Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 The effect of eight weeks of aerobic training on serum Nrf2 concentration and redox status markers in women with type 2 diabetes 1 9 FA Hanieh Panahyab Department of Exercise Physiology, Faculty of Educational Sciences and Physiology, University of Mohaghegh Ardabili, Ardabili, Iran Reza Farzizadeh Department of Exercise Physiology, Faculty of Educational Sciences and Physiology, University of Mohaghegh Ardabili, Ardabili, Iran Farnaz Seifi Asagshahr Department of Exercise Physiology, Faculty of Educational Sciences and Physiology, University of Mohaghegh Ardabili, Ardabili, Iran Background and objective: Type 2 diabetes, as one of the most prevalent metabolic diseases, is associated with an imbalance in redox balance and increased oxidative stress, and the transcription factor Nrf2, as a key regulator of cellular antioxidant and defense pathways, plays a central role in modulating this stress.  The present study was conducted to investigate the effect of 8 weeks of aerobic training on serum Nrf2 concentration and redox status markers in women with type 2 diabetes. Methods: Twenty women with type 2 diabetes (aged 40-60 years) were randomly assigned to either a control group (n = 10) or an aerobic training group (n = 10). The training group performed an 8-week treadmill running program (3 sessions per week) with progressively increasing intensity from 40% to 70% of maximum heart rate. Blood samples were collected 24 hours before and 48 hours after the intervention period. Serum levels of Nrf2, reduced glutathione (GSH), and oxidized glutathione (GSSG) were measured, and the GSH/GSSG ratio was calculated. A paired-samples t-test was used to compare within-group changes, and analysis of covariance (ANCOVA) was applied to compare between-group differences. Results: The results of the present study showed a significant increase in Nrf2 (p = 0.008), GSH (p = 0.004), GSH/GSSG ratio (p = 0.011), and a significant decrease in GSSG (p = 0.017) after 8 weeks of training in the aerobic group. However, in the control group, no significant difference was observed in any of the variables (p ≥ 0.05). Also, according to the analysis of covariance test with control of the pretest variable, a significant difference was observed between the two aerobic and control groups in GSH, GSSG, and GSH/GSSG ratio (p ≤ 0.05). Conclusion: Overall, the results of this study indicate that aerobic exercise can serve as an effective strategy for improving redox status and reducing oxidative stress in patients with type 2 diabetes. These findings highlight the importance of incorporating aerobic exercise into diabetes management programs and suggest that exercise is beneficial not only for glycemic control but also for improving metabolic health and reducing diabetes-related complications.    

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 Investigating the effects of frankincense on BDNF gene expression in striatum tissues in a paraquat-induced Parkinson animal model 10 18 FA Mohammad Amin Sharajpour Department of Animal Sciences, Faculty of Science, University of Mazandaran, Babolsar, Iran Sedigheh Khanjani Jelodar Department of Animal Sciences, Faculty of Science, University of Mazandaran, Babolsar, Iran Akbar Hajizadeh Moghaddam Department of Animal Sciences, Faculty of Science, University of Mazandaran, Babolsar, Iran Hakimeh Gavzan Department of Basic Sciences, Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran Mohammad Amin Mashayekhpour Department of Animal Sciences, Faculty of Science, University of Mazandaran, Babolsar, Iran Sakine Shalikar Department of Animal Biology, Payam Noor University, Babolsar, Iran Background and Aim: Parkinson's disease is one of the most common neurodegenerative disorders, caused by the degeneration of dopaminergic neurons in the substantia nigra. Frankincense (Boswellia resin) is an aromatic resin derived from species of the Burseraceae family, which has attracted attention for the treatment of neurodegenerative disorders due to its anti-inflammatory, antioxidant, and anti-apoptotic properties. The aim of the present study was to investigate the mechanism of action of frankincense in a paraquat-induced Parkinson's model, focusing on brain-derived neurotrophic factor (BDNF). Methods: To induce Parkinson's disease in mice, paraquat (PQ) was administered at a dose of 10 mg/kg (intraperitoneal injection, twice a week for three weeks). Animals were randomly divided into four groups (n = 6): (1) control, (2) PQ, (3) PQ + frankincense (20 mg/kg), and (4) PQ + frankincense (50 mg/kg). Motor function was assessed using the rotarod test (speed of 20 rpm). Additionally, BDNF gene expression in the striatum was measured using qRT-PCR. Results: The results showed that paraquat administration significantly impaired motor coordination (p < 0.001) and reduced BDNF gene expression (p <0.001). In contrast, treatment with frankincense at both doses significantly improved motor performance (p < 0.001) and increased BDNF expression (p < 0.05). Conclusion: In conclusion, the findings of this study indicate that frankincense can improve motor function in the paraquat-induced Parkinson's model by increasing BDNF gene expression in the striatum and its neuroprotective effects. These results suggest that neurotrophic pathways, particularly BDNF, may serve as promising therapeutic targets for natural compound-based interventions in Parkinson's disease.  

