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The beneficial effects of nettle supplementation and exercise on brain lesion and memory in rat
Abstract
Regular swimming and phytotherapeutic supplementation are assumed to alleviate the severity of neurodegeneration leading to dementia. The effect of swimming training and that of enriched lab chow containing 1% (w/w) dried nettle (Urtica dioica) leaf on the prevention of severity of brain injury caused by N-methyl-d-aspartate (NMDA) lesion in Wistar rats were investigated. Nettle supplementation and regular swimming exercise seem to improve the adverse effect of brain injury caused by NMDA lesion assessed by passive avoidance test and open-field test. Nettle supplementation decreases the level of reactive oxygen species, measured by electron paramagnetic resonance, and the DNA-binding activity of NF-kappaB. The data reveal that nettle supplementation has an effective antioxidant role, down-regulates the inflammatory transcription factors and could also promote learning performance in the brain. Regular swimming increases the concentration of reactive species in the cerebellum and alters the activity of transcription factors toward inflammation. The additive effect of the two treatments was more profound in the down-regulation of inflammatory transcription processes in NMDA lesion.
... With this review, we aim at providing an updated overview on the role of U. dioica extracts and components in counteracting neurodegeneration. In fact, mounting evidence shows that U. dioica can improve memory function and compounds isolated from this plant, such as the flavonoid rutin, improve cognition and reduce chronic stress-related dysfunctions of the central nervous system (CNS) in animal models [29,30]. Nevertheless, this field has been only explored rather recently, but it would represent an attractive option from the point of view of medicinal chemists. ...
... NMDA also impairs memory abilities, but U. dioica induced protective effects in this context. Eventually, as shown by EPR measurements, U. dioica supplementation markedly reduced free radical accumulation from the cerebellum [29,31,64]. ...
... Stimulation of NF-κB, a protein that mediates oxidative injury through stimulation of pro-inflammatory markers, was shown to be inactivated through abrogation of its nuclear translocation by both U. dioica supplementation and exercise [29]. In particular, a hydroalcoholic U. dioica extract showed neuroprotective action in a scopolamine-induced memory impairment model (15 mg/kg). ...
Urtica dioica is a perennial herb from the family of Urticaceae that is commonly known as stinging nettle. This plant is
widespread in Europe, Africa, America, and a part of Asia, as it adapts to diferent environments and climatic conditions. The leaves, stalk, and bark of U. dioica found applications in the feld of nutrition, cosmetics, textile, pest control
and pharmacology. In this connection, bioactive chemical constituents such as favonoids, phenolic acids, amino
acids, carotenoids, and fatty acids have been isolated from the plant. With this review, we aim at providing an updated
and comprehensive overview of the contributions in literature reporting computational, in vitro, pre-clinical and clinical data supporting the therapeutic applications of U. dioica. Experimental evidence shows that U. dioica constituents
and extracts can provide neuroprotective efects by acting through a combination of diferent molecular mechanisms, that are discussed in the review. These fndings could lay the basis for the identifcation and design of more
efective tools against neurodegenerative diseases.
... Memory retrieval and learning abilities, estimated by a passive avoidance test, illustrated that NMDA lesion damaged the memory retrieval; on the other hand, nettle supplementation in combination with exercise attenuated lesion induced by NMDA (p < 0.05). From the EPR measurement, it was disclosed that supplementation of nettle significantly decreased the accumulation of free radical from cerebellum caused by swimming (p < 0.05) [65,66]. ...
... The activation of NF-kβ, a transcription factor that leads to oxidative damage via activation of pro-inflammatory cytokines, was found to be substantially inactivated via inhibition of its nuclear translocation by both exercise and nettle supplementation [66]. Ghasemi et al. reported that the hydro alcoholic extract of Urtica was neuroprotective in scopolamine-induced memory impairment model. ...
Stinging nettle (Urtica dioica L., Urticaceae) is commonly found in Asia, Africa, and Europe and has a long history of being used as food and traditional medicine. Recently, this plant is gaining attention as a highly nutritious food, where fresh leaves are dried and used as powder or in other forms. Leaves are rich in many bioactive compounds. This review aims to cover the traditional uses in food and medicine, as well as its nutritional composition, including its bioactive chemical constituents and reported food functional activities. Various bioactive chemical constituents have been isolated from stinging nettle to date, such as flavonoids, phenolic acids, amino acid, carotenoids, and fatty acids. Stinging nettle extracts and its compounds, such as rutin, kaempferol, and vitamin A, are also used for their nutritional properties and as anti-inflammatory and antioxidant agents. Future studies should focus on the proper formulation and stability testing of the functional foods containing stinging nettle and their detailed activities in clinical studies.
... In folk medicine, UD seeds used for treatment of cancer (Kaya et al., 2013 andAktas et al., 2016), urinary tract disorder as well as an antiinflammatory agent (Di Lorenzo et al., 2013). The UD contains both fat soluble vitamins (A and D) and watersoluble vitamins (C and B), minerals (iron, manganese, potassium and, calcium) and proteins (Toldy et al., 2009 andUpton, 2013). Moreover, UD has salicylic acid, lecithin, sterols, thymol, chlorophyll, carotenoids, flavonoids and antioxidants (Dügenci et al., 2003;Upton, 2013 andJalili et al., 2014) that promote detoxification, antiinflammatory and antioxidant capacity (Kataki et al., 2012b). ...
... The antioxidant effect of AEDPP returns to its high concentration of vitamins C, B1, B2, nicotinic acid (Niacin) and vitamin A (Hassan, 2011). Moreover, the AEUD contains both fat soluble vitamins (A and D) and water-soluble vitamins (C and B), minerals (iron, manganese, potassium and calcium) and proteins (Toldy et al., 2009 andUpton, 2013). On the other hand, several factors can be considered to understand the action and the capacity of antioxidants: the capacity for scavenging free radicals, the localization of antioxidant, but also the interaction with other antioxidants and the mobility of antioxidant at the microenvironment (Niki, 2010). ...
This study was conducted to investigate the influence of adding aqueous extracts of Urtica dioica (AEUD) and date palm pollen powder (AEDPP) to Tris extender on some post-cryopreserved semen characteristics of Holstein bulls for different preservation periods (cooling at 5ºC, 48 hrs., 1, 2 and 3 months post cryopreservation, PC). Seven Holstein bulls of 2.5-3 years old were used in the current study during the period from 20 th November, 2017 to 20 th August, 2018. Pooled semen was equally divided into three groups within one experiment. AEUD (0.01 g / 50 ml extender) and AEDPP (0.02 g / 50 ml extender) were added to Tris extender and comparisons in response were made with the control group (Tris extender, C). The AEUD and AEDPP groups exhibited greater (P<0.01) sperm's cell individual motility percentage as compared with the C group at cooling as well as 1, 2 and 3 months PC periods. Concomitantly, greater (P<0.01) live sperm percentage was observed in AEUD and AEDPP groups in comparison with the C group at all preservation periods. Lesser (Pd<0.01) abnormal sperm percentage were noticed for AEUD and AEDPP groups as compared with the C group at 48 hr., 1, 2 and, 3 months PC. Greater (P<0.01) acrosome integrity percentage was observed for AEUD as compared with the other two groups at 1, 2 and, 3 months PC. The AEUD and AEDPP groups exhibited greater (P<0.01) plasma membrane integrity percentage in comparison with the control group at all preservation periods. In conclusion, adding AEUD and AEDPP to Tris extender had a crucial role in improving some PC semen characteristics of Holstein bulls.
