2026-10-10T11:37:17+03:30 http://ijpp.phypha.ir/browse.php?mag_id=18&slc_lang=fa&sid=1

18-693 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Maryam Hooshmand Ahmad Asoodeh* Mohamad Sayyah Hamid Gholami Pourbadie Mahbobeh Kamranimehni Background and Aim: Neurodegenerative diseases such as Alzheimer's disease are the most common cause of memory impairment worldwide. No effective drug treatment has been found to improve the memory deficit and quality of life of these patients. Considering the effects of MPL on improving memory in Alzheimer's disease and hippocampal ischemia, this study investigated the effect of monophosphoryl lipid A (MPL) on the spatial memory of rats. Methods: This study was conducted on 48 adult male Wistar rats (45-day-old) weighing 250-270 grams, which were randomly divided into two groups of “7 days” and “28 days”. Each group was divided into three subgroups (n = 8) including control, sham, and drug. The spatial learning and memory were assessed by the Morris water maze. Animals were trained to find the hidden platform in the maze for five days and 4 sessions every day. The drug was injected into the lateral cerebral ventricle at a dose of 1 µg per 5 µL per rat, 20 min after surgery. The time spent and the distance traveled in the target quadrant were assessed on the seventh and twenty-eighth days after the last day of learning. Results: No significant difference was found between the groups in the time spent and distance traveled in the target quadrant during the learning phase. Furthermore, there was no significant difference between groups in memory recall at both 7 days and 28 days after the training period (p > 0.05). Conclusion: In our study, MPL 1 µg/5 µL/rat did not affect the spatial memory of rats. ‎   Monophosphoryl lipid a spatial memory Morris water maze 2025 3 01 1 10 http://ijpp.phypha.ir/article-1-693-en.pdf

18-696 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Samira Rshtiani Mohamad Rostampour Behrooz Khakpour-Taleghani Kambiz Rohampour Background and Aim: One of the hypotheses of the pathophysiology of depression is the occurrence of functional alterations in the neural networks, including the default mode network and the salient network. This study aims to investigate the electrophysiological changes of the medial prefrontal cortex (mPFC) and the insula region of these neural networks in an animal model of depression. Methods: Twenty-eight male rats were divided into 4 control groups; chronic mild stress model (CMS), fluoxetine treated model (CMS + FLX), and fluoxetine recipient (FLX). Electrodes were placed in the mPFC and insula regions. Then, model rats were exposed to stressors every day for three weeks. The FLX group received one intraperitoneal injection of fluoxetine daily for two weeks. Finally, rats were evaluated with forced swimming, open field, and sucrose preference tests. Then the field potentials of the mentioned areas were recorded. Results: CMS rats had a lower tendency to consume sucrose (p ≤ 0.001). The CMS group had longer immobility time compared to healthy and FLX-treated mice (p ≤ 0.05). There was no significant difference in the field potentials in the stress condition or under auditory stress. In both insula and mPFC regions, theta band power in the CMS group was significantly lower than the control and CMS + FLX group (p ≤ 0.05). Conclusion: Chronic mild stress was able to reduce the theta frequency band in the insula and mPFC regions, and fluoxetine reversed these changes. This study confirms the occurrence of plastic changes in brain neural networks during depression. ‎   Chronic mild stress Depression Insula Field potentials Prefrontal cortex 2025 3 01 11 22 http://ijpp.phypha.ir/article-1-696-en.pdf

18-697 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mahbobeh Kamrani Mehni Maryam Hooshmand Mohamamd Sayyah Hamid Gholami Pourbadie* Morteza Zendehdel Background and Aim: Pam3cys is a weak agonist of toll-like receptors type 1 and 2 and is able to inhibit learning and memory impairment in an animal model of Alzheimer's disease by inhibiting the secretion of inflammatory cytokines and increasing the secretion of anti-inflammatory cytokines. This arrangement is effective in improving memory performance. Considering the improving effect of Pam3cys on learning and memory impairment of Alzheimer's disease in an animal model, in this study, the effect of Pam3cys drug alone on the spatial memory of rats was investigated Methods: In this experimental study, 48 male Wistar rats (age, 45-days old; weight, 220-270 g) were randomly divided into six groups (n = 8) as follows: There were two control groups of 7 and 28 days, two sham groups of 7 and 28 days, and two drug groups of 7 and 28 days. The spatial memory learning process of all mice was done using the Morris water maze for five days and four training sessions every day to find the hidden platform. At the last day of the learning period, the drug was injected intraventricularly with phosphate buffer (sham group) or Pam3cys (1 μg/5μl per mouse). 7 and 28 days after the injection, the memory of the rats was measured by measuring the time, speed and distance traveled in the target quarter of the maze. Results: In the learning phase, there was no significant difference between the groups in terms of the time spent and the distance traveled in the target quarter of the circle. At 7 and 28 days after the learning period, there was no significant difference between the groups in terms of memory recall between the group of animals that received Pam3cys and the group of control animals as well as sham animals without receiving the drug (p > 0.05). Conclusion: Pam3cys with the dose used in this study has no effect on the spatial memory performance of rats in the short and long term. Also, due to the lack of effect on healthy rats, it can be used as a safe medicine in disease conditions.   Pam3cys spatial memory Morris water maze Rat 2025 3 01 23 31 http://ijpp.phypha.ir/article-1-697-en.pdf

