Determination of Main Compositions in Phyllanthus Urinaria and its Effects on Cyp450 in Rats

2020 ◽  
Vol 16 (5) ◽  
pp. 520-528
Author(s):  
Zhennan Zhang ◽  
Zhe Sun ◽  
Yaozhen Ye ◽  
Xianqin Wang
Keyword(s):  
Dose Group ◽  
Chemical Constituents ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Chemical Compositions ◽  
Extract Solution ◽  
Phyllanthus Urinaria ◽  
Cyp450 Enzyme

<P>Background: Phyllanthus urinaria, a traditional herbal medicine, has aroused widespread concern at home and abroad. However, there are few studies on the effects of Phyllanthus urinaria on CYP450. Therefore, this study aims to explore the main chemical compositions of Phyllanthus urinaria and its effect on the activity of CYP450 enzyme in rats. </P><P> Methods: Acetonitrile and 0.1% Trifluoroacetic Acid (TFA) were used as mobile phase, along with the application of gradient elution to simultaneously determine the main chemical constituents in Phyllanthus urinaria by HPLC (r2>0.999). Sprague-Dawley (SD) rats, randomly divided into control group, low-dose group and high-dose group, were treated with normal saline and different doses of Phyllanthus urinaria extract solution, respectively. Additionally, the rats were given intragastric administration of cocktail probe (specific substrates of CYP450 isoenzyme) at 15th day; the plasma was collected by tail vein at various times. Furthermore, the UPLC-MS/MS method (r2>0.99) was used to detect the probe concentration, along with the evaluation of the activity of CYP450 enzyme according to the pharmacokinetic parameters of the probe. </P><P> Results: Gallic acid, 3, 4-dihydroxybenzoic acid, caffeic acid, corilagin and ellagic acid were found in the Phyllanthus urinaria extract solution by HPLC. Compared with the control group, the metabolism of bupropion, metoprolol, midazolam and tolbutamide slowed down significantly in the Phyllanthus urinaria group, with no significant metabolic changes in phenacetin. </P><P> Conclusion: Phyllanthus urinaria could induce activity of CYP2D6, CYP2B1, CYP3A4 and CYP2C9, without exerting a significant effect on CYP1A2.</P>

scholarly journals Hypoglycemic Properties of Oxovanadium (IV) Coordination Compounds with Carboxymethyl-Carrageenan and Carboxymethyl-Chitosan in Alloxan-Induced Diabetic Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Hongyu Zhang ◽  
Yuetao Yi ◽  
Dawei Feng ◽  
Yipeng Wang ◽  
Song Qin
Keyword(s):  
Dose Group ◽  
Positive Control ◽  
Carboxymethyl Chitosan ◽  
High Dose Group ◽  
Control Group ◽  
Oral Glucose ◽  
High Dose ◽  
Intragastric Administration ◽  
Diabetic Mice ◽  
Model Control

In order to avoid low absorption, incorporation, and undesirable side effects of inorganic oxovanadium compounds, the antidiabetic activities of organic oxovanadium (IV) compounds in alloxan-induced diabetic mice were investigated. Vanadyl carboxymethyl carrageenan (VOCCA) and vanadyl carboxymethyl chitosan (VOCCH) were synthesized and administrated through intragastric administration in different doses for 20 days in alloxan-induced diabetic mice. Glibenclamide was administrated as the positive control. Our results showed that low-dose group, middle-dose group, and high-dose group of VOCCA and VOCCH could significantly reduce the levels of blood glucose (P<0.05) compared with untreated group, but not in normal mice. Besides, high-dose groups of VOCCA and VOCCH exhibited more significant hypoglycemic activities (P<0.01). After treated with VOCCH, the oral glucose tolerance of high-dose group of VOCCH was improved compared with model control group (P<0.05).

scholarly journals Study on the Mechanism of Shugan Xiaozhi Fang on Cells with Non-alcoholic Fatty Liver Disease

