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Background: One of the most important metabolic disorders in the current century is diabetes, which can negatively affect the physiology of many body parts. Unfortunately, this disease is not limited to a specific part of the body and causes destructive effects on the nervous system, cardiovascular system, kidneys and many other parts of the body. The high costs and increasing prevalence of this disease have made scientists look for natural compounds to prevent and treat diabetes. Medicinal plants are a huge source of unknown compounds that can alleviate many human diseases. Objective: One of the oldest plant families that have been used medicinally is the Apiaceae family. One of the most important genera of this family is Ferula, which has 170 different species and is distributed in hot and dry regions of the earth and has various therapeutic properties. The purpose of this article is to review the anti-diabetic effects of the Ferula genus on diabetes. Methods: In this review article, key science databases, including Science Direct, PubMed, and Google Scholar, were searched to find information on Ferula genus using a combination of different keywords, including diabetes, hyperglycemia, and alpha-glucosidase inhibition. Results: A total of 9 types of Ferula have been reported in the articles that have anti-diabetic properties. Conclusion: The review of the conducted research shows that the genus Ferula has a high potential in reducing blood sugar and other aspects of diabetes, and additional research should be performed in this field.

Gemfibrozil (GFZ) is a lipid-lowering drug with several other effects, such as antioxidant and anti-inflammatory activities. In the current study, chronic d-galactose treatment (d-gal, 150 mg/kg/day; i.p., 6 weeks) induced a model of accelerated aging in male mice and was used to study the behavioral, anti-oxidative, and neuroprotective effects of GFZ (100 mg/kg/day; p.o.). Anxiety-like behaviors were assessed using the elevated plus-maze while working memory was measured by spontaneous alternation in a Y-maze. Brain oxidative stress was determined by measuring malondialdehyde (MDA) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Neuropathological evaluation of the brain with hematoxylin-eosin and Masson's trichrome staining was also performed. The results demonstrated that the anxious-like phenotype and the cognitive impairments observed in d-gal-treated mice could be prevented in those animals coadministered with GFZ. Besides, the decrease in SOD and GPx antioxidant enzymatic activities and increase of MDA levels were also prevented in the brains of d-gal plus GFZ treated mice. Preliminary hematoxylin-eosin staining also suggested neuroprotective effects of GFZ. The results of Masson's trichrome staining showed no evidence of fibrosis in brain sections of different experimental groups. The current data provide novel insights into GFZ in the d-galactose-induced aging mouse model that open promising future research lines to determine inflammatory mediators and cell signaling underlying these effects.

Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on PPAR-α and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti-inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal damages in a D-galactose (D-gal)-induced aging model. We used twenty-eight male mice, which were equally and randomly divided into four groups as follows: Normal, D-gal (150 mg/kg/day; i.p., for 6 weeks), GFZ (100 mg/kg/day GFZ, p.o. for 6 weeks) and the combined D-gal + GFZ. Liver and kidney function indices were measured as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase. Oxidative stress in hepatic and renal tissue was evaluated through malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. Finally, the liver and kidney tissues were assessed for histopathological lesions. The results showed that D-gal induced aging leads to abnormalities in liver and kidney function indices. D-gal also induced significant oxidative stress and histopathological lesions in these organs. GFZ improved function indices and oxidative stress compared to the D-gal -treated animals. Histological evaluations of the liver and kidney also confirmed these results. These data provide evidence for the potential therapeutic of GFZ in clinical practice for mitigating the hepatorenal damages of aging.

Chronic opioid abuse can impair the hippocampal region of the brain. This study evaluates the neuroprotective effect of Achillea millefolium (Ach) on chronic morphine‑induced learning and memory impairment, oxidative stress, and neuronal apoptosis in the CA1 region of the rat hippocampus. Thirty‑two male Wistar rat rats were classified into four treatment groups (n=8). Morphine sulfate was administered chronically. The treatment groups were given Ach aqueous extract (100, 250, and 500 mg/kg), orally, each day. After 28 days, the Morris water maze test was performed on all subjects. Caspase‑3, Bax, and Bcl‑2 proteins expression in the CA1 region of hippocampal tissue was analyzed using the western blot method. Also, malondialdehyde concentration, glutathione peroxidase activity, and superoxide dismutase activity were evaluated. The results indicated that Ach extract can improve spatial learning and memory defects in morphine‑treated rats. Ach administration also ameliorated apoptosis and oxidative stress indicator levels in hippocampal CA1 of morphine‑treated animals. Based on the present study, Ach improved spatial learning and memory defects, and reduced oxidative stress and apoptosis in the hippocampus CA1 region, in chronic morphine‑treated animals.

