Jundishapur Journal of Natural Pharmaceutical Products
Volume:11 Issue: 2, May 2016

Nepeta depauperata Benth is an endemic species and is extensively exploited as an anti-inflammatory agent in Iranian traditional medicine..
This study was designed to evaluate the antinociceptive activity of methanol extract of N. depauperata in male mice..
The anti-nociceptive activities of the extract were investigated by the formalin test and Hot plate test respectively. Comparisons between the groups were carried out using one-way analysis of variance (ANOVA), and post Hoc Tukey test..
N. depauperata extract showed anti-nociceptive effect. Doses of 50, 100 and 200 mg/kg reduced the paw flexing time in formalin test from the control (P This study revealed that the methanol extract of N.depauperata may minimize both the acute and chronic forms of nociception and may have potent role against inflammation..

Chronic kidney disease is a persistent disorder in kidney function. This is a progressive disorder characterized by arterial hypertension, glomerular hypertension, proteinuria and some other signs; controlling any of them can reduce the progression of chronic kidney disease. In chronic kidney disease, proteinuria is used as a measure for monitoring nephron injuries and its response to treatment. Angiotensin converting enzyme inhibitors and Angiotensin receptor blockers can reduce the progression of chronic kidney disease by inhibition of Renin-Angiotensin-Aldosterone system and reduction of glomerular pressure and controlling proteinuria. However, none of them can control plasma aldosterone level appropriately. Aldosterone produces Transforming growth factor-b (TGF-b), which induces proliferation of fibroblasts and glomerulosclerosis and accelerates chronic kidney disease. Aldosterone antagonist can increase useful effects of angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin receptor blockers (ARB) Drugs..
The study was designed to assess the effects of spironolactone as the aldosterone antagonist combined with ACEI or ARB drugs to reduce proteinuria in chronic kidney disease to prevent its progression..
Patients and This was a semi-experimental without control study. Eighty patients treated for at least two months with ACEI or ARB with uncontrolled proteinuria above 0.9g/dL were treated with 25mg/d spironolactone for two months. 24-hour urine protein and some other variables were measured at the beginning of the study, after two months treatment and one month after discontinuing the treatment..
Administration of 25 mg/d spironolactone combined with ACEI or ARB for two months led to mean reduction of 24 h-urine protein from 2796.1 to 1857.4. No hyperkalemia or change in glomerular filtration rate occurred. One month after discontinuation of spironolactone, proteinuria returned to baseline level. Persistence of reduction in proteinuria in patients receiving ARBs was more than those taking ACEIs..
Spironolactone combined with ACEIs or ARBs leads to reduction of proteinuria in chronic kidney disease and therefore reduction of progression of the disease..

Tetracyclines are antimicrobial agents that possess anti-inflammatory and matrix metalloproteinase (MMP) inhibitory effects. Tetracycline, doxycycline, and minocycline have shown different potencies in inhibiting various MMPs. MMPs are a conserved family of zinc-dependent endopeptidases, which are involved in various physiologic and pathologic conditions. MMP-9 is among the most important proteases involved in the development of cardiovascular disease, cancer, and inflammatory disease.
Considering the central role of MMP-9 in the above-mentioned diseases and the variable inhibitory potentials of routine tetracyclines, including tetracycline, doxycycline, and minocycline, this study measured the inhibitory effect of these routine tetracycline agents on MMP-9 activity obtained from U-937 cell cultures using the zymography method..
An MMP-9-rich culture medium of U-937 cells was used as the source of the enzyme. Serial dilutions of 5, 20, 100, 200, and 500 µM of each drug were placed in zymography incubation buffer. Gelatin zymography was run, and densitometry of the bands was performed using Image J software. The resulting data were used to draw dose-response curves using GraphPad Prism software..
Our results showed that tetracyclines inhibited MMP-9 activity with IC50 values of 40.0, 10.7, and 608.0 µM for tetracycline, minocycline, and doxycycline, respectively. Minocycline showed the highest potency in MMP-9 inhibition (P Our results suggest that tetracyclines dose-dependently inhibit MMP-9 activity, and among the common clinical tetracyclines, minocycline provides the most potent inhibition of excess MMP-9 activity and its consequences..

Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is widely used in the treatment of neurological disorders. However, its application carries the risk of adverse reactions, including reproductive toxicities. Grape seed is highly regarded for its pharmacological activities, specifically its antioxidant properties..
This study was designed to evaluate whether hydroalcoholic grape seed extract (GSE) could ameliorate FLX-evoked oxidative injuries in the mouse testis..
Thirty-two male mice were categorized into four groups of eight mice each. Two groups received FLX at a dose of 20 mg/kg per day over a period of six weeks by oral gavage. One of these groups received GSE at a dose of 100 mg/kg per day orally along with the FLX. An untreated control group and a GSE-only treated group were also included. Serum and testicular samples were collected 24 hours after the last treatment..
Biochemical analyses demonstrated that FLX caused significant decreases in testicular antioxidant capacity and serum testosterone concentrations, as well as lipid peroxidation elevations in testicular tissue. Morphometric and histopathological studies supported the biochemical findings. Concomitant administration of GSE with FLX markedly reduced testicular damage and significantly restored all of the mentioned markers to normal values..
The findings suggested that oxidative stress-mediated testicular damage, arising as a result of FLX administration in mice, could be reversed by GSE..

Pulmonary fibrosis is a deadly and destructive disease. Various chemicals, drugs, and environmental factors are responsible for pulmonary fibrosis. The disease can also be idiopathic. A number of inflammatory mediators and cytokines, such as interleukin-13 (IL-13), platelet‐derived growth factor (PDGF), and tumor necrosis factor α (TNF-α), play an important role in pulmonary fibrosis. Profibrotic cytokines accelerate the maturation and proliferation of fibroblasts, which ultimately increases the amount of collagen deposits in the alveolar cell wall. In contrast, the interferon-γ (INF-γ) cytokine has antifibrotic properties..
This study investigated and compared the inhibitory effects of quercetin hydrate with those of vitamin E (Vit E), a well-known antioxidant, on bleomycin (BLM)-induced pulmonary fibrosis in rats..
This study used Sprague-Dawley male rats, with a weight range of 200 - 250 g. The positive control group received a single-dose of BLM (7.5 IU/kg) through an intratracheal injection (positive control group). The negative control group received normal saline. The other groups were treated with different doses of quercetin hydrate (25, 50, and 75 mg/kg) or daily intraperitoneal injections of Vit E (10 mg/kg) for 1 week before and 3 weeks after a single dose of BLM via intratracheal administration. Four weeks later, bronchoalveolar lavage fluid (BALF) was collected for measurement of cytokines..
The administration of quercetin hydrate significantly reduced the concentration of IL-13, PDGF-β, and TNF-α and increased the concentrations of INF-γ in BALF..
According to the experimental results, quercetin hydrate reduced the concentration of inflammatory fibrotic factors, such as IL-13, PDGF-β, and TNF-α, and increased the level of the antifibrotic factor INF-γ, and the effects of quercetin hydrate appeared stronger than those of Vit E. In cases of exposure to fibrogenic factors, quercetin hydrate can be prescribed as a prophylactic agent for pulmonary fibrosis..

Nowadays, adsorption techniques are widely used to remove certain classes of pollutants from water..
The aim of this study was to remove ametryn from water solutions by natural zeolite nanoparticles from the Semnan region of Iran..
For this purpose zeolite nanoparticles were synthesized from natural zeolite using planetary ball-mill. The zeolite nanoparticles properties were verified by a particle size analyzer, XRD, XRF and TEM. To remove ametryn from water, the box-behnken design (BBD) of response surface methodology (RSM) was employed for simultaneous optimization of all parameters affecting the adsorption process. In this research, the studied parameters were pH (6 - 8), the amount of adsorbent (0.5 - 2 g) and temperature (25 - 45°C). Fifteen experimental runs were calculated using BBD for these three-levels three-factorial. To determine the effect of contact time (10 - 120 minutes) on the adsorption of ametryn under optimal conditions, seven runs were carried out. Reversed-phase HPLC-UV was used for ametryn determination, using an isocratic solvent delivery system (methanol: H2O, 60:40, pH = 4.6), flow-rate of 1.2 mL.min-1 and a UV wavelength of 228 nm..
The optimal conditions predicted by the model were pH 6, 2 g of adsorbent and 43.3°C temperature. Kinetic studies of the adsorption process specified the efficiency of the pseudo second-order kinetic model and showed that the equilibrium time was 45 minutes. The maximum percentage of ametryn removed was found to be 64.12% after 120 minutes. Regression analysis showed good fit of the experimental data and the correlation coefficient with determination (R) value of 0.9568. The adsorption isotherm fitted well with the Freundlich model..
The zeolite from Semnan, with low cost and abundant availability has a good potential to be used as an adsorbent for removal of ametryn from polluted water resources..

