sajadfakhri

Rheumatoid arthritis (RA) is a persistent inflammatory condition characterized by an imbalance in oxidative stress and chronic inflammation of joint tissues.

Fraxinus excelsior L., commonly known as ash, has demonstrated anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties. The present study aims to evaluate the therapeutic effects of F. excelsior L. bark hydromethanolic extract (FEE) in the management of RA.

Thirty male rats were randomly divided into six groups: Normal control, RA, three dosages of FEE (20, 40, 80 mg/kg/day, orally), and prednisolone (10 mg/kg/day, orally). These doses were selected to evaluate the potential dose-dependent effects of FEE. The hot plate test, serum glutathione (GSH), malondialdehyde (MDA), and histopathological investigations were assessed. The activity of matrix metalloproteinases (MMP-2 and MMP-9) was measured using zymography. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis previously confirmed the presence of coumarins in FEE.

The FEE significantly reduced pain perception in the hot plate test (P < 0.001). Malondialdehyde levels were significantly elevated in RA rats (P < 0.001) but were reduced following FEE and prednisolone treatment (P < 0.01). Similarly, GSH levels were significantly decreased in RA rats (P < 0.001) but were restored in FEE-treated groups (P < 0.01, P < 0.001 for higher doses). The FEE also significantly decreased MMP-2 and MMP-9 activity (P < 0.001), confirming its anti-inflammatory potential. Histopathological analyses corroborated these findings, demonstrating reduced synovial hyperplasia and inflammatory cell infiltration in FEE-treated groups. Coumarins in FEE are known to modulate inflammation through inhibition of MMP-2 and MMP-9 activity and regulate oxidative stress by enhancing antioxidant defenses, including increasing GSH levels and reducing MDA accumulation.

Given the improvements in behavioral, biochemical, and histopathological parameters alongside modulation of inflammation (MMP-2, MMP-9) and oxidative stress (MDA, GSH), our results suggest that FEE, rich in coumarins, could be a promising candidate for RA management.

Ulcerative colitis (UC) is a chronic inflammatory disease of the large intestine that cannot be cured, but its symptoms can be managed.

This study aimed to evaluate the protective effects of hydroalcoholic and aqueous extracts of Ulmus minor leaves on UC induced by acetic acid in rats.

Rats were randomly divided into seven groups of five, and 3% acetic acid was used to induce colitis. To assess the protective effect of Ulmus minor leaves, macroscopic, microscopic, and histological evaluations were performed on the different study groups.

Macroscopic examinations of both the hydroalcoholic and aqueous extract groups showed that the aqueous extract at a dose of 200 mg/kg provided the best protective effect on colon tissue. Rats treated with hydroalcoholic extracts at doses of 100 mg/kg and 200 mg/kg, as well as those treated with aqueous extract at 100 mg/kg, also showed favorable outcomes compared to the control group, with a significant difference (P < 0.05). Furthermore, among the groups treated with hydroalcoholic and aqueous extracts, the aqueous extract at 200 mg/kg demonstrated the most protective effects based on microscopic and histological evaluations of the colon.

The extracts of Ulmus minor leaves demonstrated anti-inflammatory properties in an animal model of colitis. Further studies are required to evaluate their potential therapeutic benefits in patients with UC.

Epilepsy is a group of chronic neurological diseases caused by a complex set of neuronal hyper electrical activities and oxidative stress of neurons. Crocin is a natural bioactive agent of saffron with different pharmacological properties and low bioavailability. This study aimed to evaluate crocin-loaded solid lipid nanoparticles (SLNC) for neuroprotection activity and efficacy against pentylenetetrazol (PTZ)- induced epilepsy.

Experimental approach: 

The rats were pretreated with SLNC and pure-crocin (PC; 25 and 50 mg/kg/day; P.O.) for 28 days before PTZ induction. Behavioral functions were evaluated by passive avoidance learning (PAL) tasks. Then, total antioxidant capacity (TAC), malondialdehyde (MDA), and pro-inflammatory factors were measured in the brain tissue using ELISA kits. Gene expression levels were analyzed with real-time polymerase chain reaction and immunohistochemical assay was used to assess the protein expression of sirtuin1 SIRT 1).

