Iranian Journal of Pharmaceutical Research最新文献

Background: The gag reflex serves as an essential protective airway mechanism but can significantly interfere with dental care, affecting up to 44% of patients and leading to treatment avoidance in severe cases.

Objectives: To evaluate the effect of the topical application of an amitriptyline solution on reducing the gag reflex intensity, measured by the Gag Trigger Point Index (GTPI).

Methods: In this randomized single-blind clinical trial, 48 participants with a GTPI score higher than two were divided into amitriptyline (treatment) and lidocaine (control) groups. In the amitriptyline group, 75 mg of amitriptyline tablets were dissolved in 5 milliliters of distilled water (15 mg/mL) and gargled for one minute by the participants. Then, the GTPI was examined after 10 minutes. In the lidocaine group, four puffs of 10% lidocaine spray were applied to the target areas of the oral mucosa, and the GTPI was measured five minutes later. The taste and smell of both medications were assessed using a self-report questionnaire to measure patient satisfaction. The data were analyzed using SPSS version 22.

Results: In both the lidocaine and amitriptyline groups, GTPI levels demonstrated significant decreases. The lidocaine group showed a change from 4.46 to 2.42 (P < 0.001), and the amitriptyline group showed a change from 4.04 to 1.29 (P < 0.001). The reflex change rate was -2.75 in the amitriptyline group and -2.04 in the lidocaine group. When comparing the groups, no statistically significant differences were observed in the extent of gag reflex reduction or in participants' perception of taste and smell (P > 0.05).

Conclusions: Amitriptyline can be considered a potential alternative to lidocaine spray in gag reflex management, particularly in lidocaine-intolerant patients. Further studies are needed to confirm long-term safety and determine the local versus systemic pharmacological effects.

Context: Breast cancer is the most prevalent malignancy among women globally, with metastasis significantly reducing survival rates. Isoliquiritigenin (ISL), a bioactive chalcone derived from Glycyrrhiza species, has shown promise in preclinical studies for its multifaceted anticancer properties, including modulation of metastatic processes.

Objectives: This systematic review evaluates preclinical evidence on ISL's mechanisms in breast cancer prevention and metastasis suppression.

Evidence acquisition: Following PRISMA guidelines, a comprehensive search was conducted across PubMed/Medline, Scopus, Embase, and grey literature up to May 2025. Quality was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for in vitro studies and SYRCLE's Risk of Bias (RoB)/Animal Research: Reporting of in vivo Experiments (ARRIVE) for in vivo studies.

Results: From 4,522 records, 33 studies (52 datasets: One in situ, 33 in vitro, 18 in vivo) met inclusion criteria. Most studies originated from China and Hong Kong, with robust methodological quality, though reporting on randomization and blinding were often unclear. The ISL demonstrated potent anticancer effects by: (1) Inducing apoptosis and autophagy via mechanistic target of rapamycin (mTOR) inhibition and disruption of arachidonic acid pathways; (2) modulating microRNAs (miRs; e.g., miR-374a, miR-200c) to suppress epithelial-mesenchymal transition (EMT); (3) altering hormone receptor [HR; ERα, breast cancer type 1 susceptibility protein (BRCA1)] expression and inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR signaling; and (4) reducing angiogenesis [vascular endothelial growth factor (VEGF)/hypoxia-inducible factor-1 alpha (HIF-1α) suppression] and inflammation [cyclooxygenase-2 (COX-2)/nuclear factor-kappa B (NF-κB) inhibition]. Nanoparticle delivery systems (e.g., iRGD-targeted nanoparticles) enhanced ISL's tumor targeting and efficacy while maintaining low toxicity.

Conclusions: Preclinical evidence highlights ISL's potential as a multi-target agent against breast cancer progression and metastasis. However, clinical trials are urgently needed to validate its efficacy, safety, and optimal delivery strategies in patients. Future research should prioritize translational studies and combinatorial therapies to bridge the gap between bench and bedside.

Background: Cardiac autonomic neuropathy (CAN) is one of the most significant complications of diabetes mellitus (DM) and is characterized by reduced heart rate variability (HRV). The CAN frequently coexists with peripheral neuropathy.

