Polysaccharide-Rich Extract of Phragmites rhizome Attenuates Water Immersion Stress and Forced Swimming Fatigue in Rodent Animal Model.

Our study aimed to investigate the effects of the polysaccharide-rich extract of Phragmites rhizoma (PEP) against water immersion restraint (WIR) stress and forced swimming-induced fatigue. Exposure to WIR stress significantly increased the ulcer index, bleeding score, the weight of the adrenal gland, blood glucose concentrations, total cholesterol, cortisol, and creatine kinase (CK). The weight of the spleen decreased significantly. In addition, myeloperoxidase (MPO) and thiobarbituric acid-reactive substance (TBARS) were significantly upregulated by WIR stress. The antioxidative factors such as glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the stomach were decreased by WIR stress. Alterations induced by WIR stress were effectively reversed by pretreatment with PEP. The swimming endurance capacity of mice was significantly prolonged by the oral administration of PEP. Swimming-induced fatigue significantly reduced the body weight; however, the injection of PEP inhibited the decrease of body weight. The PEP-treated group had significantly lower CK levels in plasma, an indicator of muscle damage. These results indicated that PEP has anti-stress and anti-fatigue effects, which are mediated by suppressing the hyperactivation of the hypothalamus-pituitary-adrenal axis, and antagonism of the oxidative damages induced by WIR stress and prolonged swimming times.

Pharmacological evaluation of HM41322, a novel SGLT1/2 dual inhibitor, in vitro and in vivo.

HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the T1/2 was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice (19.32±1.16 mg/g) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.

Inhibitory effect of acteoside on melittin-induced catecholamine exocytosis through inhibition of Ca(2+)-dependent phospholipase A2 and extracellular Ca(2+) influx in PC12 cells.

To investigate the inhibitory effect of acteoside on the process of exocytosis induced by melittin, we measured Ca(2+) mobilization, arachidonic acid (AA) release and catecholamine exocytosis in PC12 chromaffin cells. Melittin significantly increased the intracellular Ca(2+) mobilization via receptor-operated calcium channel but not the intracellular Ca(2+) release. It caused AA release via activation of Ca(2+)-dependent phospholipase A2 (PLA2) and catecholamine secretion in a dose-dependent manner. Acteoside dose-dependently inhibited the release of AA and intracellular Ca(2+) mobilization induced by melittin. Acteoside reduced the catecholamine release and raised the amount of intracellular chromogranin A which is co-released with catecholamine from melittin-stimulated PC12 cells. Taken together, our results suggest that acteoside could suppress the exocytosis via inhibition of Ca(2+)-dependent PLA2 and extracellular Ca(2+) influx in PC12 cells stimulated by melittin.

Effects of C18 Fatty Acids on Intracellular Ca(2+) Mobilization and Histamine Release in RBL-2H3 Cells.

To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and α-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular Ca(2+) mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular Ca(2+) mobilization, whereas linoleic acid and α-linolenic acid gradually increased this mobilization. In the absence of extracellular Ca(2+), stearic acid (100 µM) did not cause any increase of intracellular Ca(2+) mobilization. Both linoleic acid and α-linolenic acid increased intracellular Ca(2+) mobilization, but the increase was smaller than that in the presence of extracellular Ca(2+). These results suggest that C18 fatty acid-induced intracellular Ca(2+) mobilization is mainly dependent on extracellular Ca(2+) influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular Ca(2+) mobilization, but did not affect both linoleic acid and α-linolenic acid-induced intracellular Ca(2+) mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and α-linolenic acid on intracellular Ca(2+) mobilization may differ. Linoleic acid and α-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: ω-6)-induced intracellular Ca(2+) mobilization and histamine release were more prominent than α-linolenic acid (C18:3: ω-3). These data support the view that the intake of more α-linolenic acid than linoleic acid is useful in preventing inflammation.

The effect of acteoside on intracellular Ca(2+) mobilization and phospholipase C activity in RBL-2H3 cells stimulated by melittin.

