OBJECTIVETo assess the effects of traditional herbal formulae Sijunzi Decoction (, Sagunja-tang, SJZD), Siwu Decoction (, Samul-tang, SWD), Bawu Decoction (, Palmul-tang, BWD) and Shiquan Dabu Decoction (, Sipjeondaebo-tang, SDD) on the activities of human cytochrome P450 (CYP450), a drug-metabolizing enzyme.

METHODSHerbal formula water extracts were filtered and lyophilized after the powder extracts were dissolved in distilled water. The activities of major human CYP450 isozymes (CYP3A4, CYP2C19, CYP2D6 and CYP2E1) were measured using in vitro fluorescence-based enzyme assays. The inhibitory effects of the herbal formulas on the activities of CYP450 were characterized as half maximal inhibition concentration (IC) values.

RESULTSAll the tested herbal formulae inhibited CYP2C19 activity (IC: SJZD, 83.28 μg/mL; SWD, 235.54 μg/mL; BWD, 166.82 μg/mL; SDD, 178.19 μg/mL); SJZD (IC= 196.46 μg/mL), SWD (IC= 333.42 μg/mL) and SDD (IC= 163.42 μg/mL) inhibited CYP2E1-mediated metabolism; whereas BWD exhibited comparatively weak inhibition of CYP2E1 (IC= 501.78 μg/mL). None of the four herbal formulas significantly affected CYP3A4 or CYP2D6.

CONCLUSIONSThese results suggest that SJZD, SWD, BWD and SDD could potentially inhibit the metabolism of co-administered synthetic drugs whose primary route of elimination is via CYP2C19. In addition, clinically relevant pharmacokinetic interactions could occur when SJZD, SWD or SDD is co-administered with drugs metabolized by CYP2E1. Our findings provide information for the safety and effective clinical use of these four classic herbal formulas.

Cytochrome P-450 Enzyme System ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hot Temperature ; Humans ; Inhibitory Concentration 50 ; Isoenzymes ; metabolism ; Plant Extracts ; pharmacology ; Water ; chemistry

OBJECTIVETo assess the antinociceptive and anti-inflammatory properties of the aqueous extract of Armadillidium vulgare (AV).

METHODSThe antinociceptive effect of AV (400, 600 and 800 mg/kg) was investigated in mice using the acetic acid-induced writhing, formalin-induced nociceptive, and hot plate tests. Phlogogen-induced paw edema using carrageenan, dextran, or compound 48/80 as phlogogen was used as inflammatory models to evaluate AV's anti-inflammatory effect. Additionally, the bioactive substances glucosamine (GLcN) and taurine in AV were determined using high-performance liquid chromatography.

RESULTSOral treatment of the mice with AV (600 and 800 mg/kg) significantly reduced the number of writhes in the acetic acid-induced writhing test (P<0.01) but not the hot plate test (P>0.05). All doses tested significantly inhibited paw-withdrawal during the second phase of the formalin-induced nociceptive model (P<0.01). AV demonstrated a strong anti-inflammatory effect in all those inflammatory models (P<0.05).

CONCLUSIONSAV has antinociceptive and anti-inflammatory effects, providing scientific evidence of the efficacy of its traditional use in pain treatment. Furthermore, GLcN and taurine contribute, at least in part, to the anti-inflammatory activity of AV.

Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Edema ; drug therapy ; Female ; Inflammation ; drug therapy ; Isopoda ; chemistry ; Male ; Mice ; Pain ; drug therapy ; Pain Measurement ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; Water ; chemistry

OBJECTIVETo investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats.

METHODSTwenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques.

RESULTSIn comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01).

CONCLUSIONSAdministration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.

