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Objective: To explore the effect of black radish (Raphanus sativus L. var niger) root extract on liver enzymes, oxidative stress, and histopathological alterations in mice with sodium valproate-induced hepatotoxicity. Methods: Thirty-two mice were divided into four groups: the control group received drinking water by gavage, the second group was administered with 100 mg/kg of sodium valproate, the third group received 300 mg/kg of black radish root extract, and the fourth group was given both sodium valproate (100 mg/kg) and black radish root extract (300 mg/kg). After 28 days, the mice were euthanized, and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), along with liver malondialdehyde (MDA), reactive oxygen species (ROS), mitochondrial parameters, tumor necrosis factor-alpha (TNF-α) gene expression, and histopathological changes were assessed. Results: Sodium valproate caused hepatic damage in mice, characterized by elevated serum levels of liver enzymes, increased MDA and ROS levels and TNF-α gene expression, as well as histopathological alterations. The black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST, MDA, ROS, TNF-α gene expression, as well as mitochondrial impairment, but did not have a significant effect on sodium valproate-induced histopathological changes. Conclusions: The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury, possibly through mitigating oxidative stress, mitochondrial impairment, and inflammatory mediator expression.

Abstract The occurrence of major depressive disorder is widespread and can be observed in individuals belonging to all societies. It has been suggested that changes in the NO pathway and heightened oxidative stress may play a role in developing this condition. Anethole is a diterpene aromatic compound found in the Umbelliferae, Apiaceae, and Schisandraceae families. It has potential pharmacological effects like antioxidant, anxiolytic, analgesic, anti-inflammatory, antidiabetic, gastroprotective, anticancer, estrogenic, and antimicrobial activities. This study aimed to investigate the potential antidepressant properties of Anethole in a mouse model experiencing maternal separation stress while also examining its impact on oxidative stress and nitrite levels. The research involved the participation of 40 male NMRI mice, separated into five distinct groups to conduct the study. The control group was administered 1 ml/kg of normal saline, while the MS groups were given normal saline and Anethole at 10, 50, and 100 mg/kg doses. The study comprised various behavioural tests, including the open field test (OFT), forced swimming test (FST), and splash test, to assess the effects of Anethole on the mice. In addition to the behavioural tests, measurements were taken to evaluate the total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus of the mice. According to the findings, maternal separation stress (MS) led to depressive-like conduct in mice, including a rise in immobility duration during the FST and a reduction in the duration of grooming behaviour in the splash test. Additionally, the results indicated that MS correlated with an increase in the levels of MDA and nitrite and a reduction in the TAC in the hippocampus. However, the administration of Anethole resulted in an increase in grooming activity time during the splash test and a decrease in immobility time during the FST. Anethole also exhibited antioxidant characteristics, as demonstrated by its ability to lower MDA and nitrite levels while increasing the TAC in the hippocampus. The results suggest that Anethole may have an antidepressant-like impact on mice separated from their mothers, likely partly due to its antioxidant properties in the hippocampus.

Abstract Background and aim Social isolation stress (SIS) is a stressor known to trigger depressive behaviors. Psychiatric disorders are associated with neurobiological changes, such as neuroinflammation and an increase in nitric oxide (NO) signaling. Despite the well‐established detrimental effects of SIS and the involvement of neuroinflammation and NO in depression, potential management strategies, especially resocialization, remain insufficiently explored. Our aim was to elucidate the effects of resocialization on depressive behaviors in socially isolated mice, with a focus on the possible involvement of neuroinflammation and nitrite in the hippocampus (HIP). Methods We utilized 24 Naval Medical Research Institute male mice, maintained under both social and isolation conditions (SC and IC). After the isolation period, the mice were divided into two groups of eight, including the SIS group and a resocialized group. The SC group was kept without exposure to isolation stress. We conducted the open‐field test, forced swimming test, and splash test to evaluate depressive behaviors. Additionally, nitrite levels, as well as the gene expression of interleukin (IL)‐1β, tumor necrosis factor (TNF), and toll‐like receptor 4 (TLR4) in the HIP, were measured. Results The study found that resocialization significantly reduces depressive behaviors in SIS mice. The results suggest that the antidepressive effects of resocialization may be partially due to the modulation of the neuroinflammatory response and nitrite levels in the HIP. This is supported by the observed decrease in hippocampal gene expression of IL‐1β, TLR4, and TNF, along with a reduction in nitrite levels following resocialization. Conclusion These insights could pave the way for new management strategies for depression, emphasizing the potential benefits of social interactions.