SLNC was prepared with an average particle size of 98.25 nm and 98.33% encapsulation efficiency. Memory deficit improved in rats treated with SLNC. Administering SLNC at 25 and 50 mg/kg significantly reduced MDA and proinflammatory cytokines while increasing TAC. Additionally, administering SLNC before treatment increased the levels of SIRT1, peroxisome proliferator-activated receptor coactivator 1α, cAMP-regulated enhancer binding protein, and brain-derived neurotrophic factor. Furthermore, SLNC administration resulted in the downregulation of caspase-3 and inflammation factor expression.

Conclusion and implications: 

Overall, the obtained results showed that SLNC has better protective effects on oxidative stress in neurons, neurocognitive function, and anti-apoptotic and neuromodulatory activity than PC, suggesting that it is a promising therapeutic strategy for inhibiting seizures.

There is usually a connection between the secretion of stomach acid and stomach ulcers, but today the main cause of these ulcers is considered to be the presence and proliferation of Helicobacter pylori bacteria, which causes peptic ulcers in various ways, including damage to the protective layer. Therefore, the aim of this study is to investigate the protective effect of the aqueous and hydroalcoholic extracts of Plantago major L. leaves on gastric ulcers induced by ethanol in rats. First, 36 adult male Wistar rats were selected and divided into 9 groups including famotidine and control groups, healthy groups, and protective groups that received the aqueous and hydroalcoholic extracts of the leaves of the P. major. After preparing and checking the obtained results, quantitative data was evaluated with a one-way analysis of variance and Tukey's post hoc test using SPSS software. The macroscopic examination results showed that in both groups receiving aqueous and hydroalcoholic extracts of the P. major plant, the group receiving the extract with a dose of 200 mg/kg had the best protective effect compared to the control group. The general results of the present study showed that in both groups receiving the aqueous and hydroalcoholic extracts of the plant leaves, the group receiving the extract with a dose of 200 mg/kg had the best protective effect compared to the control group. In conclusion, our findings indicated that this extract is a potential agent that can be used for the treatment of peptic ulcers and gastric tissue wounds.

Herbal medicines can be used as a possible therapeutic agent in inflammatory diseases.

This study aimed to determine the effect of Artemisia vulgaris (AV) hydro-alcoholic extract on oxidative stress and inflammatory damage in an experimental rat model of colitis.

Thirty male Sprague-Dawley rats were randomly divided into 6 groups: Control, colitis, sulfasalazine, AV50, AV100, and AV200. The animals of the AV groups were treated with the hydro-alcoholic extract of A. vulgaris via gavage for 72 h. Body weight was measured at the beginning and end of the experiment. In the end, serum levels of malondialdehyde (MDA) as a lipid peroxidation marker, antioxidants such as glutathione (GSH), superoxide dismutase (SOD) activity, serum tumor necrosis factor- (TNF-), and nitric oxide (NO) levels as inflammatory biomarkers were measured. Macroscopic and microscopic damage in the rat’s colon was also examined in histological studies.

The A. vulgaris extract treatment dose-dependently improved colonic injury (P < 0.001 to P < 0.05) and body weight (P < 0.001) in colitis rats. Moreover, it enhanced SOD activity and GSH levels (P < 0.001) and reduced serum MDA, TNF-, and NO levels (P < 0.001 to P < 0.01) in the rats with colitis.

Treatment with A. vulgaris could mitigate ulcerative colitis (UC) symptoms, which is probably attributed to its antioxidant and anti-inflammatory properties.

Spinal cord injury (SCI) is a debilitating sensory-motor dysfunction. Neuropathic pain and motor dysfunction are the most common types of dysfunctionality after SCI, which reduces the quality of life. So far, SCI treatment has not been completely effective and researchers are seeking for novel alternative/potent therapies. Metformin has shown antioxidant and anti-inflammatory effects on the central and peripheral nervous systems. In the present study, the probable neuroprotective and antioxidant effects of intrathecal metformin administration was evaluated on the neuropathic pain and motor dysfunction after SCI.