Phenanthroindolizidine alkaloids have been isolated from many species of Vincetoxicum. These alkaloids show promising anti-cancer activity and are a current topic of interest..
The inhibition of cell viability by different extracts of V. pumilum was measured in vitro in HL-60 and K562 human leukemic cancer cell lines and in freshly-isolated peripheral blood lymphocytes as a normal cell line..
Using resazurin staining, cell viability was measured. In addition, the presence of apoptotic cells was determined using propidium iodide (PI) staining of DNA fragments (sub-G1 peak). Employing western blot analysis, levels of Bax, Bcl-2, and PARP cleavage were measured..
The CH2Cl2 fraction of V. pumilum showed a potent dose-related inhibitory effect on cell viability. The CH2Cl2 fraction showed IC50 values of 8.3 and 12.5 µg/mL in the K562 and HL-60 cell lines, respectively. A sub-G1 peak in the flow cytometry histograms of treated cells induced by the CH2Cl2 fraction suggested an induction of apoptosis. Further, both the parent methanol extract and its CH2Cl2 sub-fraction increased the expression of the pro-apoptotic protein Bax and of cleaved PARP in the cells..
Collectively, the V. pumilum extracts showed remarkable cytotoxic activity and merit further investigation as anticancer agents..

In folk medicine, Satureja khuzestanica infusion is prescribed to use before the meals to treat muscle pains, indigestion, cramps, nausea, diarrhea, and infectious diseases, especially bladder infections and inflammations..
This study aimed to evaluate the antibacterial activity of S. khuzestanica essential oil against clinical isolates of E. coli from urinary tract infections..
The chemical composition of S. khuzestanica essential oil was determined by gas chromatography (GC) and mass spectrometer (GC-MS) analyses. The antibacterial activity of S. khuzestanica essential oil and carvacrol as its main component was evaluated by disk diffusion and microbroth dilution assays. Then, the synergistic activity of essential oil and carvacrol with gentamicin were determined by checkerboard microtiter assay..
The chemical analysis of S. khuzestanica essential oil revealed the presence of carvacrol (94.1%) as its main component. The inhibition zone diameters of S. khuzestanica essential oil and carvacrol dose-dependently increased. The Minimum Inhibitory Concentration (MIC) values of S. khuzestanica essential oil and carvacrol were 0.14 ± 0.08 µL/mL and 0.09 ± 0.04 µL/mL, respectively. S. khuzestanica essential oil and carvacrol showed bactericidal effects against clinical isolates of E. coli and synergistic effect with gentamicin (fractional inhibitory concentration index The antibacterial activity of S. khuzestanica essential oil is associated with carvacrol as its main component. The presence of other minor components in essential oil decreases the antibacterial activity of S. khuzestanica essential oil. Other clinical studies are essential to demonstrate the antibacterial effects of S. khuzestanica for treatment of urinary tract infection..

Hemiscorpius lepturus is one of the most dangerous scorpion species, endemic in Khuzestan province. Its venom has hemolytic activity and can lead to hemoglobinuria and death..
The aim of this study was to determine the effects of three different time treatment protocols on changes of coagulation parameters in sheep received Hemiscorpius lepturus venom..
Sixteen healthy male lambs were divided randomly into four groups. Hemiscorpius lepturus venom (0.01 mg/kg of body weight) injected subcutaneously. Blood samples were taken at 30 minutes before and 1, 6, 12, 24, 48, 96 and 168 hours after injection. The sheep of group 1 were treated only by injection of Hemiscorpius lepturus venom. In groups 2, 3 and 4 (Experimental groups), treatment of animals began at 1, 24 and 48 hours respectively after the venom injection. In addition to intravenous injection of 5 mL antivenom, supportive therapy was performed as well. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen were measured by commercial kit and platelet (PLT) count was performed by hematology analyzer. All results were statistically analyzed using two way repeated measures analysis of variance..
In the studied groups, the effect of time on PT and platelets counts was significant (P Hemiscorpius lepturus venom in sheep can cause severe changes in some of the coagulation factors. This should be considered as part of the pathogenesis of scorpion sting and seriously in the treatment protocol of scorpion sting victims..

