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.

This research investigates the glucose-lowering activity and wound-healing effect of the methanol extract of G. angustifolia root bark (MEGR) and ethyl acetate extract of G. angustifolia root bark (EAGR) on streptozotocin-induced diabetic rats. Qualitative phytochemical analysis of the extracts was conducted according to standard procedures. The glucose-lowering ability of the extracts was assayed by in vitro inhibition of α-amylase and α-glucosidase activities. The excisional wound was adopted to evaluate the tissue repair ability of the extracts on diabetic rats. The qualitative phytochemical test identified alkaloids, flavonoids, saponins, total phenols, terpenoids, tannins, and cardiac glycosides in EAGR. The MEGR contains all the aforementioned phytochemicals except tannins and terpenoids. Glucose lowering ability of the extracts studied in vitro shows that with a significantly lower (p < 0.05) IC₅₀ value (34.54 ± 1.31 µg/mL), EAGR has a higher ability to impair the activity of α–glucosidase compared to MEGR (54.03 ± 1.31 µg/mL). Furthermore, with IC₅₀ values of 119.59 ± 1.20 µg/mL and 128.13 ± 0.35 µg/mL for EAGR and MEGR, respectively, there is no significant difference (p > 0.05) in the ability of both extracts to impair α-amylase activity. On the 20^th day post-wounding, ointment formulation from the extracts improved the tissue repair process by promoting the wound contraction rate with a percentage of 81.09 ± 1.24 % and 79.92 ± 1.64 % for EAGR and MEGR treated groups, respectively. Furthermore, the total protein content of regenerating tissues was significantly improved (p < 0.05) in the groups treated with EAGR and MEGR, respectively (1.60 ± 0.12 mg/g and 1.57 ± 0.14 mg/g) compared to the diabetic control group (0.68±0.04 mg/g). The ointment formulation from the EAGR and MEGR significantly decreased the period of epithelialization (21.50 ± 0.50 days and 22.25 ± 0.85 days, respectively) compared to the diabetic control group (30.50 ± 0.50 days). The time taken for 50% wound closure was 11.72 days and 12.54 days for groups treated with EAGR and MEGR, respectively. This indicates a shorter time than the diabetic control group (21.24 days). In conclusion, this research indicates the glucose-lowering effect of MEGR and EAGR by impairing the activities of α-amylase and α-glucosidase. Furthermore, the extracts can promote the tissue repair process in the excision wound model of diabetic rats.

One of the more complex long-term metabolic diseases, diabetes is characterised by high blood sugar levels that are either caused by insufficient or inefficient insulin production or use by the body. Antioxidant activity, in vitro and in vivo antidiabetic potency of Pyrus communis leaf ethanolic extract. The study involved collecting Pyrus communis leaves from Tamil Nadu, India, and analyzing their phytochemical properties. In vitro, antioxidant assays were conducted, and total antioxidant activity was determined. In vivo, antidiabetic activity was evaluated in streptozotocin-induced diabetic rats, and the effects of the extract with glibenclamide were evaluated over 4 weeks. Phytochemical screening identified glycosides, phenolics, flavones, flavonoids, terpenoids, and sterols in the extract, highlighting its diverse bioactive components. In vitro, antioxidant activity revealed notable concentration-dependent radical scavenging effects, with DPPH inhibition ranging from 18.86% to 50.97%, ABTS inhibition from 16.01% to 72.42%, and increasing reducing power from 0.2381 to 1.413. The ethanolic extract showed a strong in vitro antidiabetic effect by inhibiting alpha-amylase and alpha-glucosidase in a dose-dependent manner, with inhibition percentages increasing from 13.44% to 64.89% and from 7.84% to 42.79%, respectively. In vivo, studies on STZ-NA-induced diabetic rats revealed protective effects on body weight, with final weights of 163.0±2.08 g and 180.7±3.13 g for lower and higher doses, respectively. Blood glucose levels significantly decreased in test groups, reaching 230.5±2.30 mg/dl and 224.0±3.02 mg/dl, indicating potential antidiabetic efficacy. Histopathological examination revealed preserved pancreatic architecture akin to the normal and standard groups, suggesting protection against diabetes-induced structural alterations.   This thorough analysis highlights the antioxidant and antidiabetic properties of P. communis leaf extract, emphasizing its potential as a medicinal agent for treating oxidative stress and diabetes. Further clinical trials and additional mechanistic research are needed to validate this drug's therapeutic efficacy and safety.

Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease that affects young people and causes demyelination and axon loss in the central nervous system. According to several studies, rituximab (RTX) reduces inflammation and relapse in patients with relapsing-remitting MS. This study aimed to evaluate the efficacy and safety of RTX in patients suffering from MS. MS patients were treated in the comprehensive MS clinic of Ghaem Hospital, Mashhad, Iran, and RTX administration was approved for them (1000 mg). Before initiating the study, demographic characteristics (e.g., age, gender, and type of MS disease), clinical variables (e.g., annual relapse rate [ARR] in the year before the intervention, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging [MRI] findings), laboratory variables (e.g., complete blood count [CBC], liver and kidney function tests) for the patients were recorded. After the intervention, the variables were checked and re-recorded, and the patients were followed up at 6 and 12 months. In total, 50 patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), or secondary progressive MS (SPMS) with mean age and treatment duration of 37.60±8.91 and 6.72±5.28 years, respectively, were included in the study. The results showed no significant difference among the three time periods regarding the mean disability level (P=0.73). Moreover, the mean ARR decreased significantly after the intervention (P=0.007). This study showed that RTX administration effectively reduces the ARR, and no significant safety issues were recorded. However, the results of this study could not prove RTX's efficacy in preventing confirmed disability progression.

Developing materials with a high capacity for drug adsorption and slow-releasing properties is promising in drug delivery. Metal-organic frameworks (MOFs) are materials with high adsorption and desorption capacities. Therefore, they can be very effective in targeted drug therapy. In this study, two Fe-MIL101 samples with different synthesis times (24 and 48 hours) were synthesized by solvothermal method and used as a naproxen carrier for the first time. The samples were analyzed using BET, FT-IR, XRD, and FESEM structural analyses at the nanoscale. The pH_pzc of the Fe-MIL101 (48h) and Fe-MIL101/Fe₃O₄ was determined to be 3.3 and 3.5, respectively. The adsorption of the Naproxen on Fe-MIL-101/Fe₃O₄ followed the Freundlich adsorption isotherm (R²=0.996), indicating the multilayer adsorption of Naproxen molecules on the carriers. The release of naproxen from carriers was investigated at a phosphate-buffered saline (PBS( with a pH of 7.4 (the pH of human blood). The variables of release time, carrier synthesis time, and pH of the environment were considered in this study. The most effective release was with Fe-MIL-101/Fe₃O₄ synthesized over 48 hours. This method followed the kinetic model of Korsmeyer-Peppas (R²= 0.9843) with a release exponent (n) of 0.63, meaning that the naproxen release from MOFs follows the non-Fickian mechanism. To develop a magnetic and slow-releasing carrier, Fe-MIL-101/Fe₃O₄ was synthesized. The studies showed that naproxen release from Fe-MIL-101/Fe₃O₄ is slow and takes a long time. The n in Korsmeyer-Peppas mole for naproxen release from Fe-MIL-101/Fe₃O₄ was 0.886, indicating a case II transport mechanism for naproxen release with a constant release rate. The findings highlight the significant potential of Fe-MIL-101/Fe₃O₄ for enhancing targeted drug delivery, underscoring its importance in improving therapeutic outcomes.