Thirty-five rats were divided into five groups: sham, SCI, and metformin (Met) at doses of 1, 2 and 4 mM. Hot plate, acetone, and von Frey behavioral tests and weight changes were performed on days 7, 14, 21, and 28 after SCI. The changes in serum levels of catalase and glutathione, as well as nitrite level, and numbers of sensory and motor neurons were measured on day 28 after surgery.

Intrathecal injection of metformin reduced heat, cold and mechanical pain, motor activity, and modulated weight changes in rats after SCI. Intrathecal metformin also attenuated serum changes of catalase and glutathione, decreased serum nitrite, and increased survived sensory and motor neurons after SCI.

Employing the neuroprotective and antioxidant potential of intrathecal metformin administration could reduce neuropathic pain and improve motor dysfunction following SCI.
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Therapeutic strategies that facilitate extinction are promising in the treatment of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has a crucial role in neural plasticity, a process needed for the retention of fear extinction. In this study, we investigated the effects of local administration of a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu), on BDNF transcription and behavioral markers of extinction in the single prolonged stress (SPS) model of PTSD. 

NaBu was infused into the infralimbic (IL) subregion of the medial prefrontal cortex (mPFC) of male rats. The freezing response was recorded as the criterion to assess fear strength on the day of extinction as well as 24 hr later in the retention test. Other behavioral tests were also measured to evaluate the anxiety level, locomotor activity, and working memory on the retention day. HDAC activity and BDNF mRNA expression were evaluated after the behavioral experiments. 

NaBu facilitated the recall of fear extinction in SPS rats (P<0.0001). SPS rats had higher HDAC activity (P<0.0001) and lower BDNF expression (P<0.05) than non-SPS animals. Also, anxiety was higher in the SPS group (P<0.0001), but locomotor activity (P=0.61) and working memory (P=0.36) were not different between SPS and Non-SPS groups.

Our findings provide evidence that the mechanism of action of NaBu in the improvement of extinction recall is mediated, in part, by enhancing histone acetylation and reviving BDNF expression in IL.

The major secondary complications of spinal cord injury (SCI) are neuropathic pain and motor dysfunction, which remained medical challenges for clinicians. Due to the major role of glutamate in excitotoxicity and central sensitization, the present experiment was to evaluate the effects of ketamine (KET), an n-methyl-D-aspartate (NMDA) receptor blocker, on sensory-motor functions in a rat model of clip compression SCI.

Wistar rats were divided into sham, SCI and KET-treated groups. The sham group received laminectomy without any compression lesion. KET and SCI groups were subjected to severe compression injury for 1min with an aneurysm clip and then treated with KET (10mg/kg) or 5% dimethyl sulfoxide (as vehicle), respectively. The rats were assessed by pain-related and motor behavioral tests inclusive of von Frey, acetone drop, hot plate, inclined plane and Basso-Beattie-Bresnahan on day 0 prior to the injury and the 7th, 14th, 21st and 28th days following SCI.

KET group compared with the SCI group showed a significant decline in the mechanical allodynia on the 21st and 28th days, and in cold allodynia from the 1st week to the 4th week post-injury. KET treatment improved the motor function but not weight loss and auricle temperature rise during the 4 weeks of follow up from the 1st week until the 4th week.

It was ultimately attained that the advantageous effects of intrathecal KET on sensory-motor dysfunction of SCI rats could provide new approaches for KET as a neuroprotective agent toward clinical applications.

Sex differences in outcomes of Spinal Cord Injury (SCI) suggest a sex-hormone-mediated effect on post-SCI pathological events, including glutamate excitotoxicity. This study aimed to investigate the importance of gonadal hormones on glutamate release subsequent to SCI in rats. After laminectomy at T8-T9, an electrolytic lesion was applied to the spinothalamic tracts of male and female rats. Using spinal microdialysis, we assessed glutamate levels at the site of lesion in both intact and gonadectomized rats for 4 hours. In this way, we examined the sex differences in the glutamate concentrations. The peak retention time of glutamate level was 10.6 min and spinal glutamate concentration reached a maximum level 40 min following SCI. In male SCI rats, gonadectomy caused a significant elevation of glutamate level (P<0.001) following injury which was maximum 40 min post-SCI as well. However, no significant alterations were seen in gonadectomized female rats. The significant differences in glutamate levels between both intact and gonadectomized SCI male and female rats show the sex-hormone-related mechanisms underlying the molecular events in the second phase of SCI. It seems that the role of male gonadal hormones to prevent glutamate excitotoxicity is more prominent. The exact mechanisms of these hormones on the functional recovery after SCI should be clarified in further studies.