Animals ; Asteraceae ; chemistry ; Blood Glucose ; metabolism ; Cell Count ; Cholesterol ; blood ; Ethanol ; chemistry ; Gonadotropins ; blood ; Hyperglycemia ; blood ; drug therapy ; pathology ; Insulin ; blood ; Leydig Cells ; drug effects ; pathology ; Lipoproteins ; blood ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; pathology ; Testosterone ; blood ; Triglycerides ; blood ; Water ; chemistry

OBJECTIVETo investigate the role of aqueous extracts of Tribulus terrestris (TT) against oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) dysfunction in vitro.

METHODSHUVECs were pre-incubated for 60 min with TT (30 and 3 μg/mL respectively) or 10(-5) mol/L valsartan (as positive controls) and then the injured endothelium model was established by applying 100 μg/mL ox-LDL for 24 h. Cell viability of HUVECs was observed by real-time cell electronic sensing assay and apoptosis rate by Annexin V/PI staining. The cell migration assay was performed with a transwell insert system. Cytoskeleton remodeling was observed by immunofluorescence assay. The content of endothelial nitric oxide synthase (eNOS) was measured by enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) generation was assessed by immunofluorescence and flow cytometer. Key genes associated with the metabolism of ox-LDL were chosen for quantitative real-time polymerase chain reaction to explore the possible mechanism of TT against oxidized LDL-induced endothelial dysfunction.

RESULTSTT suppressed ox-LDL-induced HUVEC proliferation and apoptosis rates significantly (41.1% and 43.5% after treatment for 3 and 38 h, respectively; P<0.05). It also prolonged the HUVEC survival time and postponed the cell's decaying stage (from the 69th h to over 100 h). According to the immunofluorescence and transwell insert system assay, TT improved the endothelial cytoskeletal network, and vinculin expression and increased cell migration. Additionally, TT regulated of the synthesis of endothelial nitric oxide synthase and generation of intracellular reactive oxygen species (P<0.05). Both 30 and 3 μg/mL TT demonstrated similar efficacy to valsartan. TT normalized the increased mRNA expression of PI3Kα and Socs3. It also decreased mRNA expression of Akt1, AMPKα1, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were JAK2, LepR, PI3Kα, Socs3 and STAT3.

CONCLUSIONSTT demonstrated potential lowering lipid benefits, anti-hypertension and endothelial protective effects. It also suggested that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway which was involved in the pharmacological mechanism of TT as the vascular protective agent.

Apoptosis ; drug effects ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Cytoskeleton ; drug effects ; metabolism ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Gene Expression Regulation ; drug effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Lipoproteins, LDL ; adverse effects ; Nitric Oxide Synthase Type III ; metabolism ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Reactive Oxygen Species ; metabolism ; Tribulus ; chemistry ; Vinculin ; metabolism ; Water ; chemistry

BACKGROUND/AIMS: There are no studies that looked into the bubble eliminating efficacy of polyethylene glycol with ascorbic acid (PEGA), which has been one of the shortcomings of polyethylene glycol (PEG). In this study, we compared newly introduced PEGA regimen by adding either simethicone or 1 L of water. METHODS: A prospective randomized controlled study was carried out at Dongguk Universtiy Gyeongju Hospital from July 2014 to September 2014. A total of 90 patients were randomly assigned to 3 groups; PEGA group (n=30) which served as control, simethicone addition group (n=30) to which simethicone 400 mg was additionally prescribed, and water addition group (n=30) to whom additional 1 L of water was given. Cleansing effectiveness, gas elimination efficacy, side effects, and patient satisfaction were compared between the groups. RESULTS: PEGA group demonstrated the highest cleansing effectiveness, but there was no statistically significant difference among the groups. Simethicone addition group showed significantly lesser amount of bubbles than the other groups (2.57±2.05 vs. 1.10±1.83 vs. 2.60±2.84, p=0.017). The rates of side effects in each group were 20.00% vs. 16.77% vs. 53.33%. Water addition group had significantly more side effects than the PEGA group and the simethicone addition group (p=0.003). The patient satisfaction score of each group was 3.37±0.85 vs. 3.73±0.74 vs. 3.20±0.66 with simethicone addition group showing significantly higher satisfaction than water addition group (p=0.020). CONCLUSIONS: PEGA bowel preparation agent showed satisfactory bowel cleansing despite the decrease in dosage, and addition of simethicone resulted in better bubble elimination.
Adult ; Ascorbic Acid/*chemistry ; Cathartics/adverse effects/chemistry/*pharmacology ; Colon/*drug effects ; Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Patient Compliance ; Polyethylene Glycols/adverse effects/*chemistry/pharmacology ; Prospective Studies ; Simethicone/*chemistry ; Water/*chemistry