18-698 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Sahar Abolghasemi Mahdi Behdani Fatemeh Kazemi-Lomedasht Background and Aim: Cell adhesion plays an important role in the invasion of cancer cells. Disintegrins are considered a suitable therapeutic tool for cancer. This study aims to clone and express the disintegrin gene identified from the transcriptome of Hemiscorpius lepturus scorpion venom in a bacterial host and to investigate its function in an in vitro model.  Methods: Initially, the first, second and third structures of disintegrin protein were investigated using bioinformatics tools. Then, the gene was synthesized and cloned into pET-22b vector. The resulting construct was transformed into E.coli BL-21 bacterial host. The protein expression was induced by 0.5mM isopropyl-beta-D-thiogalactopyranoside. The expression was checked and confirmed by Sodium dodecyl sulfate-polyacrylamide gel and western blot. The protein was purified using nickel affinity chromatography under denaturing conditions. Following purification, the protein was refolded by gradually removing urea through dialysis. After protein expression and purification, the inhibitory effect of disintegrin on the survival and migration of HUVEC cell lines was investigated using MTT and transwell assay, respectively. Results: The results of structural analysis showed that the predicted disintegrin structure exhibits typical characteristics and conforms to expected structural patterns observed in disintegrin proteins. The highest level of protein expression was observed with Isopropyl-beta-D-thiogalactopyranoside concentration of 0.5mM and 5-hour incubation. The molecular weight of the expressed protein was approximately 12 kDa. The disintegrin inhibited the growth of HUVEC cells with an IC50 of 37 µg/ml after a 48-hour incubation period. Furthermore, the purified disintegrin inhibited the migration of 70% of HUVEC cells towards the vascular endothelia growth factor source, compared to the control group without disintegrin. Conclusion: These findings demonstrate the potential of the disintegrin identified from the transcriptome of the scorpion Hemiscorpius lepturus to inhibit the growth and migration of HUVEC cells.   Transcriptome Disintegrin Hemiscorpius lepturus scorpion. 2025 3 01 32 41 http://ijpp.phypha.ir/article-1-698-en.pdf

18-699 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Ali Mandegary Farzad Rafiei Saina Sadeghipour Seyed Mohammad Hossieni Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Although there are many medications available to control epilepsy, drug resistance and drug toxicity still pose significant challenges for managing this condition. Combination therapy and targeting different pathways involved in seizures can be a suitable strategy to reduce drug side effects and increase its efficacy. There are multiple reports on the relationship between epilepsy and melatonin, a neurohormone secreted by the pineal gland involved in regulating circadian rhythms. This review article will discuss recent advances in stimulating the melatonergic pathway with melatonin and melatonin agonists in the treatment of epilepsy. A comprehensive understanding of the relationship between melatonergic pathways and seizure could pave the way for future studies in treating epileptic disorders.   ‎Seizure Circadian Epilepsy Melatonin 2025 3 01 42 56 http://ijpp.phypha.ir/article-1-699-en.pdf

18-700 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mohammad Javad Esperham Sahel Motaghi Mahya Moradi Sirchi Background and Aim: The age of laboratory animals is an important variable at the time of the experiment. GABA is a neurotransmitter that is synthesized from the amino acid glutamate by the enzyme glutamate decarboxylase (GAD). GAD67 is the main enzyme responsible for the production of GABA and its reduction causes a decrease in GABA levels. Since the prefrontal cortex is one of the important brain structures in the neuronal circuits of anxiety and there has not been a comprehensive study related to anxiety and the change in gene expression of this enzyme in the prefrontal cortex at different ages, in this study, with the help of the elevated plus maze device, this assay was investigated. Methods: Rats with three age groups of 21, 42 and 360 days were used. At each age, the grouping of animals was as follows: 1) control group, 2) innate anxiety group in which the rats were placed in the elevated maze test, 3) diazepam administration group + innate anxiety group. Immediately after the test, the medial prefrontal cortex of the animals was isolated and evaluated with the help of a real time PCR technique. Results: Our results showed that anxiety in 21-day-old mice were higher than other ages. GAD67 enzyme expression of the prefrontal cortex did not change in innate anxiety and age had no effect on it (p > 0.05). Conclusion: It seems that in the prefrontal cortex, other components of the GABAergic system or other neurotransmitters such as serotonin, norepinephrine, etc. and their related mechanisms are involved in innate anxiety.   Anxiety Prefrontal cortex Glutamate decarboxylase 67 2025 3 01 57 65 http://ijpp.phypha.ir/article-1-700-en.pdf