Dorema ammoniacum gum resin is used in Iranian traditional medicine for different indications including inflammatory diseases which are on the rise. Considering the important role of inflammation in different diseases, in the present study, we aimed to investigate the in vivo anti-inflammatory activity and skin toxicity of Dorema ammoniacum gum extract (DAGE) in rats and rabbits.

The systemic anti-inflammatory effect ofDAGE (100, 200 and 300 mg/kg, i.p.) was assessed by carrageenan-induced paw edema method in 30 min, 1, 2, 3 and 4 h after the carrageenan injection to thirty male Wistar rats divided into five groups of six each. Control and standard groups received the vehicle and mefenamic acid (30 mg/kg, i.p.), respectively. To assess the topical anti-inflammatory effect ofthegum, eighteen rats were divided into three groups of six: standard, vehicle, and test groups which received topical diclofenac gel, distilled water and DAGE, respectively. The acute dermal toxicity of DAGEwas evaluated in nine white New Zealand rabbits.

The results showed significant anti-inflammatory effects of DAGE in systemic treatment.The findings also indicated that all doses of DAGE were more potent than mefenamic acid. However, the topical anti-inflammatory activity of DAGE (100 mg/kg) was comparable to that of diclofenac gel 2% and showed no skin toxicity.

The results of the present study suggest that DAGE has significant anti-inflammatory effects without any erythema and edema in topical use. These effects might be partially or wholly due to possible inhibition of or interference with the production of some inflammatory mediators, especially prostaglandins, histamine, serotonin, and bradykinin.

Date, Phoenix dactylifera, is a commonly used food in arid and semiarid regions of the world including Iran. Date seeds, are low-cost agriculture by-products and used for several medicinal uses and animal food, however, there are no records on its likely toxic effects. To investigate the safety of P. dactylifera, we investigated its acute and sub-chronic toxicity in Wistar rats in both sexes. Animals were treated with four different single doses (5g/kg) of P. dactylifera extract oral gavage (per oral, p.o.), and checked for symptoms of toxicity two weeks after dispensation. In the sub-chronic toxicity study, P. dactylifera seeds were administered in three different doses (500, 1000, 1500 mg/kg) through 45 days. Fatality, clinical symptoms, body weight alteration, gross findings, organ weights, hematological and biochemical criteria, and histological specifications were screened all along the study. We found no fatality or morbidity in clinical manifestations, corpse weight, or necropsy evidence in none of the rats in the acute study. Regarding the outcome of the sub-chronic assay, a meaningful decline in urea concentration in male animals and no significant differences observed in other hematological criteria in both sexes. No significant histopathological difference in lung and heart tissue of different groups were observed but there are kidney cortex congestion and hepatocyte focal degeneration in female and male rats taking elevated doses (1500 mg/kg) of palm kernel extract, respectively. Analyses of the obtained results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the no observed adverse effect level of P. dactylifera was defined to be 1000 mg/kg for male and female rats.

Marand plain is one of the fertile plains of East Azerbaijan Province which 80 percent of its water demands supply by groundwater. Therefore, qualitative protection of groundwater resources of this Plain is vital. In this Study, Statistical Methods and Saturation Indices are used for assessment of quality parameters. For this purpose, 48 water samples were collected from groundwater resources and analyzed for major and some minor ions and species (NO3-, F- and SiO2). Groundwater resources are separated by cluster analyzing in three distinct groups. In first group the water type is bicarbonate sodic and in second and third groups its coloro sodic. The results of factor analysis indicated that three factors such as salty geologic formations dissolve of minerals and increasing of evaporation control about 75% of the total samples variance. To identify geochemical processes governing to the aquifer, saturation indices of calcite, dolomite and gypsum of the samples were evaluated. The results showed that the chemical composition of ground water affected by recharging water from the river, water and formation reactions and evaporation from the groundwater.

