Iranian Journal of Pharmaceutical Sciences

Gastric ulcers are one of the disorders that have a substantial effect on people's lives, and many treatment options come with side effects. This study was conducted to explore the protective and therapeutic properties of the essential oil of the Pistacia atlantica subspecies kurdica gum on gastric ulcers and gastropathy in rats and its acute oral toxicity and chemical analysis. The animals were administered the essential oil at different doses (12.5, 25, 50, and 100 mg/kg of body weight orally for 21 days) before receiving 85% ethanol. The stomachs were then removed for macroscopic and microscopic examination. Then, we used the Helicobacter pylori-induced rat model of gastropathy. The oral administration of the essential oil at doses of 12.5, 25, 50, and 100 mg/kg of body weight showed strong dose-dependent protection against stomach ulcers caused by ethanol, Additionally, the histological examination shows that the essential oil can prevent ethanol-caused stomach ulcers. Administration of the gum at a dose of 100 mg/kg for 21 days may have antibacterial effects on H. pylori. The findings showed that the essential oil of Pistacia atlantica gum, which contains a high quantity of alpha-pinene (>90%), can be beneficial in treating and preventing peptic ulcers in rat models caused by ethanol and H. pylori.

Rabies is a severe public health issue, particularly in areas with limited vaccination rates. Despite significant progress in comprehending the illness and creating preventative methods, rabies poses a significant public health problem. Glucocorticoids like dexamethasone effectively reduce inflammation and immunomodulation, but their effects on viral infections, with specific reference to the central nervous system (CNS), are complex and unclear. This study focuses on the apoptosis of brain cells in NMRI (Naval Medical Research Institute) mice infected with a viral infection. Infected mice were randomly assigned to four groups (n=10 per group): a control group, a negative control group treated with dexamethasone, an untreated positive control group containing viral components, and a test group expressing viral components and treated with dexamethasone. FAT results showed that the virus components were present in the brain tissue of NMRI mice; intense positive staining was observed. AKT, BAX, and BCL2 expression were significantly lowered in rat brain tissue compared to untreated mice (p<0.05). This study demonstrates the significant change effected by dexamethasone in the pathway of brain cell death in mouse brain tissue. The findings of this study could have significant implications for the risk-benefit ratio of dexamethasone therapy in viral CNS infections and guide possibly more effective and safer treatment strategies in such conditions.

Cuminum cyminum is a famous spice used worldwide for imparting taste to diverse food provisions, culinary and medicinal purposes, and also for appetizing purposes due to its special aromatic effect. This research work aims to estimate the yield of essential oil (EO), chemical composition, antioxidant and antimicrobial activity of Cuminum cyminum  EOs extracted by conventional methods Hydrodistillation (HD) and Steam distillation (SD) towards advanced method Superheated steam distillation (SHSD). SHSD noticed the maximum EO yield compared to the HD and SD methods. Gas chromatography-mass spectrometry (GC-MS) analysis illustrated that Cumin aldehyde (51.87-23.54%) and 3-caren-10-ol (15.34-12.15%) were the most abundant compounds of Cuminum cyminum  EOs. Hydrogen peroxide scavenging, ferric-reducing power assay, and DPPH free radical scavenging assay were used to evaluate the antioxidant potential. Results revealed that SHSD EO displayed the highest antioxidant potential compared to HD and SD EOs. The antimicrobial activity was determined using the resazurin microtiter plates test, microdilution broth experiment, and disc diffusion tests contradicting food pathogenic bacterial and fungal strains. SHSD EO observed the highest antimicrobial potential. The results indicated that SHSD is an efficient and excellent method for extracting EOs from Cuminum cyminum seeds, which also engage in biological activities.