In spite of the broad biological and also anticarcinogenic effects which have been reported for galbanic acid in various studies, its toxic effects are not still well characterized. The study was accomplished to evaluate the acute oral toxicity of galbanic acid pursuant to Organisation for Economic Co-operation and Development (OECD) TG No. 425. Female rats were received asafoetida extract and galbanic acid in distilled water by oral gavage. According to the existing information, limit test was done for aqueous extract of asafoetida and main test was done for galbanic acid. The animals were monitored for 2 weeks. Then under general anesthesia, the blood samples were obtained from the heart for biochemical and hematological assessment and the vital organs of rats were isolated for pathological evaluation. The results showed that although the Median lethal dose (LD50) of asafoetida extract was above the 2000 mg/kg body weight, the galbanic acid estimated LD50 was 310.2 mg/kg. There was no considerable change in body weight of vehicle and extract treated animals but in galbanic acid treated animals, the body weights were not normally increased. A significant rise was observed in high-density lipoprotein (HDL), (aspartate aminotransferase) AST and (alanine aminotransferase) ALT levels as well as in white blood cells (WBC), platelet and lymphocytes counts in galbanic acid group compared to vehicle and extract groups. Based on the obtained results, we suggest that although the asafoetida aqueous extract could be categorized as group 5 (LD50 > 2000 mg/kg), but galbanic acid estimated LD50 is about 310.2 mg/kg and toxicity signs also appeared in lung, liver enzymes and complete blood count (CBC) of galbanic acid treated animals.

Background and aims: This study aimed to determine the effects of Astragalus fasciculifolius hydroalcoholic extract on rat ileum contractions: The role of adrenergic, opioid, and nitric oxide (NO) receptors. Methods: A. fasciculifolius extract was prepared using 70% alcohol by maceration extraction. 2 cm pieces from the end of the rat ileum were placed in a tissue bath containing Tyrode’s solution. The tissue bath solution is constantly oxygenated. Potassium chloride (KCl), naloxone, Nω-nitro-L-arginine methyl ester (L-NAME), propranolol, and different concentrations of calcium chloride were used to stimulate the ileum. Ileum contractions were recorded isotonically under 1 g of initial tension. The results were calculated as the amount of shortening (in millimeters). Results: This study showed that A. fasciculifolius extract caused a significant increase in ileum contraction compared to the control group (P < 0.001). This increase in contraction was amplified in combination with opioid or NO receptor antagonists (P < 0.001). Also, this effect was not significantly different in association with beta-adrenergic receptor antagonists. Conclusion: The results of this study showed that A. fasciculifolius extract enhances the contractile function of the ileum in rats. This function is reinforced by opioid receptor antagonists and NO.

In recent years, there has been a growing trend in the usage of traditional medicine and herbal treatments. However, the misconception that they are completely safe resulted in irreversible complications and damages. The present study was conducted to investigate the potential renal toxicity of a commonly used drug in Iran's traditional medicine and pharmacy, known as Zaravand Gerd or Nokhod Alvand (Aristolochia rotunda L.). In Iranian traditional medicine, Zaravand Gerd is used as a remedy for respiratory system ailments, back pain, anxiety, headache and septic wounds. Fifty-six male rats were divided into seven groups (n = 8). The first group served as the control and received normal saline, while the second to seventh groups were administered varying doses of the aqueous extract of Zaravand Gerd (0.1, 0.5, 1.25, 2.5, and 5 g/kg) for a period of three weeks. Various parameters were measured to evaluate the potential kidney damage caused by the extract, including serum creatinine and BUN levels, as well as urine protein and glucose levels, which were analyzed using an autoanalyzer. Additionally, kidney tissue samples were examined pathologically, and mitochondria from the kidney tissue were isolated to assess mitochondrial parameters. The results of this study revealed that high doses of Zaravand Gerd extract led to a significant increase in urinary glucose and protein excretion compared to the control group. Pathological examination of the isolated kidney tissues indicated that the concentrations of 2.5 and 5 g/kg of Zaravand Gerd extract resulted in kidney damage and dilation of proximal convoluted tubules. Furthermore, the study demonstrated that high doses of the extract (2.5 and 5 g/kg) caused damage to the mitochondria. Based on the findings of this study, it can be concluded that the administration of high doses of Zaravand Gerd extract, which are not commonly used in traditional medicine, can have toxic effects on the kidneys in rats as an animal model. These results highlight the importance of considering the potential risks associated with herbal medicines and the necessity of usage based on scientific evidence.