Introduction: During menopause, which is a part of the aging process in women, the level of sex hormones decreases, which causes problems such as memory impairment and cognitive functions. One of the treatment options for these disorders is hormone therapy, which has several side effects. The present study investigated the effect of remote ischemic conditioning (RIC) technique on memory improvement, muscle strength, motor and balance function in ovariectomized rats. Methods: In the present experimental study, 24 Wistar female rats with an approximate weight of (170-220 g) were divided into three groups (n = 8) including, 1: control group, 2: ovariectomy group and 3: ovariectomy+ treatment group. Initially, the animals in the second and third groups underwent ovariectomy surgery. The RIC techniques were performed on treatment group of rats for two months. After that, memory, muscle strength, and motor and balance function were assessed in all groups. SPSS software (V21) and one-way analysis of variance were used for statistical analysis. Results: The result of this study showed that RIC technique significantly improved memory in the ovariectomy+treatment group in comparison with the ovariectomy group (P

Background and Aims: Bromelain is a substance derived from pineapple and has antioxidant, anti-inflammatory, and analgesic effects. This study aimed to investigate the effect of bromelain on the healing of tooth extraction sockets in an animal model. Materials and Methods: This experimental study was performed on 24 male rats. After anesthesia, the first maxillary molar tooth was extracted with minimal damage using a hemostat. The rats were randomly divided into two groups, namely control and bromelain. In the bromelain group, the rats were orally administered by gavage with a 500 mg dose of bromelain that was dissolved in water twice a day for 2 days, while the control group received no medications. On the 3rd and 10th days after the surgery, 6 rats were killed per group each day. Afterward, the maxillae of rats were removed and slides were prepared from their dental sockets. The slides were examined by light microscope for histopathological variables (mean of macrophages, fibroblasts, lymphocytes, neutrophils; granulation tissue extent and angiogenesis and bone cells). Results: The results showed that the angiogenesis and granulation tissue extent increased significantly in the bromelain group, compared to the control group, on the 3rd day (P

Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti-inflammatory, anti-apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro-inflammatory cytokines like TNF-α, IL-1α, IL-1β, and IL-6. It also inhibits the transcription factor nuclear NF-κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase (ALT), against toxic chemicals like CC14, As2O3, and TTA. Due to its antioxidant, anti-inflammatory, and anti-fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals.

Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CClThirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CClCClCaD (100 mg/kg) has a protective effect against hepatorenal injury induced by CCl

Purpose: Calcium dobesilate (CaD) has antioxidant and anti-inflammatory properties. In this study, the protective effects of CaD against hepatorenal damage induced by CCL4 in male mice were evaluated. Methods: Thirty male mice randomly were divided into five groups: Control, CaD 100 mg/kg, CCL4, CCL4+CaD 50 mg/kg, and CCL4+CaD 100 mg/kg. Drugs were administered orally once a day for 4-weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase and aspartate aminotransferase levels) were determined. Also, hepatic and renal tissue oxidant/antioxidant markers (glutathione peroxidase, malondialdehyde, total antioxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, and Bcl-2 protein levels were measured by immunoblotting method. The liver and kidney histopathological changes were evaluated by H&E staining.Results: CCL4 induces significant oxidative stress in the kidney and liver that was concomitant with functional and histopathological abnormalities in these organs in the CCL4 group versus the control (PPPConclusion: The protective effect of CaD may be related to its anti-inflammatory and antioxidant properties.