Since ancient times, people have believed that certain foods or plants can affect learning and memory potency in humans. The consumption of food and beverages rich in flavonoid compounds has been proposed as a way to restrict the neuro-degeneration associated with many neurological complications and to reverse or prevent deterioration in cognitive performance..
In the present study, we have attempted to show the effect of red lentil extract (RLE), an edible legume with a high quantity of flavonoid, on retrieval and retention of memory in young and aged animals with the use of a passive avoidance apparatus..
For the experiments, after coding, the animals (128 total) were weighted and classified into different groups as follows: Group 1 as a control received only electric shock, while group 2 as a blank received electric shock plus normal saline (1 mL/100 g). The test groups (groups 3 and 4) received electric shock plus 400 and 800 mg/kg ip. RLE, respectively. The delay in leaving the platform of avoidance apparatus was measured for both retrieval and retention tests of memory in all groups, whereas experiments were conducted on two age levels - young and aged mice. In the test of retention after getting electric shock, RLE immediately, whereas in the test of retrieval 23.5 hours after the shock was administered..
Our findings demonstrated where applying both 400 mg/kg and 800 mg/kg of RLE significantly increased (the latency time increased about 2- and 3-fold respectively in comparison with the control group) retention and retrieval (at least 7-fold compared to the control group) of the memory of young (P It can be concluded that the devisable memory-enhancing effects of red lentil (lens culinaris) are due to the antioxidant activity of its flavonoid, tannins, and terpenoids..

The optimal protocol for administration of 5-fluorouracil (5-FU) in chemotherapy of colorectal cancer is unknown..
We compared treatment outcomes of short-time infusion of 5-FU (8-hour infusion) with 22-hour infusion, in chemotherapy management of colorectal cancer..
Patients and A retrospective study was conducted on colon cancer patients, who have been treated for at least 24 weeks with the FOLFOX regimen (5-FU, leucovorin, and oxaliplatin). Patients who had received infusion of 5-FU, either over 8 hours (5-FU 8h) or over 22 hours (5-FU 22h) were selected. The study endpoints were 3 and 5 years disease free survival and overall survival..
A total of 58 patients, in the 5-FU 8h, and 50 patients, in the 5-FU 22h groups, were studied. Based on the intention-to-treat analysis, there was a lower overall mortality (44% vs. 22.4%, P = 0.023) and lower overall relapse (46% vs. 18.9%, P = 0.004), as well as a higher 3 years disease free survival (81% vs. 58%, P = 0.011) in the 5-FU 8h, compared with 5-FU 22h group. The Log Rank test showed a difference between the two groups, for disease free survival (P = 0.008), as well as overall survival (P = 0.014), confirmed by Cox Regression analysis: hazard ratio [95% CI] = 0.365 [0.160 to 0.833] and 0.286 [0.100 to 0.817], respectively..
We found better outcomes for the colon cancer patients, who had received infusion of 5-FU 8h, compared with 5-FU 22h, in the FOLFOX chemotherapy. These findings should be tested in prospective clinical trials..

