Objectives: The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a glo... more Objectives: The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a global health concern. Exercise training has been reported to activate the Nrf2/Keap1/ARE signaling and enhance the antioxidant defense pathways in some animal models. This study aimed to investigate the effects of ursolic acid (UA) associated with resistance or endurance training on antioxidant markers, and the Nrf2/Keap1/ARE pathway in the brain of older diabetic rats. Materials and methods: 23-month-aged diabetes induced male Wistar rats were randomly assigned to seven groups (n=8). UA supplementation (250 mg/kg, daily) was administered along with resistance (60% maximum capacity of voluntary carrying [MVCC], 14-20 climbs) or endurance training (60-75% velocity at maximal oxygen uptake [vVO2max]), five days/week for eight weeks. Cognitive-motor functioning was assessed through open-field and passive avoidance response tests. Nrf2, Keap1, and antioxidant markers including SOD, CAT, GPx, and GSH were measured in the hippocampus tissue. Results: The results showed positive effect of resistance training (P≤0.001) on Nrf2. There was endurance training with supplementation main effect (P=0.018) on Keap1 concentration. SOD revealed a significant endurance/resistance training by supplementation interaction effect (P≤0.05); however, there was no main training or UA supplementation effects on CAT, GPx, and GSH, despite improving spatial memory changes in exercise or UA groups. Conclusion: It appears that UA treatment with resistance or endurance exercise has some beneficial effects on Nrf2 and some antioxidant markers. However, more research is needed to elucidate UA's interaction effects and exercise interventions in diabetic situations.
Central pain syndrome (CPS) is a debilitating state and one of the consequences of spinal cord in... more Central pain syndrome (CPS) is a debilitating state and one of the consequences of spinal cord injury in patients. Many pathophysiological aspects of CPS are not well documented. Spinal glia activation has been identified as a key factor in the sensory component of chronic pain. In this study, the role of glial subtypes in the process of CPS induced by unilateral electrolytic lesion of spinothalamic tract (STT) is investigated. Male rats received a laminectomy at T8-T9 and then unilateral electrolytic lesion centered on the STT. Thermal and mechanical thresholds as well as locomotor function were measured on days 0, 3, 7, 14, 21, and 28 post-injuries by tail flick, von Frey filament, and open field tests, respectively. To investigate the spinal glial activation following denervation in STT-lesioned groups, Iba1 and GFAP were detected by immunohistochemistry and Western blotting at the same time points. Data showed that STT lesion significantly decreased thermal pain at day 3 in comparison with sham groups. Significant bilateral allodynia appeared in hind paws at day 14 after spinal cord injury and continued to day 28 (P<0.05). Additionally, electrolytic spinal lesion attenuated locomotor function of injured animals after 7 days (P<0.05). In both histological assessments and Western blotting, Iba1 increased at days 3 and 7 while increased GFAP occurred from day 14 to 28 after lesion. It appears that microglial activation is important in the early stages of pain development and astrocytic activation occurs later. These events may lead to behavioral outcomes especially central neuropathic pain.
Introduction: Spinal cord injuries are accompanied with significant demyelination of axons and su... more Introduction: Spinal cord injuries are accompanied with significant demyelination of axons and subsequent locomotor dysfunction. To identify the extent of damage following electrolytic lesion of ventrolateral white matter, essential area for initiation of locomotor activity, we assessed demyelination as well as alteration in motor performance. Moreover, the protective effect of estradiol as a candidate treatment for preservation of myelin and locomotor activity after injury was examined due to its antiapoptotic and anti-inflammatory activities. Methods: A unilateral electrolytic lesion positioned in the right ventrolateral funiculus (VLF) was applied following laminectomy at T8-T9. In the estradiol-treated injury group, animals received a pharmacological single dose of estradiol valerate (4 mg/kg) at 30min post injury. Locomotor function was assessed using rotarod and open field tasks during 4 weeks after injury. Results: Obtained results showed significant demyelination at the site...
The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new a... more The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new antidepressants with high medicinal properties and low side effects is warranted. Therefore, this study was designed to determine the antidepressant-like effect of tropisetron on a maternal separation (MS) model in mice, considering the possible role of AC. NMRI male mice were divided into eleven groups. The control group was treated with saline and MS groups were treated with saline, tropisetron (a 5-HT3 receptor antagonist) at doses of 1, 3, and 5 mg/kg; forskolin (an activator of AC) at doses of 5, 10, and 25 mg/kg; a subeffective dose of forskolin with a subeffective dose of tropisetron; and an effective dose of tropisetron plus an effective dose of NB001 (3 mg/kg) (an AC inhibitor). After treatment, animals were subjected to behavioral tests including the forced swimming test (FST), splash test, and open field test (OFT). We showed that MS caused depressive-like behaviors determined as an increase in the immobility time in the forced swimming test (FST) and decreased grooming time in the splash test. Our results showed that administration of tropisetron, as well as forskolin, mitigated the depressive-like behaviors in MS mice. We found that coadministration of a subeffective dose of tropisetron plus a subeffective dose of forskolin potentiated the antidepressantlike effect of tropisetron. However, coadministration of an effective dose of NB001 with an effective dose of tropisetron did not significantly affect the antidepressant-like effect of tropisetron. We concluded that the antidepressant-like effects of tropisetron on MS mice are partially mediated through the adenylyl cyclase pathway.