Acetaminophen overdose causes renal injury via oxidative stress and apoptosis induction. Carvacrol has antioxidant effect. The aim of this study was to determine the protective effect of carvacrol on acetaminophen-induced renal damage in male rats. In this experimental study, forty male Wistar rats were randomly divided to five groups (n = 8) including control, carvacrol 10 mg/kg, acetaminophen, acetaminophen + carvacrol 5 mg/kg, and acetaminophen + carvacrol 10 mg/kg. Animals initially received a single dose of acetaminophen (500 mg/kg), then were treated with carvacrol for one week (daily). Afterwards, renal blood flow (RBF), mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), blood urea nitrogen (BUN), and serum creatinine were measured. Also, malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured in the kidney tissue. Hematoxylin and eosin method was used for histological assessment. The western blotting analysis was used to determine the Bax, Bcl-2 and cleaved caspase-3 proteins expression level in the kidney tissue. Carvacrol (10 mg/kg) could significantly increase the RBF, GPx and SOD activities and also reduced the RVR, serum creatinine, BUN, and MDA in the acetaminophen + carvacrol 10 mg/kg group versus acetaminophen group (P

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d-galactose (d-gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d-gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d-gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d-gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d-gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women. Brain functions may be affected in PCOS, and studies reported that PCOS patients are at greater risk for developing mental health conditions, including anxiety or depression. Objectives: This study was designed to evaluate the neurocognitive changes in letrozole-induced PCOS model. Methods: Twenty female Wistar rats (eight-week-old; 160 ± 10 g) were divided into two groups. Group one received vehicle only (carboxymethyl cellulose, orally) once daily, and group two received letrozole (1 mg/kg, orally) once daily. Drugs or vehicles were administered for 21 days. Afterward, behavioral tests, including forced swimming test, open field test, and Y-maze alteration task, were performed. Ovaries were removed after behavioral tests and assessed histologically to confirm the induction of PCOS. Results: Animals with PCOS developed depressive-like behaviors compared with control in forced swimming test (P < 0.001). Anxiety-like behaviors were detected in letrozole-induced PCOS group (P < 0.05). Moreover, animals with PCOS exhibited memory impairment in comparison to normal animals in Y-maze memory assessment (P < 0.05). Conclusions: Rats with PCOS showed a neurocognitive decline in the model of letrozole administration. Future studies should be conducted to clarify the exact mechanisms of these changes and possible approaches to restore them.

The Ischemia/reperfusion (I/R) phenomenon has a critical role in brain injuries induced by some kinds of stroke. The current study investigates the effects of Coenzyme Q10 (Q10) on global cerebral I/R in rats.Fifty male Wistar rats were used in this study. The global cerebral I/R was induced by obstructing both common carotid arteries for 20 min and the animals were treated with Q10 (200 mg/kg; PO.) for 6 weeks. Depressive and anxiety-like behaviors were assessed using the elevated plus-maze and forced swimming test, respectively. Working and spatial learning and memory were assessed by the Y-maze continuous alternation task and Morris water maze. The brain tissues were evaluated for brain edema, brain-derived neurotrophic factor (BDNF) levels, and superoxide dismutase (SOD) activities.Our results indicated that global cerebral I/R increased anxiety and depression-like behavior as well as reduced cognitive performance. Moreover, the levels of BDNF and activities of SOD are reduced in stroke animals. Chronic post-stroke treatment with Q10 decreased brain edema. Furthermore, Q10 administration reduced anxiety and depressive-like behavior as well as cognitive impairments in stroke animals. Q10 also increased the SOD activities and BDNF levels in the brain tissues of stroke animals.Finally, we can conclude that using Q10 supplementation may be beneficial against the global cerebral I/R complications.