Background and aims: Inflammatory bowel disease is a chronic inflammatory disease whose prevalence is rising worldwide. The treatment-related challenges of this disease have expanded the research on other compounds with suitable therapeutic properties. Carvacrol monoterpene phenolic compound, with a wide range of therapeutic properties, can be an appropriate choice. This study aims to investigate the protective effect of carvacrol on acetic acid-induced colitis in mice, further emphasizing the modulating role of oxidative stress and inflammation. Methods: This experimental study was conducted on 60 mice divided into six groups. Colitis was induced by intrarectal injection of acetic acid. Five groups of mice received carvacrol at doses of 12.5, 25, 50, and 100 mg/kg and normal saline (1 ml/kg). One group was considered normal (without colitis) and received normal saline (1 ml/kg). The severity of colitis complications was assessed through histopathological examination of colon tissue samples. Furthermore, the malondialdehyde (MDA) level, total antioxidant capacity (TAC), and gene expression of inflammatory markers were investigated in the colon samples. Data analysis was done by PRISM version 8 using one-way ANOVA and Tukey’s test. Results: The results showed that the induction of colitis caused significant damage to the intestinal mucosal layers, and the administration of carvacrol reduced the severity of this damage. Interestingly, the TAC of all groups that received carvacrol was higher than that of the group that received normal saline (P < 0.05). The administration of carvacrol decreased the MDA level (P < 0.05). In addition, the gene expression of interleukin-1beta (IL-1β), Toll-like receptor 4 (TLR4), and tumor necrosis factor-alpha (TNF-α) reduced after carvacrol administration (P < 0.05). Conclusion: Carvacrol exerted a protective effect on the acetic acid-induced colitis in mice, probably via inhibiting the inflammatory cascade and modulating oxidative stress.

Background and aims: Given the prevalence of urolithiasis and the popularity of black radish extract for the treatment of this problem, the present study was designed to investigate its effect in alkalizing urine in stone-forming patients referred to Imam Ali clinic in Shahrekord (Iran). Methods: In this clinical trial, the urine pH was measured along with the 24-hour urine assessment for urine volume and urine citrate, oxalate, calcium, uric acid, and creatinine levels of 20 patients before and after the intervention. Results: The results showed a significant increase (P < 0.001) in mean urine pH after the administration of Raphanus sativus syrup for 14 days. The mean 24-hour urine volume and citrate level increased significantly (P < 0.05). In addition, the mean uric acid and oxalate levels decreased significantly (P < 0.05). Mean changes in 24-hour urine creatinine and calcium levels were not statistically significant after intervention (P > 0.05). Conclusion: Raphanus sativus extract treatment can increase urine pH, urine citrate level, and urine volume and decreases uric acid and oxalate levels. Therefore, the plant may be used for the treatment and prevention of uric acid and cystine stones.

Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of β-catenin (β-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of β-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit β-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment.

Abstract Background Depression is one of the most common mental illnesses worldwide. Nitric oxide (NO) is involved in the pathophysiology of depression. Auraptene (a coumarin derivative) has been shown to possess pharmacological effects on neurological diseases. Purpose The present study aimed to investigate the possible role of the NO pathway in Auraptene antidepressant effects in male mice. Methods Behavioral tests were used to assess depression-like behaviors. The mice received Auraptene at 10, 30, and 100 mg/kg, the combination of the sub-effective (ineffective) dose of Auraptene (10 mg/kg) and L-NAME, and the combination of the effective dose of Auraptene (30 mg/kg) and L-arginine. Finally, OFT, TST, FST, brain, serum MDA level, antioxidant capacity, hippocampus, and serum NO level were measured. Results The data analysis showed that Auraptene (30 mg/kg) improved depression-like behaviors. Auraptene (30 mg/kg) also significantly reduced serum NO levels (P

Abstract The effects of Rheum ribes on lead acetate levels and hepatic biochemical factors due to lead acetate toxicity were investigated. Forty male Wistar rats were designated into four groups: Control; lead acetate (receiving in drinking water at 0.6 g/L, daily); hydroalcoholic extract groups (200 and 400 mg/kg doses, gavage, once daily). Treatments were conducted for 10 days. On the 11th day, blood samples were collected to measure lead acetate levels and biochemical factors. Liver tissue samples were examined for histopathological changes. Lead serum levels were increased in lead acetate-treated rats (p