Evidence-based Complementary and Alternative Medicine, Dec 21, 2020
Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main... more Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main risk factor for the occurrence and progression of cognitive and memory impairment. Available treatments such as benzodiazepine and antidepressants address only certain aspects of this stress disorder and have numerous side effects. e present study was aimed at investigating the effect of diosmetin, as a flavonoid compound with potent antioxidant and anti-inflammatory effects, on cognitive impairment and chronic stress memory. Materials and Methods. In the present experimental study, male NMRI mice were exposed to chronic unpredictable mild stress (CUMS) paradigm for 35 days. Diosmetin (at doses of 10, 20, and 40 mg/kg. i.p.) or diosmetin solvent (normal saline + DMSO, 1 ml/kg; i.p.) was administered 30 min before stress induction. After 28 days, memory and cognitive performance were assessed by shuttle box and novel object recognition tests. Finally, antioxidant capacity (FRAP) and malondialdehyde (MDA) level of serum and brain, and serum corticosterone level were evaluated. Results. Behavioral tests showed that CUMS significantly reduced the secondary latency in passive avoidance memory test and diagnosis index in novel object recognition test compared to the control group (P < 0.001), whereas treatment with diosmetin (20 and 40 mg/kg) significantly improved memory performance in the two tests (P < 0.001). In addition, diosmetin (40 mg/kg) could pronouncedly suppress increase in serum corticosterone levels, reduction in antioxidant capacity, and production of excess MDA caused by CUMS compared to the control group (P < 0.01, P < 0.001, and P < 0.001, respectively). Conclusion. Chronic stress can impair memory and cognition and treatment with diosmetin can partly improve this disorder in male mice by increasing the antioxidant capacity of brain tissue and serum and improving serum corticosterone levels.
Context: Experiencing early-life adversity plays a key role in the development of mood disorders ... more Context: Experiencing early-life adversity plays a key role in the development of mood disorders in adulthood. Experiencing adversities during early life period negatively affects brain development. Sex steroids such as progesterone affect the brain structure and functions and subsequently affects behaviour. Objective: We assess the antidepressant-like effect of progesterone in a mouse model of maternal separation (MS) stress, focussing on its anti-neuroinflammatory and antioxidative effects. Materials and methods: NMRI mice were treated with progesterone (10, 50, and 100 mg/kg, i.p., respectively) for 14 days. Valid behavioural tests including forced swimming test (FST), splash test and open field test (OFT) were used. Quantitative reverse transcription-PCR (qRT-PCR) was used for evaluation of genetic expression in the hippocampus. Antioxidant capacity was assessed by the FRAP method and the level of malondialdehide by TBA. Results: MS provoked depressive-like behaviour in mice. Treatment of MS mice with progesterone increased the grooming activity time in the splash test and decreased the immobility time in the FST. In addition, progesterone decreased the expression of inflammatory genes related to neuroinflammation (IL-1b, TNF-a, TLR4 and NLRP3) as well as increased the antioxidant capacity and decreased the lipid peroxidation (MDA) in the hippocampus. Discussion and Conclusion: Administration of progesterone significantly mitigated the negative effects of MS on behaviours relevant to depressive-like behaviour as well as attenuated neuro-immune response and oxidative stress in the hippocampus of MS mice. In this context, we conclude that progesterone, at least partially, via attenuation of oxidative stress and neuroinflammation, exerts antidepressant-like effects.
Postoperative pain and its control remain one of the most important issues in the field of surger... more Postoperative pain and its control remain one of the most important issues in the field of surgery and health care systems. Morphine is a potent and effective analgesic, but substance abuse patients can manifest crosstolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements. As carbamazepine has shown antinociceptive properties in a variety of experimental and clinical settings, in the present study, we evaluated its potential antiallodynic effects on postoperative pain in naïve and morphine-dependent rats. Male rats were assigned to morphine-dependent and naïve groups and received intraperitoneally drug vehicles as control group, 3 mg/kg morphine, 5, 10 or 15 mg/kg carbamazepine or 5 mg/kg carbamazepine plus 3 mg/kg morphine as a combination therapy 2 and 24 h after surgery. Morphine-dependency was induced with multiple doses of morphine administered i.p. and plantar incision was made on the hind paw to simulate the postoperative pain. Paw withdrawal threshold (PWT) was obtained by von Frey filaments every 30 min after drug injection for up to 180 min. Morphine at 3 mg/kg exerted antiallodynic effects in naïve rats and a decreased antinociception was observed in morphine-dependent rats. In contrast, 5 mg/kg carbamazepine did not significantly alter PWT in naives but it was effective in dependent rats. 10 and 15 mg/kg carbamazepine attenuated allodynia following surgery in both groups. Co-administration of 5 mg/kg carbamazepine with 3 mg/kg morphine produced higher analgesia in morphine-dependent incised rats and prolonged antinociception as compared to morphine alone (P b 0.05). Thus carbamazepine may potentiate the analgesic effect of chronically administered morphine on postoperative pain model in morphinedependent rats.