Objectives: We attempted to determine whether gabapentin has any impact on HRV in individuals suffering from painful diabetic peripheral neuropathy (PDPN).

Methods: In this double-blinded randomized controlled trial, 30 patients with painful peripheral neuropathy were enrolled. Fifteen patients in the intervention group were randomized to receive gabapentin capsules and capsaicin placebo cream, while 15 patients in the control group were randomized to receive gabapentin placebo capsules and capsaicin cream. The diagnosis of PDPN was established using the Neuropathy Symptom Scale (NSS), neuropathy disability score (NDS), and Visual Analogue Scale (VAS). The HRV was evaluated with the standard deviation of normal-normal beats (SDNN) via 24-hour Holter monitoring of heart rate.

Results: Of the 30 randomized patients, 26 (86.7%) were included in the analysis (n = 15 intervention, n = 11 control). There were no statistically significant differences in age, sex, or Body Mass Index (BMI) between the two groups. Gabapentin increased the average level of SDNN by 11 ms in the intervention group and decreased by 6 ms in the control group. The between-group standardized mean difference (MD, Hedges' g) was 0.756 (95% CI = -0.04 - 1.5, P-value = 0.069), indicating a moderate effect that was marginally significant.

Conclusions: Our findings in this small pilot trial suggest that gabapentin therapy may improve cardiovascular autonomic function and increase HRV in patients suffering from diabetic painful peripheral neuropathy. However, more studies with larger populations are needed to ultimately prove this.

Background: Plants of the genus Allium show significant anti-cancer properties due to various phytochemicals, including flavonoids.

Objectives: This study investigated the cytotoxic activities of the methanolic extract of Allium colchicifolium bulbs and its purified flavonoids. It also assessed the anti-angiogenic activities, a key mechanism of anti-cancer agents.

Methods: The methanolic extract was fractionated using column chromatography (CC) on silica gel RP-18 and polyamide SC-6, then purified with Sephadex LH-20. The compounds were identified through spectroscopic methods such as nuclear magnetic resonance (NMR) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Cytotoxicity and anti-angiogenic activities were evaluated using the MTT assay and the chick chorioallantoic membrane (CAM) assay, respectively. Computational modeling explored the potential anti-angiogenic mechanisms of the purified compounds. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling predicted drug-likeness features.

Results: Three flavonoids - quercetin 3-O-rutinoside (1), isorhamnetin 3-O-glucoside (2), and quercetin (3) - were isolated and identified. Compounds 2 and 3 showed the highest cytotoxicity against PC3 (prostate cancer, IC₅₀ = 1.72 ± 0.11 µg/mL) and MCF-7 (breast cancer, IC₅₀ = 1.64 ± 0.11 µg/mL) cell lines. The methanolic extract and compound 3 also had potent anti-angiogenic effects with IC₅₀ values of 4.2 ± 0.25 and 5.3 ± 0.3 µg/mL, respectively. Molecular docking indicated that compounds 1 and 3 had the strongest interactions with the vascular endothelial growth factor receptor (VEGFR)-1, consistent with their anti-angiogenic activity. The ADMET profiling showed that compound 3 had the highest similarity to drug-like molecules.

Conclusions: This was the first phytochemical study of flavonoids in A. colchicifolium bulbs. The results suggest that these bulbs could serve as a natural source for cancer prevention and treatment, owing to their cytotoxic and anti-angiogenic properties. Further research is needed to confirm these findings, and in vivo studies are essential to validate their therapeutic potential.

Background: As consumer demand for cosmetic products that enhance physical appearance continues to rise, the global oxidative hair dye market is experiencing steady growth. Para-phenylenediamine (PPD), a key ingredient in most oxidative hair dyes, is widely used due to its efficacy and low cost. However, its high chemical reactivity has been consistently linked to adverse effects, including allergic contact dermatitis (ACD), eczema, carcinogenicity, and genotoxicity.