OBJECTIVETo evaluate the effect of water pollution with dexamethasone on intestinal flora in mice.

METHODSTwenty Balb/c mice were randomly divided into control group and low-, moderate- and high-dose dexamethasone groups. The mice in dexamethasone groups were exposed to dexamethasone sodium phosphate in drinking water at doses of 0.035, 0.225, and 2.25 ng for 36 days. The changes in behaviors, fur condition, and feces of the mice were observed daily. All the mice were sacrificed at 36 days and the tissues in the ileocecal region was collected for denaturant gradient gel electrophoresis (DGGE) of 16S rDNA V6 variable regions of microbes and sequence analysis with BLAST.

RESULTSThe mice in the 3 dexamethasone groups all showed aggressive behaviors. Cluster analysis of DGGE graph showed relatively stable floras in the ileocecal region in all the mice, but principal component analysis identified differences in the dominating flora among the groups. Diversity analysis of the flora revealed significantly increased amount and types of bacteria in the intestinal flora in all the 3 dexamethasone groups (P<0.05 or 0.01) compared with the control group. Sequence analysis of 16S rDNA V6 regions showed 15 common bacterial species and 2 differential species between the dexamethasone groups and the control group with changes in the type and proportion of the dominating bacterium in the dexamethasone groups. Lactobacillus colonization was detected in the control group but not in moderate- and high-dose dexamethasone groups, and Shigella species were found in the latter two groups.

CONCLUSIONSWater contamination with dexamethasone can affect the nervous system of mice, cause changes in the types and amounts of intestinal bacteria and the dominating bacteria, and inhibit the colonization of probiotics in the intestinal floras to increase the risk of invasion by intestinal pathogenic bacteria.

Animals ; Bacteria ; classification ; Dexamethasone ; pharmacology ; Drinking Water ; chemistry ; Feces ; Gastrointestinal Microbiome ; drug effects ; Lactobacillus ; isolation & purification ; Mice ; Mice, Inbred BALB C ; Probiotics ; RNA, Bacterial ; genetics ; RNA, Ribosomal, 16S ; genetics ; Shigella ; isolation & purification

BACKGROUNDPremature ovarian failure (POF) is a disease that affects female fertility but has few effective treatments. Ovarian reserve function plays an important role in female fertility. Recent studies have reported that hydrogen can protect male fertility. Therefore, we explored the potential protective effect of hydrogen-rich water on ovarian reserve function through a mouse immune POF model.

METHODSTo set up immune POF model, fifty female BALB/c mice were randomly divided into four groups: Control (mice consumed normal water, n = 10), hydrogen (mice consumed hydrogen-rich water, n = 10), model (mice were immunized with zona pellucida glycoprotein 3 [ZP3] and consumed normal water, n = 15), and model-hydrogen (mice were immunized with ZP3 and consumed hydrogen-rich water, n = 15) groups. After 5 weeks, mice were sacrificed. Serum anti-Müllerian hormone (AMH) levels, granulosa cell (GC) apoptotic index (AI), B-cell leukemia/lymphoma 2 (Bcl-2), and BCL2-associated X protein (Bax) expression were examined. Analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA) software.