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 Exploring the potential effects of cannabidiol on the development of morphine sensitization induced by forced swim stress in rats 19 31 FA Hadi Semizeh Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Morteza Zendehdel Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Abbas Haghparast Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background and Aim: Cannabidiol, a non-psychoactive constituent of cannabis, has been proposed to modulate opioid sensitivity, but its mechanisms remain unclear. Stress is a key factor influencing opioid responses, yet its interaction with cannabidiol is not fully understood. This study investigated the effect of cannabidiol on morphine sensitization induced by forced swim stress in rats. Methods: Male Wistar rats received intracerebroventricular cannabidiol (10–200 µg/5 µl) with morphine (1 mg/kg, s.c.) or saline, in the presence or absence of forced swim stress for three days. Antinociceptive responses were assessed on day 9 using the tail-flick test. Data were analyzed using two-way repeated measures ANOVA followed by Bonferroni post hoc test. Results: Forced swim stress combined with a subthreshold dose of morphine induced significant sensitization, whereas either treatment alone had no effect. Cannabidiol attenuated morphine sensitization under stress conditions. In contrast, in the absence of stress, cannabidiol increased morphine sensitivity in a dose-dependent manner. Conclusion: Cannabidiol modulates morphine sensitization in a stress-dependent manner. However, intracerebroventricular administration and reliance on a single behavioral test limit the generalizability of these findings.  

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 Sex-related effects on cardiac function, biochemical markers, and oxidative stress in a rat model of heart failure 32 42 FA Naser Yousefi Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Sohaila Erfani Department of Biology, Faculty of Science, Ilam University, Ilam, Iran Zahra Salimi Department of Biology, Faculty of Science, University of Qom, Qom, Iran Tahere Valadbeigi Department of Biology, Faculty of Science, University of Qom, Qom, Iran Seyedeh Mahdieh Khoshnazar Gastroenterology Hepatology Research Center. Kerman University of Medical Sciences. Kerman, Iran Nahid Aboutaleb Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Background and Aim: Advances in cardiovascular research have identified oxidative stress as an important pathophysiological pathway in the creation and development of heart failure. Gender is also associated with differences in oxidative stress. This study aimed to investigate the effect of gender differences on cardiac function, biochemical parameters, and oxidative stress in an isoproterenol-induced heart failure (HF) model in rats. Methods: Forty Wistar rats (male and female) were divided into four groups: male control, female control, male HF, and female HF. HF was induced by subcutaneous injection of isoproterenol (130 mg/kg) for four consecutive days. On day 28, cardiac function was assessed using echocardiography. Serum levels of CK-MB, LDH, and cTnI were measured to evaluate myocardial injury. Oxidative stress indicators (MDA, SOD, and GSH) were examined using ELISA. Results: The study revealed no significant sex differences in serum levels of myocardial injury markers (LDH, CK-MB, and cTnI). Ejection fraction (EF) and fractional shortening (FS) were reduced in HF groups, but both parameters were significantly higher in female HF rats than in males (p < 0.05). No significant differences were observed in left ventricular internal diameters. In the female heart failure group, GSH and SOD were higher, and MDA was lower than in the male heart failure group (p < 0.05). Conclusion: These findings suggest that isoproterenol-induced HF leads to significant alterations in cardiac function, biochemical markers, and myocardial structure, with more severe effects in male rats. The study highlights the importance of considering sex differences in the pathophysiology of HF, which could inform the development of effective therapeutic strategies.  

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 Decoding the hidden mechanisms of swallowing using comparative physiology in mammalian models 43 59 FA Karaneh Mahdavi Department of Speech Therapy, School of Rehabilitation, Babol University of Medical Sciences, Babol, Iran Kimia Mahdavi Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Morteza Zendehdel Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Swallowing disorders (dysphagia) are among the most common and dangerous consequences of neurological diseases; however, their hidden mechanisms remain unknown due to limitations of invasive human studies. This narrative review adopts a "decoding" approach to demonstrate how comparative physiology in mammalian models uncovers the hidden layers of swallowing mechanisms and what insights this provides for speech therapy. At the comparative anatomical level, X-ray Reconstruction of Moving Morphology (XROMM) studies in macaques have refuted the traditional hypothesis of a dominant hyoid muscle role in tongue base retraction, instead revealing intrinsic tongue compression. At the biomechanical level, three-dimensional imaging in pigs and macaques has revealed complex tongue flexion and roll patterns during mastication and swallowing, showing striking similarity to human tongue movements. At the neural control level, simultaneous recordings from multi-electrode arrays in macaque primary motor cortex and high-speed tongue imaging have proven precise encoding of tongue shape and motion in this region; a finding that strengthens the brain-machine interface promise for swallowing rehabilitation. At the clinical level, rodent models of nerve injury and models of neurodegenerative diseases, including stroke, Parkinson's, and ALS, have enabled novel therapy screening and identification of phenotype-specific pathophysiological elements. Overall, comparative physiology, by decoding the anatomical, biomechanical, and neural layers of swallowing, has not only refuted old hypotheses but also opened practical pathways for targeted dysphagia diagnosis and treatment. Understanding mechanism diversity across mammalian species provides a systematic framework for appropriate animal model selection and designing targeted speech therapy interventions.‎