18-710 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Vida Alipour Amir Shojaei Javad Mirnajafi-Zadeh Hossein Azizi Background and Aim: More than fifty percent of drug abusers start their substance abuse in adolescence. Chronic exposure to morphine, particularly during this developmental stage, may lead to long-lasting effects that can be transmitted to subsequent generation. The present study investigated the impact of paternal morphine exposure during adolescence on anxiety-like behavior in their male offspring during adulthood. Methods: Male Wistar rats were exposed to increasing doses of morphine (5–25 mg/kg, s.c.) or saline for 10 days at postnatal days (PND) 30–39 during adolescence. Following a 20-day drug-free period, the treated male rats were mated with naïve females. Adult male offspring (PND 60–70) were assessed for anxiety-like behavior using the elevated zero maze test. The experiments were conducted on two groups of offspring. One group had a male parent that received saline, while the other group had a male parent that received morphine. The number of rats in each group was 14. Results: Offspring whose male parent was exposed to morphine exhibited reduced anxiety-like behavior compared to the control group. The findings of this study suggest that paternal exposure to morphine during adolescence may influence anxiety-like behaviors in male offspring and lead to reduced levels of anxiety in adulthood. Conclusion: These results indicate that early substance use may have complex intergenerational effects and underscore the importance of understanding the long-term consequences of drug exposure during adolescence. Further research should focus on investigating the underlying mechanisms that induce behavioral changes and their potential impacts on mental health across different generations. Anxiety-like behavior Opioid Elevated zero maze Adolescence 2025 3 01 66 72 http://ijpp.phypha.ir/article-1-710-en.pdf

18-711 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Pegah Mousavi Soudabeh Sabetian Aghdas Dehghani Clear cell renal carcinoma (KIRC) is the most common type of kidney cancer and has a poor prognosis with a low overall survival rate, resulting in thousands of deaths per year. There is a critical need to understand the molecular mechanisms of KIRC to identify new biomarkers. the renin-angiotensin system (RAS), known for its regulatory role in cardiovascular, renal, and tissue functions, has been demonstrated in numerous studies to be significantly involved in the pathogenesis of malignant tumors. While microRNA has been studied as a biomarker and prognostic tool for different cancers, it remains challenging to explore its role in kidney cancer because a single miRNA can target multiple genes within biological networks and pathways. The aim of this study is to theoretically analyze the potential impact of single nucleotide polymorphisms (SNPs) in miRNAs related to genes involved in the renin-angiotensin pathway in clear cell renal carcinoma. To accomplish this goal, several online tools, including miRTarBase, CancerMIRNome, miRNASNPV3, UALCAN, and Ncpath were used.This study provides a list of confirmed SNPs that can affect the expression or function of renin-angiotensin pathway-related miRNAs in clear cell renal cell carcinoma disease for a prospective laboratory study in the diagnosis and treatment management of clear cell renal cell carcinoma.   Clear cell renal carcinoma Single nucleotide polymorphisms Renin-angiotensin system miRNA 2025 3 01 73 89 http://ijpp.phypha.ir/article-1-711-en.pdf

18-714 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Navid Tahami Sahel Motaghi GABA neurotransmitter and GABAergic system play an important role in brain health and physiology. There are many studies about the disturbance in this system and its relation with brain diseases. Most of the studies have investigated the role of the neurotransmitter GABA, its receptors and transporters, but there are not enough studies about the role of GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), which has two isoforms, GAD-65 and GAD-67. Since drugs that target enzymes, unlike receptors, do not undergo the phenomenon of desensitization or, in other words, drug resistance, therefore, if these enzymes are involved in the pathophysiology of brain diseases, they can be used as new and effective therapeutic approaches. Therefore, in this study, an attempt has been made to investigate the role of GABA- synthesizing enzymes in some common brain diseases.   GABA GAD65 GAD67 mental disorders 2025 3 01 90 104 http://ijpp.phypha.ir/article-1-714-en.pdf

18-718 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Vahid Hamedian Asl Morteza Zendehdel Keyvan Hasani Hamed Zarei Kimia Mahdavi Background and Aim: Despite proving the role of cholecystokinin (CCK) and the central histaminergic system in the regulation of food intake in birds and mammals, no findings have been presented regarding the interaction between these two systems. Therefore, the present study was designed and implemented with the aim of investigating the role of central histaminergic receptors in changes in food intake caused by CCK8S administration in broiler chickens. Methods: For this purpose, chicks were injected intracerebroventricularly (ICV) at the age of five days. In the first experiment, control solution and CCK8S in doses of 0.25, 0.5, and 1 nmol were administered, and in the second experiment, control solution, CCK8S (1 nmol), α-FMH (histamine synthesis inhibitor) and CCK8S + α-FMH were administrated. Experiments 3-5 were similar to the second experiment except that instead of α-FMH, chlorpheniramine (H1 receptor antagonist), famotidine (H2 receptor antagonist) and thiopramide (H3 receptor antagonist) were injected. Then, cumulative food consumption was measured at 30, 60, and 120 minutes after injection. Results: According to the obtained results, CCK8S injection decreased food consumption in chickens in a dose-dependent manner (p ≤ 0.05). Also, despite the ineffectiveness of separate injection of sub-effective doses of histamine receptor antagonists, the combined injection of α-FMH and chlorpheniramine with CCK8S significantly weakened the reduction of food intake induced by CCK (p ≤ 0.05). Conclusion: These findings indicate that the hypophagic effects of CCK8S may be mediated via H1 receptors in broilers.   Food intake Broiler Histaminergic system Cholecystokinin 2025 3 01 105 114 http://ijpp.phypha.ir/article-1-718-en.pdf

