scholarly journals Antinociceptive Interaction and Pharmacokinetics of the Combination Treatments of Methyleugenol Plus Diclofenac or Ketorolac

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5106
Author(s):  
Héctor Isaac Rocha-González ◽  
María Elena Sánchez-Mendoza ◽  
Leticia Cruz-Antonio ◽  
Francisco Javier Flores-Murrieta ◽  
Xochilt Itzel Cornelio-Huerta ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Dependent Manner ◽  
Analgesic Drugs ◽  
Isobolographic Analysis ◽  
Combination Treatments ◽  
Significant Difference ◽  
Effective Doses ◽  
Inflammatory Drugs ◽  
Dose Dependent

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main types of drugs used to treat pain, they have several adverse effects, and such effects can be reduced by combining two analgesic drugs. The aim of this study was to evaluate the nociceptive activity of methyleugenol combined with either diclofenac or ketorolac, and determine certain parameters of pharmacokinetics. For the isobolographic analysis, the experimental effective dose 30 (ED30) was calculated for the drugs applied individually. With these effective doses, the peak plasma concentration (Cmax) was found and the other parameters of pharmacokinetics were established. Methyleugenol plus diclofenac and methyleugenol plus ketorolac decreased licking behavior in a dose-dependent manner in phase II, with an efficacy of 32.9 ± 9.3 and 39.8 ± 9.6%, respectively. According to the isobolographic analysis, the experimental and theoretical ED30 values were similar for methyleugenol plus diclofenac, suggesting an additive effect, but significantly different for methyleugenol plus ketorolac (3.6 ± 0.5 vs. 7.7 ± 0.6 mg/kg, respectively), indicating a probable synergistic interaction. Regarding pharmacokinetics, the only parameter showing a significant difference was Cmax for the methyleugenol plus diclofenac combination. Even with this difference, the combinations studied may be advantageous for treating inflammatory pain, especially for the combination methyleugenol plus ketorolac.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

Human MutT Homolog 1 (MTH1) Inhibitor Reduces the Biological Activity of Ovarian Carcinoma Cells

2022 ◽  
Vol 12 (5) ◽  
pp. 907-913
Author(s):  
Liyan Zhong ◽  
Yi Yi ◽  
Qian Liu ◽  
Yan Peng
Keyword(s):  
Biological Activity ◽  
Ovarian Carcinoma ◽  
Biological Activities ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
Ovarian Carcinoma Cells ◽  
Proliferative Rate ◽  
Skov3 Cells ◽  
Significant Difference ◽  
Dose Dependent

This study intends to discuss the mechanism of MTH1 inhibitor (TH588) in the biological activity of ovarian carcinoma cells. A2780 and SKOV-3 cells were treated with different concentrations of TH588 and assigned into AT group (control), BT group (8 μmol/L TH588), CT group (16 μmol/L), DT group (32 μmol/L), ET group (64 μmol/L) and FT group (128 μmol/L) followed by measuring level of Bcl-2 and Bax by Western blot and PCR, and cell biological activities by MTT, FCM and Transwell chamber assay. The cell proliferative rate was not affected in AT group, but was lower in other groups in a reverse dose-dependent manner. There was significant difference on apoptotic rate and cell invasion among groups with increased apoptosis and reduce invasion after TH588 treatment. FT group showed lowest expression of Bcl-2 and Bax compared to other groups. In conclusion, the biological activity of A2780/SKOV3 cells could be reduced by MTH1 inhibitor which was probably through regulation of Bax and Bcl-2 expression.