Ceftriaxone (CTX) is a third-generation cephalosporin antibiotic that has broad-spectrum antimicrobial activity. This agent also has anti-inflammatory and antioxidant characteristics. In the current study, the effects of CTX against hepatorenal damages in a D-galactose (DGL) induced aging model were investigated. We used twenty-eight male mice which equally and randomly were separated into four groups as follows: Control, DGL group (treated with 500 mg/kg/day DGL orally for six weeks), DGL + CTX group (treated with 500 mg/kg/day DGL orally plus 200 mg/kg/day CTX intraperitoneally for six weeks), and CTX group (treated with 200 mg/kg/day CTX intraperitoneally for six weeks). The liver and kidney function indices such as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase were measured. Also, levels of malondialdehyde, catalase, and glutathione peroxidase in hepatic and renal tissues were evaluated. Moreover, the expression profiles of interleukin 1 beta and tumor necrosis factor alpha were assessed. The liver and kidney tissues were assessed for histopathological lesions. The results showed that aging induced by DGL leads to abnormalities in functional indices of the liver and kidneys. DGL also induced significant oxidative stress and inflammation, as well as histopathological lesions, in these organs. CTX improved functional indices, as well as the parameters of oxidative stress and inflammation, compared with the DGL-treated animals. These results were also confirmed by histological evaluations of the liver and kidneys. These data provide evidence for the therapeutic value of CTX in clinical practice for mitigating the hepatorenal damages of aging.

Background and purpose: Opiates are traditionally used for the treatment of pain. Chronic consumption of opiates such as morphine (MOR) induces tolerance and dependence. This study aimed to investigate the effects of valsartan (VAL), as an angiotensin II receptor blocker, on the induction and expression of MOR analgesic tolerance and physical dependence in rats. Experimental approach: MOR 10 mg/kg was injected s.c. twice a day for 7 days to induce tolerance and dependence. For evaluating the effect of VAL on the induction of MOR analgesic tolerance and physical dependence, 20 mg/kg VAL was administered orally (once a day) during the 7 days of the examination period. The tail-flick test was performed every day. On day 7, 5 mg/kg naloxone () was injected s.c. into the morphine-dependent rats and the rats were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. For evaluating the effect of VAL on the expression of MOR-analgesic tolerance and physical dependence, 45 min before the last MOR injection, VAL was administered only on day 7. The tail-flick test was performed and naloxone was injected into the addicted rats and they were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. Findings/Results: Our results revealed that the co-administration of VAL with MOR for 7 consecutive days reduced the induction of MOR tolerance. Moreover, VAL administration for 7 days along with MOR reduced the frequency of diarrhea and defecation in naloxone-injected animals. Conclusion and implications: According to the results presented in this study, chronic administration of VAL prevented the induction of MOR-analgesic tolerance and dependence in rats.

Objective(s): Previous studies have indicated that phytoestrogens induce estrogenic as well as anti-inflammatory effects, and they are found in high abundance in the extracts of some herbs such as Vitex Agnus Castus (VAC). Therefore, we investigated the effect of VAC extract on ovariectomized mice after the induction of permanent middle cerebral artery occlusion (PMCAO) model. Materials and Methods: In this study, 50 mice ranging from 25 to 35 g were divided into five experimental groups as follows: Control, VAC, Estrogen, Tamoxifen, and Tamoxifen-VAC. Animals were ovariectomized, and after 30 days of treatment, they were given PMCAO induction. Behavioral assessment (adhesive removal and wire hanging tests) was evaluated 24 hr, 48 hr, and one week after induction of stroke. The infarct volume, as well as serum levels of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10), were measured one week after stroke. Results: One week after stroke, in both VAC and estrogen groups, the infarct size reduced in comparison with the control group. Estrogen and VAC extract improved adhesive removal and wire hanging test, increased the level of IL-10, and decreased the level of MMP-9 compared with the control group. In addition, co-administration of tamoxifen and VCA extract had no significant effect on measured indices compared with control and tamoxifen groups. Conclusion: Based on our findings, VAC extract has neuroprotective properties and can reduce stroke injuries in PMCAO-induced ovariectomized mice via anti-inflammatory and estrogenic properties.