This study was performed to investigate the effects of acteoside on various cellular functions such as, intracellular Ca(2+) mobilization, phospholipase C activity, and exocytosis induced by melittin. Melittin (0.1-1 µM) dose-dependently increased intracellular Ca(2+) mobilization in the presence of extracellular Ca(2+), but was not affected by 1 µM U73122, a specific PLC inhibitor. In the absence of extracellular Ca(2+), melittin (1 µM) did not induce a change in intracellular Ca(2+) mobilization, which suggests that melittin-induced intracellular Ca(2+) mobilization may be dependent on the influx of extracellular Ca(2+) rather than on the release of intracellular Ca(2+) storage. Acteoside (10 µM) significantly inhibited 1 µM melittin-induced Ca(2+) mobilization by 33 %. In [(3)H]inositol-labeled cells, 1 µM melittin did not increase inositol phosphate formation, but more than 5 µM melittin significantly increased inositol phosphate formation, which was significantly inhibited by acteoside. Melittin (1 µM) significantly increased histamine release from RBL 2H3 cells in the presence or absence of extracellular Ca(2+). Acteoside significantly inhibited 1-µM-melittin-induced histamine release by 74 % in the presence of extracellular Ca(2+) and by 71 % in the absence of extracellular Ca(2+). These data suggest that the inhibitory effect of acteoside on 1 µM-melittin-induced histamine release may be related to blockage of the calcium-independent pathway. Taken together, these data suggest that melittin has an influence on cellular functions such as intracellular Ca(2+) mobilization, the PLC pathway, and exocytosis via various independent signalling pathways in RBL-2H3 cells, and was significantly inhibited by acteoside.

Effect of Lutein on L-NAME-Induced Hypertensive Rats.

We investigated the antihypertensive effect of lutein on N(G) -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Daily oral administration of L-NAME (40 mg/kg)-induced a rapid progressive increase in mean arterial pressure (MAP). L-NAME significantly increased MAP from the first week compared to that in the control and reached 193.3±9.6 mmHg at the end of treatment. MAP in the lutein groups was dose-dependently lower than that in the L-NAME group. Similar results were observed for systolic and diastolic blood pressure of L-NAME-induced hypertensive rats. The control group showed little change in heart rate for 3 weeks, whereas L-NAME significantly reduced heart rate from 434±26 to 376±33 beats/min. Lutein (2 mg/kg) significantly prevented the reduced heart rate induced by L-NAME. L-NAME caused hypertrophy of heart and kidney, and increased plasma lipid peroxidation four-fold but significantly reduced plasma nitrite and glutathione concentrations, which were significantly prevented by lutein in a dose-dependent manner. These findings suggest that lutein affords significant antihypertensive and antioxidant effects against L-NAME-induced hypertension in rats.

Competitive inhibition of cytosolic Ca2+-dependent phospholipase A2 by acteoside in RBL-2H3 cells.

The aim of this study was to investigate whether acteoside isolated from Clerodendron trichotomum Thunberg may act as a selective inhibitor of phospholipase A(2) in RBL-2H3 cells. Acteoside dose-dependently inhibited 0.5 µM melittin-induced release of [(3)H]arachidonic acid, which was due to the inhibition of cytosolic Ca(2+)-dependent phospholipase A(2) (cPLA(2)) rather than secretory PLA(2) (sPLA(2)). In Dixon plots, the apparent K ( i ) value of acteoside on cPLA(2) was 5.9 µM and the inhibitory pattern appeared to be a competitive inhibitor. The above data, suggests that acteoside acts as a competitive inhibitor of cPLA(2) in RBL-2H3 cells.

Intracellular Ca Mobilization and Beta-hexosaminidase Release Are Not Influenced by 60 Hz-electromagnetic Fields (EMF) in RBL 2H3 Cells.

The effects of extremely low frequency electromagnetic fields (EMF) on intracellular Ca(2+) mobilization and cellular function in RBL 2H3 cells were investigated. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not produce any cytotoxic effects in RBL 2H3 cells. Melittin, ionomycin and thapsigargin each dose-dependently increased the intracellular Ca(2+) concentration. The increase of intracellular Ca(2+) induced by these three agents was not affected by exposure to EMF (60 Hz, 1 mT) for 4 or 16 h in RBL 2H3 cells. To investigate the effect of EMF on exocytosis, we measured beta-hexosaminidase release in RBL 2H3 cells. Basal release of beta-hexosaminidase was 12.3±2.3% in RBL 2H3 cells. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not affect the basal or 1 µM melittin-induced beta-hexosaminidase release in RBL 2H3 cells. This study suggests that exposure to EMF (60 Hz, 0.1 or 1 mT), which is the limit of occupational exposure, has no influence on intracellular Ca(2+) mobilization and cellular function in RBL 2H3 cells.

The effect of quercetin-3-O-ß-D-glucuronopyranoside on indomethacin-induced gastric damage in rats via induction of mucus secretion and down-regulation of ICAM-1 expression.