18-720 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Ali Dehghani Hedayat Sahraei Gholam Hossein Meftahi Background and Aim: The noradrenergic system in the basolateral amygdala and hippocampus regulates cognitive functions. These brain regions are susceptible to the damaging effects of exposure to stress. In this study, by infusing an antagonist of alpha-adrenergic receptors (phentolamine) in the basolateral amygdala following stress, we investigated the involvement of these receptors in this area in the changes in passive avoidance memory and the morphology of neurons in the CA1 area of ​​the hippocampus. Methods: Cannulation was performed bilaterally in the basolateral-amygdala in male rats using a stereotaxic device. Seven days after recovery, the animals were placed in the communication box and were subjected to stress for four days. Twenty minutes before stress, phentolamine (one microgram/one microliter) was injected bilaterally into the basolateral amygdala. The shuttle box test and Golgi-Cox staining were used. Results: The results of the shuttle box test showed that four days of foot-shock stress decreased step-through latency time. Also, the injection of phentolamine in the basolateral amygdala in with and without stress conditions significantly reduced the step-through latency time compared to the stress group. The results of Golgi-Cox staining showed that the number of dendritic spines in hippocampal CA1 neurons decreases under stress conditions and phentolamine injection in the basolateral amygdala compared to the control group. Conclusion: According to the results of the present study, stress causes memory impairment and changes in the morphology of hippocampal CA1 pyramidal neurons, which may be mediated through the mechanism of alpha-adrenergic receptors in the basolateral amygdala.   Stress Memory Dendritic spines Hippocampal CA1 region 2025 3 01 115 124 http://ijpp.phypha.ir/article-1-720-en.pdf

18-722 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Donya Zare Ameneh Omidi Mohammad Javan Forough Foulad Shahram Pourbeiranvand Background and Aim: Multiple sclerosis (MS) is a heterogeneous demyelinating disease of the central nervous system, in which patients experience a wide range of sensory, motor, cognitive, and psychological symptoms. Depression as one of the neuropsychological symptoms is observed with relatively high prevalence in MS patients. This study aims to investigate depression-like behaviors in acute MS model mice induced by a diet containing cuprizone neurotoxin. Methods: In this study, 14 male C57BL/6 mice were randomly divided into two groups as follows: a group that received a normal diet for 6 weeks (control group) and a group that received a diet containing 2 0.0% received cuprizone poison (cuprizone group). In addition to measuring the weight of the animals, two specific tests related to depression-like behaviors, including the forced swimming test and the tail suspension test, were taken weekly from the mice. At the end of the sixth week, the prefrontal cortex region of the brain tissue underwent histopathological evaluation. Results: Behavioral evaluations performed by the forced swimming test between the cuprizone and control groups showed a statistically significant difference in the fifth and sixth weeks (p < 0.05). However, the tail suspension test data showed a statistically significant difference between the two cuprizone and control groups only at the end of the sixth week (p < 0.05). Histopathological evaluations showed that following six weeks of a diet containing 0.2% cuprizone toxin, significant demyelination did not occur in the brain's prefrontal cortex. Conclusion: The diet containing cuprizone neurotoxin can lead to depression-like behaviors in C57BL/6 mice, although the observation of these behaviors was not accompanied by significant demyelination in the prefrontal cortex of the animals. ‎ Depression Prefrontal cortex Cuprizone Multiple sclerosis Demyelination ​​​​​​​ 2025 3 01 125 136 http://ijpp.phypha.ir/article-1-722-en.pdf

18-723 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Zeynab Zare Mehdi Imani Safiyeh Aghazadeh Background and Aim: Endolysin of phage KP27 is a protein with a molecular mass of 14.7 kDa, which has endopeptidase activity against bacterial cell walls. Due to limited research on endolysin KP27 and its superiority against harsh environmental conditions such as temperature and pH, the aim of this study is recombinant production and investigation of its antibacterial activity against two gram-negative and positive bacteria Methods: KP27 endolysin gene was cloned between two restriction enzymes NcoI and XhoI in plasmid pET-28a(+). E. coli BL21 (DE3) was used for expression and production and Purification was performed by Ni2+-NTA sepharose chromatography. Bactericidal activity tests, MIC and MBC against Escherichia coli and Staphylococcus aureus bacteria and cell wall degradation were used to investigate the antibacterial and enzymatic activities of endolysin, respectively. Statistical analysis and generation of graphs were achieved by Graphpad Prism software. Results: Endolysin KP27 was successfully cloned and produced with high efficiency in the amount of 28.5 mg/L of culture medium. Bactericidal activity against Escherichia coli and Staphylococcus aureus bacteria was over 50% at the concentrations of 4 µg/ml. For Escherichia coli, MIC and MBC were calculated 16 and 64 µg/ml while for  Staphylococcus aureus they were 8 and 32 µg/ml, respectively. Evaluating the cell wall degradation activity of endolysin indicated a 20% decrease in the turbidity of the solution after half an hour incubation with endolysin. Conclusion: Considering the high expression and production as well as its high activity against both Gram-negative and Gram-positive bacteria, endolysin KP27 can be suggested as a convenient candidate for further applied research and subsequent industrialization instead of antibiotics. ‎   Endolysin KP27 Bacteriophage Recombinant protein Cell wall Antibiotic resistance 2025 3 01 137 148 http://ijpp.phypha.ir/article-1-723-en.pdf

