Iranian Journal of Pharmaceutical Sciences

Organophosphate (OP) poisoning accounts for approximately 300,000 annual global deaths. Despite WHO recommendations, pralidoxime's efficacy alongside atropine for OP poisoning treatment remains uncertain. This study aimed to evaluate whether the addition of pralidoxime to atropine and supportive care provides clinical benefits. A double-blind, randomized, placebo-controlled trial was conducted at Loghman Hakim Hospital in Tehran, Iran, between April 2022 and March 2023. Patients with OP poisoning were randomly allocated to either an intervention group (pralidoxime plus atropine) or a control group (atropine alone). The primary outcome was patient recovery. Secondary outcomes included duration of hospitalization and alteration in paraclinical parameters such as VBG, serum cholinesterase, sodium, potassium, blood glucose, etc., within the initial four hours post-treatment. Sixty participants were included, with 30 patients in each group. The odds of recovery were significantly higher in the control group compared to the intervention group (OR: 4 [95%CI: 1.3-12.6], p = 0.018). However, this difference became nonsignificant after adjusting for baseline discrepancies (adjusted OR: 6.5 [95% CI: 0.96-43.96], p = 0.054). Hospitalization duration was significantly shorter in the control group (6.23 vs 13.31; mean difference: 7.08 [95% CI: 2.17-11.98], p = 0.006). There was no significant between-group difference regarding alteration in paraclinical parameters during the first four hours post-treatment.

The addition of pralidoxime to atropine did not improve survival or reduce hospitalization in OP poisoning. The reasons for this lack of efficacy remain unclear. Further multi-center randomized controlled trials with larger sample sizes are needed to investigate alternative dosing regimens or other oximes.

Since di-2-ethylhexyl phthalate (DEHP) from medical bags and tubes induces oxidative stress in bone marrow mesenchymal stem cells (BMSCs). Therefore, the aim was to use Catechin hydrate (CH) as a natural antioxidant to prevent lipid peroxidation. In this experimental study, BMSCs were treated with 0.063, 0.125, 0.25, 1, and 10 μM of CH for 4 days. Based on its effect on cell viability, 0.25 μM of CH was selected for further analysis. The cell was treated with 0.25 μM of CH as well as 100 and 500 μM of DEHP individually and in combination for 4 and 8 days to study cell viability, population doubling number (PDN), total protein, malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD) activity, nucleus and cytoplasm morphology and expression of Nrf2 and NFkB genes. Viability and proliferation ability of BMSCs were significantly (p<0.0001) decreased by DEHP in a dose and time-dependent manner, while CH caused a significant increase (P<0.0001). DEHP decreased (P < 0.0001) total protein, TAC, and the activity of antioxidant enzymes, and increased (P < 0.001) the MDA level, as well as causing morphological changes. In addition, DEHP caused a significant decrease in NF-κB and an increase in Nrf2 expression. Although CH in simultaneous treatment was able to completely compensate for the toxic effect of DEHP at 100 μM, especially at 8 days, when compared to the control, it could not prevent the toxic effect at 500 μM. In addition, CH was able to compensate for the imbalance of the NFkB/Nrf2 caused by DEHP. The consumption of fruits, vegetables, and especially tea, which contains a low concentration of CH, may be an alternative medicine for patients undergoing hemodialysis and blood transfusion.

Given the absence of an established gold standard for managing sleep disturbances in patients with cirrhosis, the present randomized double-blind trial was conducted to evaluate the efficacy and safety of melatonin (5 mg/night) versus zinc (50 mg/night) in alleviating sleep disorders within this population. A total of 42 eligible participants were enrolled and randomly assigned to receive either melatonin or zinc. The Pittsburgh Sleep Quality Index (PSQI) was evaluated at baseline and again after one month of treatment. All participants tolerated the interventions well, and no dropouts occurred during the study period. Statistical analysis revealed that PSQI scores significantly improved in both treatment groups compared with baseline (p = 0.001 for both the melatonin and zinc groups). However, there was no statistically significant difference between the two interventions in PSQI scores at the end of the trial (p = 0.936). Based on the observed efficacy and tolerability, both melatonin at 5 mg nightly and zinc at 50 mg nightly may be considered as viable options for addressing sleep disorders in individuals with cirrhosis.