Background and Aims: Anxiety is one of the symptoms of menopause, which is due to stopping of ovarian activity. The aim of this study was to investigate the effect of Foeniculum vulgare L. extract on anxiety-like behaviors in ovariectomized mice.Methods: Eighty female mice weighing 25-30 g and aged 6-8 weeks were divided into 10 groups of eight each, controls: the group without ovariectomy given distilled water, positive controls: the ovariectomized group receiving 40 µg/kg of estradiol valerate, the groups without ovariectomy given F. vulgare extract by gavage at 200, 500, and 750 mg/kg, the ovariectomized group given distilled water, the ovariectomized groups given F. vulgare extract at 200, 500, and 750 mg/kg, and the ovariectomized group given diazepam at 1 mg/kg. Elevated plus maze (EPM) and open field were used to investigate anxiety in mice. The level of malondialdehyde (MDA) and total antioxidant capacity (TAC) of the brain and serum were also measured. Results: In ovariectomized mice, the number of entries to the closed arms of EPM was significantly increased compared with control group (P

Abstract Background Previous studies have shown that seizures can cause cognitive disorders. On the other hand, the Curcuma zedoaria (CZ) has beneficial effects on the nervous system. However, there is little information on the possible effects of the CZ extract on seizures. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats. Methods Rats were randomly divided into different groups. In all rats (except the sham group), kindling was performed by intraperitoneal injection of pentylenetetrazol (PTZ) at a dose of 35 mg/kg every 48 h for 14 days. Positive group received 2 mg/kg diazepam + PTZ; treatment groups received 100, 200 or 400 mg/kg CZ extract + PTZ; and one group received 0.5 mg/kg flumazenil and CZ extract + PTZ. Shuttle box and Morris Water Maze tests were used to measure memory and learning. On the last day of treatments PTZ injection was at dose of 60 mg/kg, tonic seizure threshold and mortality rate were recorded in each group. After deep anesthesia, blood was drawn from the rats’ hearts and the hippocampus of all rats was removed. Results Statistical analysis of the data showed that the CZ extract significantly increased the tonic seizure threshold and reduced the pentylenetetrazol-induced mortality and the extract dose of 400 mg/kg was selected as the most effective dose compared to the other doses. It was also found that flumazenil (a GABAA receptor antagonist) reduced the tonic seizure threshold compared to the effective dose of the extract. The results of shuttle box and Morris water maze behavioral tests showed that memory and learning decreased in the negative control group and the CZ extract treatment improved memory and learning in rats. The CZ extract also increased antioxidant capacity, decreased MDA and NO in the brain and serum of pre-treated groups in compared to the negative control group. Conclusion: It is concluded that the CZ extract has beneficial effects on learning and memory impairment in PTZ-induced epilepsy model, which has been associated with antioxidant effects in the brain or possibly exerts its effects through the GABAergic system.

Abstract Background Today, the attention of researchers has been drawn to the use of medicinal plant for the treatment of kidney stones. The aim of this study was to investigate the effect of five plants used in traditional medicine on the dissolution of calcium oxalate and calcium phosphate stones. Then, the ability of more effective plants to dissolve stones collected from patients after Percutaneous Nephrolithotripsy was investigated. Methods The aerial part of plants were extracted by maceration method. The synthesized stones in laboratory were incubated with different concentrations of the extract. Next, the concentrations of calcium oxalate and calcium phosphate were measured by a calcium kit and BT 3000. The effect of the extract with the best activity on the stones collected from the patients was also studied. The composition of clinical stones was determined by colorimetric method. The total phenolic content (TPC) of the extracts was determined. Results The highest dissolution of calcium oxalate stones was observed by the G. struthium extract and the highest dissolution of calcium phosphate stones by the A. euchroma and A. officinalis root extracts. The dissolution percentage of clinical stones by the A. euchroma extract was significantly higher than other extract (P

Context There are numerous pharmacological activities for Ruta graveolens and its bioactive constituent, rutin, on learning and memory. Objective This study aimed to examine the effect of R. graveolens and rutin on memory in rats. Materials and methods In this study animals were treated with the hydroalcholic extract of R. graveolens and rutin by IP injection for 10 days. Behavioural and biochemical tests as well as HPLC analysis and antioxidant activity of extract have been evaluated. Results R. graveolens extract and rutin significantly increased learning and improved spatial memory, as well as secondary latency; moreover, there were significant increases in the serum and brain antioxidant capacity as well as the level of TBARS in serum and brain tissues. Results also showed that R. graveolens has significant DPPH radical scavenging effect (IC50: 159.17 ± 1.56 μg/mL). The HPLC analysis of extract showed that caffeic acid (19.92 ± 0.01), rutin (40.15 ± 0.01), and apigenin (0.84 ± 0.01) mg/g of dry extract are the main components of the extract. Discussion and conclusion Regarding the effects of R. graveolens extract and rutin on animal brain cells, memory function, and learning, additional studies, including clinical trials, might be beneficial in producing natural supplementary drugs from this herb.