Voluntary running of defined distances reduces body adiposity and its associated inflammation in C57BL/6 mice fed a high-fat diet

2017 ◽  
Vol 42 (11) ◽  
pp. 1179-1184 ◽  
Author(s):  
Lin Yan ◽  
Sneha Sundaram ◽  
Forrest H. Nielsen
Keyword(s):  
High Fat Diet ◽  
Plasma Concentrations ◽  
Standard Diet ◽  
Dependent Manner ◽  
High Fat ◽  
Body Adiposity ◽  
Chemotactic Protein ◽  
Voluntary Running ◽  
Significant Difference ◽  
Dose Dependent

This study investigated the effect of voluntary running of defined distances on body adiposity in male C57BL/6 mice fed a high-fat diet. Mice were assigned to 6 groups and fed a standard AIN93G diet (sedentary) or a modified high-fat AIN93G diet (sedentary; unrestricted running; or 75%, 50%, or 25% of unrestricted running) for 12 weeks. The average running distance was 8.3, 6.3, 4.2, and 2.1 km/day for the unrestricted, 75%, 50%, and 25% of unrestricted runners, respectively. Body adiposity was 46% higher in sedentary mice when fed the high-fat diet instead of the standard diet. Running decreased adiposity in mice fed the high-fat diet in a dose-dependent manner but with no significant difference between sedentary mice and those running 2.1 km/day. In sedentary mice, the high-fat instead of the standard diet increased insulin resistance, hepatic triacylglycerides, and adipose and plasma concentrations of leptin and monocyte chemotactic protein-1 (MCP-1). Running reduced these variables in a dose-dependent manner. Adipose adiponectin was lowest in sedentary mice fed the high-fat diet; running raised adiponectin in both adipose tissue and plasma. Running 8.3 and 6.3 km/day had the greatest, but similar, effects on the aforementioned variables. Running 2.1 km/day did not affect these variables except, when compared with sedentariness, it significantly decreased MCP-1. The findings showed that running 6.3 kg/day was optimal for reducing adiposity and associated inflammation that was increased in mice by feeding a high-fat diet. The findings suggest that voluntary running of defined distances may counteract the obesogenic effects of a high-fat diet.

scholarly journals Anticonvulsant effects of nimodipine alone and combination with phenytoin on MES induced seizures

2018 ◽  
Vol 7 (6) ◽  
pp. 1160
Author(s):  
Raina Jain ◽  
Ashish Jain
Keyword(s):  
Synergistic Effect ◽  
Anticonvulsant Activity ◽  
Hind Limb ◽  
Channel Blockers ◽  
Dependent Manner ◽  
The Novel ◽  
Antiepileptic Activity ◽  
Effective Doses ◽  
Dose Dependent ◽  
Anticonvulsant Effects

Background: To evaluate the anticonvulsant activity of Nimodipine alone and in combination with Phenytoin, in MES induced seizures.Methods: The study was conducted in mice and MES seizure was induced by Techno electroconvulsometer. In first part of study, animals were treated with Nimodipine (20mg/kg i.p. and 40mg/kg i.p.) and Phenytoin (0.5 mg/100g i.p. and 1.0mg/100g i.p.), MES was induced and durations of various phases were noted. Duration of Tonic hind limb extension (THLE) was taken as index for antiepileptic activity. In second part, the animals were treated with combination of sub effective doses of Nimodipine (20mg/kg i.p.) and Phenytoin (0.5mg/100g i.p.), MES was induced and durations of various phases were noted.Results: Nimodipine produced significant antiepileptic activity, in dose dependent manner. Phenytoin produced significant antiepileptic effect in dose of 1.0mg/100g but failed to produce any such effect in dose of 0.5mg/100g, when administered alone. But when sub effective doses.Of Nimodipine and Phenytoin were combined, a synergistic effect was seen.Conclusions: Nimodipine possess significant antiepileptic activity, alone, as well as it potentiates the antiepileptic effect of Phenytoin, suggesting the novel application of already proven safe and efficacious calcium channel blockers.

scholarly journals Targeting study of HepG2 hepatoma cells in vitro by drug-loaded pectin-based nanoparticles

2019 ◽  
Author(s):  
Anil Shumroni ◽  
David Gupta
Keyword(s):  
Mtt Assay ◽  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Drug Loading ◽  
A549 Cells ◽  
Cell Uptake ◽  
Dependent Manner ◽  
Human Hepatoma Cell ◽  
Significant Difference ◽  
Dose Dependent