A spectrophotometric method was derived to determine 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-[4-[(4-amino N-acetyl) phenoxy carbonyl methyl]-1-piperazinyl]-3-quinoline carboxylic acid (PPQC). This analytical method was simple, sensitive and low-cost. Based on forming of a chelate complex between PPQC and Fe(III), the developed method produced a yellow-colored complex that was detectable at 418 nm at room temperature. As per the International Conference on Harmonization guidelines, several analytical parameters for the suggested method were verified. With a correlation coefficient of 0.9998 (n=6) and a molar extinction coefficient of 1.2967 × 10⁴ L mol^-1 cm^-1, the method was linear from 5 to 46 µg mL^-1. The limit of detection (LOD) and limit of quantitation (LOQ) for the described method were 0.69 µg mL^-1 and 2.09 µg mL^-1, respectively. It was carefully examined and optimized how different parameters affected the chelate complex reaction. The recoveries of PPQC from spiked blood samples were 98.40-100.40%. The developed method’s coefficient of variation (CV) was less than 2.07%. The method validation was determined in accuracy, precision, absolute recovery, freeze–thaw stability, bench-top stability and long-term stability. After oral administration of PPQC to Wistar albino rats, the method’s analytical recovery, sensitivity, and accuracy were adequate to characterize the pharmacokinetics study. Thus, pharmacokinetics data for pre-clinical research have been obtained efficiently through the assay method.

Antibacterial and free radical scavenging properties of Pilea symmeria, a traditional medicinal plant from Mizoram, India, have been examined in this study. Chloroform, ethanol, and aqueous were used to extract the plant components. Extracts were phytochemically analyzed qualitatively and quantitatively. The extracted sample were tested for their ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3- ethylbenzothiazoline-6-sulfonic acid) ABTS, and superoxide anion (O2^•(-)) radicals. An antibacterial susceptibility test was performed against the bacterial strain Escherichia. coli, Bacillus subtilis and Klebsiella pneumoniae using disc diffusion method. The broth microdilution method determined the minimum inhibitory concentration (MIC). Plating samples from a well of MIC and above concentrations on a new agar plate determined minimum bactericidal concentration (MBC). Various phytochemicals, including terpenoids, tannins, flavonoids, cardiac glycosides, steroids, alkaloids, saponins, and phlobatannins, were present in the various extracts of P. symmeria. Phytochemical analysis by LC-MS revealed the presence of 34 major compounds having various biological activities. The most potent radical scavenger was ethanol extract, which contains the highest overall phenolic and flavonoid content with the lowest IC50 value. The various extracts also suppressed the tested organisms' growth in a concentration-dependent manner. Therefore, our results suggested that P. symmeria extracts contain various phytochemicals with anti-radical and anti-bacterial activities and can potentially develop into novel phytomedicines.

Recurrent Aphthous Stomatitis (RAS) is a prevalent inflammatory disorder that affects the mouth and is defined by painful ulcers. The precise cause of the condition is still unknown, and the major approach to treatment is mainly centered around managing the symptoms. Triamcinolone acetonide (TA) is a commonly used medication for several conditions. However, due to its potential benefits, there is growing interest in exploring novel drug delivery systems, such as medicated chewing gum (MCG). This study introduces a novel MCG formulation containing TA (T-MCG). We investigated its in vitro drug release and content uniformity before conducting a clinical trial comparing the efficacy of T-MCG versus placebo in patients with RAS. The T-MCG formulation exhibited a sustained release of TA for 120 minutes. The clinical findings demonstrated a notable decrease in the ulcer's size and the mean wound healing period. The results suggest that T-MCG not only improves the effectiveness of TA treatment by releasing the drug over a longer period and allowing it to stay in the mouth longer but also increases patient adherence due to its pleasant composition.

Sodium phenylbutyrate (SPB) and taurursodiol (TRS) are commonly used in combination therapy to treat amyotrophic lateral sclerosis, popularly known as Lou Gehrig's disease. Using Ultra-Performance Liquid Chromatography, a stability-indicating analytical approach was designed and validated to evaluate SPB and TRS in bulk and dosage form simultaneously. Acquity UPLC BEH Shield RP-18 column (50 x 1.0 mm, 1.7µm) was used for the chromatographic separation. Next, a mobile phase was added at a 0.5 ml/min flow rate. The mobile phase included acetonitrile and 0.1% perchloric acid (20:80) v/v. Analytes were found at a wavelength of 287 nm with a photodiode array detector. An autosampler injected a five μl sample into the column, which was kept at 25 ^o C. SPB and TRS eluted values were 0.522 min and 1.311 min, respectively. For SPB and TRS, linearity was determined within the range of 75–450 μg/ml and 25–150 μg/ml, respectively. The method's robustness was evaluated by purposefully changing parameters like flow rate, detector wavelength, and column temperature. Additionally, research on forced degradation in the presence of different stress conditions, such as heat, peroxide, acid, and ultraviolet light, showed that the approach could identify stable materials. In conclusion, it was found that the developed analytical method for simultaneously determining SPB and TRS in bulk and their formulation was more precise, reliable, and specific.