Alzheimer's disease (AD) is a common neurodegenerative condition that affects the elderly populat... more Alzheimer's disease (AD) is a common neurodegenerative condition that affects the elderly population. Its primary symptom is memory loss. The memory dysfunction in AD has been associated with cortical cholinergic deficiency and loss of cholinergic neurons of the nucleus basalis of Meynert (NBM). Zizyphus jujube (ZJ) activates choline acetyltransferase and may have beneficial effects in AD patients. This study investigates the effect of ZJ extract in intact rats and in rat model of AD. 49 male Wistar rats were divided into seven equal groups (1control, without surgery, received water), 2-AD (bilateral NBM lesion, received water), 3 and 4-AD ? ZJ (NBM bilateral lesion, received ZJ extract 500 and 1,000 mg/kg b.w. per day for 15 days), 5-sham (surgery: electrode introduced into NBM without lesion, received water), 6 and 7-without surgery and lesion, received ZJ extractthe same as groups 3 and 4). The learning and memory performance were assessed using passive avoidance paradigm, and the memory cognition for spatial learning and memory was evaluated by Morris water maze. In shuttle box test ZJ extract (500 and 1,000 mg) significantly increased step-through latency in AD ? ZJ groups compared with AD group. In Morris water maze test (in probe day), both AD ? ZJ groups receiving extract (500 and 1,000 mg) demonstrated significant preference for the quadrant in which the platform was located on the preceding day as compared with AD group. Our results suggested that ZJ has repairing effects on memory and behavioral disorders produced by NBM lesion in rats and may have beneficial effects in treatment of AD patients.
Postoperative pain and its control remains one of the most important issues in the field of surge... more Postoperative pain and its control remains one of the most important issues in the field of surgery and health care system. Morphine is a potent and effective analgesic. But substance abuse patients can manifest cross tolerance to drugs, making it difficult to predict their analgesic or anesthetic requirements. The anticonvulsant drug, carbamazepine (cbz), has many pharmacological effects. In this study we evaluated the effect of various doses of carbamazepine injected Intraperitoneally (i.p.) on postoperative pain in morphine-dependent and naive rats. Rats were addicted by i.p. morphine. After anesthesia a 1-cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hind paw and then sutured. Both morphine-dependent and naive rats received carbamazepine or/and morphine i.p. 2h and 24h after surgery. Paw Withdrawal Threshold by Von Frey Filament obtained every 0.5h after drug injection up to 3h (at surgical day and next day). We saw that the combination of carbamazepine 5mg/kg+morphine 3mg/kg produced more analgesic effects in morphinedependent rats compared to cbz or morphine alone and this combination had same effect of morphine 3mg/kg alone in naive rats (P<0.05). carbamazepine may potentiate the analgesic effect of chronically administration of morphine.
Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and di... more Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and different pathophysiological mechanisms. Currently there is no effective response to conventional therapy. Co-administration of nonanalgesic dose of drugs can reduce both pain and their adverse effects. The goal of this study was to determine the analgesic effect of three drugs (nimesulide, nefopam, morphine) with different mechanisms of action as a single and combination form in a model of neuropathic pain. Neuropathic pain was induced using CCI model in male wistar rats (n=6, 180-220g) and divided into different groups: 1) sham, saline 2) CCI , saline 3) CCI , nimesulide (1.25, 2.5, 5 mg/kg) 4) CCI, nefopam (10, 20, 30 mg/kg) 5) CCI , morphine (1, 3, 5 mg/kg) 6) CCI, nimesulide (1.25 mg/kg)/morphine (3 mg/kg) 7) CCI , nimesulide (1.25 mg/kg)/nefopam (10 mg/kg) 8) CCI , nefopam (10 mg/kg) /morphine (3mg/kg). Pain behavior was assessed using allodynia tests (Vonfrey filaments and acetone test) before and days 1, 5,7,10 and 14 after surgery. The data were analyzed using ANOVA and p<0.05 was considered significant. Morphine, nefopam and nimesulide (5mg/kg, 10 -20mg/kg and 2.5-5mg/kg, respectively) reduced allodynia. The non analgesic doses of drugs reduced pain behavior when used in combination. It seems that analgesic drugs used in combination with low doses controlled pain effectively with less adverse effects seen when they are used alone
Journal of Biomolecular Structure & Dynamics, Dec 21, 2021
Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor fo... more Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reviewed through molecular docking and sequent molecular dynamics (MD) simulations against this condition. The crystal structures of ACE2 receptors of SARS-CoV-2 and SARS-CoV, applied in docking analysis, were taken from the Protein Data Bank (PDB). The receptors were then prepared using the Molecular Operating Environment (MOE), as a drug-discovery software platform for docking. Supplements such as quercetin and beta glucan (β-glucan) were the top docked compounds to ACE2 receptor though they strongly interacted with CoV target protein. The study data showed that immune responses to immunonutrient-based sports compounds (viz. quercetin and β-glucan) in Coronavirus disease 2019 (COVID-19) were essential in mounting successful immune responses by athletes. While awaiting the development of an effective vaccine, there is a need to focus on immunonutrient-based sports supplements as preventive and therapeutic options that can be implemented in a safe and quick manner to bolster immune responses in athletes.Communicated by Ramaswamy H. Sarma.
Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor fo... more Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reviewed through molecular docking and sequent molecular dynamics (MD) simulations against this condition. The crystal structures of ACE2 receptors of SARS-CoV-2 and SARS-CoV, applied in docking analysis, were taken from the Protein Data Bank (PDB). The receptors were then prepared using the Molecular Operating Environment (MOE), as a drug-discovery software platform for docking. Supplements such as quercetin and beta glucan (β-glucan) were the top docked compounds to ACE2 receptor though they strongly interacted with CoV target protein. The study data showed that immune responses to immunonutrient-based sports compounds (viz. quercetin and β-glucan) in Coronavirus disease 2019 (COVID-19) were essential in mounting successful immune responses by athletes. While awaiting the development of an effective vaccine, there is a need to focus on immunonutrient-based sports supplements as preventive and therapeutic options that can be implemented in a safe and quick manner to bolster immune responses in athletes.Communicated by Ramaswamy H. Sarma.