... On the other hand, unexpectedly, it's helpful effect observed in detraining period. Several studies showed positive effects of physical activity that were in agreement with our results [27][28][29][30][31] . Mechanisms of exercise effects on brain function are different. ...
... Previous studies reported that exercise improved memory in normal and some disorders in rats [27,28,52] , but all of them did not use synchronized exercise. ...
Impairment of learning and memory processes has been demonstrated by many studies using different stressors. Other reports suggested that exercise has a powerful behavioral intervention to improve cognitive function and brain health. In this research, we investigated protective effects of treadmill running on chronic stress-induced memory deficit in rats.
Fifty male Wistar rats were randomly divided into five groups (n=10) as follows: Control (Co), Sham (Sh), Stress (St), Exercise (Ex) and Stress and Exercise (St & Ex) groups. Chronic restraint stress was applied by 6h/day/21days and also treadmill running at a speed 20-21m/min for 1h/day/21days. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock.
OUR RESULTS SHOWED THAT: 1) Although exercise alone showed beneficial effects especially on short and mid-term memory (P<0.05) in comparison with control group, but synchronized exercise with stress had not significantly improved short, mid and long-term memory deficit in stressed rats. 2) Short and mid-term memory deficit was significantly (P<0.05) observed in synchronized exercise with stress and stress groups with respect to normal rats. 3) Memory deficit in synchronized exercise with stress group was nearly similar to stressed rats. 4) Helpful effects of exercise were less than harmful effects of stress when they were associated together.
The data correspond to the possibility that although treadmill running alone has helpful effects on learning and memory consolidation, but when it is synchronized with stress there is no significant benefit and protective effects in improvement of memory deficit induced by chronic stress. However, it is has a better effect than no training on memory deficit in stressed rats.
... [16,17] Some animal studies have revealed that treadmill running improves spatial and passive avoidance learning in NBM-lesion rats. [4,18] In previous studies, transgenic and NBM-lesion models, they investigated the effects of physical activity after onset of AD in these models and, there have been no basic researches performed to estimate the preventive effects of exercise. The aims of this study were to investigate preventive effects of treadmill running in NBM-lesion rats on learning and memory deficit by passive avoidance task in order to examine whether treadmill running can prevent learning impairment in this model of AD. ...
... These results were in agreement with those of previous studies. [12,18] Chopin et al. [20] demonstrated significant performance deficits in both passive avoidance and Morris water maze tests in bilateral NBM-lesion rats. They showed that regular exercise significantly attenuated lesion-associated decrease in brain functions. ...
Alzheimer's disease was known as a progressive neurodegenerative disorder in the elderly and is characterized by dementia and severe neuronal loss in the some regions of brain such as nucleus basalis magnocellularis. It plays an important role in the brain functions such as learning and memory. Loss of cholinergic neurons of nucleus basalis magnocellularis by ibotenic acid can commonly be regarded as a suitable model of Alzheimer's disease. Previous studies reported that exercise training may slow down the onset and progression of memory deficit in neurodegenerative disorders. This research investigates the effects of treadmill running on acquisition and retention time of passive avoidance deficits induced by ibotenic acid nucleus basalis magnocellularis lesion.
MALE WISTAR RATS WERE RANDOMLY SELECTED AND DIVIDED INTO FIVE GROUPS AS FOLLOWS: Control, sham, Alzheimer, exercise before Alzheimer, and exercise groups. Treadmill running had a 21 day period and Alzheimer was induced by 5 μg/μl bilateral injection of ibotenic acid in nucleus basalis magnocellularis.
Our results showed that ibotenic acid lesions significantly impaired passive avoidance acquisition (P < 0.01) and retention (P < 0.001) performance, while treadmill running exercise significantly (P < 0.001) improved passive avoidance learning in NBM-lesion rats.
Treadmill running has a potential role in the prevention of learning and memory impairments in NBM-lesion rats.
... :5,[84][85][86][87][88][89][90][91][92] It is a deciduous woody flowering plant in North east countries it is widely cultivated. Consumed a table grape or transformed into wine, jam, jelly, extracts, seed oils, raisins. ...
Alzheimer's disease (AD) is related to cognitive impairment, dementia observed generally in aged population due to neurodegeneration in an ongoing manner. It gradually worsens memory power of the patient. The hallmark diagnosis features includes formation of senile plaques and Neurofibrillary tangles (NFT'S). Too little availability of Acetyl choline (ACh) a neurotransmitter in the cerebral region due to metabolism by an enzyme Acetyl choline esterase before showing its action and neural death are the primary reasons for AD. There are many categories of Anti-Alzheimer's drugs available for management of AD in the market but due to lack of patient compliance successful outcomes were not observed. Apart from this including Nutraceuticals in diet daily routine, Aromatherapy, modifications in the regular schedule, practicing yoga regularly relaxes mind and body from tensions, insomnia, blood circulation, detoxification of organs due to rhythmic breathings and reduce frequency of incidence of headache are proven to show best results by relieving stress according to survey. At present herbal medicine has turn out to be best choice for the management of AD because of its availability, very economic, good patient compliance, ease of formulation and lower deleterious side effects. Novel techniques can be used for the development of herbal medicine. This review totally discuses about the occurrence of AD, its Pathophysiology, different stages in the disorder, various selective therapeutic targets for AD, available Anti-AD herbal drugs such as Curcumin, Withania somnifera, Bhrami, Ginkgo biloba, guggul, ginseng, herbs with essential oils, volatile oils, source and cultivation of the herbs, mechanism of action of the Phytochemicals in the herb responsible for treating AD.
... The open-field test is widely used to study the reaction to novelty and provides some insight into the state of anxiety in rodents [12]. Mice were positioned in the center of an open-field box consisting of a cylindrical arena of 80 cm diameter, divided into 20 sectors by concentric and radial lines, and surrounded by a 35 cm-high wall. ...
Extensive research has confirmed numerous advantages of exercise for promoting brain health. More recent studies have proposed the potential benefits of lactate, the by-product of exercise, in various aspects of brain function and disorders. However, there remains a gap in understanding the effects of lactate dosage and its impact on aged rodents. The present study first examined the long-term effects of three different doses of lactate intervention (2000 mg/kg, 1000 mg/kg, and 500 mg/kg) and high-intensity interval training (HIIT) on aging mice (20–22 months) as the 1st experiment. Subsequently, in the 2nd experiment, we investigated the long-term effects of 500 mg/kg lactate intervention and HIIT on brain neuroplasticity in aged mice (25–27 months).