Integrating scientific and technological development in medicinal chemistry implies a great leap forward and speeds up the low-cost drug discovery process from natural resources. Therefore, in silico approaches were performed through molecular docking involving receptors crucial in metabolic processes, aiming to gain insights into how free radicals bind and how blood sugar levels can be lowered. The research aims to study the inhibitory mechanisms of phthalic acid derivatives such as tyrosine enzymes, alpha-glucosidase, and dipeptidyl peptidase-4 with in silico predictions. The in silico prediction instrument is in the form of computing software. Additional ligand sources were gained from a database of tyrosinase enzyme receptor (6JU9), alpha-glucosidase receptor (2JKE), and dipeptidyl peptidase-4 (1N1M). The active ingredients of Kenikir and Yacon leaves are used as test compounds with comparison drugs such as acarbose. The Diisooctyl Phthalate compound has an antioxidant potential through the 6JU9 target protein, with the most stable docking score of -81, 07. The target proteins for reducing blood sugar levels each have a value of -61.606 (2JKE ligand) and -86.945 (1N1M ligand). It is concluded that natural resources (Cosmos caudatus and Smallanthus sonchifolius) showed potential as natural drugs with an in silico approach study.

Vitamin D is an old supplementation with a new mode of action as an encouraging alternative to current therapies for PCOS, and this research is designed to analyze the ability of vitamin D to rebalance hormonal abnormalities, antioxidant capacity, and ovarian morphology in letrozole-induced rats. Thirty-five female Sprague Dawley rats were used, and then they separated into five groups with seven animals each: the first group received only water, the second group received DMSO, the third group signed as PCOS group, Group IV received metformin, Group V received Topferol (vitamin D). PCOS was induced by administration of a daily dose of 1 mg per weight of letrozole for 21 days; after induction, the animals were treated with metformin and vitamin D for 19 days, and at the end of the experiment blood samples and ovarian tissues were taken for analysis. The results show that vitamin D normalized the estrus cycle in rats, restored the normal follicular development process, decreased the high levels of LH and testosterone, and enhanced the total antioxidant capacity. In conclusion, vitamin D is as effective as metformin in the reduction of several hormonal and biochemical features that are usually associated with PCOS mainly by restoring normal estrus cycle, renovating morphological features and folliculogenesis, and organizing abnormalities in hormone levels; however, it showed superior action regarding the antioxidative effect.

Oxidative stress and inflammation play a significant role in the development of testosterone-induced benign prostatic hyperplasia (BPH) and prostate cancer. Quercetin, a polyphenolic compound with antioxidant and anti-inflammatory properties, has limited gastrointestinal absorption. Pumpkin seed oil, rich in β-sitosterol, provides anti-inflammatory and antioxidant benefits. This study evaluated the protective effects of a quercetin-loaded pumpkin seed oil nano-emulsion on BPH in rats. Thirty-six adult male Wistar rats were divided into six groups (n=6 each): control, healthy, quercetin-loaded pumpkin seed oil nano-emulsion, pumpkin seed oil nano-emulsion, quercetin, and finasteride. Except for the healthy group, all groups received intramuscular testosterone enanthate (100 mg/mL) for five consecutive days each week over four weeks. Blood and pathological assessments were conducted to evaluate the effects of the treatments. Statistical analyses were performed using One-Way ANOVA, Paired T-Test, Kruskal-Wallis, and IBM SPSS version 25, with a significance level of p < 0.05. Significant improvements in inflammatory and antioxidant markers were observed in the quercetin-loaded pumpkin seed oil nano-emulsion group and the finasteride group compared to the quercetin, pumpkin seed oil nano-emulsion, and control groups (P<0.05). Hyperplastic and hypertrophic lesions were markedly reduced in the quercetin-loaded pumpkin seed oil nano-emulsion group compared to the control group, demonstrating superior efficacy relative to finasteride (P<0.05). The quercetin-loaded pumpkin seed oil nano-emulsion showed better outcomes in treating or preventing BPH than finasteride, with fewer side effects. This nano-emulsion could be a promising alternative or adjunct therapy for individuals at risk of BPH, such as athletes and the elderly.

Tabernaemontana alternifolia, a plant of the Apocynaceae family and commonly referred to as Kampillakah, is a medicinal plant recognized for its remarkable therapeutic benefits. The plant stems, roots, and leaves are abundant in alkaloids, which have been traditionally used to treat cancer, diarrhea, and syphilis. Due to bioactive alkaloids and phenolic compounds, the current study aimed to evaluate the immunomodulatory effects of methanolic extracts from Tabernaemontana alternifolia leaves (TAL). It stems (TAS) in mitigating cyclophosphamide-induced myelosuppression in rats. Preliminary phytochemical analyses revealed the presence of compounds known for immunomodulatory properties. The administration of these extracts resulted in a notable recovery of hemoglobin levels and red and white blood cell and platelet counts, with TAL demonstrating greater effectiveness compared to TAS. Body weight measurements corroborated the protective effects, such as TAL and TAS significantly increased rat body weight during treatment. Furthermore, TAL and TAS enhanced neutrophil adhesion, an important marker of immune system activation. Overall, the results indicate that TAL, in particular, offers notable immunomodulatory benefits that may help mitigate the adverse effects of chemotherapy-induced myelosuppression and boost immunity against infections, delineating its potential for therapeutic use in integrative medicine.