AbstractThe biodegradable and biodegradable natural polysaccharide has always been used as a drug delivery system, and has the following advantages: It can prolong the biological half life of the drug and reduce the side effects of the drug. This experiment aimed to prepare a 5-fluorouracil (5-FU) nanoparticle (P-5-FU) drug-loading system based on pectin, and explored a large number of pectin-based nano drug-loading systems. The galactose residue is a natural target that targets human hepatoma cell HepG2. MTT assay was used to determine the proliferation inhibition effect of drug-loaded pectin-based nanoparticles on HepG2 and A549 cells. MTT assay showed that P-5-FU inhibited the proliferation of HepG2 cells in a dose-dependent manner, and the effect was stronger than 5-FU. P-5-FU also inhibited the proliferation of A549 cells in a dose-dependent manner, but there was no significant difference compared with 5-FU. High performance liquid chromatography (HPLC) on two kinds of cells loaded with drug-loaded nanoparticles the uptake and targeting were measured. The results of cell uptake showed that the uptake of P-5-FU by HepG2 cells was significantly higher than that of 5-FU, but there was no significant difference in the uptake of P-5-FU and 5-FU by A549 cells. There was no significant difference in the uptake of P-5-FU and 5-FU between the two cells after the galactose-saturated ASGPR binding site. The results indicate that pectin-based nano drug-loaded particles can specifically target highly expressed cells.

In vitro anti-diabetic activity of Tribulus terrestrisL. fruits extracts

2019 ◽  
Vol 50 (4) ◽  
pp. 631-640
Author(s):  
Kholowd AlKhaldi ◽  
Manal Daghestani ◽  
Thanaa Al-Haddad
Keyword(s):  
Acetone Extract ◽  
Hexane Extract ◽  
Tribulus Terrestris ◽  
Dependent Manner ◽  
Inhibition Activity ◽  
Content Type ◽  
Significant Difference ◽  
Ethanol Extracts ◽  
Dose Dependent

Purpose The purpose of this paper is to evaluate the inhibition activity of Tribulus terrestris L. (T. terrestris) fruits extracts with solvents of increasing polarity against α-glucosidase and α-amylase, and to determine the inhibition mode of the most effective extract against both enzymes. Design/methodology/approach Hexane, acetone, ethanol and aqueous extracts of T. terrestris fruits were prepared using ultrasonic sequential extraction and analyzed for their α-amylase and α-glucosidase inhibitory activities by specific assay for each enzyme. The modes of inhibitions were detected using Lineweaver–Burk plots. Findings T. terrestris fruits extracts showed inhibition activity against α-glucosidase and α-amylase which was in the dose-dependent manner. Hexane extract had the highest α-glucosidase inhibition activity (IC50 = 27.28 μg/ml, p = 0.003), followed by acetone and ethanol extracts (IC50 = 60.58 μg/ml and IC50 = 84.21 μg/ml, respectively). The inhibition mode of hexane extract was noncompetitive. While acetone extract showed the highest inhibition activity against α-amylase (IC50 = 6.18 mg/ml, p = 0.002), hexane and ethanol extracts showed no significant difference (IC50 = 13.04 mg/ml and IC50 = 14.20 mg/ml, respectively, p = 0.09). The inhibition mode of acetone extract was competitive. Originality/value T. terrestris fruits extracts had strong inhibition activity against α-glucosidase and α-amylase, and they can be used as a promising anti-diabetic agent.

scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PENTOXIFYLLINE USING NATURAL MUCOADHESIVE POLYMERS

2019 ◽  
pp. 153-157
Author(s):  
GNANASEKARAN JOHN SELVARAJ ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Drug Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Fold Increase ◽  
Ocimum Basilicum ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Time Curve ◽  
Significant Difference