RESULTSImmune POF model, model group exhibited markedly reduced serum AMH levels compared with those of the control group (5.41 ± 0.91 ng/ml vs. 16.23 ± 1.97 ng/ml, P = 0.033) and the hydrogen group (19.65 ± 7.82 ng/ml, P = 0.006). The model-hydrogen group displayed significantly higher AMH concentrations compared with that of the model group (15.03 ± 2.75 ng/ml vs. 5.41 ± 0.91 ng/ml, P = 0.021). The GC AI was significantly higher in the model group (21.30 ± 1.74%) than those in the control (7.06 ± 0.27%), hydrogen (5.17 ± 0.41%), and model-hydrogen groups (11.24 ± 0.58%) (all P < 0.001). The GC AI was significantly higher in the model-hydrogen group compared with that of the hydrogen group (11.24 ± 0.58% vs. 5.17 ± 0.41%, P = 0.021). Compared with those of the model group, ovarian tissue Bcl-2 levels increased (2.18 ± 0.30 vs. 3.01 ± 0.33, P = 0.045) and the Bax/Bcl-2 ratio decreased in the model-hydrogen group.

CONCLUSIONSHydrogen-rich water may improve serum AMH levels and reduce ovarian GC apoptosis in a mouse immune POF model induced by ZP3.

Animals ; Anti-Mullerian Hormone ; blood ; Apoptosis ; drug effects ; Female ; Granulosa Cells ; cytology ; Hydrogen ; chemistry ; pharmacology ; Mice ; Mice, Inbred BALB C ; Ovarian Reserve ; drug effects ; physiology ; Ovary ; drug effects ; metabolism ; Primary Ovarian Insufficiency ; blood ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Water ; administration & dosage ; chemistry ; pharmacology ; Zona Pellucida ; drug effects ; physiology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo examine the relaxant effects of hydro-ethanolic, macerated aqueous (MA) and lipidfree macerated aqueous (LFMA) extract of Tymus vulgaris on tracheal chains of guinea pigs.

METHODSThe relaxant effects of five cumulative concentrations of each extract (0.4, 0.8, 1.2, 1.6 and 2.0 g/100 mL) were compared with saline as negative control and five cumulative concentrations of theophylline (0.1, 0.2, 0.4, 0.6 and 0.8 mmol/L) on precontracted tracheal smooth muscle of guinea pig with 60 mmol/L KCl (group 1) and 10 µmol/L methacholine (group 2, n=6 for each group).

RESULTSIn group 1 all concentrations of theophylline, three higher concentrations of hydro-ethanolic, two concentrations of LFMA and last concentration of MA extracts showed significant relaxant effects compared with that of saline (P<0.05 or P<0.01). Two lower concentrations of LFMA and all concentrations of MA except higher one caused contraction compared with saline (P<0.05 or 0.01). In group 2 experiments, all concentrations of theophylline, hydro-ethanolic, MA and LFMA extracts showed significant relaxant effects compared to that of saline (P<0.05 or P<0.01). In both groups, the relaxant effect of all concentrations of hydro-ethanolic extract were significantly higher than most concentrations of others (P<0.05 or P<0.01). The relaxant effect of different concentrations of three extracts were significantly greater in group 2 compared with group 1 experiments (all P<0.01). There were significantly positive correlations between the relaxant effects and concentrations for theophylline and all extracts in both groups (P<0.05 or P<0.01).

CONCLUSIONHydro-ethanolic extract has a potent weaker relaxant effect for other extracts from Tymus vulgaris on tracheal chains of guinea pigs.

Animals ; Bronchodilator Agents ; pharmacology ; Guinea Pigs ; In Vitro Techniques ; Lamiaceae ; chemistry ; Lipids ; chemistry ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Plant Extracts ; pharmacology ; Solubility ; Solutions ; Theophylline ; Trachea ; physiology ; Water ; chemistry

OBJECTIVETo evaluate the effect of Nigella sativa (NS) extract on memory performance and its possible mechanisms in scopolamine (Sco)-induced spatial memory impairment model using Morris water maze test.