Journal of Clinical Nursing and Midwifery, May 10, 2020
Background & Objective: Polycystic ovary syndrome is the most common endocrine disorder in women.... more Background & Objective: Polycystic ovary syndrome is the most common endocrine disorder in women. Multiple-drug treatments and prolonged treatments often cause patients to discontinue the treatment. Considering the side-effects of chemical drugs, the present study aimed to investigate the effects of the combination of cumin and fennel extract on the clinical symptoms of women with polycystic ovary syndrome. Materials and Methods: This clinical trial was conducted on 70 patients with polycystic ovary syndrome, who were selected randomly from the patients referring to the teaching hospitals in Shahrekord, Iran. The patients were randomly divided into two groups of intervention and control. The intervention group received capsules containing fennel and black cumin, and the control group received placebo twice per day for four months. Before and after the intervention, the clinical symptoms of the subjects were evaluated in both groups. Data analysis was performed in SPSS. Results: In the intervention group, a significant reduction was observed in hirsutism, while the menstrual duration increased compared to the control group (P<0.05). However, these changes were not considered significant in the control group (P>0.05). Conclusion: According to the results, the combination of fennel and cumin extract could effectively improve the clinical symptoms of the patients with polycystic ovary syndrome. Therefore, the herbal mixture could be used as a non-toxic medication for the treatment of these patients.
Postoperative pain and its control remains one of the most important issues in the field of surge... more Postoperative pain and its control remains one of the most important issues in the field of surgery and health care system. Morphine is a potent and effective analgesic. But substance abuse patients can manifest cross tolerance to drugs, making it difficult to predict their analgesic or anesthetic requirements. The anticonvulsant drug, carbamazepine (cbz), has many pharmacological effects. In this study we evaluated the effect of various doses of carbamazepine injected Intraperitoneally (i.p.) on postoperative pain in morphine-dependent and naive rats. Rats were addicted by i.p. morphine. After anesthesia a 1-cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hind paw and then sutured. Both morphine-dependent and naive rats received carbamazepine or/and morphine i.p. 2h and 24h after surgery. Paw Withdrawal Threshold by Von Frey Filament obtained every 0.5h after drug injection up to 3h (at surgical day and next day). We saw that the c...
Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and di... more Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and different pathophysiological mechanisms. Currently there is no effective response to conventional therapy. Co-administration of nonanalgesic dose of drugs can reduce both pain and their adverse effects. The goal of this study was to determine the analgesic effect of three drugs (nimesulide, nefopam, morphine) with different mechanisms of action as a single and combination form in a model of neuropathic pain. Neuropathic pain was induced using CCI model in male wistar rats (n=6, 180-220g) and divided into different groups: 1) sham, saline 2) CCI , saline 3) CCI , nimesulide (1.25, 2.5, 5 mg/kg) 4) CCI, nefopam (10, 20, 30 mg/kg) 5) CCI , morphine (1, 3, 5 mg/kg) 6) CCI, nimesulide (1.25 mg/kg)/morphine (3 mg/kg) 7) CCI , nimesulide (1.25 mg/kg)/nefopam (10 mg/kg) 8) CCI , nefopam (10 mg/kg) /morphine (3mg/kg). Pain behavior was assessed using allodynia tests (Vonfrey filaments and acetone t...
The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new a... more The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new antidepressants with high medicinal properties and low side effects is warranted. Therefore, this study was designed to determine the antidepressant-like effect of tropisetron on a maternal separation (MS) model in mice, considering the possible role of AC. NMRI male mice were divided into eleven groups. The control group was treated with saline and MS groups were treated with saline, tropisetron (a 5-HT3 receptor antagonist) at doses of 1, 3, and 5 mg/kg; forskolin (an activator of AC) at doses of 5, 10, and 25 mg/kg; a subeffective dose of forskolin with a subeffective dose of tropisetron; and an effective dose of tropisetron plus an effective dose of NB001 (3 mg/kg) (an AC inhibitor). After treatment, animals were subjected to behavioral tests including the forced swimming test (FST), splash test, and open field test (OFT). We showed that MS caused depressive-like behaviors determined ...
Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce eff... more Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce effective agents to reduce complications of the ischemia. Involvement of PI3K/AKT/mTOR signaling pathway has been determined in the neuroprotective effect of various agents. Selegiline (deprenyl) possessed neuroprotective properties. In this study global ischemia/reperfusion was established in rats. Selegiline (5 mg/kg for 7 consecutive days) administrated via intraperitoneal route. Possible involvement of PI3K/AKT/mTOR signaling pathway was evaluated using qRT-PCR, immunohistochemistry and histophatologic evaluations in the hippocampus. Spatial memory was evaluated by morris water maze (MWM). Results showed that ischemia impaired the memory and ischemic rats spent more time to find hidden platform in the MWM. Ischemia significantly decreased levels of PI3K, AKT and mTOR in the hippocampus. Histopathologic assessment revealed that the percent of dark neurons significantly increased in the CA1 area of the hippocampus of ischemic rats. Selegiline improved the memory as ischemic rats spent fewer time to find hidden platform in the MWM. Findings showed that selegiline increased the level and expression of PI3K, AKT and mTOR as well as decreased the proportion of dark neurons in the CA1 area of the pyramidal layer of the hippocampus. We concluded that selegiline, partially at least, through increases the expression of PI3K, AKT and mTOR as well as decreases the percent of dark neurons in the hippocampus could improve the memory impairment following the ischemia in rats.