Chronic inflammatory diseases are characterized by persistent immune responses in genetically predisposed individuals. Environmental factors trigger these responses and are often accompanied by increased inflammatory factors, such as inflammatory cytokines or oxidative stress. Phycocyanin (PC), a pigment extracted from Spirulina platensis, has anti-oxidant and anti-inflammatory properties and has been shown to have beneficial effects in patients with inflammatory disease. In this study, we aimed to evaluate the impact of both encapsulated and non-encapsulated forms of PC on the expression of Catalase, Superoxide dismutase 1 (SOD1), Superoxide dismutase 2 (SOD2), and IL-17 genes in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals. For the experiment, Spirulina platensis (Arthrospira) PCC9108 was obtained from the microalgae bank of the Science and Research Branch of Islamic Azad University in Tehran, Iran. The optimal non-toxic concentration of PC was determined using an MTT assay. PBMCs were isolated from the whole blood, cultured, and stimulated with phytohemagglutinin (PHA) (10 µg/ml) in either encapsulated or non-encapsulated PC form. Following 48 hours, the gene expression analysis was assessed using Real-time PCR. Multi-group analysis of Catalase, SOD1, SOD2, and IL-17 gene expressions between unstimulated cells and stimulated cells under different conditions (treated with a high or low concentration of non-encapsulated (NEC-PC) and encapsulated PC (EC-PC)) revealed no significant difference (P=0.06, P=0.5, P=0.3 and P=0.2, respectively). However, the pairwise analysis showed that encapsulated PC (1000µg/ml) significantly decreases the IL-17 level (p=0.05). Our findings indicated that a high concentration of encapsulated PC reduces IL-17 levels. The results may inform future clinical trials for patients with inflammatory and autoimmune diseases that involve inflammatory responses.

Surgical site infections (SSI) rank among the most prevalent healthcare-associated infections, leading to increased use of antibiotics, higher healthcare costs, extended hospital stays, and elevated rates of morbidity and mortality. This study focuses on assessing the proper use of surgical antibiotic prophylaxis and analyzing the microbial spectrum in one of the largest hospitals in northeastern Iran. This retrospective, hospital-based cross-sectional study was conducted at Imam Reza Hospital from September 2018 to 2019, focusing on patients diagnosed with surgical site infections (SSI) according to the criteria established by the Centers for Disease Control and Prevention (CDC). Data were collected through a review of medical records, encompassing patient demographics, underlying conditions, reasons for surgery, type and location of the operation, classification of the surgical wound, prophylactic antibiotic used, prophylaxis duration, and the infection site's microbial profile. The study included 82 patients with a mean age of 43.2 ± 15.5 years, 61 (74.4%) female. Most surgical site infection (SSI) cases were associated with the obstetrics and gynecology ward (39.0%). Preoperative antibiotic prophylaxis was administered to 42.7% of patients, with ceftriaxone and metronidazole being the most prescribed regimen (40%). Antibiotics were administered more than 120 minutes before the surgical incision in 54.3% of cases. The antibiotic type adhered to the protocol in only 33 patients (40.2%), while the correct dosage was administered to just 16 patients (19.5%). The abdomen was the most frequently affected surgical site, accounting for 73.2% of SSIs, with 61.7% of infections occurring in incisions below the umbilicus. Cesarean section was the most common procedure leading to SSI (34.1%). Clean wounds were reported in 62.2% of cases. None of the cardiovascular surgery patients received antibiotics appropriately postoperatively, and only 16.9% of patients undergoing other procedures were given prophylactic antibiotics at the correct time after surgery. The most frequently isolated microorganism from wound cultures was Staphylococcus epidermidis (25.8%). The study revealed poor adherence to established protocols for administering antibiotic prophylaxis in surgical wards. It highlights the need for developing standardized and comprehensive local hospital guidelines tailored to various surgical procedures. Additionally, surgical residents should receive targeted training on the appropriate indications, selection, and duration of prophylactic antibiotic administration to improve compliance and patient outcomes.

There are some promising bioactivities related to Brassicaceae plants, including chemoprotective and anti-cancer effects, through various mechanisms which are mainly related to the number of phytochemicals such as glucosinolates and their hydrolysis products, isothiocyanates. The dietary intake of glucosinolate constituents, which are dominant in Brassicaceae plants, has been shown to interfere with the thyroid gland's iodine uptake and metabolism through competitive inhibition. Descurainia sophia L. (D. sophia) seeds, commonly named Khakshee, possess a great amount of gluconapin, a glucosinolate known for its goitrogenic properties, which potentially may have protective effects on thyroid dysfunctions. The present study evaluated the possible ameliorative activities of hydroalcoholic extract from D. sophia seeds in regulating hyperthyroidism in a levothyroxine-induced rat model. The 70% hot methanol extract from the plant seeds was prepared using the maceration method, and the total glucosinolate content was determined using UV spectrophotometry. The serum thyroid hormone levels and histopathological features of the thyroid gland were assessed to evaluate the protective effects of extract in hyperthyroidism induced by injection of levothyroxine in rats. The administration of the extract by oral route has been associated with a significant decrease in the levels of FT4 and FT3. Further, the treatment group showed a notable reduction in TSH levels. The histopathological findings showed that the consumption of extract attenuated the adverse effects of levothyroxine. Spectrophotometric analysis revealed the presence of glucosinolates in the extract, which was calculated at 24.14 ± 0.8 mmol equivalent of sinigrin per kilogram of dried seeds. Based on the results of this study, it appears that glucosinolates are responsible for protecting D. sophia against levothyroxine-induced thyroid damage in rats. While Brassicaceae plants are recognized for their potential health benefits, particularly in reducing the risk of various diseases, including cancer, limiting the consumption of certain species, such as Khakshee, is important due to the possibility of affecting thyroid hormone levels by these plants.

Methicillin-resistant Staphylococcus aureus (MRSA) has been associated with substantially higher morbidity and mortality rates due to the acquired multidrug resistance. Accordingly, there exists a growing demand for development of natural products as alternative treatments or combination drug therapies against this infection. This study aimed to assess the synergistic effect of sumac in combination with clinically important antibiotics against ten clinical isolates of MRSA. A total of 50 staphylococci clinical isolates were screened for susceptibility to antibiotics, and 10 isolates were selected for further studies. The disc diffusion method (DDM) was used to screen the synergy effects of the sumac extract with 7 antibiotics against clinical isolates of MRSA. The broth microdilution method determined the minimum inhibitory concentration (MICs) of sumac extract and three selected antibiotics. The synergistic effect of the sumac extract and three antibiotics was assessed and evaluated using checkerboard dilution methods. The three antibiotics, i.e., cloxacillin, cephalexin, and vancomycin, showed considerable synergistic effects with sumac extract based on DDM. The MICs of sumac against ten clinical MRSA isolates ranged from 1600 to 6400 µg/ml. In the checkerboard dilution method, sumac markedly reduced the MICs of the antibiotics cloxacillin and cephalexin, and a significant synergistic effect was recorded by sumac in combination with these two antibiotics. Our results demonstrated that sumac extract enhances the antibiotic potential against MRSA in vitro conditions. This study suggested that sumac, in combination with antibiotics, could lead to the development a new combination of antibiotics against MRSA.