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 Effects of concurrent training and fenugreek supplementation on liver function indices in overweight women 60 70 FA Sadegh Abdollahi . Department of Physical Education and Sport Sciences, Bushehr Branch, Islamic Azad University, Bushehr, Iran Kamal Azizbeigi Department of Physical Education, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran Mohammad Ali Azarbayjani Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran Nastaran Keshtekar Department of Physical Education and Sport Sciences, Bushehr Branch, Islamic Azad University, Bushehr, Iran Background and Aim: Elevated liver enzymes are common consequences of overweight, serving as indicators of hepatocellular damage. Exercise training can effectively improve liver function. On the other hand, fenugreek (Trigonella foenum-graecum) has drawn attention due to its hepatoprotective effects. This study aimed to investigate the effects of six weeks of combined training along with fenugreek supplementation on liver function indicators in overweight women. Methods: This quasi-experimental study was conducted using a pretest-posttest design with a control group. Participants were randomly divided into four groups: combined training, fenugreek supplementation, combined training + supplementation, and control. The training program consisted of aerobic and resistance exercises for six weeks, three sessions per week. The supplement-receiving groups consumed 670 mg/day of dry fenugreek seed extract. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels were measured before and after the intervention. Data were analyzed using analysis of variance (ANOVA) and Bonferroni post-hoc test at a significance level of (p < 0.05). Results: In the combined training group, significant reductions were observed in ALT (33.05%), AST (18.29%), and ALP (10.80%). In the fenugreek supplementation group, ALT, AST, and ALP levels decreased by 13.83%, 19.24%, and 14.79%, respectively. In the combined training + fenugreek supplementation group, AST, ALP, and ALT levels were reduced by 30.19%, 26.95%, and 21.82%, respectively (p < 0.05). The greatest reduction in ALT was observed in the combined training group, whereas the greatest reductions in AST and ALP were noted in the combined training + fenugreek group, while the control group showed no significant changes. Conclusion: Combined training and fenugreek supplementation (individually or interactively) reduced ALT, AST, and ALP levels in overweight women. Combined training alone resulted in the greatest reduction in ALT, whereas combined training paired with fenugreek yielded the highest reduction in AST and ALP levels.  

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 Transcriptomic analysis of the effect of silibinin on human adipose tissue-derived mesenchymal stem cells using RNA sequencing 71 81 FA Sogand Abedi 1. Department of Biology, Faculty of Basic Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran Farshid Kafilzadeh 2. Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran Soheila Zamanlui Benisi 3. Department of Biomedical Engineering, Islamic Faculty of Engineering, Central Tehran Branch, Islamic Azad University, Tehran, Iran Yaghoob Tahery 5. Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran Background: Human adipose-derived stem cells (hADSCs) are vital in regenerative medicine due to their high differentiation potential and immunomodulatory properties. Silibinin, the primary bioactive compound in milk thistle, possesses diverse pharmacological effects, including anti-inflammatory and antioxidant properties. However, its impact on the genomic expression patterns of hADSCs remains unexplored. Methods: hADSCs were treated with varying silibinin concentrations (0.5, 1, and 10 μg/mL) for 24 hours, and viability was assessed via MTT assay. To identify differentially expressed genes (DEGs), RNA sequencing (RNA-Seq) was performed on control and 0.5 μg/mL-treated cells on day 12. Gene set enrichment analysis was conducted using WebGestalt (2024) and relevant biological databases. Results: MTT assays revealed that 0.5 and 1 μg/mL concentrations enhanced cell proliferation, whereas 10 μg/mL exhibited cytotoxicity. RNA-Seq identified 257 DEGs, with 89 genes significantly involved in various biological processes. Key findings included significant differential expression of ARHGDIB (fold change: -14.67), CD36 (+8.65), TNFSF18 (-18.64), and FGF1 (+8.95). Conclusion: Silibinin (0.5 μg/mL) promotes hADSC proliferation and induces a specific transcriptomic profile. This profile significantly enriches genes associated with cell adhesion, extracellular structure organization, angiogenesis, and ribonuclease activity regulation. The coordinated regulation of genes involved in inflammation, vascular differentiation, and bioadhesion highlights silibinin’s therapeutic potential for tissue repair and enhancing cellular functions in regenerative therapies.    