Administration of tissue plasminogen activator (tPA) during first 3-4.5 h after ischemic stroke is the main therapeutic strategy; however, its using after that, leads to reperfusion injury and neurotoxic effects. Additionally, inflammation has a critical role in secondary injury after late reperfusion therapy. Thus, this project was designed to explore the effects of JZL-184 (JZL), an agonist of type 1 cannabinoid receptor (CB1), on the side effects of recombinant tPA (r-tPA), which is administrated after 5 h of stroke onset in the mice middle cerebral artery occlusion (MCAO) model. After established the model of MCAO mouse, they were put to six groups, including intact, control, vehicle, JZL (4 mg/kg), r-tPA (9 mg/kg), and JZL plus r-tPA. Thereafter, brain levels of IL-10, TNF-α, and matrix metalloproteinase - 9 (MMP9), brain edema and infarction, and behavioral functions have been determined in the groups. JZL alone or in combination with r-tPA, but not r-tPA, reduced brain edema, infarct volume, brain levels of TNF-α, MMP9, and also improved behavioral tests. JZL and JZL plus r-tPA also increased brain levels of IL-10. According to the results, JZL can improve the effects of r-tPA to overcome stroke SSE, when used after 5 h of stroke onset. Based on the fact that there is limitation regarding using r-tPA after 3 h of stroke onset, using a combination of r-tPA/JZL can be considered for a future therapeutic strategy.

Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant, and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. This study was designed to investigate the possible effect of Met on the d-galactose (d-gal)-induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. d-gal was administered orally at a dose of 500 mg/kg, and Met was administrated orally at doses of 1 and 10 mg/kg for 6 weeks. Anxiety-like behavior was evaluated by the elevated plus-maze. Physical power was assessed by vertical grid holding test and forced swimming capacity test. The brains were assessed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Ovariectomy caused anxiety and declined the physical power as well as BDNF and SOD levels. d-gal administration in ovariectomized mice exacerbated these deleterious effects. Met hampered the anxiety-like behavior and strengthened the physical power of d-gal-treated ovariectomized mice. Met also increased the SOD and BDNF levels in the brains of d-gal-treated ovariectomized animals. Based on the obtained results, we suggest Met administration as a novel therapeutic approach for the treatment of age-related conditions in the absence of female sex hormones.

Exercise preconditioning has been shown to be effective in improving behavioral and neuropathological indices after cerebral ischemia. We evaluated the effect of exercise preconditioning, 17β-estradiol, and their combination on stroke outcome using an experimental model of stroke in ovariectomized (OVX) mice. OVX mice were randomly assigned to 4 groups as follows: control (stroke), exercise (exercise and stroke), estradiol (17β-estradiol and stroke), and exercise+estradiol (exercise and 17β-estradiol and stroke). Exercise preconditioning was performed on a treadmill 5 days/week, 40 min/day, at a speed of 18 m/min for 4 weeks. 17β-estradiol was gavaged (40 μg/kg per day) for 4 weeks. Stroke was induced by permanent middle cerebral artery occlusion (pMCAO), and neurological deficits were evaluated 1, 2, and 7 days after stroke. Then, the serum concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10) and infarct volumes were assessed. Exercise preconditioning and 17β-estradiol induced a better outcome compared with the control ischemic mice, which was manifested by decrease in MMP-9, increase in IL-10, diminished infarct volume, and improved neurological deficits. Concomitant administration of 17β-estradiol and exercise also significantly improved these parameters. Exercise preconditioning or administration of 17β-estradiol alone or in combination before pMCAO induced significant neuroprotection in OVX mice.

Oxidative stress plays a critical role in ischemic brain injury. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are the enzymes underlying the endogenous antioxidant mechanisms affected by stroke and are considered as oxidative stress biomarkers. Brown propolis (BP) is a bioactive natural product with a set of biological activities that in turn may differ depending on the area from which the substance is originated. The aim of this study was to investigate the effect of water-extracted brown propolis (WEBPs), from two regions of Iran, against cerebral ischemia-induced oxidative injury in a mouse model of stroke. Experimentally, the chemical characterization and total polyphenol content were determined using GC/MS and Folin-Ciocalteu assay respectively. Seventy-two adult male mice were randomly divided into the surgical sham group, control group (treated with vehicle), and four groups of WEBPs-treated animals. The WEBPs were administered at the doses of 100 and 200mg/kg IP, during four different time points. Oxidative stress biomarkers (SOD and GPx activity, SOD/GPx ratio), lipid peroxidation (LPO) index (malondialdehyde content) and infarct volume were measured 48h post stroke. Behavioral tests were evaluated 24 and 48h after stroke. WEBPs treatment resulted in significant restoration of antioxidant enzymes activity and a subsequent decrease in LPO as well as the infarct volume compared to the control group. Sensory-motor impairment and neurological deficits were improved significantly as well. These results indicate that Iranian BP confers neuroprotection on the stroke-induced neuronal damage via an antioxidant mechanism which seems to be mediated by the endogenous antioxidant system.