The mechanism of the protective effect of quercetin-3-O-ß-D-glucuronopyranoside (QGC) from the leaves of Rumex aqauticus on indomethacin (IND, a representative NSAID)-induced gastric damage in rats was investigated. Pre-treatment with QGC significantly attenuated IND-induced gastric mucosal injury. An increase in myeloperoxidase (MPO) activity and expression of intercellular adhesion molecule (ICAM)-1 protein and mRNA expression of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1ß, as well as a decrease in gastric mucus secretion were detected in the gastric mucosa of IND-treated rats. QGC reversed the side effect of IND on MPO activity and mucus production. Furthermore, QGC pre-treatment notably decreased ICAM-1 protein and mRNA expression of the pro-inflammatory cytokines, suggesting that QGC protection from IND-induced damage is associated with increased gastric mucus secretion, inhibition of free radical production by activated neutrophils via ICAM-1, and pro-inflammatory cytokine downregulation.

Anti-asthmatic effects of phenylpropanoid glycosides from Clerodendron trichotomum leaves and Rumex gmelini herbes in conscious guinea-pigs challenged with aerosolized ovalbumin.

Clerodendron trichotomum leaves and Rumex aquatica herbs are used as a folk medicine for the treatment of inflammatory diseases, but their active ingredients are not known until now. We isolated caffeic acid and phenylpropanoid glycosides, 1-O-caffeoyl glycoside and acteoside [ß-(3',4'-dihydroxyphenyl) ethyl-O-α-l-rhamnopyranosyl(1→3)-ß-d-(4-O-caffeoyl)-glucopyranoside] from their ethylacetate fractions, respectively, and evaluated their anti-asthmatic effects on the aerosolized ovalbumin (OA) challenge in the OA-sensitized guinea-pigs measuring the specific airway resistance (sRaw) during the immediate-phase response (IAR) and late-phase response (LAR), and also measured recruitment of leukocytes and chemical mediators on the bronchoalveolar lavage fluids (BALF) in LAR, as well as histopathological survey. Acteoside and 1-O-caffeoyl glycoside (25mg/kg) significantly (P<0.05) inhibited sRaw by 32.14 and 26.79% in IAR, and by 55.88% and 52.94% in LAR, respectively, whereas caffeic acid (25mg/kg) inhibited sRaw by 30.36% in IAR and 44.12% in LAR, compared to control, but with less effective than dexamethasone, disodium cromoglycate, and salbutamol, respectively. In addition, phenylpropanoid glycosides (25mg/kg) significantly inhibited the recruitments of leukocytes, particularly neutrophils and eosinophils into lung, Furthermore, 1-O-caffeoyl glycoside, acteoside and caffeic acid significantly (P<0.05) inhibited protein content at a dose of 25mg/kg, and histamine content and PLA(2) activity at a dose of 50mg/kg, in BALF. Acteoside had more active than caffeic acid and 1-O-caffeoyl glycoside. However, their anti-asthmatic effects were less than the reference drugs. These results indicated that caffeic acid and its glycosides (25mg/kg) have anti-asthmatic effect as the same manner with dexamethasone and disodium cromoglycate.

Lutein is a competitive inhibitor of cytosolic Ca²+-dependent phospholipase A2.

OBJECTIVES: We have investigated the effect of lutein on phospholipase A2 (PLA2) isozymes. METHODS: We measured arachidonic acid release in [³H]arachidonic acid-labelled Raw 264.7 cells and PLA2 activity using 1-palmitoyl-2-[¹4C]arachidonyl phosphatidylcholine ([¹4C]AA-PC) and 10-pyrene phosphatidylcholine in vitro. KEY FINDINGS: Lutein suppressed the release of arachidonic acid and inhibited Raw 264.7 cell-derived cytosolic Ca²+-dependent PLA2 (cPLA2-induced hydrolysis of [¹4C]AA-PC in a dose- and time-dependent manner. In contrast, lutein did not affect secretory Ca²+-dependent PLA2 (sPLA2)-induced hydrolysis of [¹4C]AA-PC. A Dixon plot showed that the inhibition by lutein on cPLA2 appeared to be competitive with an inhibition constant, K(i) , of 13.6 µm. CONCLUSIONS: We suggest that lutein acted as a competitive inhibitor of cPLA2 but did not affect sPLA2.

Dibenzylbutyrolactone lignans from Forsythia koreana fruits attenuate lipopolysaccharide-induced inducible nitric oxide synthetase and cyclooxygenase-2 expressions through activation of nuclear factor-κb and mitogen-activated protein kinase in RAW264.7 cells.