Curcumin has anti-inflammatory and antioxidative properties. The objective of this study was to investigate the therapeutic effects of curcumin on functional disturbances, oxidative stress, and leukocyte infiltration induced by renal ischemia/reperfusion (I/R). Animals were randomly divided into 9 groups. The groups with 24-h reperfusion consisted of sham-24h, I/R-24h, and three I/R groups treated with curcumin at 10, 20, or 30 mg kg-1, i.p. after the ischemic period. The 72-h reperfusion groups also included Sham-72h, I/R-72h, I/R treated with curcumin at single dose of 20 mg kg-1, i.p., and I/R group which received three doses of curcumin at 20 mg kg-1, i.p., consecutively. Renal functional injury was assessed by measuring serum creatinine and urea-nitrogen concentrations. Oxidative stress was evaluated by assessment tissue malondialdehyde (MDA) and the ferric reducing/antioxidant power (FRAP) levels. Moreover, renal tissue leukocyte infiltration was measured by histopathology examination. Ischemia/reperfusion resulted in a significant increase in serum concentration of creatinine, urea-nitrogen, tissue MDA level, and leukocytes infiltration as well as reduced FRAP level. Treatment with curcumin in 24-h reperfusion groups could only lead to a significant change in the levels of MDA and FRAP. However, in 72-h reperfusion groups, curcumin was able to correct all functional disturbances, oxidative stress, and leukocytes infiltration with more effectiveness in groups that received three doses of curcumin. The administration of curcumin during 72-h reperfusion following 30 minutes of ischemia can decrease renal oxidative stress and leukocytes infiltration as well as improve kidney function. However, during first 24-h reperfusion, curcumin only decreased oxidative stress.

Curcumin has anti-inflammatory and anti-oxidative properties, and the aim of this study was to investigate the therapeutic effects of Curcumin on tissue damages induced by renal ischemia/ reperfusion. In this research, male Wistar rats were studied in 9 groups which were include sham with 24h reperfusion period, ischemia followed by 24h reperfusion, ischemia/reperfusion-24h which received a single dose 10, 20, or 30 mg/kg (i.p), Curcumin 30 min after ischemia, sham with 72h reperfusion period, ischemia followed by 72h reperfusion, ischemia/reperfusion-72h which received a single dose 20 mg/kg (i.p), Curcumin and ischemia/reperfusion-72h which received three doses of Curcumin (20 mg/kg, i.p) every 24 hours. At the end of reperfusion period, the left kidney tissue were collected and after staining with hematoxylin-eosin, subjected to microscopic study. Ischemia/reperfusion leads to increased Bowman's space size, tubular necrosis, vascular congestion and intra-tubular proteinaceous casts in kidney; which Curcumin therapy could partially improve all of them. But its effect in groups with 72h reperfusion period and receiving 3 dose of Curcumin was significantly greater than those received single dose and 24h reperfusion in comparison with their own sham groups. The results of this study demonstrated that three successive doses of curcumin can be more effective than single-dose treatment on tissue damages resulting from renal ischemia/ reperfusion in rat

In published high performance liquid chromatographic (HPLC) methods for analysis of topiramate (TPM) in pharmaceutical dosage forms and raw materials Refractive Index Detector (RID) has been used which is not available in many laboratories and has low sensitivity. We described a new, sensitive and simple HPLC method for determination of topiramate in pharmaceutical forms and In-virto dissolution studies which avoids the use of RID detector. The method is based on derivatization of topiramate and an internal standard by reaction with 4-chloro-7-nitrobenzofurazan (NBD-CL), and reverse-phase chromatography using phenyl column and spectrophotometer detection at 264 nm. A mixture of phosphate buffer (0. 05 M) containing triethylamine (0. 1٪ V/V; pH=2. 3) and methanol (28:72, V/V) at a flow rate of 2. 2 ml/min was used as mobile phase. The analysis performance was studied and the method was shown to be selective and linear for determination of topiramate in pharmaceutical forms and dissolution studies.