Unilateral ureteral obstruction (UUO) induces kidney injury. Oleuropein as a major compound of olive leaves modulates the inflammatory parameters and decreases oxidative stress. Accordingly, we evaluate the renoprotective effect of oleuropein against 3-day UUO rats. Forty rats were randomly divided into five groups (n = 8) including control, UUO and UUO + oleuropein groups (50, 100 and 200 mg/kg). UUO model was induced by left ureter ligation and continued for 3-day. Rats were treated synchronic daily for 3-day, then mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), serum creatinine level, and also superoxide dismutase (SOD), glutathione peroxidase (GPx) activity levels and malondialdehyde (MDA) concentration (in the obstructed kidney) were measured. The western blotting method was applied to evaluate the Bax, Bcl-2, cleaved caspase-3 and TNF-α proteins expression level. The hematoxylin and eosin method was applied to evaluate the kidney tissue damage score (KTDS). UUO significantly increased RVR, KTDS, and MDA, cleaved caspase-3, Bax, serum creatinine and TNF-α protein levels (P

Metformin (MET),an antidiabetic drug, has shown antioxidative and neuroprotective effects. In the present investigation, we aimed to study the probable effects of MET on cerebral ischemia/reperfusion in rats. Rats underwent cerebral ischemia/reperfusion and MET was administered orally at doses of 100 and 200 mg/kg for 56 days. Anxiety- and depressive-like behaviors were evaluated by elevated plus-maze or forced swimming tests, respectively. was assessed by. Cognitive functions were assessed by Y-maze continuous alternation task and morris water maze. The activity of SOD and the level of BDNF were measured in brains samples. Our results showed that administration of 200 mg/kg MET reduced the percent of brain edema (84.00 ± 2.13) in comparison with the ischemic animals (91.25 ± 2.25) (p < 0.05). Administration of 200 mg/kg MET in ischemic animals improved anxiety-like behavior by increasing the percentage of the open arms entries (46.51 ± 3.13) and the percentage of the open arms time (32.70 ± 2.49) in comparison with the cerebral ischemia group (26.35 ± 7.02 and 15.32 ± 5.78, respectively) (all p < 0.001). MET treatment (200 mg/kg) increased the cognition index of correct alternations (90.20 ± 4.95) in comparison with the cerebral ischemia group (59.50 ± 8.01) (p < 0.05). MET at the both doses reduced escape latency compared to the cerebral ischemia animals (all p < 0.05). In addition, 200 mg/kg MET increased the time spent in the target quadrant (16.06 ± 0.58) in comparison with the ischemic animals (9.84 ± 0.92) (p < 0.001) and the both doses of the drug increased the number of crossing (5.42 ± 0.36 and 6.5 ± 0.42, respectively) compared to the cerebral ischemia group (3.75 ± 0.31) (p < 0.05 and p < 0.001, respectively). Moreover, 200 mg/kg MET reduced the immobility time (47.50 ± 9.00) in comparison with the cerebral ischemia group (93.43 ± 8.28) (p < 0.001). Furthermore, the both doses of MET increased the BDNF levels (4590 ± 197.6 and 4767 ± 44.10, respectively) in comparison with the ischemic animals (3807 ± 42.56) (p < 0.01 and p < 0.001, respectively). Also, the both doses of the drug increased the SOD activity of brain (52.67 ± 0.33 and 55.00 ± 0.57, respectively) compared to the ischemic animals (49.33 ± 0.33) (p < 0.01 and p < 0.001, respectively). Based on our data, long-term MET therapy may improve behavioral disorders following cerebral ischemia/reperfusion and can be considered as a novel therapeutic approach for the treatment of brain ischemic conditions.