The results of the 1st experiment demonstrated that both HIIT and different doses of lactate intervention (500 mg/kg and 2000 mg/kg) positively impacted the neuroplasticity biomarker VEGF in the hippocampus of aging mice. Subsequently, the 2nd experiment revealed that long-term HIIT significantly improved the performance of mice in open-field, novel object recognition, and passive avoidance tests. However, lactate intervention did not significantly affect these behavioral tests. Moreover, compared to the control group, both HIIT and lactate intervention positively influenced the angiogenesis signaling pathway (p/t-AKT/ENOS/VEGF), mitochondrial biomarker (SDHA), and metabolic protein (p/t-CREB, p/t-HSL, and LDH) in the hippocampus of aged mice. Notably, only lactate intervention significantly elevated the BDNF (PGC-1α, SIRT1, and BDNF) signaling pathway and metabolic content (lactate and pyruvate). In the end, long-term HIIT and lactate intervention failed to change the protein expression of p/t-MTOR, iNOS, nNOS, HIF-1α, SYNAPSIN, SIRT3, NAMPT, CS, FNDC5 and Pan Lactic aid-Lysine in the hippocampus of aged mice.
In summary, the present study proved that long-term HIIT and lactate treatment have positive effects on the brain functions of aged mice, suggesting the potential usage of lactate as a therapeutic strategy in neurodegenerative diseases in the elderly population.
... By reducing the presence of the peptides in mitochondria, postbiotic treatment may also help in reducing mitochondrial dysfunction. Inflammation is a concomitant and/or causative process of AD [32][33][34]. Transcription factors such as SP1 and NF-kB are mediators of inflammatory processes, and downregulation of these transcription factors not only suppresses inflammation but also decreases reactive oxygen species production (ROS) [4]. Here, we confirmed that exercise especially in conjunction with postbiotic treatment reduces the involvement of NF-kB [35,36] in the inflammatory process, and our data showed that this process plays a neuroprotective role in APP/PS1 model [10]. ...
Background
It has been suggested that exercise training and postbiotic supplement could decelerate the progress of functional and biochemical deterioration in double transgenic mice overexpresses mutated forms of the genes for human amyloid precursor protein (APPsw) and presenilin 1 (m146L) (APP/PS1TG). Our earlier published data indicated that the mice performed better than controls on the Morris Maze Test parallel with decreased occurrence of amyloid-β plaques in the hippocampus. We investigated the neuroprotective and therapeutic effects of high-intensity training and postbiotic supplementation.
Methods
Thirty-two adult APP/PS1TG mice were randomly divided into four groups: (1) control, (2) high-intensity training (3) postbiotic, (4) combined (training and postbiotic) treatment for 20 weeks. In this study, the whole hemibrain without hippocampus was used to find molecular traits explaining improved brain function. We applied qualitative RT-PCR for gene expression, Western blot for protein level, and Zymography for LONP1 activity. Disaggregation analysis of Aβ-40 was performed in the presence of Lactobacillus acidophilus and Bifidobacterium longum lysate.
Results
We found that exercise training decreased Alzheimer’s Disease (AD)-related gene expression (NF-kB) that was not affected by postbiotic treatment. The preparation used for postbiotic treatment is composed of tyndallized Bifidobacterium longum and Lactobacillus acidophilus. Both of the postbiotics effectively disaggregated amyloid-β/Aβ-40 aggregates by chelating Zn²⁺ and Cu²⁺ ions. The postbiotic treatment decreased endogenous human APPTG protein expression and mouse APP gene expression in the hemibrains. In addition, the postbiotic treatment elevated mitochondrial LONP1 activity as well.
Conclusion
Our findings revealed distinct mechanisms behind improved memory performance in the whole brain: while exercise training modulates NF-kB signaling pathway regulating immune response until postbiotic diminishes APP gene expression, disaggregates pre-existing amyloid-β plaques and activates mitochondrial protein quality control in the region of brain out of hippocampus. Using the above treatments complements and efficiently slows down the development of AD.
... In ammation is a co-existing and/or causative process of AD (31)(32)(33)(34). Transcription factors like SP1 and NF-kB are mediators of in ammatory process and downregulation of these transcription factors not just suppress in ammation but decrease production of reactive oxygen species (ROS) as well (4). ...
Background It has been suggested that exercise training and postbiotic supplement could decelerate the progress of functional and biochemical deterioration in double transgenic mice overexpresses mutated forms of the genes for human amyloid precursor protein (APPsw) and presenilin 1 (m146L) (APP/PS1TG). Our earlier published data indicated that the mice performed better than controls on the Morris Maze Test parallel with decreased occurrence of amyloid-β plaques in the hippocampus. We investigated the neuroprotective and therapeutic effects of high-intensity training and postbiotic supplementation.
Methods Thirty-two adult APP/PS1 TG mice were randomly divided into four groups: 1. control, 2. high-intensity training 3. postbiotic, 4. combined (training and postbiotic) treatment for 20 weeks. In this study, the whole hemibrain without hippocampus was used to find molecular traits explaining improved brain function. We applied qualitative RT-PCR for gene expression, Western blot for protein level, and Zymography for LONP1 activity. Disaggregation analysis of Ab-40 was performed in the presence of Lactobacillus acidophilus and Bifidobacterium longum lysate.
Results We found that exercise training decreased Alzheimer’s Disease (AD)-related gene expression (NF-kB) that was not affected by postbiotic treatment. The preparation used for postbiotic treatment is composed of tyndallized Bifidobacterium longum and Lactobacillus acidophilus. Both of the postbiotics effectively disaggregated amyloid-β/Aβ-40 aggregates by chelating Zn2+ and Cu2+ ions. The postbiotic treatment decreased endogenous human APPTG protein expression and mouse APP gene expression in the hemibrains. In addition, the postbiotic treatment elevated mitochondrial LONP1 activity as well.
Conclusion Our findings revealed distinct mechanisms behind improved memory performance in the whole brain: while exercise training modulates NF-kB signaling pathway regulating immune response until postbiotic diminishes APP gene expression, disaggregates pre-existing amyloid-β plaques and activates mitochondrial protein quality control in the region of brain out of hippocampus. Using the above treatments complements and efficiently slows down the development of AD.
... Exercise training can slow the progression of AD and PD [110]. In rodent models, exercise has also been shown to play a beneficial role in several other brain diseases, such as ischemic stroke, spontaneous hypertension, and N-methyl-D-aspartic acid (NMDA) lesions in AD [111][112][113]. ...