2019 ◽  
Vol 17 (1) ◽  
pp. 1328-1338
Author(s):  
Yufeng Xing ◽  
Chuantao Zhang ◽  
Fenfen Zhai ◽  
Tianran Zhou ◽  
Xiang Cui ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Dose Group ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Alcoholic Fatty Liver ◽  
Oil Red O Staining ◽  
Alcoholic Fatty Liver Disease ◽  
Oil Red O

AbstractCells with non-alcoholic fatty liver disease (NAFLD) were studied to determine the mechanism of liver deficiency via the AdipoR2-PPARa pathway. NAFLD cells were randomly divided into a normal control group, blank control group, model group, low dose group, medium dose group, and high dose group. The NAFLD models were established by incubating the cells with linoleic acid (LA) and palmitic acid (PA) (2:1) for 24 h. The test groups were incubated with different doses of Shugan Xiaozhi Fang extract. The pathological changes in cells that accumulated lipids were detected by Oil Red O staining. Malondialdehyde (MDA) and triglyceride (TG) levels were measured. The apoptosis of cells was evaluated by flow cytometry. The levels of AdipoR2, PPARa, CD36, acyl-CoA mRNA, and protein were confirmed by RT- PCR and Western blot. The results of the Oil Red O staining demonstrated that the NAFLD cell model was successfully established. Compared with the model group, the levels of TG and MDA in the groups that received low, medium, and high doses of Shugan Xiaozhi were significantly lower (P<0.01), and a dose effect was evident. In addition, the expression of AdipoR2, PPARa, CD36, acyl-CoA protein, and mRNA in the Shugan Xiaozhi-treated groups was upregulated. Furthermore, the levels of AdipoR2, PPAR, CD36, acyl-CoA protein, and mRNA in all drug treatment groups that were extracted from L-O2 normal human hepatocytes were significantly upregulated (P<0.01). Moreover, the factor pattern of HepG2 human liver carcinoma cells was similar to that of L-O2. The levels of AdipoR, CD36, acyl-CoA, and AdipoR mRNA in the HepG2 low group were increased (P<0.05). AdipoR, PPAR, CD36, and acyl-CoA protein levels and AdipoR mRNA expression were significantly increased in the intermediate dose group and high dose group (P<0.01). Shugan Xiaozhi Fang attenuates hepatic lipid deposition in NAFLD induced by incubating with LA and PA for 24 h, which is associated with the activation of the AdipoR2-PPARα pathway.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

scholarly journals Effect of Natural Chinese Herbal Supplements (TCMF4) on Lactation Performance and Serum Biomarkers in Peripartal Dairy Cows

2022 ◽  
Vol 8 ◽  
Author(s):  
Yizhe Cui ◽  
Zhuorui Shan ◽  
Lintong Hou ◽  
Qiuju Wang ◽  
Juan J. Loor ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Milk Production ◽  
Total Protein ◽  
Dose Group ◽  
Production Performance ◽  
High Dose Group ◽  
Holstein Cows ◽  
Control Group ◽  
High Dose ◽  
Lactation Performance

This study examined the effect of mixed medicinal herbs from China in the ground form on milk yield and various blood metabolites before and after parturition in Holstein cows. Crushed Agastache rugosus, Scutellaria barbata, Pericarpium citri reticulate, and Radix glycyrrhizae were used to develop TCMF4. Thirty-two Chinese Holstein cows were randomly divided into a control group or groups receiving 0.1, 0.3, or 0.5 kg TCMF4/cow/d from −7 through 21 d relative to parturition. Blood samples for serum isolation were collected at −7, −1, 1, 7, 14, and 21 d relative to parturition and used to measure glucose, β-hydroxybutyric acid (BHBA), total protein, albumin, globulin, and alkaline phosphatase. Milk production was recorded daily for the first 21 d postpartum, and composition was analyzed at 7, 14, and 21 d. Data were analyzed using a one-way analysis of variance (ANOVA) for multiple comparisons. The average milk production during the first 21-d postpartum was 28.7 ± 6.9, 27.2 ± 7.1, 31.2 ± 6.8, and 38.5 ± 6.1 kg/d for control group and groups receiving 0.1, 0.3, or 0.5 kg TCMF4. Thus, average daily milk production increased between 9 to 34% by supplementation with TCMF4 compared with the control group. Compared with the control group, in the middle dose group, milk concentrations of lactose and total protein decreased by 21 and 19%, respectively, at d 7 around parturition, while total solids increased by 23% at d 21 in the high-dose group. Furthermore, compared with the control group, serum BHBA decreased by 50 and 20% at d −1 and 21 around parturition in the high-dose group. Overall, TCMF4 supplementation improved dry matter intake (DMI) and milk production of dairy cows during the periparturient period without adverse effects on liver function, and plasma BHBA concentrations of dairy cows tended to decrease when dietary TCMF4 increased, which suggested that TCMF4 might be used as potential additives in dairy cows to improve production performance.