METHODSThirty-two male Wistar rats were randomly divided into four groups. The control group received saline instead of both NS extract and Sco. The Sco group was treated by saline for two weeks, and was injected by Sco (2 mg/kg, intraperitoneally) 30 min before each trail in Morris water maze test. Sco+NS 200 and Sco+NS 400 groups were daily treated by 200 or 400 mg/kg of NS (intraperitoneally) for two weeks, respectively, and were finally injected by Sco 30 min before Morris water maze test. The brains of animals were removed to determine the acetylcholinesterase (AChE) activity and oxidative stress criteria in cortical tissues.

RESULTSTime latency and path length in the Sco group were significantly higher than in the control group (P<0.01), while the Sco+NS 400 group showed a significantly shorter traveled path length and time latency compared with the Sco group (P<0.01). AChE activity in the cortical tissues of the Sco group was significantly higher than the control group (P<0.01), while AChE activity in the Sco+NS 200 and Sco+NS 400 groups was lower than the Sco group (P<0.01). Following Sco administration, malondialdehyde (MDA) concentrations were increased (P<0.01) in comparison with the control group, while cortical total thiol content decreased (P<0.01). Pretreatment with extracts caused a significant elevation in cortical total thiol content (P<0.01) and reduction in cortical MDA concentration (P<0.01) compared with the Sco group.

CONCLUSIONSHydro-alcoholic extract of NS prevents Sco-induced spatial memory deficits and decreases the AChE activity as well as oxidative stress of brain tissues in rats. Our results support the traditional belief about the beneficial effects of NS in nervous system. Moreover, further investigations are needed for better understanding of this protective effect.

Acetylcholinesterase ; metabolism ; Animals ; Ethanol ; chemistry ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory Disorders ; drug therapy ; physiopathology ; Nigella sativa ; chemistry ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Reaction Time ; drug effects ; Scopolamine Hydrobromide ; Spatial Memory ; drug effects ; Sulfhydryl Compounds ; metabolism ; Water ; chemistry

OBJECTIVETo study the effect of aqueous extract of several kinds of herbs on human platelet aggregation and expression of P-selectin in vitro.

METHODSBlood was collected from volunteers. Effects of the prepared water extracts of herbs on platelet aggregation were monitored on a Packs-4 aggregometer. The fluorescence intensity of water extracts of Caulis Spatholobi, Flos Carthami and Rhizoma Curcumae on the expression of P-selectin in human platelets of healthy persons was measured with flow cytometry.

RESULTSOut of several herbs investigated, Flos Carthami and Rhizoma Curcumae potently inhibited platelet aggregation after incubation with platelet-rich plasma (PRP) for 15 min. Caulis Spatholobi Flos Carthami and Rhizoma Curcumae inhibited adenosine-5'-diphosphate (ADP) or platelet activating factor (PAF)-induced platelet aggregation in PRP in a dose-dependent manner. In contrast to Flos Carthami and Rhizoma Curcumae, Caulis Spatholobi could not inhibit thrombin-induced platelet aggregation. Despite its inability to inhibit thrombin-induced platelet aggregation in PRP, Caulis Spatholobi had a greater anti-aggregating activity in PRP induced by ADP or PAF. Caulis Spatholobi and Flos Carthami showed significant inhibitory effects on the expression of P-selectin.

CONCLUSIONSCaulis Spatholobi, Flos Carthami and Rhizoma Curcumae have potent anti-platelet properties, and their inhibitory actions are mediated via different mechanisms. Caulis Spatholobi inhibited ADP-induced platelet aggregation but not by thrombin, indicating that its mechanism of action might be independent of the thromboxane pathway. The effect of Caulis Spatholobi and Flos Carthami were associated with suppressing the expression of P-selectin.

Adult ; Blood Platelets ; drug effects ; metabolism ; Curcuma ; chemistry ; Fabaceae ; chemistry ; Humans ; P-Selectin ; metabolism ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Function Tests ; Water ; chemistry ; Young Adult