Objectives: Given the concerns over the long-term use of conventional therapies such as topical corticosteroids (TCS) and calcineurin inhibitors, this study aimed to identify a plant-derived compound with protective properties in a keratinocyte model of PPD-induced toxicity.

Methods: To assess the cytoprotective potential of 14 selected plant metabolites, water-soluble tetrazolium salt-1 (WST-1) and lactate dehydrogenase (LDH) assays were performed. Western blotting and reverse transcription-polymerase chain reaction were used to evaluate the anti-apoptotic, anti-DNA damage, and anti-inflammatory effects of geranyl acetate (GA), the most promising candidate.

Results: Among the 14 tested plant metabolites, GA was identified as the most effective compound in mitigating cytotoxicity in HaCaT keratinocytes. Co-treatment with GA significantly attenuated PPD-induced phosphorylation of p53 and MAPK, indicating inhibition of the DNA damage response (DDR) pathway. Further experiments revealed that GA suppressed the upregulation of apoptosis-related proteins [p53 upregulated modulator of apoptosis (PUMA), B-cell lymphoma 2 (BCL-2)-associated X protein (BAX), cytochrome c, and cleaved poly (ADP-ribose) polymerase (PARP)]. Moreover, GA treatment decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and NF-κB p65, thereby downregulating five pro-inflammatory cytokines [interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-24] and five chemokines [C-C motif chemokine ligand (CCL) 5/RANTES, CCL20/MIP-3α, CCL26/eotaxin-3, C-X-C motif chemokine ligand (CXCL) 1/GRO-α, and CXCL8/IL-8], confirming its anti-inflammatory efficacy.

Conclusions: Collectively, this study suggests GA as a promising plant-derived metabolite with cytoprotective, genoprotective, anti-apoptotic, and anti-inflammatory effects in PPD-stimulated HaCaT cells.

Background: Decentralization policies are essential for reforming administrative structures and improving service efficiency in government. Proper implementation of these policies promotes effective governance within administrative systems.

Objectives: This study proposes a framework for decentralizing regulatory tasks in the pharmaceutical sector to improve good governance indicators.

Methods: In the qualitative phase, an Interview Question Guide (IQG) was used to examine the decentralization framework through focused group discussions (FGDs) with relevant experts. The quantitative phase evaluated a sample of domestically produced and imported medicines, collecting perspectives from pharmaceutical companies, Iran Food and Drug Administration (IFDA) employees, and vice-chancelleries of food and drug affairs (VCFDA) staff at universities of medical sciences. The assessed indicators included transparency, rule of law, accountability and responsibility, effectiveness and efficiency, and stakeholder participation.

Results: Experts agreed on delegating tasks related to scientific examination and drug procurement policy-making. For supervisory and inspection tasks, deconcentration with VCFDA oversight was recommended. Key suggestions included legislative amendments, strengthening regulatory infrastructure, reforming processes, and learning from past decentralization efforts. In the quantitative phase, 169 companies responded, with over 59% of respondents holding professional doctoral degrees. Among VCFDA respondents, 33 individuals participated, with more than 60% having over ten years of work experience. Transparency scored highest among pharmaceutical companies, while IFDA and VCFDA employees emphasized responsiveness and accountability. Statistical analysis revealed significant differences across all dimensions between IFDA and pharmaceutical company perspectives.

Conclusions: Decentralization policies can improve good governance indicators in the pharmaceutical sector if critical requirements are met. Strengthening regulatory infrastructure and clearly defining tasks will enable effective use of governmental and non-governmental capacities.

Background: Diabetes is a contemporary ailment characterized mainly by elevated blood glucose levels. Diabetic foot ulcers (DFUs) significantly impact the patient's quality of life and pose challenges for the healthcare system. Microalgae have emerged as effective agents for controlling inflammation owing to their elevated levels of active chemicals.

Objectives: In the present study, we isolated and identified the Haematococcus pluvialis species of freshwater algae and investigated its effect on inhibiting the growth of diabetic wound bacteria.