Levetiracetam (LEV), an antiepileptic compound with a bitter taste, is used to treat different types of epilepsy in both adult and pediatric patients. While a wide range of doses is required for various age groups, some patients have difficulties in swallowing large solid dosage forms. Therefore, this study aimed to prepare and evaluate taste-masked LEV coated pellets with immediate and extended release behavior for flexible drug dosing, ease of swallowing, and higher patient compliance. LEV core pellets were prepared using the extrusion-spheronization technique and evaluated in terms of physical properties. In the next step, two coating processes were performed separately on the optimal formulation using different polymers to prepare a taste-masked immediate release formulation and to achieve an extended release product. Further experiments were conducted on the coated pellets, such as dissolution, morphology, and taste-masking evaluations.

Based on the results, optimum LEV-loaded core pellets with suitable physical properties were prepared with the size, aspect ratio, and projection sphericity of 1.18 mm, 1.08, and 0.92, respectively. Coating the pellets with Eudragit E, while having appropriate dissolution in an acidic medium, provided an acceptable taste-masking, confirmed by in-vitro and in-vivo analysis. Extended release LEV pellets were obtained by coating the core pellets with a proper Eudragit RL/RS combination. Desirable dissolution profiles were achieved using 30 % coating polymer on the surface of the pellets. In addition to the advantages of taste-masked immediate and extended release LEV pellet formulations, it should be pointed out that preparing these multi-particulate systems by coating similar core pellets with various polymers can be cost-effective from the production point of view.

This study explores the chemical composition and anthelmintic activity of essential oils and extracts derived from the roots of Kalanchoe petitiana (Crassulaceae), a plant traditionally used in Ethiopian and Eritrean medicine. Essential oils were extracted through hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC-MS), revealing 30 volatile compounds, with trans-myrtanol (43.23%), 1-octen-3-ol (5.43%), and bisabolene (6.02%) as the major components. The anthelmintic efficacy of the extracts and essential oil was evaluated in vitro against Caenorhabditis elegans nematodes. The methanol root extract exhibited significant nematocidal activity, achieving 91.5% mortality at a concentration of 10 mg/mL, while the chloroform root fraction demonstrated 61.7% efficacy at 2 mg/mL. The essential oil showed a potent effect with a 92.4% nematocidal rate at 60 μg/mL, closely comparable to the reference drug ivermectin (97.6% at 10 μg/mL). These results suggest that K. petitiana possesses substantial anthelmintic potential, likely due to its rich terpene content, particularly trans-myrtanol. This study provides the first report of trans-myrtanol identification from Kalanchoe species and supports using K. petitiana as a natural alternative for managing helminthic infections. Further research is recommended to isolate and characterize the active compounds and evaluate their vivo efficacy and safety.

Recurrent Aphthous Stomatitis (RAS) is a widespread oral condition characterized by painful lesions on the oral mucosa, affecting about 20-25% of the population, with a higher occurrence in females. The etiology remains unclear, but factors such as infections, nutritional deficiencies, and stress have been implicated. Current treatments often focus on symptom relief, and while topical formulations are common, their efficacy is limited by poor retention at the site of action. This study aims to develop a mucoadhesive gel containing Tetracycline (TC) and evaluate its effectiveness compared to a Triamcinolone (Tri) gel in treating RAS.

60 participants aged between 20-50 with RAS were recruited for a randomized double-blind clinical evaluation. Two groups of patients were formed, one of which received TC-gel and the other Tri-gel. Gel formulations were prepared using carboxymethyl cellulose (CMC) and Carbopol, with pH, in vitro drug release, mucoadhesive strength, and residence time assessed. Clinical evaluations included measuring ulcer diameter, pain intensity via the Visual Analogue Scale (VAS), and patient satisfaction over a 10-day treatment period.

The TC-gel demonstrated a mean pH of 6.63 and released 95.74% of TC after 240 minutes. The mucoadhesive strength was 1.59 N, with a residence time of 78 minutes. Both gels significantly reduced ulcer diameter and pain levels by day 10, with no significant differences between groups. Patient satisfaction was high, with 73% reporting excellent or good outcomes for both gels.

The TC-gel is an effective treatment for RAS, comparable to Tri-gel, with promising mucoadhesive properties and patient satisfaction. These findings support the potential of TC-gel as a viable therapeutic option for managing RAS symptoms

This study investigated the mechanism of the analgesic effect of oak fruit extract in interference with an opioidergic system in female mice under acute stress induction. Adult female mice were divided into groups of control, oak extract 1, 10, and 100 mg/kg, morphine and naloxone 1 mg/kg, morphine or naloxone/oak 1 and 100 mg/kg, restraint stress (60 minutes), stress/ naloxone 1 mg/kg and stress/ naloxone/oak 1 or 100 mg/kg. All mice were co-cycled before the beginning of the study; the formalin test induced inflammatory pain. Components were injected after stress induction, and formalin tests were done 30 minutes after injections. Oak fruit hydroalcoholic extract was obtained using the maceration method. Serum total oxidant status (TOS) and total antioxidant capacity (TAC) were measured. Oak extract 100 mg/kg induced analgesia in the acute phase of pain, and all doses induced analgesia in the chronic phase. Morphine improved the analgesic effect of oak extract 100 mg/kg in the acute phase. Naloxone in the stressed mice induced analgesia in the acute phase and improved the analgesic effect of Oak 100 mg/kg in the chronic phase. In the stressed mice, the TOS level was increased by the oak 1 mg/kg and decreased by the oak 100 mg/kg. Probably part of the analgesic effect of oak is due to the activity of the opioid system in acute stress situations. In addition, the change in the ratio of oxidant/antioxidant compounds in this process indicates that the mechanism of action of oak fruit in modulating pain and inflammation is multifactorial.

Genistein, a naturally occurring isoflavone in soybeans, has gained attention for its phytoestrogenic and antioxidant properties. Its role in endocrine modulation, oxidative stress regulation, and apoptosis suggests therapeutic potential in cancer and metabolic disorders. Foreskin fibroblasts serve as a model for studying genistein’s effects on cell proliferation, oxidative stress, and cytotoxicity. This study examines genistein’s influence on gene expression related to cell growth and stress responses, offering insights into its therapeutic or adverse effects. Human foreskin samples from seven donors (6–12 years old) were used. Fibroblasts were isolated via collagenase and trypsin digestion and cultured in DMEM with 10% FBS. Cells were treated with genistein (20–100 µM), and viability was assessed using MTT assays. Antioxidant enzyme activities (SOD, GPx, CAT) were quantified spectrophotometrically. Gene expression of Bax, Bcl-2, IGF-1, and Casp3 was analyzed via real-time PCR. Data were evaluated using t-tests and ANOVA, with p<0.05 considered significant. Genistein induced dose- and time-dependent cytotoxicity, significantly reducing cell survival above 40 µM. IC50 values decreased over time, confirming enhanced cytotoxicity. Enzyme activity assays showed reduced CAT, SOD, and GPx levels. Gene analysis revealed upregulation of pro-apoptotic markers (BAX, Casp3) and downregulation of anti-apoptotic genes (Bcl-2, IGF-1), with a BAX/Bcl-2 ratio exceeding one, indicating apoptosis. These findings highlight genistein’s potential as a therapeutic agent via oxidative stress modulation and apoptosis induction. This study confirms genistein’s cytotoxic effects on fibroblast cells through oxidative stress and apoptosis. Further research is needed to clarify its molecular mechanisms and optimize therapeutic applications.