Previously, we reported that dibenzylbutyrolactone lignans (DBLLs) from the fruit of Forsythia koreana NAKAI (Oleaceae) has anti-inflammatory, antioxidant, and anti-asthmatic effects. In this study, to clarify the anti-inflammatory mechanisms of DBLL, we evaluated the effects of DBLLs on lipopolysaccharide-stimulated inducible nitric oxide synthetase (iNOS) and cyclooxygenase-2 (COX-2) expressions, nitric oxide (NO) and prostaglandin E(2) (PGE(2)) productions, nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activations, inhibitor of κB (IκB) and inhibitor of κB kinase (IKK) phosphorylations in cytosolic proteins, and cytotoxicity in Raw264.7 cells. DBLLs potently suppressed both the enzyme expression and DNA-binding activity of NF-κB. Arctiin, arctigenin (1.0 µM) and matairesinol (10 µM) inhibited the expression of iNOS by 37.71±2.86%, 32.51±4.28%, and 27.44±2.65%, respectively, and arctiin, arctigenin (0.1 µM) and matairesinol (1.0 µM) inhibited COX-2 expression by 37.93±7.81%, 26.70±4.61% and 29.37±5.21%, respectively. The inhibitory effects of DBLLs on NO and PGE(2) productions were the same patterns as those seen for the reductions in iNOS and COX-2 expression, respectively. Arctiin, arctigenin (1.0 µM) and matairesinol (10 µM) significantly (p<0.05) inhibited NF-κB DNA binding by 44.85±6.67%, 44.16±6.61%, and 44.79±5.62%, respectively, and arctiin (0.1 µM) and arctigenin (1.0 µM) significantly (p<0.05) inhibited the phosphorylation of IκB by 20.58±3.86% and 25.99±6.18%, respectively. Furthermore, arctiin, matairesinol (1.0 µM) and arctigenin (10 µM) inhibited the phosphorylation of IKK by 38.80±6.64%, 38.33±6.65%, and 38.57±8.14%, respectively. In addition, DBLLs potently inhibited the lipopolysaccharide (LPS)-induced activation of MAPKs (SAPK/c-Jun NH(2)-terminal kinase (JNK), p38, and extracellular signal receptor-activated kinase (ERK)1/2). Overall, arctiin was the most effective; its effect was nearly the same as that of 10 µM helenalin. These findings suggest that treatment with non-toxic DBLLs inhibits not only NF-κB and NF-κB-regulated protein activation, but also potently inhibits the activations of specific MAPKs.

Morinda citrifolia Inhibits Both Cytosolic Ca-dependent Phospholipase A(2) and Secretory Ca-dependent Phospholipase A(2).

This study investigated the effects of the methanol extracts of Morinda citrifolia containing numerous anthraquinone and iridoid on phospholipase A(2) (PLA(2)) isozyme. PLA(2) activity was measured using various PLA(2) substrates, including 10-pyrene phosphatidylcholine, 1-palmitoyl-2-[(14)C]arachidonyl phosphatidylcholine ([(14)C]AA-PC), and [(3)H]arachidonic acid (AA). The methanol extracts suppressed melittin-induced [(3)H]AA release in a concentration-dependent manner in RAW 264.7 cells, and inhibited cPLA(2)/sPLA(2)-induced hydrolysis of [(14)C]AA-PC in a concentration- and time-dependent manner. A Dixon plot showed that the inhibition by methanol extracts on cPLA(2) and sPLA(2) appeared to be competitive with inhibition constants (K(i)) of 3.7microg/ml and 12.6microg/ml, respectively. These data suggest that methanol extracts of Morinda citrifolia inhibits both Ca(2+)-dependent PLA(2) such as, cPLA(2) and sPLA(2). Therefore, Morinda citrifolia may possess anti-inflammatory activity secondary to Ca(2+)-dependent PLA(2) inhibition.

Hydrolysable tannins depress cardiac papillary muscle contraction and propranolol-induced negative inotropism.

We studied effects of hydrolysable tannins on rat papillary muscle contractions induced by propranolol. The developed force of papillary muscle was measured isometrically with an inductive force transducer. The IC(50) values for digallic acid, gallic acid, germin D, praecoxin A and 1-desgalloyl rugosin F were 4.2 x 10(-5) M, 1.3 x 10(-4) M, 1,4 x 10(-4) M, 1.5 x 10(-4) and 1.7 x 10(-4) M, respectively. Incubation with tannins significantly attenuated the propranolol-induced negative inotropic contractile response. These results show that hydrolysable tannins depress muscle contractions and potentiate the activities of ß-adrenergic blocker.