Methamphetamine can cause oxidative stress-centered lipid peroxidation, endoplasmic reticulum stress, mitochondrial dysfunction, excitatory neurotoxicity, and neuroinflammation and ultimately lead to nerve cell apoptosis, abnormal glial cell activation, and dysfunction of blood-brain barrier. Protecting nerve cells from oxidative destroy is a hopeful strategy for treating METH use disorder. Nrf2 is a major transcriptional regulator that activates the antioxidant, anti-inflammatory, and cell-protective gene expression through endogenous pathways that maintains cell REDOX homeostasis and is conducive to the survival of neurons. The Nrf2-mediated endogenous antioxidant pathway can also prevent neurodegenerative effects and functional defects caused by METH oxidative stress. Moderate exercise activates this endogenous antioxidant system, which involves in many diseases, including neurodegenerative diseases. Based on evidence from existing literature, we argue that appropriate exercise can play an endogenous antioxidant regulatory role in the Nrf2 signaling pathway to reduce a number of issues caused by METH-induced oxidative stress. However, more experimental evidence is needed to support this idea. In addition, further exploration is necessary about the different effects of various parameters of exercise intervention (such as exercise mode, time, and intensity) on the Nrf2 signaling pathway intervention. Whether there are synergistic effects between exercise and plant-derived Nrf2 activators is worth further investigation.
... Urtica dioica (Ud) (from the plants' family of Urticaceae) is a perennial plant that has long been used as a medicinal plant in many parts of the world. Ud has been shown to have antioxidant, anti-inflammatory and immunosuppressive properties [9]. Chemical analysis shows that Ud extract contains thymol, quercetin, flavonoids, carotenoids, carvacrol, and salicylic acid. ...
Introduction:
Diabetes mellitus is related to cognitive impairments and molecular abnormalities of the hippocampus. A growing body of evidence suggests that Urtica dioica (Ud) and exercise training (ET) have potential therapeutic effects on diabetes and its related complications. Therefore, we hypothesized that the combined effect of exercise training (ET) and Ud might play an important role in insulin signaling pathway, oxidative stress, neuroinflammation, and cognitive impairment in diabetic rats.
Methods:
Forty animals were divided into five groups (N = 8): healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-exercise training (D-ET), diabetes-Urtica dioica (D-Ud), diabetes-exercise training-Urtica dioica (D-ET-Ud). Streptozotocin (STZ) (Single dosage; 45 mg/kg, i.p.) was used to induce diabetes. Then, ET (moderate intensity/5day/week) and Ud extract (50 mg/kg, oral/daily) were administered for six weeks. We also investigated the effects of ET and Ud on cognitive performance (assessed through Morris Water Maze tests), antioxidant capacity, and lipid peroxidation markers in hippocampus. Furthermore, we measured levels of insulin sensitivity and signaling factors (insulin-Ins, insulin receptor-IR and insulin-like growth factor-1 receptor-IGF-1R), and neuroinflammatory markers (IL-1 β, TNF-α). This was followed by TUNEL assessment of the apoptosis rate in all regions of the hippocampus.
Results:
D-sed rats compared to H-sed animals showed significant impairments (P < 0.001) in hippocampal insulin sensitivity and signaling, oxidative stress, neuroinflammation, and apoptosis, which resulted in cognitive dysfunction. Ud extract and ET treatment effectively improved these impairments in D-ET (P < 0.001), D-Ud (P < 0.05), and D-ET-Ud (P < 0.001) groups compared to D-sed rats. Moreover, diabetes mediated hippocampal oxidative stress, neuroinflammation, insulin signaling deficits, apoptosis, and cognitive dysfunction was further reversed by chronic Ud+ET administration in D-ET-Ud rats (P < 0.001) compared to D-sed animals.
Conclusions:
Ud extract and ET ameliorate cognitive dysfunction via improvement in hippocampal oxidative stress, neuroinflammation, insulin signaling pathway, and apoptosis in STZ-induced diabetic rats. The results of this study provide new experimental evidence for using Ud+ET in the treatment of hippocampal complications and cognitive dysfunction caused by diabetes.
... In addition to exercise, diet also plays a remarkable role in brain functioning. [14,15] Phytochemicals have been proven to be effective free radical scavengers because of their potent antioxidant activity. [16] Recent studies have been carried out on indigenous medicines exhibiting neuroprotective activities. ...
... :5,[84][85][86][87][88][89][90][91][92] It is a deciduous woody flowering plant in North east countries it is widely cultivated. Consumed a table grape or transformed into wine, jam, jelly, extracts, seed oils, raisins. ...
Alzheimer’s disease (AD) is related to cognitive impairment, dementia observed generally in aged population due to neurodegeneration in an ongoing manner. It gradually worsens memory power of the patient. The hallmark diagnosis features includes formation of senile plaques and Neurofibrillary tangles (NFT’S) [1, 2]. Too little availability of Acetyl choline (ACh) a neurotransmitter in the cerebral region due to metabolism by an enzyme Acetyl choline esterase before showing its action and neural death are the primary reasons for AD. There are many categories of Anti-Alzheimer’s drugs available for management of AD in the market but due to lack of patient compliance successful outcomes were not observed [3]. Apart from this including Nutraceuticals in diet daily routine, Aromatherapy, modifications in the regular schedule, practicing yoga regularly relaxes mind and body from tensions, insomnia, blood circulation, detoxification of organs due to rhythmic breathings and reduce frequency of incidence of headache are proven to show best results by relieving stress according to survey[4-9]. At present herbal medicine has turn out to be best choice for the management of AD because of its availability, very economic, good patient compliance, ease of formulation and lower deleterious side effects [10, 11]. Novel techniques can be used for the development of herbal medicine. This review totally discuses about the occurrence of AD, its Pathophysiology, different stages in the disorder, various selective therapeutic targets for AD, available Anti-AD herbal drugs such as Curcumin, Withania somnifera, Bhrami, Ginkgo biloba, guggul, ginseng, herbs with essential oils, volatile oils, source and cultivation of the herbs, mechanism of action of the Phytochemicals in the herb responsible for treating AD. Keywords: Alzheimer’s disease (AD), cognitive impairment, Dementia, Senile plaques, Nutraceuticals, Herbal medicine, Phytoconstituents.
... In fact, despite some reports demonstrating a beneficial effect of high-intensity exercise, studies often show that heavy intensity exercise negatively affects cognitive performance, especially by means of an increased stress response [15][16][17]. Other factors are also important in this context, as the intervals between one session and another, the total duration of the training and development phase in which exercise is applied [18][19][20][21][22]. ...