18-726 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Reza Sadri Ghader Najafi Saeid Abbasi-Maleki Background and Aim: Berberis vulgaris L. has analgesic, anti-inflammatory, antioxidant, and reducing morphine withdrawal signs effects. With this background, the aim of the present study is to investigate the antidepressant effect of B. vulgaris hydroalcoholic extract (BVHE) in forced swimming test (FST) and tail suspension test (TST). Methods: 84 male albino mice (6 mice in each group) were injected intraperitoneally with normal saline, fluoxetine (20 mg/kg), imipramine (30 mg/kg), and different doses of BVHE (40, 20, 80, and 160 mg/kg) and then they were subjected to FST and TST. The open-filed test (OFT) was also used to assess mice locomotion. Results: All doses of BVHE (except the dose of 20 mg/kg) decrease the duration of immobility in both FST and TST (p < 0.001). In addition, BVHE increased the duration of swimming (p < 0.001) without a significant change in the climbing time in FST (p > 0.05). The locomotion of mice (the number of crossings and rearings) did not show any significant change in the OFT (p > 0.05). Conclusion: Due to B. vulgaris anti-depressant effects in both mouse models, its antidepressant effects are similar to those of serotonergic drugs (such as fluoxetine). However, determining the exact mechanism of its action requires more and more extensive studies.   Forced swimming test Oxidative stress Berberis vulgaris L. Antidepressant 2025 3 01 149 157 http://ijpp.phypha.ir/article-1-726-en.pdf

18-730 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Maryam Alimohammadi Kataneh Abrari Afsaneh Goudarzi Background and Aim: Nowadays, humans are immersed in a sea of electromagnetic waves of natural or artificial origin and at the same time lead a stressful life. The aim of this study is to investigate the simultaneous effect of mobile phone electromagnetic waves and post-traumatic stress disorder (PTSD) on spatial memory. Methods: For this study, 40 rats were divided into 4 groups: naive group, PTSD group, electromagnetic wave group, and electromagnetic wave + PTSD group. A single long-term stress model was used to induce PTSD, and a cell phone was used to induce cell phone electromagnetic waves. The duration of cell phone radiation was 28 days and 50 min per day. Spatial memory was assessed with the Morris water maze. The anxiety was evaluated by open field test. The expression levels of Bcl2 and BAX genes in hippocampal tissue were measured by quantitative real-time polymerase chain reaction (RT-qPCR). Results: Spatial memory was significantly reduced in the naive and electromagnetic wave + PTSD groups compared to the naive group whereas the anxiety was significantly increased. Chronic exposure to mobile phone waves did not significantly alter the performance of animals in the water maze and open field test compared to controls. The ratio of Bax to Bcl-2 gene expression was higher in the naive and electromagnetic wave PTSD groups than the naive group Conclusion: Cell phone radiation, for 28 days and 50 minutes a day, did not have a synergistic effect with post-traumatic stress disorder on spatial memory and anxiety in rats, as well as indicators of neuronal death in their hippocampus.   Post-traumatic stress disorder electromagnetic waves cell phone Neural apoptosis hippocampus 2025 3 01 158 168 http://ijpp.phypha.ir/article-1-730-en.pdf

18-731 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Kimia Mahdavi Morteza Zendehdel Hamed Zarei The regulation of food intake is a complex process influenced by various neurochemical signals, including hormones and neurotransmitters. This review discusses the critical role of the central nervous system in regulating food intake, focusing on the effects of nitric oxide and its interactions with neurotransmitters and hormones. Nitric oxide, as a gaseous messenger molecule, plays an important role in regulating appetite through its interactions with neurotransmitters such as neuropeptide Y, dopamine and serotonin, as well as with hormones such as leptin and ghrelin. Understanding these interactions could provide novel insights into potential therapeutic approaches for appetite-related disorders such as obesity and anorexia nervosa. Furthermore, this review highlights the current knowledge regarding the diverse mechanisms of nitric oxide effects on appetite regulation and opens new avenues for future research pathways.‎   Food intake Appetite Nitric oxide Neurotransmitters Hormones 2025 3 01 169 182 http://ijpp.phypha.ir/article-1-731-en.pdf