Chlorhexidine (CHX) is a widely used antiseptic agent in oral healthcare. However, conventional mouthwash formulations are limited by poor retention time on mucosal surfaces. This study aimed to develop and compare two mucoadhesive CHX 0.2% gels using Hydroxypropyl Methylcellulose (HPMC) and chitosan polymers to improve drug retention and release performance. Two gel formulations were prepared using HPMC and chitosan as the polymeric base. Their physicochemical properties (pH, viscosity, spreadability), rheological behavior, mucoadhesive strength, in vitro drug release, antimicrobial activity against Staphylococcus aureus and Escherichia coli, and six-week stability were evaluated using validated protocols. Drug release kinetics were modeled using Korsmeyer–Peppas and Higuchi equations. Both gels exhibited pseudoplastic rheology and remained stable throughout storage. The HPMC gel had lower viscosity and greater spreadability, resulting in faster drug release. The chitosan gel demonstrated significantly stronger mucoadhesive strength and sustained drug release over 8 hours. Antimicrobial activity was comparable between formulations. No significant changes in pH or viscosity were observed during the stability period. Both polymers are suitable for CHX gel formulation, with HPMC offering ease of application and rapid release, while chitosan provides superior mucoadhesion and prolonged release. These findings support further in vivo evaluation and highlight the potential of polymer-based CHX gels as improved alternatives to traditional mouthwashes in oral infection management.

Helminthiasis is a global health issue that is particularly prevalent in developing countries. Current anthelmintic drugs, mainly benzimidazoles, have side effects and are resistant to parasites. This study investigated the anthelmintic activity of syringic acid (SYR), a natural polyphenolic compound, against Pheretima posthuma, which targets β-tubulin, using both in silico and in vitro approaches. Drug likeness and ADME/T showed that SYR has a better pharmacokinetic profile than albendazole (ALB). Density functional theory calculations provided insight into the electronic properties and reactivity of SYR and ALB. Molecular docking studies revealed that SYR has a strong binding affinity (ΔG = -6.3 kcal/mol) for β-tubulin, similar to that of ALB (ΔG = -7.2 kcal/mol). Molecular dynamics simulations confirmed the stable binding of SYR in the β-tubulin active site for 100 ns. An in vitro anthelmintic assay on Pheretima posthuma demonstrated that SYR exhibits dose-dependent activity in inducing paralysis and mortality, but is less potent than ALB. The consistency between the computational predictions and empirical bioactivity assays provided preliminary evidence that SYR is a genuine anthelmintic agent. However, further in vivo studies are needed to evaluate the pharmacodynamics, safety, and immunological effects of SYR in complex biological systems before clinical trials. This study provides a basis for the development of new, safer, and more effective anthelmintic agents that target β-tubulin, addressing the problems associated with drug resistance and the side effects of current treatments.

This study evaluated the memory-enhancing potential of Neolamarckia cadamba (Roxb.) Bosser ethanolic extract (200 and 400 mg/kg, orally) in scopolamine-induced amnesic rats, with piracetam as a standard. Cognitive function was assessed using the elevated plus maze, hole board test, and Morris water maze, along with locomotor activity and brain acetylcholinesterase (AChE) levels. Phytochemical analysis revealed 0.515 g% phenolics (gallic acid equivalents) and 2.129 g% flavonoids (quercetin equivalents). GC–MS profiling identified 11 major bioactive compounds with reported antioxidant, anti-inflammatory, and neuroprotective activities. In vitro antioxidant evaluation by the DPPH assay demonstrated concentration-dependent radical scavenging, with an IC₅₀ of 337.42 µg/mL. Oral administration of N. cadamba extract for 14 days significantly reversed scopolamine-induced memory deficits. The extract reduced transfer latency in the elevated plus maze, shortened escape latency in the Morris water maze, and increased exploratory behavior in the hole board test. It also enhanced locomotor activity and decreased AChE levels, indicating improved cholinergic function. The high dose (400 mg/kg) consistently produced superior effects, suggesting dose-dependent efficacy. These findings suggest that N. cadamba ethanolic extract exhibits nootropic and neuroprotective effects, likely through antioxidant and cholinergic mechanisms, and may be a promising candidate for managing cognitive impairments, including Alzheimer’s disease.

Depression is a mental health disorder characterized by profound feelings of sadness and a sense of hopelessness. It is a life-threatening disorder and approximately 20% of world’s population is affected by depression. Drotaverine is used as an anti-spasmodic drug. It is structurally like Papaverine. It selectively inhibits the phosphodiesterase-4 (PDE-4) enzyme.