Background and Aim. Depression is a social problem with high economic burden in the society. Finding an effective agent with high efficacy and few side effects is therefore needed. Involvement of neuroimmune response as well as nitric oxide (NO) has been determined in the pathophysiology of depression. Limonene is a terpene with various pharmacological properties. Thus, we aimed to evaluate antidepressant-like effect of limonene on a mouse model of maternal separation (MS) focusing on neuroinflammation and NO level in the hippocampus. Methods. Mice were randomly divided into experimental groups as follows: the control group received normal saline and MS groups received normal saline, limonene (10 and 20 mg/kg), L-NAME (10 mg/kg), L-arginine (L-arg) (75 mg/kg), limonene (10 mg/kg) plus L-NAME, and limonene (20 mg/kg) plus L-arg. Behavioral tests including the forced swimming test (FST), open field test (OFT), and splash test were performed. Finally, serum and hippocampal nitrite levels as well as the expression of inflammatory genes (IL-1β and TNF-α) in the hippocampus were measured. Results. We showed that MS caused depressive-like behavior. Treatment of MS mice with limonene reduced the duration of immobility time in FST and increases the grooming activity time in the splash test. Limonene also reduces serum and brain nitrite levels and reduces the expression of IL-1β and TNF-α in the hippocampus. We found that L-NAME potentiated the effects of a subeffective dose of limonene. Conclusion. We concluded that the antidepressant-like effects of limonene are probably mediated through inhibition of neuroinflammation and attenuation of nitrite levels in the hippocampus.

Background and aim: Anxiety disorders are one of the most common psychiatric disorders worldwide. Common anti-anxiety medications are associated with several side effects. Caffeic acid (CA) is a phenolic compound with several pharmacological effects. The aim of this study was to investigate the anxiolytic-like effect of CA in maternally separated (MS) mice focusing on the possible involvement of the NMDA receptor. Materials and methods: In this study, we used the MS paradigm (as a valid animal model of anxiety) in male mice and examined their anxiety-like behavior in postnatal day (PND) 45. The animals were divided into 12 experimental groups. Mice treated with CA alone and in combination with the NMDA receptor agonist/antagonist and then using open field (OFT) and elevated plus maze (EPM) anxiety-like behavior was assessed. Finally, the expression of NMDA receptor subtypes was assessed in the hippocampus using RT- PCR. Results: Finding showed that CA exerted anxiolytic –like effects in the OFT and EPM tests. We showed that administration of effective dose of NMDA significantly reversed the anxiolytic-like effect of effective dose of CA and co-administration of ketamine (a NMDA receptor antagonist) significantly potentiated the effect of sub-effective dose of CA. Furthermore, ketamine enhanced the CA-reducing effect on NMDA receptors in the MS mice. Conclusion: Our finding demonstrated that, probably at least, NMDA receptors are involved in the anxiety-like properties of CA in MS mice.

Background: In the recent years, the prevalence of metal-induced toxicity, especially leadinduced toxicity, has increased considerably. Metals including lead cause oxidative stress. Therefore Rheum ribes L. as a medicinal plant with antioxidant activity may reduce the complications of these toxicities. Objectives: The aim of the current study was to investigate the protective effect of hydroalcoholic R. ribes L. extract in male rat model of lead acetate-induced nephrotoxicity. Materials and Methods: In this experimental study, 40 male Wistar rats were randomly assigned to four groups: Normal saline (control) group, positive control group treated with 0.6 g/L/d of lead acetate in drinking water, and two R. ribes groups treated with 200 and 400 mg/kg/d of R. ribes extract in addition to lead acetate for 10 days. After treatment, the rats were anesthetized, blood samples were taken, and kidneys were removed and fixed in 10% formalin. Then, serum antioxidant capacity was measured and kidney tissue specimens histopathologically studied. Results: Serum antioxidant capacity was significantly different between lead acetate group and the group treated with lead acetate + R. ribes extract (400 mg/kg). Additionally mice receiving lead acetate + R. ribes extract (400 mg/kg) had significantly higher antioxidant capacity than the control group (P