We aimed to create a gel to treat acne. It contains quercetin-loaded niosomes. The thin film hydration method formulated quercetin-loaded niosomes made of cholesterol, maltodextrin, and span 60. The best batch of niosomes showed entrapment efficiency (97.10±0.10%), particle size (62.37±2µm), zeta potential (-43.4±6mv), and polydispersity index of 0.0554. The best batch (F7) was composed of quercetin (50 mg), Span 60 (180 mg), cholesterol (20 mg), maltodextrin (120 mg), hydration time (120 s), and hydration volume (30 ml). Further, F7 was subjected to a sonicator to reduce the particle size to 593.5±2.0 nm. Niosomes with spherical shapes were evenly dispersed, as shown by SEM analysis. Next, using a cold mechanical technique, quercetin niosomes loaded gel was prepared using carbopol 940. Gel exhibited a pH of 6.4, a high viscosity of 12,500 cP, quercetin diffusion through goat skin (93.56±2.19% within six h), and a zone of inhibition against Cutibacterium acnes (5.2± 0.9 mm). In conclusion, niosomal gel loaded with quercetin was thus shown to be a viable delivery strategy to treat acne.

Fungal infections of the skin are prevalent worldwide, and effective treatment requires innovative drug delivery systems. Emulgel, a novel formulation, offers several advantages, including non-greasiness, stain-free properties, improved patient compliance (particularly for individuals with hairy skin), enhanced spreadability, increased stability, and controlled drug release. This study investigates using emulgel as a delivery system for hydrophobic drugs, specifically Clotrimazole, in a hydrophilic base. Nine emulgel formulations were evaluated, focusing on three key factors: polymer type (Carbomer 940, Hydroxypropyl Methylcellulose K4M (HPMC K4M)), or a combination of both), and the type and percentage of the oily phase (5% Paraffin, 5% Isopropyl Myristate, and 7.5% Isopropyl Myristate). Three formulations failed to meet the mechanical stability criteria, while six formulations demonstrated stability across all tests. Drug release rates were as follows: F1 (81.43%), F2 (76.87%), F3 (85.56%), F7 (91.56%), F8 (87.89%), and F9 (97.64%). Over six hours, a commercially available Clotrimazole cream (Pars Daroo Company) released 71.11% of its drug content. Formulation 9 is the most effective formula, incorporating 5% Paraffin and a blend of Carbomer 940 and HPMC, and it followed the zero-order kinetic model. The inclusion of Paraffin, compared to Isopropyl Myristate, enhanced drug release due to the lower solubility of Clotrimazole in Paraffin. The Carbomer 940 and HPMC combination also provided optimal viscosity, ensuring stability, ease of application, and controlled release. It has also been shown that increasing oil concentration increases the drug's loading capacity while its release decreases.

Schisandra chinensis, a classical natural adaptogen, is utilized in official medicine for its fruits and seeds due to its pharmacological properties, such as adaptogenic, immunostimulating, antioxidant, hepatoprotective, antitumor, and membrane-stabilizing effects. These properties are attributed to a complex of biologically active substances, including lignans, essential oils, polysaccharides, triterpene saponins, vitamins, and macro- and microelements. The study also explores the potential use of plants with various biological components and detoxifying effects, using the example of histogenesis changes in jaw bone tissue and dental rudiments of laboratory animals exposed to ecotoxicants. These ecotoxicants, even in small doses, exhibit strong mutagenic and carcinogenic effects with high cumulative ability and toxicity. The research focuses on identifying marker components with physiological activity in the metabolic profile of Schisandra chinensis leaves and examining the impact of its extract, combined with Malus domestica and Beta vulgaris powders, on dental bud histogenesis. Gas chromatography with a mass-selective detector (GC/MS) was used to analyze three Schisandra chinensis leaf extract samples, identifying 34 organic compounds, primarily hydrocarbons, lignans, and terpenoids. Chloroform-based extracts contained the highest number of compounds. The effect of ecotoxicants on rat jaw tissues and dental rudiments was examined in five experimental groups via histological microscopy. Various degrees of dental histogenesis abnormalities and structural changes in dental tissues were observed, including impaired blood circulation, histogenesis of dental rudiments, and viability of ameloblasts and odontoblasts during dental hard tissue formation. Pregnant rats exposed to ecotoxicants and treated with a mixture of Malus domestica, Beta vulgaris powders, and Schisandra chinensis leaf extract gave birth to offspring with fewer dental rudiment and tissue changes.

Wound care involves various methods, including dressing to prevent bacterial infection at the wound site. Typically, these dressings are made from synthetic materials lacking biocompatibility. Many researchers have explored alternative wound dressings derived from natural polymers due to their non-toxic, biocompatible properties and natural degradation, such as starch. However, starch exhibits low mechanical strength, necessitating its combination with other polymers. Additionally, high-quality wound dressings require additional components that can expedite wound healing. Therefore, this study aims to develop a hydrogel-based wound dressing using a combination of cassava starch, polyvinyl alcohol (PVA), and aloe vera extract.

The simplex lattice design (SLD) determined the optimal hydrogel film formula. A comprehensive examination was conducted, encompassing a multitude of parameters; including pH value, swelling index ratio, degradation ratio, and water vapor transmission rate (WVTR). The ideal formula comprised 5% cassava starch, 5% PVA, and 2% aloe vera extract. Characteristics included a swelling ratio of 399.33 ± 33.13% and WVTR of 816.13±87.72 g/m² day, film degradation of 85.93 ± 0.1% after 14 days, pH of 5.88 ± 0.22, and tensile strength of 17.92 ± 12.80 MPa, with a transparent and slightly yellowish appearance. This optimal hydrogel film showed promise as a wound dressing alternative.

The researchers optimized the concentrations of components in the SNEDDS formulation using a D-optimal mixture design, aiming to achieve favorable physicochemical characteristics like dissolution and droplet size. The optimized formulation of pranlukast-loaded SNEDDS, comprising 22.44 mg of Benzyl alcohol, 67.55 mg of Tween 20, and 10 mg of Span 20, resulted in a droplet size of 65.866 nm, saturated solubility of 20.56 mg/g, and drug release of 90.84%, with a desirability index value of 1. The comparison of among experimental and predicted values for the droplet size, saturated solubility, and the drug release showed good agreement. Consequently, they successfully developed an SNEDDS formulation using a D-optimal mixture design, which is promising for enhancing weakly water-soluble drugs' oral absorption.

Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that plays a key role in tumor progression, metastasis, and angiogenesis by degrading extracellular matrix components and modulating cell signaling pathways. Due to its overexpression in various cancers and contribution to tumor microenvironment remodeling, MMP-9 is a critical therapeutic target for cancer therapy. This study employed a comprehensive computational strategy to identify natural MMP-9 inhibitors from phytochemical databases. Different bioinformatics methods, such as molecular docking, ADME/T profiling, PASS analysis, pIC50 analysis, drug-likeness prediction, and molecular dynamic (MD) simulation, were carried out. Molecular docking analysis revealed strong binding affinities for Naringenin (-9.5 kcal/mol) and Rhamnetin (-8.9 kcal/mol), which formed stable interactions with MMP-9's catalytic domain. PASS analysis further validated their inhibitory potential (Naringenin: Pa = 0.764; Rhamnetin: Pa = 0.755). Crucially, both compounds exhibited exceptional ADME/T properties, such as high oral bioavailability, optimal metabolic stability, and low toxicity risks, which are essential for preclinical drug development. The molecular dynamics simulations confirmed their binding stability, with favorable hydrogen bonding patterns and minimal structural fluctuations. Other promising candidates like Epigallocatechin-gallate, Naringenin, and Rhamnetin emerged as beautiful leads due to their dual advantages of potent MMP-9 inhibition and drug-like pharmacokinetic profiles. The findings support advancing these phytochemicals into experimental studies as potential anti-cancer agents targeting MMP-9-mediated pathological processes in cancer development.

This study examines the efficacy of selenium as a therapeutic agent for reversing neurobehavioral deficits. A docking analysis was conducted to elucidate the interaction between selenium and the NLRP3 inflammasome residue. The research involved synthesizing and validating selenium nanoparticles within a controlled experimental design that employed Aluminium chloride (AlCl₃) to induce neurotoxicity, followed by comprehensive neurobehavioral evaluations in Wistar rats. The results revealed that a one-month oral selenium administration led to significant enhancements in cognitive and motor functions, reduced proinflammatory cytokine levels, and decreased β-amyloid aggregation within the brain. Quantitative findings demonstrated that selenium treatment led to a marked enhancement in locomotor activity (from 54.83±0.60 to 60.5±0.76 counts, p<0.0001), improved performance within the radial arm maze (with baited arm entries rising from 9.83±0.58 to 16.5±0.43, p<0.0001). They augmented the recognition index in the novel object recognition assessment (from 33.77±0.74% to 61.38±1.10%, p<0.0001). On a biochemical level, selenium was found to decrease malondialdehyde concentrations and elevate antioxidant enzyme levels (SOD, CAT, GSH, p<0.01) while also significantly reducing levels of β-amyloid and TNF-α in the brain tissue. Additionally, selenium exhibited neuroprotective properties through both antioxidant mechanisms and cholinesterase pathways, thereby establishing it as a promising candidate for treating neurobehavioral deficits and neuroinflammation.

Diabetes mellitus (DM) is among the most prevalent chronic metabolic disorders worldwide. According to the World Health Organization (WHO) and the International Diabetes Federation (IDF), the incidence of diabetes is rising sharply in both India and Western countries. In silico approaches, including molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, drug-likeness prediction, and virtual screening, offer valuable insights for identifying effective ligands from phytochemicals that may serve as potential antidiabetic agents. This study focused on the evaluation of 277 phytochemicals derived from 20 plants reported to have antidiabetic properties, targeting six key receptors involved in the development of diabetes mellitus. Molecular docking was conducted at the active sites of these receptors, and Discovery Studio V24 was employed to map the interactions of the amino acid residues in both two- and three-dimensional representations with the phytochemical ligands. The docking study was validated by superimposing the re-docked complex onto the native co-crystallized ligand. Additionally, the Ramachandran plot was utilized to confirm the secondary structural integrity of the protein models. The in-silico analysis revealed that phytochemicals such as Quercetin, isomonospermoside, isocoreopsin, lukianol, ellagic acid, isosteviol, glutinone, monospermoside, and cadabicine exhibited significant binding affinities with the target proteins. Furthermore, these compounds demonstrated favorable oral bioavailability, drug-like properties, and ADMET profiles compared to standard antidiabetic drugs. Medicinal plants such as Butea monosperma (Palash), Coccinia grandis (Telakucha), Carissa carandas (Koromcha), Euphorbia neriifolia (Indian Spurge Tree), and Capparis decidua (Karil), which contain these bioactive phytochemicals, hold promise for the development of novel antidiabetic therapies within conventional medicine. These findings suggest that natural compounds with these core structures could serve as valuable lead compounds for diabetes treatment, contingent upon further validation through comprehensive in vitro and in vivo studies.

Mesalamine is an anti-inflammatory drug for the treatment of ulcerative colitis-related colon cancer. The present study aims to evaluate the rectal suspension of mesoporous mesalamine for improved localized effect of the drug in the ulcerative colon of rodents. Syloid 244FP and Syloid XDP were employed to form a solid dispersion of mesalamine using the solvent evaporation technique, with a drug-to-carrier ratio of 1:1. The formulations were evaluated for drug loading, and an in vitro drug release study was conducted over 8 hours. The drug and excipients were subjected to studies on incompatibility, surface characteristics, and surface morphology. A reconstitutable suspension (9% w/w) was prepared using carbomer 934 and Xanthum gum as suspending agents. Ulceration was induced in the animals, and the effect of the formulations on the ulcerative colon was observed through a histopathological study. The FTIR study revealed the compatibility between the drug and the carriers, while surface morphology and surface characteristics studies revealed the amorphization of the drug. Syloid 244FP was found to be the best carrier in terms of loading mesalamine and releasing the drug in a sustained manner for 8 hours. The histopathological study revealed that prolonged localization of the drug could provide significant healing in the ulcerative colons of the animals. Therefore, it can be concluded that the sustained release solid dispersion of mesalamine in mesoporous silica could enhance the local activity of mesalamine in the treatment of ulcerative colitis.

Manilkara hexandra (Sapotaceae) is an evergreen, medium-sized tree that grows in tropical and temperate regions. The different parts of this plant are traditionally used as an expectorant, antileprotic, febrifuge, purgative, aphrodisiac, and anthelmintic. At dosages of 50, 100, 200, 400, and 800 µg/mL, the anti-cancer efficacy of the ethanolic extract of Manilkara hexandra (EELMH) against Ehrlich Ascites Carcinoma (EAC) cells was evaluated using MTT and trypan blue assays. It exhibited a cytotoxic effect with IC50 values of 612 µg/mL and 624.97 µg/mL in MTT and trypan blue assays, respectively, after 48 hours. DAPI staining after treating the EAC cells at an IC50 value of 612 µg/ml showed morphological changes in the nucleus. The further anti-tumor activity of EELMH was evaluated in vivo using EAC-bearing Swiss albino mice at 200 and 400 mg/kg body weight. The effect of EELMH on tumor growth, cell viability, lifespan, hematological, and biochemical parameters of EAC-bearing mice was assessed. In addition to extending the lifespan of EAC-bearing mice, EELMH demonstrated a significant reduction in tumor volume, packed cell volume, and viable cell count. The hematological and serum biochemical parameters returned to nearly their original levels in mice treated with EELMH, specifically at a dose of 400 mg/kg.