The antispasmodic medication drotaverine was utilized as a test drug in this investigation, and its effects as an antidepressant were examined. Compared to the standard drug imipramine used for depression therapy, it has fewer negative effects. For a variety of behavioral (in vivo) and non-behavioral (in vitro) investigations, we have employed Swiss Albino mice. The Forced Swim Test, Tail Suspension Test, and Elevated Plus Maze Model Test are three behavioral models that were applied to estimate the antidepressant influence of drugs. The non-behavioral techniques of MAO-A and MAO-B inhibition were employed to assess the antidepressant action of medications. We have also conducted an antioxidant investigation using the Nitric Oxide Scavenging Assay and Glutathione (GSH) estimate. Additionally, histopathological investigations and protein measurements were carried out. The outcomes were noteworthy and excellent.

The test drug has shown considerable efficacy and promise as an antidepressant agent in the Tail Suspension Test (TST) (*p<0.05), Elevated Plus Maze Model Test (EPM) (*p<0.05), as well as Forced Swim Test (FST) (*p<0.01). The results were compared to the reference drug. The test medication had little to no effect on MAO inhibition, in accordance with assessment of MAO-A alongwith MAO-B. Nitric oxide (*p<0.05), glutathione (GSH) estimation (****p<0.0001), and total protein estimation (****p<0.0001) all showed considerable scavenging effects. The histopathological results provided a quick overview of the effects of both experimental and prescription medications, as well as the alterations to the cerebellar granular neurons, Purkinje cells, and cerebrum cell bodies. This points to the drug's protective function in the brain.

Gotu kola leaves (Centella asiatica Urb.) contain asiaticoside compounds that have been demonstrated to possess bactericidal properties against Mycobacterium tuberculosis (M. tuberculosis), as evidenced by inhibition tests. Several studies have reported that M. tuberculosis has developed resistance to tuberculosis (TB) drugs. The nanoemulsion delivery system represents an innovative therapeutic approach for TB patients, demonstrating significant promise in the diagnosis, treatment, and prevention of infectious diseases such as TB. This study aims to optimize and formulate the manufacture of a gotu kola leaf extract nanoemulsion as an alternative TB treatment. Maceration was employed to obtain a gotu kola leaf extract, yielding 34.7%. Thin-layer chromatography (TLC) analysis revealed a single spot, confirming the presence of asiaticoside. A gotu kola leaf nanoemulsion was developed using the Box-Behnken Design method, incorporating variations in gotu kola leaf extract loading, tween 80, and sonication time. The optimal formula was determined based on particle size parameters, particle size distribution, entrapment efficiency (EE), and extract loading (EL) using Stat-Ease® Design-Expert 360 software. The writing has been corrected. The optimal formula exhibited a particle size of 154.715 nm, a particle size distribution of 0.246, an EE of 92.512%, and an EL of 98.298 mg/g. In vitro testing demonstrated the antibacterial potential of the optimum formula, achieving a 56.2% antibacterial effect. In contrast, the positive control rifampicin showed an 89.1% antibacterial effect.

Neuroblastoma is a common and aggressive cancer in children characterized by metastasis and uncontrolled cell proliferation. The Aryl Hydrocarbon Receptor (AhR) is a crucial regulator of diverse biological processes, such as cell growth, immune responses, and metabolism. However, its role in neuroblastoma progression is inadequately investigated. SH-SY5Y neuroblastoma cells were treated with the AhR antagonist CH223191, the agonist benzo[a]pyrene (BaP), and the endogenous ligand 6-Formylindolo[3,2-b]carbazole (FICZ). Cell viability was evaluated by MTT assay, and ROS levels were measured by dichlorofluorescein (DCF) assay, while EMT-related gene expression (vimentin and E-cadherin) was analyzed using qPCR. Compared to control, treatment with CH223191 and BaP significantly decreased cell viability and increased ROS production, respectively. BaP induced a greater reduction in viability and increase in ROS than FICZ (p < 0.01). Gene expression analysis revealed that CH223191 and BaP decreased vimentin expression (p < 0.05 and p < 0.001) and increased E-cadherin expression (p < 0.05 and p < 0.001), indicating the inhibition of EMT and promotion of epithelial characteristics. These findings highlight the pivotal role of AhR in modulating proliferation, mitochondrial function, and EMT in neuroblastoma cells, indicating that targeting AhR signaling may offer a novel therapeutic strategy to impede neuroblastoma progression and metastasis.

Adriamycin, as a drug, is known to induce hepatotoxicity at high doses. This study investigated the preventive effect of Chenopodium botrys extract on Adriamycin-induced liver damage in rats.