Objectives: The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a glo... more Objectives: The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a global health concern. Exercise training has been reported to activate the Nrf2/Keap1/ARE signaling and enhance the antioxidant defense pathways in some animal models. This study aimed to investigate the effects of ursolic acid (UA) associated with resistance or endurance training on antioxidant markers, and the Nrf2/Keap1/ARE pathway in the brain of older diabetic rats. Materials and methods: 23-month-aged diabetes induced male Wistar rats were randomly assigned to seven groups (n=8). UA supplementation (250 mg/kg, daily) was administered along with resistance (60% maximum capacity of voluntary carrying [MVCC], 14-20 climbs) or endurance training (60-75% velocity at maximal oxygen uptake [vVO2max]), five days/week for eight weeks. Cognitive-motor functioning was assessed through open-field and passive avoidance response tests. Nrf2, Keap1, and antioxidant markers including SOD, CAT, GPx, and GSH were measured in the hippocampus tissue. Results: The results showed positive effect of resistance training (P≤0.001) on Nrf2. There was endurance training with supplementation main effect (P=0.018) on Keap1 concentration. SOD revealed a significant endurance/resistance training by supplementation interaction effect (P≤0.05); however, there was no main training or UA supplementation effects on CAT, GPx, and GSH, despite improving spatial memory changes in exercise or UA groups. Conclusion: It appears that UA treatment with resistance or endurance exercise has some beneficial effects on Nrf2 and some antioxidant markers. However, more research is needed to elucidate UA's interaction effects and exercise interventions in diabetic situations.
Central pain syndrome (CPS) is a debilitating state and one of the consequences of spinal cord in... more Central pain syndrome (CPS) is a debilitating state and one of the consequences of spinal cord injury in patients. Many pathophysiological aspects of CPS are not well documented. Spinal glia activation has been identified as a key factor in the sensory component of chronic pain. In this study, the role of glial subtypes in the process of CPS induced by unilateral electrolytic lesion of spinothalamic tract (STT) is investigated. Male rats received a laminectomy at T8-T9 and then unilateral electrolytic lesion centered on the STT. Thermal and mechanical thresholds as well as locomotor function were measured on days 0, 3, 7, 14, 21, and 28 post-injuries by tail flick, von Frey filament, and open field tests, respectively. To investigate the spinal glial activation following denervation in STT-lesioned groups, Iba1 and GFAP were detected by immunohistochemistry and Western blotting at the same time points. Data showed that STT lesion significantly decreased thermal pain at day 3 in comparison with sham groups. Significant bilateral allodynia appeared in hind paws at day 14 after spinal cord injury and continued to day 28 (P<0.05). Additionally, electrolytic spinal lesion attenuated locomotor function of injured animals after 7 days (P<0.05). In both histological assessments and Western blotting, Iba1 increased at days 3 and 7 while increased GFAP occurred from day 14 to 28 after lesion. It appears that microglial activation is important in the early stages of pain development and astrocytic activation occurs later. These events may lead to behavioral outcomes especially central neuropathic pain.
Introduction: Spinal cord injuries are accompanied with significant demyelination of axons and su... more Introduction: Spinal cord injuries are accompanied with significant demyelination of axons and subsequent locomotor dysfunction. To identify the extent of damage following electrolytic lesion of ventrolateral white matter, essential area for initiation of locomotor activity, we assessed demyelination as well as alteration in motor performance. Moreover, the protective effect of estradiol as a candidate treatment for preservation of myelin and locomotor activity after injury was examined due to its antiapoptotic and anti-inflammatory activities. Methods: A unilateral electrolytic lesion positioned in the right ventrolateral funiculus (VLF) was applied following laminectomy at T8-T9. In the estradiol-treated injury group, animals received a pharmacological single dose of estradiol valerate (4 mg/kg) at 30min post injury. Locomotor function was assessed using rotarod and open field tasks during 4 weeks after injury. Results: Obtained results showed significant demyelination at the site...
The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new a... more The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new antidepressants with high medicinal properties and low side effects is warranted. Therefore, this study was designed to determine the antidepressant-like effect of tropisetron on a maternal separation (MS) model in mice, considering the possible role of AC. NMRI male mice were divided into eleven groups. The control group was treated with saline and MS groups were treated with saline, tropisetron (a 5-HT3 receptor antagonist) at doses of 1, 3, and 5 mg/kg; forskolin (an activator of AC) at doses of 5, 10, and 25 mg/kg; a subeffective dose of forskolin with a subeffective dose of tropisetron; and an effective dose of tropisetron plus an effective dose of NB001 (3 mg/kg) (an AC inhibitor). After treatment, animals were subjected to behavioral tests including the forced swimming test (FST), splash test, and open field test (OFT). We showed that MS caused depressive-like behaviors determined as an increase in the immobility time in the forced swimming test (FST) and decreased grooming time in the splash test. Our results showed that administration of tropisetron, as well as forskolin, mitigated the depressive-like behaviors in MS mice. We found that coadministration of a subeffective dose of tropisetron plus a subeffective dose of forskolin potentiated the antidepressantlike effect of tropisetron. However, coadministration of an effective dose of NB001 with an effective dose of tropisetron did not significantly affect the antidepressant-like effect of tropisetron. We concluded that the antidepressant-like effects of tropisetron on MS mice are partially mediated through the adenylyl cyclase pathway.