18-735 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Rusul Abdulhamid Kadhim Amir Erfanparast Esmaeal Tamaddonfard Davoud Amirkashani Mehdi Imani Background and Aim: When glucose homeostasis is disrupted, acute or chronic hyperglycemia may occur. Linalool is a bioactive compound present in several plant species. In the present study, we investigated the effect of linalool on acute hyperglycemia and hypoinsulinemia caused by ketamine-xylazine administration. To clarify the involved mechanism, yohimbine (an α2-adrenergic receptor antagonist) was used. Methods: Linalool (2.5, 10, and 40 mg/kg) and yohimbine (0.5 and 2 mg/kg) were injected intraperitoneally (IP) 25 and 20 min before acute hyperglycemia induction, respectively. Acute hyperglycemia was induced with IP administration of a mixture of ketamine (100 mg/kg) and xylazine (10 mg/kg). The tail blood glucose levels were measured. After the last blood glucose level measurement, blood samples were taken to determine serum insulin concentration. To clarify the effects of drugs on blood glucose and serum insulin alterations in conscious animals, IP injections of the high doses of linalool (40 mg/kg) and yohimbine (2 mg/kg) were also performed without ketamine-xylazine treatment. The area under the curves (AUC) and the percentage of blood glucose changes in the period of 30-120 min after ketamine-xylazine injection and the percentage of serum insulin alterations were also calculated. Results: Blood glucose levels were significantly (p < 0.05) increased at 30, 60, 90, and 120 minutes after ketamine-xylazine injection. In addition, serum insulin concentrations were decreased by ketamine-xylazine administration. Linalool (10 and 40 mg/kg) and yohimbine (2 mg/kg) significantly (p < 0.05) inhibited acute hyperglycemia and hypoinsulinemia. Furthermore, co-administration of ineffective doses of linalool (2.5 mg/kg) and yohimbine (0.5 mg/kg) significantly prevented hyperglycemia and hypoinsulinemia. In conscious animals, no significant differences were observed between groups receiving vehicle and high doses of linalool and yohimbine. Conclusion: These results showed that linalool could decrease blood glucose levels and increase insulin concentration in the rat model of acute hyperglycemia. Alpha-2 adrenergic receptors might be involved in this effect of linalool.   Insulin Xylazine Linalool Hyperglycemia Yohimbine 2025 3 01 183 194 http://ijpp.phypha.ir/article-1-735-en.pdf

18-742 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mohaddeseh Mohammadi-Sardoo Ali Mandegary The increasing use of pesticides has raised concerns about their harmful effects on human health. Various evidences indicate a link between pesticide exposure and higher rates of chronic diseases. Mancozeb, a fungicide composed of a polymer of ethylene bis dithiocarbamate (EBDC) with elements of manganese and zinc, has a wide range of agricultural and industrial applications. Recent studies confirm that mancozeb has adverse effects on humans and in different animal models. This effect is due to mancozeb's ability to induce genetic toxicity, mitochondrial dysfunction, and oxidative stress, which are strongly associated with structural changes and functional impairments in organs such as the liver, nervous system, and reproductive system. This article reviews the toxic effects of mancozeb exposure in human and animal models. Also, this compound's main known molecular mechanisms of toxicity are reviewed.       Toxicity Mancozeb In vivo and In vitro study Molecular mechanism 2025 3 01 195 219 http://ijpp.phypha.ir/article-1-742-en.pdf

18-741 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mozhgan Jahani Omid Mohammaddoost Background and Aim:Insulin resistance is characterized by the lack of tissue response to insulin secretion and plays a fundamental role in the pathogenesis of diseases. The aim of the study was to investigate the effect of eight weeks of consumption water extract of Booghnagh and total body resistance Exercise (TRX) on resistin and insulin resistance index in overweight and obese women. Methods: The statistical population of this semi-experimental study was obese and overweight women in Torbat-Jam city. Forty eight people were selected as a sample purposefully and randomly divided into 4 groups: 1: TRX exercise + consumption of Boqnaq extract, 2: TRX exercise + placebo, 3: consumption of Boqnaq, 4: control. Blood samples were taken before and after the study to determine resistin and insulin resistance. TRX exercise was performed for eight weeks and 8 ml of the extract was consumed daily by dissolving it in 250 ml of water after lunch for eight weeks. Analysis was performed in SPSS-25 software with t-test and one-way analysis of variance statistical methods and, if significant, Scheffe test; at a significance level (p < 0.05). Results: The results showed that eight weeks of consumption of water extract of Booghnagh or TRX training did not have a significant effect on the subjects' resistin levels (p = 0.21), but it did cause a significant decrease in the insulin resistance index (p = 0.00). Conclusion: It seems that consuming water extract of Booghnagh or TRX training may be a strategy to modulate insulin resistance index levels and can be considered as an effective intervention method.       Exercise TRX Risintin Water extract of Booghnagh Insulin Resistance 2025 3 01 220 228 http://ijpp.phypha.ir/article-1-741-en.pdf