Diet and exercise are known to affect learning and memory. However, the effects of these interventions in the brain under development remains to be better investigated as the effects of high-intensity exercise. Moreover, it is still unclear how long the influence of diet and exercise lasts after the interventions are ceased. To investigate this, juvenile Wistar rats (30 days old) were supplemented with fish oil rich in polyunsaturated fatty acids (PUFAs) and performed swimming training for 50 days, 45 min per day, 5 times/week. The animals were assessed for locomotor activity with the open field test and for spatial memory with the object location task. To investigate neurochemical parameters such as fatty acids incorporation within the plasma membrane and brain-derived neurotrophic factor (BDNF) levels, the animals were euthanized, and the hippocampus dissected. These investigations were made at the end of the supplementation and exercise protocols and 21 days after the protocol has ended. Results indicate that high-intensity exercise impaired the spatial memory and decreased the levels of BDNF. Although supplementation led to PUFAs incorporation in plasma membrane, it did not prevent the harmful effect of exercise on memory. After 21 days of interruption, we observed that the supplementation reversed not only the deleterious effect of exercise on memory but also increased the BDNF levels. These results point to a complex influence of diet and exercise on spatial memory of juvenile rats, persisting after 21 days of interruption.
... These results demonstrated that UD reduce brain damage and ameliorate functional outcome during chronic diabetes. The beneficial effect of UD administration on N-methyl-D-aspartate induced brain lesion in rat model has been reported (Toldy et al. 2009). Earlier studies reported that, UD leaves constituents reduce diabetes as well as neurological deficits in different experimental models (Capra et al. 2010;Holzmann et al. 2015;Machado et al. 2008;Patel et al. 2016a;Zhu et al. 2016), which might indicate UD extract constituents cross the blood brain barrier. ...
The present study was aimed to investigate the effect of Urtica dioica Linn. (UD) extract against chronic diabetes mediated anxiogenic and depressive like behavior in mice. Streptozotocin (STZ) (50 mg/kg, i.p.) for 5 consecutive days was used to induce diabetes followed by treatment with UD leaves extract (50 mg/kg, p.o.) and rosiglitazone (ROSI) (5 mg/kg, p.o.) for 8 weeks. STZ induced chronic diabetes significantly induced anxiety and depressive like behavior in mice. Chronic diabetes significantly downregulated BDNF (p < 0.001), TrKB (p < 0.001), Cyclin D1 (p < 0.001), Bcl2 (p < 0.05) and autophagy7 (p < 0.001), while upregulated iNOS (p < 0.05) mRNA expression in the hippocampus as compared to control mice. In addition, chronic diabetes significantly increased the expression of TNF-α in CA1 (p < 0.001), CA2 (p < 0.01), CA3 (p < 0.001) and DG (p < 0.001) regions of hippocampus as compared to control mice. Chronic diabetes mediated neuronal damage in the CA2, CA3 and DG regions of hippocampus. Chronic administration of UD leaves extract significantly reversed diabetes mediated anxiogenic and depressive like behavior in mice. Further, UD treatment significantly upregulated BDNF (p < 0.01), TrKB (p < 0.001), Cyclin D1 (p < 0.001), Bcl2 (p < 0.01), autophagy5 (p < 0.01) and autophagy7 (p < 0.001), while downregulated iNOS (p < 0.05) mRNA expression in the hippocampus of diabetic mice. Concomitantly, UD administration significantly decreased the expression of TNF-α in hippocampal CA1 (p < 0.001), CA2 (p < 0.01), CA3 (p < 0.001) and DG (p < 0.001) regions of diabetic mice. Diabetes mediated neuronal damage and DNA fragmentation in the hippocampus was substantially attenuated following UD treatment. UD leaves extract might prove to be effective for diabetes mediated anxiety and depressive like behavior.
... Compared to moderate training (swimming 1 hr/day for 8 weeks), very hard training (progressively increasing swim-time to 4.5 hr/day) and over-training (abruptly increasing swim-time from 1 hr/day to 4.5 hr/day) decreased brain protein oxidation products and improved performance in an associated rat memory task [199]; however, this tolerance has its limits as others report increased ROS and lipid peroxidation and impaired memory following intense or exhaustive exercise [202][203][204]. Exercise has been shown to exert beneficial effects in rodent models of several brain disorders including, but not limited to, models of ischemic stroke, stroke-prone spontaneously hypertensive rats and N-methyl-D-aspartate (NMDA) lesion models for Alzheimer's disease [205][206][207]. ...
There is an increasing need for effective treatments to reduce propensity for relapse to the illicit psychostimulant methamphetamine in addicted individuals. Cognitive behavioral therapies are currently used with limited success and therefore pharmacotherapies could assist, yet no FDA approved medications are available. Preclinical studies demonstrate that this is partially attributed to the complex and dynamic neurobiology underlying methamphetamine addiction-like behavior. Therefore, therapeutic strategies to treat methamphetamine addiction, particularly the relapse stage of addiction, could revolutionize addiction treatment. In this context, preclinical studies demonstrate that voluntary exercise (sustained physical activity) may be beneficial. This chapter discusses the neurobiology of methamphetamine addiction and sustained physical activity deciphered using animal models and highlights the emerging mechanisms of wheel running in attenuating intake and in preventing relapse to methamphetamine seeking behavior in preclinical models of compulsive-like methamphetamine intake.
... Nettle (Urtica dioica) is both a dietary supplement and a source of official and folk medicine for the treatment of many diseases [8][9][10], and the methanolic extract of Turkish nettle has been shown to contain quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, and isorhamnetin-3-O-glycoside [9]. ...
Quercetin (3,3′,4′,5,7-pentahydroxyflavone, QC) is a health-beneficial flavonoid, widely occurring in leaves, fruits, and flowers of various plants. In this work aiming isolation, purification and pre-concentration of QC, QC imprinted polymers (QC-MIPs) in different molar ratios {template:monomer:cross-linker (1:4:20, 1:5:30, 1:8:40, 1:10:50)} were prepared thermally through bulk polymerization by using QC as the template molecule, 4-vinylpyridine (4-VP), methacrylic acid (MAA), acrylamide (AA) as the functional monomers, ethylene glycol dimethacrylate (EDMA) as the cross-linker and 2,2′-azobisisobutyronitrile (AIBN) as initiator in the porogens of acetone and tetrahydrofuran. Their recognition and selectivity properties were investigated in solutions containing QC and other similar-structure phenolics by equilibrium binding experiments using different proportions of acetonitrile (ACN)-dimethylsulfoxide (DMSO) mixtures and methanol (MeOH) as solvents. The MIP with 1:4:20 molar ratio of QC:4-VP:EDMA was established as the most suitable for recognition of QC. Sorption parameters of the MIP and the NIP (non-imprinted polymer) were calculated by using Freundlich and Langmuir isotherms with QC solutions in ACN:DMSO (98:2, v/v). The mentioned MIP was found to be highly selective for quercetin over other phenolic compounds (rutin, catechin, etc.). Thus, molecularly imprinted solid-phase extraction (MISPE) procedures were applied for selective pre-concentration and purification of QC from synthetic mixtures of phenolic compounds and nettle extract, known as a source of official and folk medicine. The results demonstrated the possibility of direct extraction of certain pharmacophoric constituents such as QC and QC derivatives from nettle by MIP separation.