Evidence-based Complementary and Alternative Medicine, Dec 21, 2020
Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main... more Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main risk factor for the occurrence and progression of cognitive and memory impairment. Available treatments such as benzodiazepine and antidepressants address only certain aspects of this stress disorder and have numerous side effects. e present study was aimed at investigating the effect of diosmetin, as a flavonoid compound with potent antioxidant and anti-inflammatory effects, on cognitive impairment and chronic stress memory. Materials and Methods. In the present experimental study, male NMRI mice were exposed to chronic unpredictable mild stress (CUMS) paradigm for 35 days. Diosmetin (at doses of 10, 20, and 40 mg/kg. i.p.) or diosmetin solvent (normal saline + DMSO, 1 ml/kg; i.p.) was administered 30 min before stress induction. After 28 days, memory and cognitive performance were assessed by shuttle box and novel object recognition tests. Finally, antioxidant capacity (FRAP) and malondialdehyde (MDA) level of serum and brain, and serum corticosterone level were evaluated. Results. Behavioral tests showed that CUMS significantly reduced the secondary latency in passive avoidance memory test and diagnosis index in novel object recognition test compared to the control group (P < 0.001), whereas treatment with diosmetin (20 and 40 mg/kg) significantly improved memory performance in the two tests (P < 0.001). In addition, diosmetin (40 mg/kg) could pronouncedly suppress increase in serum corticosterone levels, reduction in antioxidant capacity, and production of excess MDA caused by CUMS compared to the control group (P < 0.01, P < 0.001, and P < 0.001, respectively). Conclusion. Chronic stress can impair memory and cognition and treatment with diosmetin can partly improve this disorder in male mice by increasing the antioxidant capacity of brain tissue and serum and improving serum corticosterone levels.
Context: Experiencing early-life adversity plays a key role in the development of mood disorders ... more Context: Experiencing early-life adversity plays a key role in the development of mood disorders in adulthood. Experiencing adversities during early life period negatively affects brain development. Sex steroids such as progesterone affect the brain structure and functions and subsequently affects behaviour. Objective: We assess the antidepressant-like effect of progesterone in a mouse model of maternal separation (MS) stress, focussing on its anti-neuroinflammatory and antioxidative effects. Materials and methods: NMRI mice were treated with progesterone (10, 50, and 100 mg/kg, i.p., respectively) for 14 days. Valid behavioural tests including forced swimming test (FST), splash test and open field test (OFT) were used. Quantitative reverse transcription-PCR (qRT-PCR) was used for evaluation of genetic expression in the hippocampus. Antioxidant capacity was assessed by the FRAP method and the level of malondialdehide by TBA. Results: MS provoked depressive-like behaviour in mice. Treatment of MS mice with progesterone increased the grooming activity time in the splash test and decreased the immobility time in the FST. In addition, progesterone decreased the expression of inflammatory genes related to neuroinflammation (IL-1b, TNF-a, TLR4 and NLRP3) as well as increased the antioxidant capacity and decreased the lipid peroxidation (MDA) in the hippocampus. Discussion and Conclusion: Administration of progesterone significantly mitigated the negative effects of MS on behaviours relevant to depressive-like behaviour as well as attenuated neuro-immune response and oxidative stress in the hippocampus of MS mice. In this context, we conclude that progesterone, at least partially, via attenuation of oxidative stress and neuroinflammation, exerts antidepressant-like effects.
Postoperative pain and its control remain one of the most important issues in the field of surger... more Postoperative pain and its control remain one of the most important issues in the field of surgery and health care systems. Morphine is a potent and effective analgesic, but substance abuse patients can manifest crosstolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements. As carbamazepine has shown antinociceptive properties in a variety of experimental and clinical settings, in the present study, we evaluated its potential antiallodynic effects on postoperative pain in naïve and morphine-dependent rats. Male rats were assigned to morphine-dependent and naïve groups and received intraperitoneally drug vehicles as control group, 3 mg/kg morphine, 5, 10 or 15 mg/kg carbamazepine or 5 mg/kg carbamazepine plus 3 mg/kg morphine as a combination therapy 2 and 24 h after surgery. Morphine-dependency was induced with multiple doses of morphine administered i.p. and plantar incision was made on the hind paw to simulate the postoperative pain. Paw withdrawal threshold (PWT) was obtained by von Frey filaments every 30 min after drug injection for up to 180 min. Morphine at 3 mg/kg exerted antiallodynic effects in naïve rats and a decreased antinociception was observed in morphine-dependent rats. In contrast, 5 mg/kg carbamazepine did not significantly alter PWT in naives but it was effective in dependent rats. 10 and 15 mg/kg carbamazepine attenuated allodynia following surgery in both groups. Co-administration of 5 mg/kg carbamazepine with 3 mg/kg morphine produced higher analgesia in morphine-dependent incised rats and prolonged antinociception as compared to morphine alone (P b 0.05). Thus carbamazepine may potentiate the analgesic effect of chronically administered morphine on postoperative pain model in morphinedependent rats.