Paraquat (PQ) is a dipyridyl herbicide that sustains damage due to redox cycling. An important aspect of PQ toxicity is defined by its interactions with mitochondria..
This study was designed to evaluate the ability of naringenin (NG) to prevent PQ-induced mitochondrial dysfunction in rat-isolated liver mitochondria..
To determine the IC50 of PQ, the mitochondrial viability was specified using an MTT assay. Different concentrations of PQ (0, 2.5, 5, and 10 mM) were used, and the IC50 of PQ was assigned as approximately 2 mM. The suspensions of mitochondria at concentrations of 0.5 mg protein/ml were exposed to different concentrations of NG (100, 200, and 400 µM) for 30 minutes and were then treated with PQ at a concentration of IC50 (2 mM) for another 30 minutes at 37°C. The ameliorative effects of NG on PQ toxicity were evaluated by determining the glutathione (GSH) content, the damage to the mitochondrial membrane, the reactive oxygen species (ROS), and lipid peroxidation (LPO)..
The results reveal that PQ can decrease mitochondrial viability, deplete GSH content, increase mitochondrial ROS formation, and enhance LPO and mitochondrial membrane damage. The pretreatment of mitochondria with NG has the ability to reduce the toxic effects of PQ in isolated mitochondria..
The results suggest that the toxic effects of PQ that are mediated through NG and mitochondria can be reversed in a concentration-dependent manner. In addition, NG may prevent the oxidative stress induced by PQ. These results suggest that the administration of antioxidants such as NG may either restore the mitochondrial antioxidant status or improve mitochondrial functions, thus protecting mitochondria from oxidative damage..

Due to their optimal mechanical and biological properties, nanofibers have numerous medical applications. Electrospinning is one of the widely used techniques for generating drug-containing nanofibers..
The aim of this study was to assess the use of the electrospinning method to prepare fast-dissolving loratadine nanofibers..
Polyvinylpyrrolidone (PVP) nanofibers containing loratadine were produced using the electrospinning method. A full factorial design was employed to evaluate the formulations, including the four following variables: the concentration of PVP, the ratio of drug to polymer, the feed rate, and the voltage applied at two levels. After preparing the samples, assessments were carried out using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC). Dissolution tests and determination of the time of disappearance were also carried out. It was observed that reducing the concentration of polymer, reducing the feed rate, and increasing the voltage applied to the polymeric solution up to an adequate amount allowed the possibility of creating nanofibers with a smaller diameter and greater uniformity..
The results showed that the fiber diameter and the amount of loratadine affected the drug release and the disappearance time of nanofibers. The smaller the fiber diameter and drug amount, the faster the solubility and the release time of nanofibers..
It was concluded that electrospinning can be a suitable method for preparing fast-dissolving loratadine nanofibers..

Methotrexate is a folic acid antagonist that has been in clinical use for five decades. Its use in patients with brain tumors is primarily confined to primary central nervous system lymphoma (PCNSL), in which it is the cornerstone of chemotherapy..
A selective and sensitive high-performance liquid chromatography-electrospray ionization-mass spectrometry method was developed for the determination of methotrexate in human plasma..
Methotrexate was extracted from plasma with acetonitrile. The mobile phase consisted of acetonitrile/water/formic acid 74:25:1 (v/v/v), and 20 µL of the sample was chromatographically analyzed using a repacked ZORBAX-XDB-ODS C18 column (2.1 × 30 mm, 3.5 microns). The mode of mass spectrometry was selected-ion monitoring (SIM). The standard curve was linear (r = 0.998) over a concentration range of 0.1 - 100.0 ng/mL, and showed suitable accuracy and precision..
The limit of detection (LOD) was 0.05 ng/mL. The mean (± SD) Cmax, Tmax, AUC0-t, and AUC0–∞ values after administration of the test and reference formulations, respectively, were as follows: 13.94 (± 4.36) versus 13.49 (± 3.67) ng/mL, 2.63 (± 1.45) versus 2.75 (± 1.74) hours, 122.57 (± 54.34) versus 125.94 (± 53.09) ng/mL/h, and 140.74 (± 56.69) versus 155.80 (± 65.11) ng/mL/h. The mean (± SD) t1/2 was 5.32 (± 2.01) hours for the test formulation and 5.34 (± 2.13) hours for the reference formulation. No statistical differences were shown for Cmax or the area under the plasma concentration-time curve for the test and reference tablets. The calculated 90% confidence intervals, based on ANOVA analysis for the mean test/reference ratios of Cmax, AUC0-∞, and AUC0-th of methotrexate, were in the bioequivalence range (96% - 101%)..
The developed LC-MS method is quick, easy, stable, and precise for the partition, assignment, pharmacokinetic, and bioavailability evaluation of methotrexate in healthy Iranian adult male volunteers..