Achieving and maintaining optimal tacrolimus trough levels for immunosuppression is challenging in kidney transplant patients due to its narrow therapeutic index. Ketoconazole is known for inhibiting the drug efflux activity of P-glycoprotein and CYP3A enzymes, which are involved in tacrolimus pharmacokinetics. Therefore, there is a need to investigate tacrolimus–ketoconazole coadministration. The study aims to assess the effect and safety of tacrolimus-ketoconazole coadministration in renal transplant recipients. Ethical approval was obtained from the Institutional Human Ethics Committee (IHEC/2023/038) to conduct an ambispective observational study on 14 renal transplant recipients. Tacrolimus total daily dose (TDD) and trough levels were measured before and after initiating oral ketoconazole. The concentration/dose (C₀/D) ratio was calculated, followed by safety assessments, including blood counts and renal function tests. Statistical analyses employed paired t-tests, and the significance level was <0.05. Coadministration resulted in a significant 102.45% increase in tacrolimus trough levels (p<0.001) and a 2.19% reduction (p=0.33) in TDD. The C₀/D ratio showed a mean increase of 127.74%. Blood counts remained within normal ranges, but a significant decrease in sodium (p=0.01) and an increase in potassium (p=0.03) were observed within the normal range. Tacrolimus-ketoconazole co-administration in renal transplant recipients demonstrated a substantial elevation in tacrolimus trough levels, suggesting a potential strategy for achieving therapeutic concentrations without escalating tacrolimus doses. Despite significant changes in sodium and potassium, they remained within acceptable ranges, supporting the safety of this coadministration strategy.

Obesity, caused by an inequality between energy production and consumption, is characterized by lipid accumulation in adipose tissues. Currently, around 650 million adults and roughly 340 million children and adolescents (aged 5-19 years) are affected by obesity. This condition tends to be more common among women and older populations. It is imperative to develop uncomplicated therapeutic approaches to prevent obesity-related metabolic diseases in conjunction with lifestyle modifications. Forty-three rats were randomly divided into five groups: 1. normal diet (ND), 2. High-fat diet (HFD), 3. HFD + adenosine, 4. HFD + High-intensity interval training (HIIT) + adenosine, and 5. HFD + HIIT. Gene expression of CGI-58, HSL, and AMPK in subcutaneous adipose tissues and serum level of glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), free fatty acid (FFA), and lipid profile (Triglyceride (TG), Total cholesterol (TC), Low density lipoprotein (LDL), High density lipoprotein (HDL), and Very low density lipoprotein (VLDL)) were assessed. The rats were fed HFD-induced obesity for 13 weeks. Following, adenosine 0.2 mg/ml/kg and 0.4 mg/ml/kg, as well as HIIT, were administered over 12 weeks. CGI-58, HSL and AMPK gene expression showed significant expression in all groups. HFD+HIIT+adenosine, HFD+adenosine, and HFD+HIIT groups significantly increased all genes. Conversely, FFA and glucose serum levels were significantly reduced in intervention groups. Insulin had higher serum levels in ND, HFD + adenosine, and HFD+HIIT groups, and adenosine caused decreased glucose. Also, favorable effects of HIIT and adenosine on lipid profile were observed. HIIT and adenosine can affect lipid metabolism, improve insulin resistance, and increase lipolysis in adipose tissue. Furthermore, adenosine can boost the effect of HIIT on gene expression, triggering lipolysis to prevent obesity.