Alzheimer's disease (AD) is a common neurodegenerative condition that affects the elderly populat... more Alzheimer's disease (AD) is a common neurodegenerative condition that affects the elderly population. Its primary symptom is memory loss. The memory dysfunction in AD has been associated with cortical cholinergic deficiency and loss of cholinergic neurons of the nucleus basalis of Meynert (NBM). Zizyphus jujube (ZJ) activates choline acetyltransferase and may have beneficial effects in AD patients. This study investigates the effect of ZJ extract in intact rats and in rat model of AD. 49 male Wistar rats were divided into seven equal groups (1control, without surgery, received water), 2-AD (bilateral NBM lesion, received water), 3 and 4-AD ? ZJ (NBM bilateral lesion, received ZJ extract 500 and 1,000 mg/kg b.w. per day for 15 days), 5-sham (surgery: electrode introduced into NBM without lesion, received water), 6 and 7-without surgery and lesion, received ZJ extractthe same as groups 3 and 4). The learning and memory performance were assessed using passive avoidance paradigm, and the memory cognition for spatial learning and memory was evaluated by Morris water maze. In shuttle box test ZJ extract (500 and 1,000 mg) significantly increased step-through latency in AD ? ZJ groups compared with AD group. In Morris water maze test (in probe day), both AD ? ZJ groups receiving extract (500 and 1,000 mg) demonstrated significant preference for the quadrant in which the platform was located on the preceding day as compared with AD group. Our results suggested that ZJ has repairing effects on memory and behavioral disorders produced by NBM lesion in rats and may have beneficial effects in treatment of AD patients.
Postoperative pain and its control remains one of the most important issues in the field of surge... more Postoperative pain and its control remains one of the most important issues in the field of surgery and health care system. Morphine is a potent and effective analgesic. But substance abuse patients can manifest cross tolerance to drugs, making it difficult to predict their analgesic or anesthetic requirements. The anticonvulsant drug, carbamazepine (cbz), has many pharmacological effects. In this study we evaluated the effect of various doses of carbamazepine injected Intraperitoneally (i.p.) on postoperative pain in morphine-dependent and naive rats. Rats were addicted by i.p. morphine. After anesthesia a 1-cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hind paw and then sutured. Both morphine-dependent and naive rats received carbamazepine or/and morphine i.p. 2h and 24h after surgery. Paw Withdrawal Threshold by Von Frey Filament obtained every 0.5h after drug injection up to 3h (at surgical day and next day). We saw that the combination of carbamazepine 5mg/kg+morphine 3mg/kg produced more analgesic effects in morphinedependent rats compared to cbz or morphine alone and this combination had same effect of morphine 3mg/kg alone in naive rats (P<0.05). carbamazepine may potentiate the analgesic effect of chronically administration of morphine.
Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and di... more Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and different pathophysiological mechanisms. Currently there is no effective response to conventional therapy. Co-administration of nonanalgesic dose of drugs can reduce both pain and their adverse effects. The goal of this study was to determine the analgesic effect of three drugs (nimesulide, nefopam, morphine) with different mechanisms of action as a single and combination form in a model of neuropathic pain. Neuropathic pain was induced using CCI model in male wistar rats (n=6, 180-220g) and divided into different groups: 1) sham, saline 2) CCI , saline 3) CCI , nimesulide (1.25, 2.5, 5 mg/kg) 4) CCI, nefopam (10, 20, 30 mg/kg) 5) CCI , morphine (1, 3, 5 mg/kg) 6) CCI, nimesulide (1.25 mg/kg)/morphine (3 mg/kg) 7) CCI , nimesulide (1.25 mg/kg)/nefopam (10 mg/kg) 8) CCI , nefopam (10 mg/kg) /morphine (3mg/kg). Pain behavior was assessed using allodynia tests (Vonfrey filaments and acetone test) before and days 1, 5,7,10 and 14 after surgery. The data were analyzed using ANOVA and p<0.05 was considered significant. Morphine, nefopam and nimesulide (5mg/kg, 10 -20mg/kg and 2.5-5mg/kg, respectively) reduced allodynia. The non analgesic doses of drugs reduced pain behavior when used in combination. It seems that analgesic drugs used in combination with low doses controlled pain effectively with less adverse effects seen when they are used alone
Journal of Biomolecular Structure & Dynamics, Dec 21, 2021
Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor fo... more Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reviewed through molecular docking and sequent molecular dynamics (MD) simulations against this condition. The crystal structures of ACE2 receptors of SARS-CoV-2 and SARS-CoV, applied in docking analysis, were taken from the Protein Data Bank (PDB). The receptors were then prepared using the Molecular Operating Environment (MOE), as a drug-discovery software platform for docking. Supplements such as quercetin and beta glucan (β-glucan) were the top docked compounds to ACE2 receptor though they strongly interacted with CoV target protein. The study data showed that immune responses to immunonutrient-based sports compounds (viz. quercetin and β-glucan) in Coronavirus disease 2019 (COVID-19) were essential in mounting successful immune responses by athletes. While awaiting the development of an effective vaccine, there is a need to focus on immunonutrient-based sports supplements as preventive and therapeutic options that can be implemented in a safe and quick manner to bolster immune responses in athletes.Communicated by Ramaswamy H. Sarma.
Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor fo... more Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reviewed through molecular docking and sequent molecular dynamics (MD) simulations against this condition. The crystal structures of ACE2 receptors of SARS-CoV-2 and SARS-CoV, applied in docking analysis, were taken from the Protein Data Bank (PDB). The receptors were then prepared using the Molecular Operating Environment (MOE), as a drug-discovery software platform for docking. Supplements such as quercetin and beta glucan (β-glucan) were the top docked compounds to ACE2 receptor though they strongly interacted with CoV target protein. The study data showed that immune responses to immunonutrient-based sports compounds (viz. quercetin and β-glucan) in Coronavirus disease 2019 (COVID-19) were essential in mounting successful immune responses by athletes. While awaiting the development of an effective vaccine, there is a need to focus on immunonutrient-based sports supplements as preventive and therapeutic options that can be implemented in a safe and quick manner to bolster immune responses in athletes.Communicated by Ramaswamy H. Sarma.