Methods: The ethanolic extract of this algae was investigated on antibiotic-resistant Staphylococcus aureus isolated from antibiotic-resistant wounds of diabetic patients. For this statistical study, a central composite design was used, considering factors such as gender, age, level of non-healing of the wound, and the effectiveness of the extract in inhibiting bacterial growth as the response.

Results: The results showed that compared to other extracts, the ethanolic extract effectively inhibits bacterial growth up to 70% and 30%, respectively, of levofloxacin and ceftazidime antibiotics. The study of this extract with liquid chromatography-mass spectrometry led to the identification of the astaxanthin compound as the main component of the extract.

Conclusions: This study has substantial prospects for future therapeutic uses and instills hope for enhanced therapies for DFUs.

Background: Epilepsy is a condition characterized by frequent bursts of neuro-electrical impulse activity in the brain, involving the expression of transient receptor potential vanilloid receptor 1 (TRPV1). Zingerone (ZO) is known to possess a multitude of regulatory mechanisms for TRP channels. However, clear evidence of ZO in the regulation of TRPV1 expression has not yet been reported.

Objectives: The present study was designed to evaluate the therapeutic role of ZO against pentylenetetrazole (PTZ)-induced kindled seizures (KS) in mice.

Methods: The KS were induced by intraperitoneal (i.p.) administration of three doses of PTZ (35 mg/kg/day) in mice on every alternate day (day 1, 3, and 5). Additionally, the PTZ challenge test was performed on day 20. The ZO doses of 25 and 50 mg/kg; TRPV1 antagonist, i.e., selective TRPV1 antagonist (SB-366791, 10 mg/kg); and a combination of ZO and SB-366791 were administered orally (p.o.). The seizure score was assessed using Racine's scoring system on day 20. Changes in KS-associated spatial cognition were assessed by the water Y-maze and water T-maze tests. The hippocampal tissue biomarkers, i.e., thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α), and TRPV1 expression were estimated.

Results: The ZO attenuates the PTZ-induced changes in Racine's scores and spatial cognition effects in Y-maze and water T-maze tests. Furthermore, ZO also ameliorates the PTZ-induced biomarker changes.

Conclusions: Hence, ZO possesses therapeutic potential against KS conditions in mice via regulation of TRPV1 channel functions. However, more extensive studies are required to prove this therapeutic potency in different seizure conditions across various animal species.

Background: Cerebral ischemia-reperfusion (I/R) injury is a significant pathological process in ischemic stroke, marked by oxidative stress, inflammation, and neuronal damage once blood flow is restored.

Objectives: The present study investigates the neuroprotective effects of phellopterin, a natural coumarin derivative, in a rat model of cerebral I/R injury.

Methods: The I/R injury was induced using the middle cerebral artery occlusion (MCAO) method, subjecting rats to 120 minutes of ischemia followed by 24 hours of reperfusion. Phellopterin was administered intragastrically at doses of 0.5 and 2.0 mg/kg, based on prior studies indicating effective therapeutic ranges in preclinical models. Neurological deficit scores (NDS) assessed functional impairments. Molecular markers of oxidative stress, including malondialdehyde (MDA) and superoxide dismutase (SOD), alongside inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were measured using enzyme-linked immunosorbent assays (ELISA). Gene expression analysis utilized quantitative reverse transcription polymerase chain reaction (RT-PCR) to evaluate mRNA levels of key oxidative stress and inflammatory markers.

Results: Our results indicated that phellopterin significantly reduced NDS in a dose-dependent manner. Molecular analyses demonstrated decreased MDA levels and increased SOD activity, reflecting reduced oxidative damage, alongside lowered TNF-α and IL-6 levels, indicating suppressed inflammation. The RT-PCR confirmed the upregulation of antioxidant genes [nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1)] and downregulation of pro-inflammatory genes [nuclear factor kappa B (NF-κB), iNOS].

Conclusions: In conclusion, phellopterin exhibits dual antioxidant and anti-inflammatory effects, suggesting its potential as a therapeutic agent for ischemic stroke. These findings underscore the potential of phellopterin as a promising candidate for the development of new treatments for ischemic stroke.