To develop the views and application profiles of pyrano[2,3-d]pyrimidinedione, attempts have been made to account for drug/ligand or receptor/protein interactions by categorizing the suitable active site against the crystal structure of plant urease from jack bean (Canavalia ensiformis). The interaction was evaluated using the delta G value as the scoring function. The molecule with the most excellent negative delta G value is considered to have higher binding efficiency to the protein. The ligands AH4, AH8, and AH1 were shown to possess favorable negative values, indicating that these molecules have a greater affinity for the receptor's active site. The present research article also represents the Insilco ADMET and moderate biological activity of pyrano[2,3-d]pyrimidinedione. Some of the analogues exhibit hepatotoxicity and mutagenicity, as well as hERG K+ channel blocking activity. AH1 and AH2 inhibit cytochrome CYP1A2, affecting the metabolism of numerous xenobiotics. The present research work is beneficial for chemists working in the field of medicinal chemistry.

Anxiety disorders are prevalent worldwide, significantly impacting various aspects of patients’ lives. The use of Salvia species in ethnobotanical medicine has been well documented, with applications as diuretics, analgesics, anti-hyperhidrosis agents, laxatives, antipyretics, and antitussives. Among these, Salvia hypoleuca, an endemic plant in Iran, is recognized for its tonic, carminative, digestive, antispasmodic, anti-inflammatory, antioxidant, antimicrobial, and anti-nociceptive properties. The objectives of this study were to assess the anxiolytic effects of S. hypoleuca ethanolic extract and its potential neurotoxicity using established pharmacological models in mice. Animals were randomly allocated into five groups: one control group, three groups underwent treatment that received oral doses of S. hypoleuca at 30, 100, and 300 mg/kg, and a positive control group given diazepam at 10 mg/kg. Behavioral evaluations were performed using the light/dark test (LDT) and the elevated plus maze (EPM) tests. To evaluate potential neurotoxic effects, open-field and rotarod tests were also performed. The results specified that S. hypoleuca extract at doses of 30 and 100 mg/kg significantly enhanced entries and time spent in the open arms of the EPM, suggesting anxiolytic effects. In the LDT, the 30 mg/kg dose notably increased the time spent in the light box. However, the rotarod test showed a slight decrease in latency to fall at both 30 and 300 mg/kg doses, indicating possible motor impairment at higher concentrations. Open-field analysis revealed significant reductions in total distance moved and velocity at 30 and 300 mg/kg doses, suggesting potential locomotor suppression.

Additionally, the total phenolic and total flavonoid contents of S. hypoleuca ethanolic extract were measured as 47.26 ± 2.87mg GAE/g DW and 31.73 ± 5.38 mgRE/g DW, respectively. In conclusion, our efforts suggest that oral administration of S. hypoleuca extract exhibits anxiolytic effects in mice, as demonstrated by improved performance in the EPM and LDT. However, the observed locomotor impairment at higher doses warrants further investigation to determine the optimal therapeutic dose and potential safety concerns.

Although many medications are available to treat infectious infections, their therapeutic efficacy is hampered by systemic toxicities, drug resistance, hypersensitivity, and a narrow antibacterial spectrum. Based on the above facts, we synthesized and evaluated some new chalcones' antibacterial and antifungal properties. A group of natural compounds called chalcones has a broad spectrum of biological activity. The Claisen-Schmidt condensation of 4-tert-butyl-2,6-dimethyl-3,5-dinitro acetophenone with a variety of substituted aromatic and heteroaromatic aldehydes yielded some new chalcones with different substituents in consideration of the wide range of biological activities related to chalcones. Column chromatography and recrystallization techniques were used to purify the produced chalcones. IR, ¹H NMR, and elemental analysis data characterized the purified chalcones. These substances underwent additional testing for antimicrobial activity using the serial tube dilution technique. Antibacterial testing revealed potent activity for chalcones R1, R5, R6, and R18 (MIC: 32 µg/mL), attributed to electron-withdrawing groups like dichloro, nitro, and difluoro substituents. Antifungal studies identified R1, R3, and R18 as the most effective (MIC: 16 µg/mL against Aspergillus niger and Candida tropicalis), with SAR analysis emphasizing the roles of halogens and methoxy groups in enhancing activity. Quality evaluation of the protein PDB: 4AMV confirmed its suitability for molecular docking studies using the SAVES server and binding pocket analysis using CASTp and BIOVIA Discovery studio. Docking of chalcones against PDB: 4AMV using Auto Dock Vina module of PyRx 0.8 revealed binding affinities ranging from −7.2 to −8.4 kcal/mol, with ciprofloxacin (standard) showing −8.3 kcal/mol. Chalcone R6 exhibited the greatest affinity for binding (-8.4 kcal/mol) and robust interactions, including hydrogen bonds and hydrophobic contacts. R1, R5, and R9 also demonstrated significant affinities (−8.2 to −8.0 kcal/mol). These findings highlight chalcones, particularly R6, as promising candidates for further antimicrobial development.

Herbal remedy remains a fundamental alternative to conventional medicine. However, the proliferation of herbal remedies in our society calls for a scientific evaluation of their safety profile. This study evaluated the safety profile of a Polyherbal Stem Cell Remedy (PSCR) using a preclinical model in rodents. A total of 24 adult Wistar rats were randomized into four (4) groups of six (6) animals each. Group 1 served as control (10 ml/kg of vehicle) while groups 2, 3, and 4 received 2.07 ml/kg (half-therapeutic dose), 4.13 ml/kg (therapeutic dose), and 8.26 ml/kg (double-therapeutic dose) of PSCR for a period of 30 days. Body weight, behavioral changes, feed, and water intake were measured. Animals were euthanized on the 31^st day, and samples were collected for haematology, biochemical, semen, testosterone, and histological analyses using standard methods. The PSCR did not produce remarkable changes (^nsp>0.05) in body weight, behavior, feed-intake, water-intake, organs weight, antioxidant, and glucose, semen count, morphology, testosterone, semen quality, haematology parameters, except statistically significant (*p<0.05) increase in chloride, alkaline phosphatase (ALP) level (at high dose), super oxide dismutase (SOD) and decrease in sluggish spermatozoa and WBC (at high dose). Kidney, pancreas, and testes histology showed normal architecture, while hepatic and cardiac tissues showed mild changes at high dose. The study suggests that the PSCR is safe at the recommended dose, but monitoring hepatic and electrolyte levels of subjects using the PSCR above the recommended dose and duration is necessary for precautionary measures.