18-743 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Ali Tahamtan nezhad Emran Hamed Manouchehri Reza Changizi Mohadeseh Najarzadeh Ahangarkolaei Shahab Tirgar Fakheri Ali Siahposht Khachaki Background and aim: Depression is a mental disorder that, according to statistics, is becoming more serious each day, indicating an increasing need for research on depression models and the development of antidepressant drugs. The aim of this study was to evaluate the individual and combined effects of diazepam and escitalopram on behavioral and biochemical parameters in zebrafish (Danio rerio).  Methods: In this study, Depression was induced in zebrafish using the Unpredictable Chronic Stress (UCS) protocol. A total of 384 zebrafish were divided into two main groups: control (without stressors) and UCS (with stressors). Within each main group, the fish were further divided into four subgroups: control, diazepam, escitalopram, and diazepam + escitalopram, with three replicates per subgroup. Behavioral assessments were conducted using the novel tank test, and biochemical analyses were performed by measuring whole-body cortisol levels.  Results: Diazepam, escitalopram, and their combination significantly improved behavioral parameters (significant increase in the time spent at the top level and the number of transitions to the top level) and also prevented depressive effects by significantly reducing cortisol levels (from 1.0.1 ± 0.07 to 0.61 ± 0.12 ng of cortisol per gram of tissue).  Conclusion: This study confirms previous findings indicating that the UCS protocol induces behavioral and neuroendocrine changes in zebrafish, which can be prevented by diazepam and escitalopram administration. Furthermore, the findings support the use of zebrafish as a model organism for studying the behavioral and physiological effects of stress. Depression UCS protocol Zebrafish Diazepam Escitalopram 2025 3 01 229 238 http://ijpp.phypha.ir/article-1-743-en.pdf

18-744 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mohammad Nemati Morteza Zendehdel Keyvan Hasani Vahid Hamedian Asl Hamed Zarei Kimia Mahdavi Background and Aim: The central dopaminergic system plays a crucial role in appetite regulation; however, its interaction with neuropeptide W (NPW) in birds remains poorly understood. This study was designed and conducted to investigate the role of dopaminergic receptors in hyperphagia induced by central NPW23 injection in broiler chicks. Methods: A total of 220 broiler chicks (Ross-308) were involved in five experiments. In each experiment, the control solution, NPW23, dopaminergic receptor antagonists (D1: SCH23390, D2: AMI-193, D3: NGB2904, D4: L-741,742), or the dopaminergic neurotoxin (6-OHDA) were administered intracerebroventricularly (ICV) in sequence, either independently or in combination with NPW23. Subsequently, cumulative food intake was measured at 30, 60, and 120 minutes after injection. Results: Injection of NPW23 at a dose of 3 nanomoles significantly increased food intake in the chicks (p ≤ 0.05). The concurrent injection of the D1 receptor antagonist with NPW23 enhanced this effect (p ≤ 0.05), whereas combined injections of D2, D3, and D4 receptor antagonists with NPW23 had no significant effect on NPW23-induced hyperphagia (p>0.05). Furthermore, although administration of 6-OHDA alone did not affect the chicks' appetite, its simultaneous injection with NPW23 significantly increased hyperphagia induced by NPW23 (p ≤ 0.05). Conclusion: These findings indicate that the increase in appetite induced by NPW23 is mediated through interactions with the central dopaminergic system, particularly via D1 receptors in broiler chicks.   Appetite Broiler Dopaminergic system Neouropeptide W 2025 3 01 239 249 http://ijpp.phypha.ir/article-1-744-en.pdf

18-745 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mohammad Amin Mashayekhpour Hakimeh Gavzan Akbar Hajizadeh Moghadam Hamid Talayeh Ebrahimian Background and Aim: Depression is a serious mental disorder. Despite the availability of numerous medications, there are still constraints, such as high cost and adverse effects in the pharmacological treatment of depression. The Identification of bioactive plant compounds is of interest as an alternative treatment. Citral is one of the monoterpenes found in lemon peel oil with numerous therapeutic effects. This study investigated the effects of Citral on depression-like behaviors in mice under chronic unpredictable mild stress (CUMS). Methods: 48 male mice were randomly divided into 6 groups of 8: control, CUMS, vehicle + CUMS, fluoxetine 20 mg/kg + CUMS, Citral 100 mg/kg + CUMS, and Citral 200 mg/kg + CUMS. Except for the control group, mice were exposed to stressors according to a schedule for 6 weeks. In the last two weeks, treatments were administered orally. Then, depression-like behaviors were evaluated with sucrose preference, open field, forced swimming, and tail suspension tests. Results: Compared to vehicle, Citral decreased the sucrose preference in CUMS-mice (p < 0.001). Citral 200mg/kg increased the locomotor activities in the center zone (p < 0.05), and citral 100 and 200 mg/kg decreased the locomotor activities in the peripheral zone of an open field (p < 0.001). In the tail suspension test citral 100 and 200 mg/kg respectively with significant levels p < 0.05 and p < 0.01, the forced swimming test with significant levels p < 0.01 and p < 0.001 reduced the immobility time. Conclusion: Citral, like the standard drug, fluoxetine, could exert significant antidepressant effects in depressed and CUMS-mice.‎     Depression Citral CUMS Mice 2025 3 01 250 258 http://ijpp.phypha.ir/article-1-745-en.pdf