Twenty-four rats were randomly divided into control, Adriamycin, and prevention groups, including the extract of Chenopodium botrys combined with Adriamycin and silymarin combined with Adriamycin. The experimental period was 30 days. Ultimately, blood was drawn, and liver tissue was removed for evaluation of oxidation markers and biochemical analysis.

Administration of Chenopodium botrys significantly decreased the biochemical parameters related to liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), compared to the Adriamycin group. Oxidative parameters, including total thiol content, superoxide dismutase (SOD), and catalase, were improved in the preventive groups compared to Adriamycin in liver tissues.

The data confirm that Adriamycin induces hepatic oxidative stress and liver damage. At the same time, co-treatment with the Chenopodium botrys effectively attenuates these adverse effects by restoring redox balance and preserving liver integrity. These findings highlight the therapeutic potential of natural antioxidants in preventing Adriamycin-induced hepatotoxicity.

Diabetes remains a pressing global health challenge, demanding innovative biochemical interventions for effective management. This study evaluates the effects of taurine and metformin on glucose regulation, lipid metabolism, and antioxidant enzyme activity in diabetic rats. Diabetes was induced in mice using a single intraperitoneal dose of streptozotocin (60 mg/kg), and animals with blood glucose levels exceeding 300 mg/dL were considered diabetic. The experimental subjects were systematically classified into four groups: healthy controls, diabetic controls, metformin-treated diabetics, and taurine-treated diabetics. Metformin and taurine were each administered via oral gavage at a dosage of 500 mg/kg/day for a period of one month, beginning seven days post-diabetes induction. Key indicators assessed included changes in body weight, fasting glucose levels, serum lipid components, and paraoxonase enzymatic activity. Metabolic evaluations included fasting blood glucose, body weight, lipid profile parameters, and paraoxonase enzyme activity. Metformin treatment did not significantly alter weight relative to the diabetic group, whereas taurine led to a notable improvement. Hyperglycemia was markedly reduced in both treatment groups compared to diabetic controls. Furthermore, analysis of lipid components revealed significant normalization: triglyceride, cholesterol, and LDL levels decreased, while HDL concentrations increased with both interventions. Antioxidant assessment showed restored paraoxonase activity in taurine- and metformin-treated animals.

These outcomes support the hypothesis that taurine and metformin contribute to the restoration of biochemical equilibrium in diabetic conditions. Both Taurine and metformin can modulate Diabetes-related metabolic disturbances, aiding in physiological stabilization. Both agents promoted glycemic correction, lipid improvement, and enzymatic recovery. Their efficacy suggests promise in supportive metabolic care for diabetes.

This study investigates the anticancer potential of Ficus hispida fruit extract, focusing on its phytochemical composition and molecular interactions with skin cancer targets. Fruits were collected from Jamia Salafiya Pharmacy College, and 500 g were subjected to Soxhlet extraction using methanol, yielding a concentrated ethyl acetate extract. LC-MS/MS analysis identified key bioactive compounds, including quercetin (m/z 302.33), kaempferol (m/z 284.26), gallic acid (m/z 169.14), lupeol (m/z 434.48), and β-sitosterol (m/z 414.58), confirming the extract's chemical diversity. In-silico molecular docking showed that gallic acid exhibited notable binding affinities with skin cancer-related proteins: 1M17 (-6.3 kcal/mol), 4QTB (-5.4 kcal/mol), and 5MP8 (-5.6 kcal/mol). Hydrogen bonding, van der Waals interactions, and π-alkyl interactions were observed, particularly with residues Asp831, Arg-84, and Asn118, indicating the formation of stable ligand-protein complexes. Molecular dynamics (MD) simulations further validated stability, with low RMSD (2.0 Å) and compact radius of gyration (19.8 Å). MM-GBSA binding free energy analysis yielded a favorableΔG_bind of -58.61 kcal/mol for the gallic acid-1P7K complex. In vitro MTT assays revealed dose-dependent cytotoxicity of gallic acid against SKML skin cancer cells, with an IC50 value of 13.601±0.488 µg/mL. AO/EB staining confirmed effective induction of apoptosis in treated cells. These results collectively highlight the effectiveness of gallic acid from Ficus hispida as a promising candidate for skin cancer therapy, warranting further preclinical and clinical investigations for therapeutic development.