Objective: The present study was aimed to alter the pharmacokinetic parameters of the drug pentoxifylline using a novel natural mucoadhesive polymer from two different plants, Manilkara zapotta Linn and Ocimum basilicum Linn. Methods: The polymer was isolated and six batches of mucoadhesive tablets of pentoxifylline was formulated with 3 different concentrations of each polymer. The best formulation from each of the polymer was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as such as Cmax, tmax, AUC, AUMC, λz, t1/2, and MRT were determined. Results: The plasma drug concentration vs time curve shows the extended-release of pentoxifylline when compared with the conventional marketed formulation. The results show that there is no change in the peak plasma concentration, but the significant difference was observed in t½, which showed approximately 2.5 fold increase from 2.44 to 6.87 h and the AUC showed five-fold increase from 22.40 to 117.19 μg*h/ml, and other pharmacokinetic parameters, when compared with the marketed formulation. Conclusion: The isolated polymer from the plants Manilkara zapotta Linn. and Ocimum basilicum Linn can be used as a carrier for developing mucoadhesive formulations and it alter the pharmacokinetic of pentoxifylline positively.

Synergistic Antinociceptive Effects of Ketamine and Morphine in the Orofacial Capsaicin Test in the Rat

2003 ◽  
Vol 99 (4) ◽  
pp. 969-975 ◽  
Author(s):  
Pedro Alvarez ◽  
Gloria Saavedra ◽  
Alejandro Hernández ◽  
Carlos Paeile ◽  
Teresa Pelissier
Keyword(s):  
Animal Behavior ◽  
Orofacial Pain ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Nociceptive Behavior ◽  
Isobolographic Analysis ◽  
Aspartate Receptor ◽  
Sprague Dawley Rats ◽  
Antinociceptive Effects ◽  
Dose Dependent

Background The clinical efficacy of the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine for treating orofacial pain has already been reported. Side effects related to psychotomimetic disturbances, however, limit ketamine use as an analgesic. Theoretically, this limitation could be minimized by using low doses of ketamine in combination with other analgesics. In the present study, the potential synergistic antinociceptive interaction between ketamine and morphine in the orofacial capsaicin test in rats was investigated. Methods Male Sprague-Dawley rats were subcutaneously injected with solvent, ketamine, morphine, or combination of both drugs. Thirty minutes later, the orofacial capsaicin test was performed by injecting of 1.5 microg/25 microl of a capsaicin solution into the vibrissa pad. Animal behavior was recorded on videotape and analyzed off-line. The total time spent on rubbing-scratching nociceptive behavior during a period of 42 min was measured. Results Subcutaneously administered ketamine (0.4, 1.25, 4, 12.5 mg/kg), morphine (0.5, 1, 2, 4 mg/kg) and ketamine + morphine (0.20 + 0.12, 0.40 + 0.24, 0.80 + 0.49, 1.61 + 0.97, 3.21 + 1.94 mg/kg) reduced the rat facial rubbing-scratching behavior in a dose-dependent manner. Isobolographic analysis showed that the ketamine + morphine association inhibited the studied behavior in a superadditive manner. Conclusions These results indicate that ketamine and morphine have antinociceptive effects on the orofacial capsaicin test. Furthermore, their combination produces synergistic antinociception. It is therefore suggested that, used together, ketamine and morphine might be clinically efficient at lower doses than those currently used when administered separately. This could provide a useful strategy for the clinical management of orofacial pain.

scholarly journals Dose-Dependent Effect of Cordycepin on Viability, Proliferation, Cell Cycle, and Migration in Dental Pulp Stem Cells

2021 ◽  
Vol 11 (8) ◽  
pp. 718
Author(s):  
Nezar Boreak ◽  
Ahmed Alkahtani ◽  
Khalid Alzahrani ◽  
Amani Hassan Kenani ◽  
Wafa Hussain Faqehi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Growth Curve ◽  
Dental Pulp ◽  
Phase Cell ◽  
Ros Generation ◽  
Dependent Manner ◽  
Significant Difference ◽  
Dose Dependent