Flavonols attenuate the immediate and late-phase asthmatic responses to aerosolized-ovalbumin exposure in the conscious guinea pig.

We previously reported that quercetin and rutin have potent, anti-asthmatic activity, but the structure-activity relationships of flavonoids and anti-asthmatic agents are still poorly understood. In the current study, the effects of kaempferol, fisetin, and morin on the immediate-phase response (IAR) and late-phase response (LAR) caused by exposure to aerosolized-ovalbumin (OA) in OA-sensitized guinea pigs were evaluated by determining the specific airway resistance (sRaw), recruitment of leukocytes and chemical mediators in bronchoalveolar lavage fluid (BALF), histopathological surveys, and determination of neutrophil chemotaxis. Fisetin and kaempherol (30 mg/kg, p.o.) significantly (P<0.01) inhibited sRaw by 47.93% and 30.05% in IAR, and 54.45% and 40.50% in LAR, when compared to vehicle control, respectively. Furthermore, all three studied flavonols (30 mg/kg, p.o.) significantly (P<0.05) inhibited the recruitment of total, as well as subtypes of, leukocytes into the lung BALF. This recruitment inhibition corresponded to the inhibition of leukocyte infiltration, particularly of eosinophils and neutrophils, into the lung in pathological surveys and formly-methionyl-leucyl-phenylalanine (FMLP)-induced neutrophil chemotaxis studies. Kaempferol inhibited FMLP-induced neutrophil chemotaxis in a concentration-dependent manner in a tested range of 1-100 µM. Fisetin inhibited histamine content and peroxidase (EPO) activity in BALF in a dose-dependent manner. All three tested flavonols significantly (P<0.01) inhibited histamine content at 10 mg/kg, and phospholipase A(2) (PLA(2)) and EPO activities at 30 mg/kg (p.o.) in BALF. Kaempherol had a greater anti-asthmatic effect than other flavonols. Fisetin demonstrated the greatest inhibition of sRaw, whereas morin had lesser effects. These results indicate that the lower the molecular weight, the greater the anti-asthmatic activities of these compounds.

MLCK and PKC Involvements via Gi and Rho A Protein in Contraction by the Electrical Field Stimulation in Feline Esophageal Smooth Muscle.

We have shown that myosin light chain kinase (MLCK) was required for the off-contraction in response to the electrical field stimulation (EFS) of feline esophageal smooth muscle. In this study, we investigated whether protein kinase C (PKC) may require the on-contraction in response to EFS using feline esophageal smooth muscle. The contractions were recorded using an isometric force transducer. On-contraction occurred in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME), suggesting that nitric oxide acts as an inhibitory mediator in smooth muscle. The excitatory composition of both contractions was cholinergic dependent which was blocked by tetrodotoxin or atropine. The on-contraction was abolished in Ca(2+)-free buffer but reappeared in normal Ca(2+)-containing buffer indicating that the contraction was Ca(2+) dependent. 4-aminopyridine (4-AP), voltage-dependent K(+) channel blocker, significantly enhanced on-contraction. Aluminum fluoride (a G-protein activator) increased on-contraction. Pertussis toxin (a G(i) inactivator) and C3 exoenzyme (a rhoA inactivator) significantly decreased on-contraction suggesting that Gi or rhoA protein may be related with Ca(2+) and K(+) channel. ML-9, a MLCK inhibitor, significantly inhibited on-contraction, and chelerythrine (PKC inhibitor) affected on the contraction. These results suggest that endogenous cholinergic contractions activated directly by low-frequency EFS may be mediated by Ca(2+), and G proteins, such as Gi and rhoA, which resulted in the activation of MLCK, and PKC to produce the contraction in feline distal esophageal smooth muscle.

Inhibitory effects of diterpene acids from root of Aralia cordata on IgE-mediated asthma in guinea pigs.