... Therefore, most investigators detect the quite stable end product of ROS fat-protein-or DNA interactions. We have tried to directly detect the level of ROS by electron paramagnetic resonance (EPR) and our results revealed that swimming and running exercise can increase the level of ROS in the cerebellum and frontal lobe of rats [99,100]. In these studies, the presence of neurogenesis was not measured. ...
Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity- dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-α, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS- mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox- associated adaptation.
... The chronic administration of hydroalcoholic extract of UD (100 mg/kg/day p.o.) enhanced spatial and associative memory at the end of 12 weeks (13). Nettle supplementation for 8 weeks had a potential effect of decreasing the level of brain injury caused by Nmethyl-D-aspartate lesions in rats (19). In previous studies, chronic administration of UD enhanced cognitive function and there were beneficial effects of UD in cognitive disorders (13,14). ...
Background: Urtica dioica (nettle) has a variety of uses in traditional medicine for the treatment of certain urogenital problems, gastrointestinal disorders, and diabetes. Objectives: Recent studies have implicated the effect of U. dioica on brain functions such as pain and memory. However, there is no direct evidence of the acute effects of this plant on cognition. The aim of the present study was to evaluate the effect of U. dioica aqueous extract on the novel object-recognition task (NOR) in mice. Materials and Methods: First, U. dioica aqueous extract was prepared, then adult male mice were randomly divided into four experimental groups. During the training session, the mice were placed in a box and given 5 minutes to explore two identical objects. The next day, they were again placed in the box and allowed to explore one familiar and one novel object. They received intraperitoneal injections of saline or U. dioica aqueous extract (100 mg/kg) before or immediately after the training session or before the test session of the NOR task. Results: The results showed that there was a preference for the novel object compared to the familiar one in each of the experimental groups. The object-recognition discrimination index in the group of mice that received U. dioica before training was significantly less than in the other experimental groups. There was no significant difference in the discrimination index between the other groups. U. dioica did not decrease the time spent exploring familiar and unfamiliar objects, or the total time spent exploring both objects. Conclusions: Acute administration of U. dioica impairs the object-recognition task if it is used only before the training session. This may be due to its modulation on the acquisition processing of object-recognition. U. dioica has no significant effects on the consolidation or retrieval processing stages of the NOR task. These results emphasize the unfavorable effect on cognitive function of pre-training with acute supplementation of U. dioica.
... [88] The N-Methyl-D-aspartate (NMDA) injection-induced brain lesion and subsequent inflammation in wistar rats significantly decreasing the nuclear factor kappa B (NF-kB) binding activity to DNA on administration of Urtica dioica leaf supplementation which suggests a significant anti-inflammatory effect. [89][90][91] In acetic acid induced writhing test in mice, aqueous extract in a dose 50, 100 and 200 mg/ kg (i.p.) produce a dose dependent inhibition in writhing. [14] Leaves extract has been used as anti-inflammatory remedies in rheumatoid arthritis due to suppression of cytokine production. ...
Urtica dioica L. belongs to the family Urticaceae, is a perennial herb commonly known as ′stinging nettle′. This herb is found in many South Asian Countries, Indian subcontinent and has been known in the world as a medicinal herb for a long time. U. dioica is widely used by the traditional medicinal practitioners for curing various diseases such as nephritis, haematuria, jaundice, menorrhagia, arthritis and rheumatism. Phytochemical studies revealed the presence of many valuable chemical compounds like phytosterols, saponins, flavanoids, tannins, proteins and amino acids. The plant also has been used as food, fiber, paint, manure and cosmetics. U. dioica has been reported to have various pharmacological activities like antibacterial, antioxidant, analgesic, anti-inflammatory, antiviral, immunomodulatory, hepatoprotective, anti-colitis and anticancer effects. The current review summarizes published information about the ethnopharmacology, phytochemistry, biological activities and toxicological reports of U. dioica. The present review summarizes all the research work carried out on this plant in order to provide updated information for future works.
... In the present study, lesions of the NBM produced severe memory deterioration in the passive avoidance response in rats, which was shown by decreased latency to enter the dark room (Fig. 3). These results were in agreement with the previous studies (Chen et al., 2008;Toldy et al., 2009). Some studies (Frank et al., 1992,Chopin et al., 2002Hoveida et al., 2011) also have demonstrated significant performance deficits in both the passive avoidance and the Morris water maze tests in the NBM-lesion rats. ...
Some studies have shown the effects of exercise training in retarding onset and progression of memory deficit in neurodegenerative disorders such as Alzheimer's disease. In this research, we investigated the effect of treadmill running on memory function; before, after, and continually (before and after) the nucleus basalis magnocellularis lesions. 66 male rats were randomly divided into six groups, including control, sham operation, the NBM-lesion, exercise before the NBM-lesion, exercise after the NBM-lesion, and exercise before and after the NBM-lesion. Lesion was induced by 5 μg/μl bilateral injection of Ibotenic acid. Memory function was assessed by using the passive avoidance learning test.
Our results showed that treadmill running delays cognitive decline in the NBM-lesion rats, prevented memory deficit, and has advantageous effects on short-term, intermediate and long-term memory. Exercising on a regular basis may impede memory loss significantly, which may be attributed to specific molecular pathways in the brain.
... Compared to moderate training (swimming 1 hr/day for 8 weeks), very hard training (progressively increasing swim-time to 4.5 hr/day) and over-training (abruptly increasing swim-time from 1 hr/day to 4.5 hr/day) decreased brain protein oxidation products and improved performance in an associated rat memory task [199]; however, this tolerance has its limits as others report increased ROS and lipid peroxidation and impaired memory following intense or exhaustive exercise [202][203][204]. Exercise has been shown to exert beneficial effects in rodent models of several brain disorders including, but not limited to, models of ischemic stroke, stroke-prone spontaneously hypertensive rats and N-methyl-D-aspartate (NMDA) lesion models for Alzheimer's disease [205][206][207]. ...
The need for effective treatments for addiction and dependence to the illicit stimulant methamphetamine in primary care settings is increasing, yet no effective medications have been FDA approved to reduce dependence [1]. This is partially attributed to the complex and dynamic neurobiology underlying the various stages of addiction [2]. Therapeutic strategies to treat methamphetamine addiction, particularly the relapse stage of addiction, could revolutionize methamphetamine addiction treatment. In this context, preclinical studies demonstrate that voluntary exercise (sustained physical activity) could be used as an intervention to reduce methamphetamine addiction. Therefore, it appears that methamphetamine disrupts normal functioning in the brain and this disruption is prevented or reduced by engaging in exercise. This review discusses animal models of metham-phetamine addiction and sustained physical activity and the interactions between exercise and methamphetamine behaviors. The review highlights how methamphetamine and exercise affect neuronal plasticity and neurotoxicity in the adult mammalian striatum, hippocampus, and prefrontal cortex, and presents the emerging mechanisms of exercise in attenuating intake and in preventing relapse to methamphetamine seeking in preclinical models of methamphetamine addiction.