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 The effect of low-volume high-intensity interval training (LV-HIIT) combined with low-dose crocin consumption on body mass index, insulin resistance, and insulin sensitivity in overweight women 82 91 FA Fahimeh Kazemi Nazanin Mohammadzadeh Background: Exercise training and herbal supplements are considered effective interventions for improving overweight and obesity. The present study aimed to determine the effect of low-volume high-intensity interval training (LV-HIIT) combined with low-dose crocin consumption on body mass index (BMI), insulin resistance, and insulin sensitivity in overweight women. Methods: In a randomized controlled trial, 40 volunteer overweight women (age range: 25–40 years, BMI: 25–30 kg/m²) were randomly assigned to four groups of 10: control (placebo), LV‑HIIT + placebo, crocin, and LV‑HIIT + crocin. The training groups performed the LV‑HIIT protocol (2 minutes of activity followed by 2 minutes of rest) for 8 weeks (two sessions per week), and the supplement groups took 15 mg/day of crocin orally for 8 weeks. Blood samples were collected 24 hours before and 48 hours after the intervention period, and serum glucose and insulin levels were measured. Data were analyzed using a two‑way repeated‑measures analysis of variance (ANOVA). Results: A significant group × time interaction was observed for BMI, the homeostatic model assessment of insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) (p < 0.05). In the LV-HIIT + placebo, crocin, and LV-HIIT + crocin groups, BMI and HOMA-IR significantly decreased, while QUICKI significantly increased from pre-test to post-test (p < 0.05). In addition, BMI was significantly lower in the LV-HIIT + placebo group than in the crocin group (p < 0.05). However, no significant between-group differences were observed in HOMA-IR or QUICKI between the crocin and placebo groups or between the LV-HIIT + crocin and LV-HIIT + placebo groups (p > 0.05). Conclusion: Eight weeks of LV-HIIT was associated with improvements in BMI and indices of insulin resistance and sensitivity in overweight women. Although within-group improvements in these indices were also observed in the low-dose crocin-treated groups, the between-group comparisons did not provide sufficient evidence to support an independent effect of crocin or an additional benefit of adding crocin to LV-HIIT. Therefore, an additive or synergistic effect of crocin combined with LV-HIIT cannot be confirmed in the present study.  

Iranian association of Physiology and Pharmacology Iranian Journal of Physiology and Pharmacology 2588-4042 10 2026 5 1 Evaluation of the effect of piperine on the expression of morphine-induced conditioned place preference in male mice: Possible role of dopamine receptors 92 107 FA Ali Rezaei 1. Department of Pathobiology, Faculty of Veterinary Medicine, Ur.C., Islamic Azad University, Urmia, Iran Ghader Najafi 1. Department of Pathobiology, Faculty of Veterinary Medicine, Ur.C., Islamic Azad University, Urmia, Iran Saeid Abbasi Maleki 2. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran 3. Department of Pharmacology & Toxicology, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran Background: Piperine, the main alkaloid of black pepper, increases brain dopamine release. Given the importance of dopaminergic pathways in opioid-induced reward behaviors, this study aimed to investigate the effect of piperine on the expression of morphine-induced conditioned place preference (CPP) and the role of dopamine D1 and D2 receptors. Methods: Male NMRI mice were evaluated in a 6-day protocol consisting of pre-conditioning, conditioning, and post-conditioning phases. After determining the effective dose of morphine in inducing CPP, the effects of piperine (10, 20, and 40 mg/kg) alone and in combination with morphine were assessed. Locomotor activity and exploratory behavior of the animals were also recorded in the open field test (OFT). To evaluate the dopaminergic mechanism, morphine-conditioned mice received a D1 receptor antagonist (SCH-23390; 0.05 mg/kg) or a D2 receptor antagonist (sulpiride; 5 mg/kg) 60 minutes prior to the administration of piperine (40 mg/kg). Results: Morphine at doses of 5 and 10 mg/kg significantly induced CPP (p < 0.001; an increase of 1049.6% and 1140.8%, respectively). Piperine alone did not induce CPP or aversion (CPA) and did not cause locomotor changes in the OFT (p > 0.05). However, piperine (40 mg/kg) significantly potentiated the expression of morphine CPP by 51.6% (p < 0.001). Pretreatment with SCH-23390 and sulpiride significantly inhibited the potentiating effect of piperine (p < 0.001; a decrease of 154.7% and 142.3%, respectively). Conclusion: Piperine administration alone did not induce significant CPP or CPA. However, acute piperine administration may enhance morphine-induced CPP. This effect is likely mediated, at least in part, through the involvement of dopaminergic pathways.