Journal of Clinical Nursing and Midwifery, May 10, 2020
Background & Objective: Polycystic ovary syndrome is the most common endocrine disorder in women.... more Background & Objective: Polycystic ovary syndrome is the most common endocrine disorder in women. Multiple-drug treatments and prolonged treatments often cause patients to discontinue the treatment. Considering the side-effects of chemical drugs, the present study aimed to investigate the effects of the combination of cumin and fennel extract on the clinical symptoms of women with polycystic ovary syndrome. Materials and Methods: This clinical trial was conducted on 70 patients with polycystic ovary syndrome, who were selected randomly from the patients referring to the teaching hospitals in Shahrekord, Iran. The patients were randomly divided into two groups of intervention and control. The intervention group received capsules containing fennel and black cumin, and the control group received placebo twice per day for four months. Before and after the intervention, the clinical symptoms of the subjects were evaluated in both groups. Data analysis was performed in SPSS. Results: In the intervention group, a significant reduction was observed in hirsutism, while the menstrual duration increased compared to the control group (P<0.05). However, these changes were not considered significant in the control group (P>0.05). Conclusion: According to the results, the combination of fennel and cumin extract could effectively improve the clinical symptoms of the patients with polycystic ovary syndrome. Therefore, the herbal mixture could be used as a non-toxic medication for the treatment of these patients.
Postoperative pain and its control remains one of the most important issues in the field of surge... more Postoperative pain and its control remains one of the most important issues in the field of surgery and health care system. Morphine is a potent and effective analgesic. But substance abuse patients can manifest cross tolerance to drugs, making it difficult to predict their analgesic or anesthetic requirements. The anticonvulsant drug, carbamazepine (cbz), has many pharmacological effects. In this study we evaluated the effect of various doses of carbamazepine injected Intraperitoneally (i.p.) on postoperative pain in morphine-dependent and naive rats. Rats were addicted by i.p. morphine. After anesthesia a 1-cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hind paw and then sutured. Both morphine-dependent and naive rats received carbamazepine or/and morphine i.p. 2h and 24h after surgery. Paw Withdrawal Threshold by Von Frey Filament obtained every 0.5h after drug injection up to 3h (at surgical day and next day). We saw that the c...
Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and di... more Neuropathic pain is a chronic pain due to disorder in peripheral or central nervous system and different pathophysiological mechanisms. Currently there is no effective response to conventional therapy. Co-administration of nonanalgesic dose of drugs can reduce both pain and their adverse effects. The goal of this study was to determine the analgesic effect of three drugs (nimesulide, nefopam, morphine) with different mechanisms of action as a single and combination form in a model of neuropathic pain. Neuropathic pain was induced using CCI model in male wistar rats (n=6, 180-220g) and divided into different groups: 1) sham, saline 2) CCI , saline 3) CCI , nimesulide (1.25, 2.5, 5 mg/kg) 4) CCI, nefopam (10, 20, 30 mg/kg) 5) CCI , morphine (1, 3, 5 mg/kg) 6) CCI, nimesulide (1.25 mg/kg)/morphine (3 mg/kg) 7) CCI , nimesulide (1.25 mg/kg)/nefopam (10 mg/kg) 8) CCI , nefopam (10 mg/kg) /morphine (3mg/kg). Pain behavior was assessed using allodynia tests (Vonfrey filaments and acetone t...
The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new a... more The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new antidepressants with high medicinal properties and low side effects is warranted. Therefore, this study was designed to determine the antidepressant-like effect of tropisetron on a maternal separation (MS) model in mice, considering the possible role of AC. NMRI male mice were divided into eleven groups. The control group was treated with saline and MS groups were treated with saline, tropisetron (a 5-HT3 receptor antagonist) at doses of 1, 3, and 5 mg/kg; forskolin (an activator of AC) at doses of 5, 10, and 25 mg/kg; a subeffective dose of forskolin with a subeffective dose of tropisetron; and an effective dose of tropisetron plus an effective dose of NB001 (3 mg/kg) (an AC inhibitor). After treatment, animals were subjected to behavioral tests including the forced swimming test (FST), splash test, and open field test (OFT). We showed that MS caused depressive-like behaviors determined ...
Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce eff... more Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce effective agents to reduce complications of the ischemia. Involvement of PI3K/AKT/mTOR signaling pathway has been determined in the neuroprotective effect of various agents. Selegiline (deprenyl) possessed neuroprotective properties. In this study global ischemia/reperfusion was established in rats. Selegiline (5 mg/kg for 7 consecutive days) administrated via intraperitoneal route. Possible involvement of PI3K/AKT/mTOR signaling pathway was evaluated using qRT-PCR, immunohistochemistry and histophatologic evaluations in the hippocampus. Spatial memory was evaluated by morris water maze (MWM). Results showed that ischemia impaired the memory and ischemic rats spent more time to find hidden platform in the MWM. Ischemia significantly decreased levels of PI3K, AKT and mTOR in the hippocampus. Histopathologic assessment revealed that the percent of dark neurons significantly increased in the CA1 area of the hippocampus of ischemic rats. Selegiline improved the memory as ischemic rats spent fewer time to find hidden platform in the MWM. Findings showed that selegiline increased the level and expression of PI3K, AKT and mTOR as well as decreased the proportion of dark neurons in the CA1 area of the pyramidal layer of the hippocampus. We concluded that selegiline, partially at least, through increases the expression of PI3K, AKT and mTOR as well as decreases the percent of dark neurons in the hippocampus could improve the memory impairment following the ischemia in rats.
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