active against aromatase.

Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats.

We investigated the effect of an aqueous extract of Schizonepeta tenuifolia (STAE) on mast cell-mediated immediate-type hypersensitivity. STAE inhibited systemic allergic reaction induced by compound 48/80 in rats dose-dependently. STAE also inhibited plasma histamine levels induced by compound 48/80. STAE inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. In addition, STAE does-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. However, STAE had a significant enhancing effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from RPMC. These results indicate that STAE inhibits immediate-type hypersensitivity and suggest that STAE can selectively activate the TNF-alpha production from RPMC.

New flavonoids from the aerial parts of Aconitum chiisanense.

The studies were carried out to evaluate the constituents in the aerial part of Aconitum chiisanense (Ranunculaceae). From the butanol fraction of the methanol extract, kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (I), quercetin 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (II), kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-feruloyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (III), kaempferol 3- O-beta-glucopyranoside-7- O-(6-benzoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (IV), kaempferol 7- O-(6-trans)-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (V), and kaempferol 7- O-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (VI) were isolated and identified on the basis of their physicochemical and spectroscopic evidence (UV, IR, FAB(-)MS, (1)H-NMR, (13)C-NMR, (1)H- (1)H COSY, HMQC and HMBC). New compounds I-VI were named chiisanin (I), chiiribanin (II), chiiribaconin (III), chiirin (IV), chiiricanin (V), and chiirirhamnin (VI), respectively.