Health promotion and healthy nutrition significantly increased life expectancy around the world. Aging is associated with an increase in age-related diseases. The use of metformin (Met) as an anti-aging drug has recently been proposed based on its widespread use in clinical practice. Reports have shown that Met acts as an anti-aging agent. In this study, the effects of long-term, 1 year, Met administration on aging-related behaviors and longevity in ovariectomized mice was studied. Met (1 and 10 mg/kg, daily) was administered orally in ovariectomized mice. The anxiety-like behavior, working memory, and physical strength were measured through elevated plus maze, Y-maze, vertical grid holding, and the obligatory swimming capacity tests. Brains were harvested to measure brain-derived neurotrophic factor (BDNF) level. Also, the Kaplan-Meier survival curves were used to show differences and similarities in survival patterns. Met (10 mg/kg) decreased anxiety-like behaviors as well as increased muscle strength and working memory in the ovariectomized mice. Moreover, Met increased the physical strength and longevity as well as the level of BDNF in the ovariectomized mice. Our results indicate that Met administration can be an effective strategy for having a healthy aging in the absence of female gonadal hormones and reverses deleterious effects of ovariectomy-induced aging possibly through BDNF.

BACKGROUND: Cisplatin (CP) is a synthetic and anticancer drug, and one of the major side effects of CP is nephrotoxicity. This study was done to evaluate the renoprotective effects of troxerutin (Tro) in nephrotoxicity induced by CP in male mice. METHODS: In this experimental study, 28 male mice were divided randomly into four groups. Mice were treated with CP (20 mg/kg, i.p.) then Tro (75 and 150 mg/kg/day, po) was administered for three consecutive days. Blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidney tissues were used for histological examination and biochemical assays. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were assessed in renal tissue. RESULTS: Results showed a significant increase in the Cr, BUN and MDA levels and a significant decrease in the renal SOD and GPx activity by CP administration. Treatment with Tro for three consecutive days attenuated these changes. Also, the renoprotective effect of the Tro was confirmed by the histological examination of the kidneys. CONCLUSIONS: Our results demonstrated that Tro has protective effects against CP-induced nephrotoxicity through improving the biochemical indices and the oxidative stress parameters.

CCR5 is an important chemokine receptor involved in the recruitment of specific anti-viral immune cells (e.g., NK cells and T cytotoxic cells) to the liver. Previous studies indicated that the Δ 32 mutation in CCR5 gene led to inactivation of CCR5. Several conflicting studies have suggested that this mutation may be associated with either recovery or persistence of HBV infection. The main purpose of this study was to compare the frequency of the Δ 32 mutation within the CCR5 gene in a group of patients infected chronically with HBV with healthy individuals from South-East of Iran. Sixty patients with chronic HBV infection as well as 300 age-, and sex-match healthy individuals were enrolled in this study. Gap-PCR was applied to determine the frequency of CCR5 Δ 32 mutation in both groups. The results demonstrated that none of the patients infected with HBV carried the CCR5 Δ 32 mutation while, 3 (1%) of the healthy individuals were found to be heterozygotic for this mutation. The CCR5 Δ 32 mutation is not a prevalent mutation in either the patients infected chronically with HBV or their health counterparts in the South-East region of Iran. This may be attributed to either different genetic settings of the investigated population or lack of any significant correlation between this mutation and HBV pathogenicity.

Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke.

Background: Stroke is a major cause of mortality and long term disability in adults. TRPV1 has a pivotal role in neuroinflammation. Among TLRs, TLR2 significantly participate in induction of inflammation in brain. In this study, the effect of TRPV1 receptor agonist and antagonist on outcome and gene expression of TLR2 in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated.Methods: Forty male rats were assigned to the following groups: sham, vehicle )stroke), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and behavioral functions were assessed 1, 3, and 7 days after stroke. Infarct volume, brain edema and mRNA expression of TLR2 were also evaluated at the end of the study.Results: While stroke animals showed infarctions and behavioral functions, we did not observe any cerebral infarction and behavioral functions in sham-operated animals. AMG9810 decreased neurological deficits 7 days after cerebral ischemia (P