Objective: To examine the effect of Cordycepin on the viability, proliferation, and migratory properties of dental pulp-derived mesenchymal stem cells. Materials and methods: The pulp was derived from human premolar teeth extracted for orthodontic purposes after obtaining informed consent. The samples were transferred to the laboratory for processing. DPSCs were expanded and characterized using flow cytometry and differentiation to the bone, adipose, and cartilage cells was examined. MTT Assay was performed using various concentrations of Cordycepin. The growth curve was plotted for 13 days. Cell cycle analysis was performed by flow cytometry. Migratory ability was assessed by wound healing assay. ROS generation was detected by flow cytometry. Gene expression was quantified by RT-qPCR. Statistical analysis was performed. p < 0.05 was considered as significant and p < 0.01 was considered as highly significant (* p < 0.05, and ** p < 0.01). Results: DPSCs expressed characteristic MSC-specific markers and trilineage differentiation. Cordycepin at lower concentrations did not affect the viability of DPSCs. The growth curve of cells showed a dose-dependent increase in cell numbers till the maximum dose. DPSCs treated with 2.5 µM Cordycepin was found to have a reduced G1 phase cell percentage. DPSCs treated with 2.5 µM and 5 µM Cordycepin showed a significant decrease in G2 phase cells. No significant difference was observed for S phase cells. Cordycepin treatment affected the migratory ability in DPSCs in a concentration-dependent manner. Conclusion: Cordycepin can be used at therapeutic doses to maintain stem cells.

scholarly journals Cardioprotective effects of Citrullus lanatus rinds in male wistar rats

2020 ◽  
Vol 44 (1) ◽  
pp. 123-129
Author(s):  
O. G. Akintunde ◽  
E. S. Ajibola ◽  
S. A. V. Abakpa ◽  
B. O. Oluwo ◽  
J. O. Olukunle
Keyword(s):  
Risk Ratio ◽  
Wistar Rats ◽  
Citrullus Lanatus ◽  
Ethanol Extract ◽  
Cardiac Risk ◽  
Control Group ◽  
Dependent Manner ◽  
Significant Difference ◽  
Male Wistar Rats ◽  
Dose Dependent

Water melon, citrullus lanatus is a common edible fruit belongs to the family of cucumber (Cucurbitacea). The outer part of citrullus lanatus known as the rind is always discarded. This study investigated the effects of ethanol extract of citrullus lanatus rinds orally administered on some liver function enzymes, kidney function markers, cardiac risk ratio, and the atherogenic coefficient indices in male wistar rats. Twenty-five male Wistar albino rats were randomly distributed into five groups (I, II, III, IV and V) of five rats each received 0mg/kg, 100 mg/kg, 200mg/kg, 400mg/kg and 800mg/kg of ethanol extract of Citrullus lanatus rinds respectively for 35days. The result showed that the effects of ethanol extract of citrullus lanatus rinds was not significant difference (p > 0.05) in serum liver enzymes (Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase) in increasing dose dependent manner when compared with control group. There were no significant differences (p > 0.05) in serum levels of urea and creatinine with increasing dose of ethanol extract of Citrullus lanatus rinds in rats when compared with control group. The extract showed significantly higher (p< 0.05) values in the serum HDL, cholesterol but there were significant reduction (p< 0.05) in the serum total cholesterol, triglycerides, LDL, VLDL and non-HDL values in rats at higher doses of the extract when compared with control group. While it was observed that the cardiac risk ratio, the atherogenic coefficient and indices decreased significantly (p< 0.05) in rats at increasing doses of ethanol extract of Citrullus lanatus rinds when compared with control group. This may suggest a likely cardio-protective effects of ethanol extract of Citrullus lanatus rinds in increasing dose dependent manner in rats when compared with control group. In conclusion, it can be inferred that Citrullus lanatus rinds can be consumed by animals without detrimental effect.

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