... On the other hand, when rats brain were treated by N-methyl-D-aspartate (NMDA) to induce lesion, a method used to mimic Alzheimer diseases (AD), it was found that exercise alone and with supplementation of nettle reduced ROS formation and levels of carbonyl groups. 42 We could also show in this study, that lower level of oxidative damage was associated with better function, assessed by passive avoidance test. ...
Reactive oxygen species (ROS) are continuously generated during aerobic metabolism and at moderate level. They play a role in redox signaling, but in significant concentration they cause oxidative damage and neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain the normal redox state in different types of neuron cells. In last decade it became clear that regular exercise beneficially affects brain function, and can play an important preventive and therapeutic role in stroke, Alzheimer, and Parkinson diseases. The effects of exercise appear to be very complex and could include neurogenesis via neurotrophic factors, increased capillariszation, decreased oxidative damage, and increased proteolytic degradation by proteasome and neprilysin. Data from our and other laboratories indicate that exercise-induced modulation of ROS levels plays a role in the protein content and expression of brain-derived neurotrophic factor, tyrosine-related kinase B (TrkB), and cAMP response element binding protein, resulting in better function and increased neurogenesis. Therefore, it appears that exercise-induced modulation of the redox state is an important means, by which exercise benefits brain function, increases the resistance against oxidative stress, facilitates recovery from oxidative stress, and attenuates age-associated decline in cognition.
... Antimicrobial activity [337]. Promotes learning performance in the brain of rats [338]. Immunostimulatory activity of the flavonoid fraction and intracellular killing activity of the isolated flavonoid glycosides suggesting that they could possibly be useful for treating patients suffering from neutrophil function deficiency and chronic granulomatous diseases [317]. ...
Plant species have long been regarded as possessing the principal ingredients used in widely disseminated ethnomedical practices. Different surveys showed that medicinal plant species used by the inhabitants of Jordan for the traditional treatment of diabetes are inadequately screened for their therapeutic/preventive potential and phytochemical findings. In this review, traditional herbal medicine pursued indigenously with its methods of preparation and its active constituents are listed. Studies of random screening for selective antidiabetic bioactivity and plausible mechanisms of action of local species, domesticated greens, or wild plants are briefly discussed. Recommended future directives incurring the design and conduct of comprehensive trials are pointed out to validate the usefulness of these active plants or bioactive secondary metabolites either alone or in combination with existing conventional therapies.
... Regular aerobic exercise is a promising nonpharmacological approach that can ameliorate memory impairment in a variety of conditions including brain injury [278][279][280], and can enhance cognitive function [281], prevent memory decline in aging [282,283], decrease anxiety related behaviors [139,187] and attenuate oxidative stress [284,285,287]. ...
Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed.
... The effect of the stinging nettle extract was similar to diclofenac (Strathmann GmbH, proprietary data on file). Toldy et al. (2009) investigated the effects of stinging nettle leaf supplementation and swimming exercise on N-Methyl-D-aspartate (NMDA) injection-induced brain lesion, and subsequent inflammation, in Wistar rats. Sixty-eight fourmonth-old male Wistar rats were divided into 8 experimental groups: sham control (SH), NMDA lesion (NM), swimmer and sham-operated (SWSH), and swimmer and NMDA lesion (SWNM) groups fed with either standard or 1% w.w nettleenriched lab chow. ...
The efficacy and safety of herbal medicines are dependent upon the standards by which they are made and our knowledge base when prescribing them. Stinging nettles is a staple among Western herbalists and is widely used as a vegetable green, juice, tea, and freeze dried products, predominantly as a blood nourishing tonic and for seasonal rhinitis. The following botanical profile is excerpted from the American Herbal Pharmacopoeia (R) and Therapeutic Compendium. (c) 2012 Elsevier GmbH. All rights reserved.
... Moreover, UD significantly increases the density of granule cells in the diabetic rat dentate gyrus, which can ameliorate cognitive impairment in diabetes [10]. UD also showed a protective effect against NMDA induced cerebral lesion and memory impairment [32]. In addition, UD is also a rich source of acetylcholine, cholineacetyltransferase [36], 5-HT [11], etc. which are known for its involvement in neuronal functioning. ...
Diabetic neuropathy is considered as a disease of the peripheral nervous system, but recent evidences suggest the involvement of central nervous system as well. In this study we evaluated the effect of Urtica dioica (UD) extract against memory dysfunction and hypoalgesia on a mouse model of streptozotocin (STZ) induced diabetic neuropathy. STZ (50mg/kg, i.p. consecutively for 5 days) was used to induce diabetes, followed by treatment with the UD extract (50mg/kg, oral) and rosiglitazone (5mg/kg, oral) for 8 weeks. Cognitive functions were evaluated using Morris water maze and passive avoidance step through task. Pain thresholds were measured using thermal, mechanical and chemical induced hyperalgesia. We observed that chronic diabetes resulted in a decline in circulating insulin level, elevated blood glucose, reduced body weight, increased water intake, cognitive impairment and hypoalgesia. UD significantly reduced the blood glucose and polydypsia, as well as improved the body weight, insulin level, cognition and insensate neuropathy. In conclusion, UD showed results comparable to rosiglitazone in reversing the long standing diabetes induced complications such as central and peripheral neuronal dysfunction.
... In rodents, cognitive benefits of physical exercise seem to be more consistent in animal models of memory impairment (Aguiar et al., 2009;Griesbach et al., 2009;Reisi et al., 2009;Ben et al., 2010;Hoveida et al., 2011) and aging (van Praag et al., 2005;Kim et al., 2010;Adlard et al., 2011). Voluntary (free running wheel) and forced (treadmill running) exercise are the most common types of exercise employed for investigating the effects of physical exercise on learning and memory in rodents (Barnes et al., 1991;Ogonovszky et al., 2005;Uysal et al., 2005;Van Praag et al., 2005;Alaei et al., 2006;Ang et al., 2006;Blustein et al., 2006;Radak et al., 2006;Toldy et al., 2009). Treadmill running is widely used by human subjects in exercise training programs (Winter et al., 2007). ...
The participation of the brain-derived neurotrophic factor (BDNF) in the benefits of physical exercise on cognitive functions has been widely investigated. Different from voluntary exercise, the effects of treadmill running on memory and BDNF are still controversial. Importantly, the impact of the frequency of physical exercise on memory remains still unknown. In this study, young adult and middle-aged rats were submitted to 8 weeks of treadmill running at moderate intensity and divided into 4 groups of frequency: 0, 1, 3 and 7 days/week. Aversive and recognition memory were assessed as well as the immunocontent of proBDNF, BDNF and tyrosine kinase receptor type B (TrkB) in the hippocampus. Frequencies did not modify memory in young adult animals. The frequency of 1 day/week increased proBDNF and BDNF. All frequencies decreased TrkB immunocontent. Middle-aged animals presented memory impairment along with increased BDNF and downregulation of TrkB receptor. The frequency of 1day/week reversed age-related recognition memory impairment, but worsened the performance in the inhibitory avoidance task. The other frequencies rescued aversive memory, but not recognition memory. None of frequencies altered the age-related increase in the BDNF. Seven days/week decreased proBDNF and there was a trend toward increase in the TrkB by the frequency of 1 day/week. These results support that the frequency and intensity of exercise have a profound impact on cognitive functions mainly in elderly. Thus, the effects of physical exercise on behavior and brain functions should take into account the frequency and intensity.