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

scholarly journals Effect of Astragalus membranaceus Oral Solution on Lifespan and Learning and Memory Ability of Honey Bees

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tao Hong ◽  
Long-Xue Li ◽  
Xiao-ping Han ◽  
Jing-liang Shi ◽  
Cai-yun Dan ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Honey Bees ◽  
Dose Group ◽  
Low Dose ◽  
Oral Solution ◽  
Astragalus Membranaceus ◽  
Control Group ◽  
High Dose ◽  
The Mean ◽  
And Control

In this study, the effects of Astragalus membranaceus oral solution on lifespan and learning and memory abilities of honey bees were evaluated. Two groups of bees were fed with sucrose syrup (50%) containing low dose (1.33%) and high dose (13.3%) of A. membranaceus oral solution, respectively. The proboscis extension response (PER) analysis was applied to examine the learning and memory capabilities of bees. Two genes related to memory formation in honey bees were determined by real-time PCR. High dose (13.3%) of A. membranaceus significantly decreased the mean lifespan of bees compared to the bees fed with low dose (1.33%) and control bees. No significant differences in lifespan of bees were found between low-dose-fed bees and control bees. The results of PER experiments showed apparent improvement in the memorizing ability of the high-dose group (in comparison with the control group). Moreover, the relative expression levels of Nmdar1 in the low-dose group and control group were significantly lower than those in the high-dose group. It is preliminarily concluded that A. membranaceus has an adverse effect on the mean lifespan of honey bees but might be helpful in strengthening memories.

scholarly journals The effects of intramuscular administration of scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled trial

2020 ◽  
Vol 10 ◽  
pp. 204512532093855
Author(s):  
Jingjing Zhou ◽  
Jian Yang ◽  
Xuequan Zhu ◽  
Tarek Zghoul ◽  
Lei Feng ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Dose Group ◽  
Response Rate ◽  
Secondary Outcome ◽  
Control Group ◽  
Placebo Control ◽  
High Dose ◽  
Major Depressive ◽  
Double Blind

Introduction: Major depressive disorder (MDD) is a common affective disorder. Currently established pharmacotherapies lack rapid clinical response, thereby limiting their ability to bring instant relief to patients. A series of clinical trials has demonstrated the antidepressant effects of scopolamine, yet few have studied the effects of add-on scopolamine to currently available antidepressants. It is not known whether conventional antidepressant treatment with a 3-day scopolamine injection could speed up oral antidepressant efficacy. The main focus of this study is to detect the capacity of the rapid-onset efficacy of such a treatment option. Methods and analysis: This study consisted of a single-centre, double-blind, three-arm randomized trial with a 4-week follow-up period. Sixty-six participants meeting entry criteria were randomly allocated to three treatment groups: a high-dose group, a low-dose group and a placebo control group. Psychiatric rating scales were administered at baseline and seven viewing points following the administration of intramuscular injections. The primary outcome measure was length of time from randomization (baseline) to early improvement. Results: Both primary and secondary outcome measures consistently showed no differences among the three groups. The cumulative response rate and the remission rate were 72.7% (48/66) and 47.0% (31/66). Intramuscular scopolamine treatment was relatively well tolerated. Two subjects with high-dose injections dropped out because of a drug-related side effect. Conclusion: Contrary to our prediction, we found that, compared to placebo (0.9% saline i.m.), scopolamine was not associated with a significantly faster antidepressant response rate. Trial registration: ClinicalTrials.gov, NCT03131050. Registered on 18 April 2017.