The hypothetical plasma concentration-time profiles of ibuprofen pediatric formulations using in-vitro release data of the mini-paddle apparatus and the USP apparatus were proposed. Dissolution conditions were as follows: a mini-paddle apparatus at 75 rpm, 200 mL of medium, a USP apparatus 4 laminar flow at 16 mL/min, and phosphate buffer (pH 6.8). Five commercial formulations (reference and four multi-source drug products) were used. Samples were taken at previously established times for up to 60 minutes. The dissolved drug was quantified by UV derivative spectrophotometric analysis. Profiles were compared with different approaches, and dissolution data were fitted with several mathematical equations. Predicted in vivo behavior was calculated using dissolution data from both apparatuses and published pharmacokinetic information through a convolution approach. Validation of the results was carried out by calculating the prediction error (PE) for the hypothetical peak plasma level (Cmax) as well as the area under the curve from zero to infinity (AUC_0-inf). Calculations are valid if PE is equal to or less than 10%. Considering the f₂ value, similar in-vitro release curves of all suspensions were found using data from the USP apparatus 4 (f₂ > 50). No statistically significant differences were calculated for the release parameters of B and C drug products, respectively, using data from the USP apparatus 4. PE < 10% for C_max and AUC_0-inf in the same formulation was only found with R, B, and C drug products, based on data from the USP apparatus 4. This apparatus appears to be the appropriate choice for assessing the biopharmaceutical quality of pediatric ibuprofen formulations.

Alcohol abuse is a widespread mental disorder with significant health complications. A relationship between vitamin D (VitD) and ethanol abuse has been established. VitD, as a vital element for the development and metabolism of dopaminergic neurons, affects dopamine and glial cell line-derived neurotrophic factor (GDNF) synthesis and may play a role in the pathogenesis of alcohol-related disorders. In this study, we aimed to examine the role of VitD in the attenuation of ethanol-induced conditioned place preference in rats via dopamine D2 receptor-GDNF and antioxidant signaling in vivo. Rats were randomly divided into control, ethanol (Eth), and three Eth+VitD groups for behavioral experiments in conditioned place preference (CPP) and an open field. The activities of different brain oxidants (MDA, NO, and TOS), as well as antioxidative parameters (CAT, GPx, SOD, and TAC), plus oxidative stress index (OSI) and plasma VitD levels, were measured. Finally, hippocampal NOX, GDNF, and DRD2 expression were examined by western blotting. VitD (500 IU) combined with the effective dose of Eth (1.25 g/kg) resulted in the maximum decrease in CPP with no effect on locomotion. VitD supplementation elevated plasma VitD levels post-conditioning, increased the activities of brain antioxidants, and overexpressed hippocampal NOX, GDNF, and DRD2 proteins. We demonstrate that VitD attenuates alcohol-induced conditioning in rats via DRD2-GDNF and antioxidant signaling in vivo. Hence, targeting GDNF signaling may be a novel approach for the development of new drugs to treat Eth-related disorders among VitD users.

In the current study, methanolic extracts (DCME) along with their fractions (n-hexane (DCHF), chloroform (DCBF), ethyl acetate (DCEF), n-butanol (DCBF), and aqueous (DCAF) of Datisca Cannabina Linn. were examined for in vitro biological activities, i.e., phytotoxicity, cytotoxicity, antioxidant, hemagglutination bioassay, urease, and spasmogenic and spasmolytic activities. Our findings revealed that the study plant is non-toxic, as neither its crude extract nor its subfractions exhibited toxic effects against brine shrimp. Additionally, no significant insecticidal activity was observed in the crude extracts or subfractions. Furthermore, the crude extract showed significant analgesic potential compared to the other tested samples, indicating the presence of bioactive constituents in the crude methanol extract. In the case of hemagglutination activity, all extracts exhibited a high (+++) or medium (++) agglutination effect against all human blood groups at a 5 mg/mL concentration, except for blood groups B and A, where the effect was low. Similarly, the crude methanol and aqueous fractions were found to have maximum (90%) and minimum (80%) phytotoxic activity, respectively, at a higher concentration (1000 μg/mL) only. In the case of urease enzyme inhibition studies, the ethyl acetate fraction showed maximum inhibition (90%), followed by DCBF (88%) and DCAF (70%), while the other fractions were found to be inactive. Among all the fractions screened, the same fraction (DCEF, 86.0%) displayed the highest antioxidant activity, followed by the chloroform fraction (75%) compared to standard BHA (92.25%) at a concentration of 1.0 mg/ml. In terms of spasmogenic and spasmolytic significance, D. cannabina's fractions were found to have a mild contracting and relaxing effect, varying from low to high doses, which may explain the traditional use of the plant in treating constipation and abdominal cramps, respectively.

Tramadol overdose is a significant global health issue with a rising prevalence. Several studies have highlighted a notable occurrence of seizures in individuals experiencing tramadol overdose. The incidence of seizures following the administration of naloxone in patients with tramadol overdose remains a topic of debate. This systematic review and meta-analysis assessed the incidence of tramadol-induced seizures after the administration of naloxone in individuals who had overdosed on tramadol.

Our study conducted a comprehensive search across multiple medical databases to identify articles reporting tramadol-induced seizures following naloxone therapy. The search encompassed Cochrane Central Register of Controlled Trials, MEDLINE-PubMed, Scopus, Ovid, Embase, Springer, Web of Sciences, Science Direct, and PubMed, with all searches completed by November 30, 2023. Additionally, the search encompassed reference lists of included studies and gray literature sources such as dissertations, organizational publications, and websites to gather supplementary data. The analysis involved calculating pooled odds ratio for seizure incidence between groups based on subgroups related to tramadol abuse history, seizure history, and intubation needs using fixed-effect models and odds ratios for gender distribution using random-effect models, all with 95% confidence intervals (CI).

The results indicate a marginally elevated seizure risk in the naloxone group versus controls; however, this difference did not reach statistical significance (OR: 0.91, 95% CI: 0.63–1.31; p=0.62). Subgroup analyses based on previous seizure history and tramadol abuse revealed slight differences between the naloxone and control groups in these subgroups, leading to an overall odds ratio of 0.89, 95% CI: 0.64, 1.23, with a P-value of 0.48. Further subgroup analysis indicated no significant disparity between the two groups concerning the need for intubation (p=0.13) and male gender distribution (p=0.49).

In conclusion, the study suggests that the use of naloxone in patients with tramadol toxicity does not independently trigger seizures. Naloxone administration was not associated with an increased risk of intubation or seizures. However, the lack of randomized clinical trials in this area necessitates more robust investigations to draw definitive conclusions.