18-746 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Motahara Mirmahzoon Abbas Salehikia Omid Mohammaddoost Background and Aim: Physical activity causes the production of free radicals. In inflammation, mediators are secreted by immune system cells, such as tumor necrosis factor alpha. The aim of the study was to investigate the effect of eight weeks of curcumin extract consumption and aerobic + resistance training on TNF-α and body mass index in inactive obese women Methods: In this semi-experimental study, 48 obese inactive obese women aged 25-30 years were selected purposively and randomly divided into 4 groups: control, curcumin, Exercise + Placebo, and exercise + curcumin. They performed aerobic exercise with an intensity of 60 to 80% of maximum heart rate and resistance exercise with an intensity of 55 to 75% of one repetition maximum and consumed curcumin for eight weeks (three sessions per week). Blood sampling was performed 24 hours before the first session and 48 hours after the last training session, and serum TNF-α levels were measured by ELISA. Data were analyzed by paired t-test and one-way analysis of variance with a significance level of less than 0.05 in SPSS-25 (p < 0.05). Results: Based on the test, a significant difference was observed in the levels of TNF-α and body mass index in the exercise and exercise + curcumin groups compared to the pre-test (p = 0.00). The differences between the groups on the serum levels of TNF-α and body mass index were significant among the research groups (p = 0.00). Conclusion: Eight weeks of curcumin consumption and aerobic + resistance training reduced TNF-α and also reduced body mass index by affecting women's weight. It seems that the combined consumption of curcumin and exercise can have better results on the serum levels of inflammatory factors in obese women. Aerobic + Resistance Training BMI Curcumin inactive obese women TNF-α 2025 3 01 259 269 http://ijpp.phypha.ir/article-1-746-en.pdf

18-748 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mina Ghavidel Marghzari Fatemeh Valinezhad Sani Davood Zaeifi Shahram Eslami Bahman Sharifzadeh Fatemeh Gheybi Khadijeh Jamialahmadi Background and Objective: Plant polyphenols are natural sources of antioxidants that can help prevent many diseases, including cancer. Silymarin (SLM) and Ellagic acid (ELG) are two natural polyphenols, and in this study, for the first time, their cytotoxic effects and antioxidant activity were investigated individually and in combination in breast cancer cells. Methods: The cytotoxicity of Silymarin and Ellagic acid, alone and in combination, was investigated in the 4T1 breast cancer cell line using the MTT assay. Their antioxidant activity was also evaluated through the Ferric Reducing Antioxidant Power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods, both alone and in combination. Results: The findings revealed that Ellagic acid resulted in a more significant reduction in cell growth compared to Silymarin. The combined application of Silymarin and Ellagic acid demonstrated superior efficacy in inhibiting cancer cell proliferation compared to either compound used alone. Silymarin exhibited more antioxidant activity in the FRAP assay than Ellagic acid, while Ellagic acid outperformed Silymarin in the DPPH assay. Notably, the combination of these two substances enhanced antioxidant properties in both tests, particularly at molar ratios of 8:1 (p < 0.001) and 4:1(p < 0.05), as well as 50:6.25 and 50:12.5 SLM: ELG, indicating significant synergistic inhibitory effects. Conclusion: The results underscore Silymarin and Ellagic acid's cytotoxic effects and antioxidant activity. Furthermore, their combined use leads to a synergistic effect, suggesting that this combination treatment could represent a promising candidate for further research in breast cancer studies.   Antioxidant Breast cancer Combination therapy Ellagic acid Silymarin 2025 3 01 270 281 http://ijpp.phypha.ir/article-1-748-en.pdf

18-749 2026-10-10 10.1002

Iranian Journal of Physiology and Pharmacology Ir J Physiol Pharmacol 2588-4042 2588-4050 2025 8 Mahbubeh Masoompour-Askari Majid Vahidian-Rezazadeh Omid Mohammaddoost The aim of the study was to investigate the effect of six weeks of TRX training and curcumin consumption on liver enzymes in female athletes. This quasi-experimental study was conducted on 36 female athlete students aged 18-25 years. Targeted subjects were selected and randomly assigned to three groups (12 people). The intervention protocol was: six weeks of resistance training and curcumin supplement consumption (500 mg daily). AST, ALT, and ALP kits were used to measure enzymes. Data were analyzed with paired t-tests and one-way ANOVA at a significance level of p < 0.05. AST values ​​in the exercise+placebo group (p = 0.03) and exercise+curcumin (p = 0.02) decreased significantly, and ALT in the exercise+placebo group (p = 0.01) and exercise+curcumin (p = 0.02) increased significantly, and ALP enzyme in the exercise+placebo group (p = 0.02). Significant differences were observed between the exercise+placebo group and the curcumin group in AST and ALT (p = 0.00) and between the exercise+curcumin group and the curcumin group in AST (p = 0.01) and ALT (p = 0.02). Therefore, the use of curcumin along with TRX training as a non-invasive method will not have a protective role in the health of individuals and cannot have a positive effect on the levels of liver enzymes.   Curcumin female athletes liver enzyme TRX exercises 2025 3 01 282 288 http://ijpp.phypha.ir/article-1-749-en.pdf