Pharmacokinetic Evaluation of anti-HIV Drug Interactions: Effect of Zidovudine on 2′-3′-Dideoxyinosine Kinetics in Monkeys

1993 ◽  
Vol 4 (3) ◽  
pp. 155-159 ◽  
Author(s):  
M. Qian ◽  
A. R. Swagler ◽  
M. Mehta ◽  
C.T. Vishwanathan ◽  
J. M. Gallo
Keyword(s):  
Dose Group ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Combination Regimen ◽  
Time Profiles ◽  
Elimination Half ◽  
Constant Rate ◽  
Rate Infusion

The current investigation was conducted to determine if zidovudine (AZT) altered the pharmacokinetics of dideoxyinosine (ddl) in non-hurnan primates, an appropriate animal model for AZT and ddl pharmacokinetics in human. Each of nine animals received 20 mg kg−1 of ddl intravenously in the absence and presence of two different dosage regimens of AZT. For each combination regimen, AZT was administered as a combined i.v. bolus-constant rate infusion regimen for 30 min that produced AZT plasma concentrations of about 4 μg ml−1 in six animals (low dose group) and 11 μg ml−1 in three others (high dose group). Serial blood samples were collected, and pharmacokinetic parameters for ddl were calculated based on plasma ddl concentrations measured by HPLC techniques. The pharmacokinetics of ddl given alone in the first phase of the low ( n = 6) and high ( n = 6) dose AZT groups, resulted in a mean elimination half-life 1.54 and 1.9h, a mean total clearance of 0.62 and 0.731 h−1 kg−1, and a mean steady state volume of distribution of 1.02 and 0.891 kg−1, respectively. Following combined ddl and AZT administrations, in both the low and high dose AZT groups, plasma concentration-time profiles of ddl were similar for each monkey, and no statistical differences were observed in the pharmacokinetic parameters compared to those obtained when ddl was given alone. The fact that AZT does not alter the pharmacokinetics of ddl at the range of AZT dose studied provides a basis for rational dosage design for combined ddl and AZT treatments in HIV infection.

scholarly journals The Effects of Formaldehyde on Cytochrome P450 Isoform Activity in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Min Xu ◽  
Huaqiao Tang ◽  
Qian Rong ◽  
Yuanli Zhang ◽  
Yinglun Li ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
High Dose ◽  
Blood Samples ◽  
Time Points ◽  
Indoor Pollutant ◽  
Carcinogenic Effects

Formaldehyde (FA) is an occupational and indoor pollutant. Long-term exposure to FA can irritate the respiratory mucosa, with potential carcinogenic effects on the airways. The effects of acute FA poisoning on the activities of CYP450 isoforms CYP1A2, CYP2C11, CYP2E1, and CYP3A2 were assessed by determining changes in the pharmacokinetic parameters of the probe drugs phenacetin, tolbutamide, chlorzoxazone, and testosterone, respectively. Rats were randomly divided into three groups: control, low FA dose (exposure to 110 ppm for 2 h for 3 days), and high FA dose (exposure to 220 ppm for 2 h for 3 days). A mixture of the four probe drugs was injected into rats and blood samples were taken at a series of time points. Plasma concentrations of the probe drugs were measured by HPLC. The pharmacokinetic parameters t1/2, AUC(0-t), and Cmax of tolbutamide, chlorzoxazone, and testosterone increased significantly in the high dose versus control group (P<0.05), whereas the CL of chlorzoxazone and testosterone decreased significantly (P<0.05). However, t1/2, AUC(0-t), and Cmax of phenacetin decreased significantly (P<0.05), whereas the CL of phenacetin increased significantly (P<0.05) compared to controls. Thus, acute FA poisoning suppressed the activities of CYP2C11, CYP2E1, and CYP3A2 and induced the activity of CYP1A2 in rats. And the change of CYP450 activity caused by acute FA poisoning may be associated with FA potential carcinogenic effects on the airways.

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