This study evaluated the anti-asthmatic activities of four diterpene acids isolated from Aralia cordata root that are proposed to be the active ingredients in its traditional use as a treatment for inflammation, overheating, pain and spasm in Korea. The diterpene acids were identified as kaurenoic acid, 7-oxo-sandaracopimaric acid, 17-hydroxy-ent-kaur-15-en-19-oic acid, and hederagenin, by comparing their phytochemical and spectroscopic data with previous reports. The effects of diterpene acids on asthma were evaluated by determining the specific airway resistance (sRaw) during the immediate asthmatic response (IAR) and the late-phase asthmatic response (LAR) in guinea pigs with IgE-mediated asthma. Recruitment of leukocytes and the presence of chemical mediators in bronchoalveolar lavage fluid (BALF) were determined, and histopathological surveys performed. The four diterpene acids dosed at 25 approximately 100 mg/kg had dose-dependently anti-asthmatic effects: 7-oxo-sandaracopimaric acid > 17-hydroxy-ent-kaur-15-en-19-oic acid > kaurenoic acid > hederagenin. 7-oxo-sandaracopimaric acid (25 mg/kg) significantly (p < 0.05) inhibited sRaw by 59.5% in IAR and LAR, and also dose-dependently inhibited recruitment of eosinophils and neutrophils into lung and release of chemical mediators, histamine, and the activity of phospholipase A(2) and eosinophil peroxidase in BALF. 7-Oxo-sandaracopimaric acid had the highest activity among the diterpene acids. But its effect was lower than cromolyn sodium, salbutamol, or dexamethasone in both the IAR and the LAR. These results suggested that C(7)-oxo radical of 7-oxo-sandaracopimaric acid was more active than the C(7)-hydroxy and hydrogen of the other compounds, and showed diterpene acids have anti-asthmatic effects, supporting the traditional application of this herb in treating IgE-mediated asthma.

Effect of Extremely Low Frequency Electromagnetic Fields (EMF) on Phospholipase Activity in the Cultured Cells.

This study was conducted to investigate the effects of extremely low frequency electromagnetic fields (EMF) on signal pathway in plasma membrane of cultured cells (RAW 264.7 cells and RBL 2H3 cells), by measuring the activity of phospholipase A(2) (PLA(2)), phospholipase C (PLC) and phospholipase D (PLD). The cells were exposed to the EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h. The basal and 0.5 µM melittin-induced arachidonic acid release was not affected by EMF in both cells. In cell-free PLA(2) assay, we failed to observe the change of cPLA(2) and sPLA(2) activity. Also both PLC and PLD activities did not show any change in the two cell lines exposed to EMF. This study suggests that the exposure condition of EMF (60 Hz, 0.1 or 1 mT) which is 2.4 fold higher than the limit of occupational exposure does not induce phospholipases-associated signal pathway in RAW 264.7 cells and RBL 2H3 cells.

The Inhibitory Effect of Quercetin-3-O-beta-D-Glucuronopyranoside on Gastritis and Reflux Esophagitis in Rats.

It was evaluated the inhibitory action of quercetin-3-O-beta-D-glucuronopyranoside (QGC) on reflux esophagitis and gastritis in rats. QGC was isolated from the herba of Rumex Aquaticus. Reflux esophagitis or gastritis was induced surgically or by administering indomethacin, respectively. Oral QGC decreased ulcer index, injury area, gastric volume, and acid output and increased gastric pH as compared with quercetin. Furthermore, QGC significantly decreased gastric lesion sizes induced by exposing the gastric mucosa to indomethacin. Malondialdehyde levels were found to increase significantly after inducing reflux esophagitis, and were reduced by QGC, but not by quercetin or omeprazole. These results show that QGC can inhibit reflux esophagitis and gastritis in rats.

Antioxidant Effect of CoQ(10) on N-nitrosodiethylamine-induced Oxidative Stress in Mice.

The antioxidant effect of CoQ(10) on N-nitrosodiethylamine (NDEA)-induced oxidative stress was investigated in mice. Food intake and body weight were similar in both CoQ(10) and control groups during the 3-week experimental period. NDEA significantly increased the activities of typical marker enzymes of liver function (AST, ALT and ALP) both in control and CoQ(10) groups. However, the increase of plasma aminotransferase activity was significantly reduced in the CoQ(10) group. Lipid peroxidation in various tissues, such as heart, lung, liver, kidney, spleen and plasma, was significantly increased by NDEA, but this increase was significantly reduced by 100 mg/kg of CoQ(10). Superoxide dismutase activity increased significantly upon NDEA-induced oxidative stress in both the control and CoQ(10) groups with the effect being less in the CoQ(10) group. Catalase activity decreased significantly in both the control and CoQ(10) groups treated with NDEA, again with the effect being less in the CoQ(10) group. The lesser effect on superoxide dismutase and catalase in the NDEA-treated CoQ(10) group is indicative of the protective effect CoQ(10). Thus, CoQ(10) can offer useful protection against NDEA-induced oxidative stress.