Rothmannia octomera is a plant of the Rubiaceae family used in traditional medicine to treat bronchopulmonary infections. To contribute to the valorization initiatives of this plant, we undertook a study of its root phytochemistry. We assessed its antibacterial potential against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, which are considered bacterial etiologies of respiratory infections. The phytochemical screening of the hydroethanolic (30:70 v/v) and CH₂Cl₂/MeOH (50:50 v/v) extracts of Rothmannia octomera, obtained by maceration, was carried out using colorimetric and precipitation tests for several groups of secondary metabolites. For the antibacterial potential of the extracts, minimal inhibitory and bactericidal concentrations (MICs and MBCs) were determined by macrodilution in a liquid medium. Results revealed the presence of phenols, tannins, flavonoids, sterols, anthraquinones, and saponins in both extracts. MIC values for the hydroethanolic extract ranged from 12.5 to 200 mg/mL, while MBC values varied from 50 to 400 mg/mL. For the CH₂Cl₂/MeOH extract, the MIC values recorded ranged from 50 to 200 mg/mL, and the related BMCs ranged from 100 to 200 mg/mL. The BMCs/MICs ratios revealed a bactericidal effect of the hydroethanolic extract on Pseudomonas aeruginosa and Klebsiella pneumoniae, as well as a bacteriostatic potential on Staphylococcus aureus. With the CH₂Cl₂/MeOH extract, bactericidal action was observed against all the bacteria tested. This study justifies, for the first time, at least in part, the use of Rothmannia octomera in traditional medicine. Indeed, investigations on the safety of this plant and dosages required for its optimal use in disease control are necessary.

Risperidone, an antipsychotic drug, is widely used for treating mental health disorders such as schizophrenia, psychosis, etc. Despite its therapeutic benefits, Risperidone has been linked to oxidative stress through several pathways, including increased lipid peroxidation, mitochondrial and lysosomal dysfunction, excessive production of reactive oxygen species (ROS), and depletion of intracellular antioxidants such as glutathione (GSH). These changes impair membrane integrity, disrupt cellular redox balance, and increase the cytotoxic consequences. To address this, the current study examined how N-acetylcysteine (NAC), a potent thiol antioxidant and glutathione precursor, protects against oxidative damage induced by Risperidone. We assessed oxidative stress indicators such as ROS, lipid peroxidation (MDA), antioxidant enzyme activities (GSH, SOD, CAT), and oxidative stress tolerance (tBHP assay) using Caenorhabditis elegans as a model organism. Results showed decreased worm survival, increased oxidative stress markers, and compromised antioxidant defences with 50 μM risperidone exposure. However, pretreatment with 10 mM NAC effectively reduced ROS levels, enhanced GSH, and reduced lipid peroxidation, thereby improving survival under oxidative stress conditions (tBHP assay), which supports its role in maintaining redox balance. These findings suggest that risperidone-induced toxicity is mediated through oxidative stress, and NAC may offer a protective effect, presenting a potential therapeutic approach to mitigate its damaging effects.

The kidneys are essential organs that perform key functions for maintaining homeostasis. Cyclophosphamide (CP), a widely used chemotherapy agent, can cause nephrotoxicity through multiple mechanisms driven by oxidative stress. Allium ampeloprasum subsp. Iranicum, known for its antioxidant and anti-inflammatory properties, contains bioactive compounds that may mitigate these adverse effects. The study aims to determine whether the antioxidant properties of A. ampeloprasum can help maintain kidney function and enhance the effectiveness of treatment during CP therapy. Mice were divided into four groups: negative control, A. ampeloprasum only (150 mg/kg), CP-treated (20 mg/kg), and combined A. ampeloprasum (150 mg/kg) with CP (20 mg/kg). Treatments were administered both orally and intraperitoneally over 14 days. Blood and tissue samples were analyzed for biochemical, histopathological, and molecular markers, including lipid peroxidation, antioxidant enzymes, and inflammatory cytokines. The data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test for multiple comparisons. CP treatment resulted in significant weight loss, tissue inflammation, and structural kidney damage, along with elevated serum markers of kidney injury, increased lipid peroxidation, and decreased antioxidant enzyme activities. Histopathological analysis confirmed inflammatory changes and tissue disruption caused by CP, which were significantly mitigated by pretreatment with A. ampeloprasum extract. This extract reduced serum levels of urea, creatinine, and uric acid, and decreased lipid peroxidation in tissues. It boosted antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Additionally, A. ampeloprasum pretreatment markedly reduced levels of inflammatory cytokines compared with CP alone. This study demonstrates that A. ampeloprasum extract effectively mitigates CP-induced toxicity by reducing oxidative stress, inflammation, and tissue damage, indicating its potential as a natural protective agent during chemotherapy.