... Studies on the phytochemical profile of weeds frequently appear in the recent literature and show the growing interest on the exploitation of this essentially unexplored plant material. For example, aqueous infusions of nettle (Urtica dioica L.) have been shown to possess noteworthy anti-oxidant activity and have proven to cause a distinct reduction in lipid peroxidation and extend storage time in aerobically packaged fish products (Arashisar et al., 2008), whereas nettle supplementation showed beneficial effects on brain lesion and memory in rats owing to its antioxidant and anti-inflammatory properties (Toldy et al., 2009). ...
Phytochemical analyses of weeds, many of which have been used in traditional medicine worldwide, could lead to the identification of secondary metabolites with significant biological activity.
To perform an assessment of the chemical composition and exploitation potential of the invasive weed Oxalis pes-caprae. To evaluate the anti-oxidant activity of its extracts and isolate and characterise polyphenolic metabolites using LC-DAD-MS (ESI+) and NMR methods.
Aerial parts of the invasive weed O. pes-caprae were extracted with solvents of increasing polarity and their major polyphenolic metabolites were identified by LC-DAD-MS (ESI+). The total phenolic content of the extracts was determined using the Folin-Ciocalteu method, while their anti-oxidant activity was evaluated on the basis of their ability to scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl and hydrogen peroxide.
The major polyphenolic constituents of the extracts were tentatively characterised as chlorogenic acid, quinic ferulate, luteolin glucoside and cernuoside according to their MS and UV spectroscopic data. Cernuoside, an aureusidin glucoside, was isolated from the methanolic extract of the weed's flowers and its structure was unambiguously identified by 1D- and 2D-NMR spectroscopy. The butanol extract of O. pes-caprae displayed the highest anti-oxidant activity.
The metabolic profile of O. pes-caprae was studied and the structures of the major polyphenolic metabolites based on their MS and UV-vis spectra were tentatively assigned. The aureusidin glucoside cernuoside was isolated and characterised for the first time from O. pes-caprae. The extracts exhibited high levels of anti-oxidant activity. Copyright © 2012 John Wiley & Sons, Ltd.
... When blood flow to the brain is reduced, survival of the tissue at risk depends on several modifying factors: the availability of collateral circulation, the duration of ischemia time and the intensity and speed of flow reduction [1][2][3] . These factors determine, in turn, the location and size of the lesion 4. The changes caused by lack of blood supply to brain metabolic trigger cellular and molecular processes that induce self-destruction of neural cells 5 . Therefore, neuronal death can result from the combination of the processes of necrosis and apoptosis [6][7][8] . ...
This study aimed to assess the effects of preconditioning with mixtures of oils containing high/low ratio of ω-6/ω-3 and ω-9/ω-6, respectively, in an experimental model of cerebral ischemia-reperfusion (I/R).
Forty-two Wistar rats were randomly distributed into two groups: control (n=24) and test (n=18). Control group was subdivided in 4 subgroups (n=6): G1: Sham-Water; G2: I/R-Water; G3: Sham-Isolipidic and G4: I/R-Isolipid. The animals received water or a isolipid mixture containing ω-3 oils (8:1 ratio) and ω-9/ω-6 (0.4:1 ratio) by gavage for seven days. Test group included 3 subgroups (n=6) G5: I/R-Mix1, G: 6 I/R-Mix2 and G7: I/R-Mix3. Test group animals received oily mixtures of ω-3 (1.4:1 ratio) and ω-6 (3.4:1 ratio), differing only in source of ω-3: G5 (alpha-linolenic acid); G6 (alpha-linolenic, docosahexaenoic and eicosapentaenoic acids), and G7 (alpha-linolenic and docosahexaenoic acids). On day 7 I/R rats underwent cerebral ischemia with bilateral occlusion of common carotid arteries for 1 hour followed by reperfusion for 3 hours. G1 and G3 animals underwent sham operation. Concluded the experiment, animals were decapitated and their brains sliced for red neurons (RN) count in CA3 area of the hippocampus. Variables were compared using ANOVA-Tukey test.
The use of different mix preparations promoted a decrease in red cell count in all three groups (G5/G6/G7), compared with G2/G4, confirming the protective effect of different oil blends, regardless of ω-3 source.
Pre-conditioning with mixtures of oils containing high ratio ω-6/ω-3 and low ω-9/ω-6 relationship protects brain neurons against I/R injury in an experimental model.
... Antimicrobial activity [337]. Promotes learning performance in the brain of rats [338]. Immunostimulatory activity of the flavonoid fraction and intracellular killing activity of the isolated flavonoid glycosides suggesting that they could possibly be useful for treating patients suffering from neutrophil function deficiency and chronic granulomatous diseases [317]. ...
Plant species have long been used as principal ingredients in traditional medicine. Different surveys showed that ethnomedicinal plant species used by the inhabitants of Jordan for the treatment of cancer are inadequately screened for their therapeutic/chemopreventive potential and phytochemical findings. In this mini review, traditional herbal medicines pursued indigenously with their methods of preparation and active constituents are listed. Studies of random screening for selective cytotoxicity and antiproliferative activity of local spices, domesticated greens, or wild plants are briefly discussed. Recommended future directives for the design and conduct of comprehensive trials are pointed out to validate the usefulness of these active plants or bioactive phytoconstituents either alone or in combination with existing therapies or complementing pharmacologies.
Potassium bromate is used in cheese production, beer making and is also used in pharmaceutical and cosmetic. It is a proven carcinogen as it is a strong oxidizing agent that generates free radicals during xenobiotic metabolism. Urtica dioica (Ud) (from the plants' family of Urticaceae) is a plant that has long been used as a medicinal plant in many parts of the world. It has been shown to have anti-inflammatory, antioxidant and immunosuppressive properties. So, this study aimed to clarify the effect of Potassium bromate on the histological structure of cerebral cortex of adult male albino rats, evaluate the possible protective role of Urtica dioica. Thirty adult healthy male albino rats were divided into three groups; group I (Control group), group II (KBrO3 treated group). Group III (KBrO3 and Urtica dioica treated group).At the end of the experiment, rats in all groups were anesthetized and specimens were processed for light and electron microscope. Morphometric and statistical analyses were also performed. Nerve cells of the treated group showed irregular contours, dark nuclei, irregular nuclear envelopes, dilated RER cisternae, and mitochondria with ruptured cristae. Vacuolated neuropil was also observed. Immunohistochemically, stained sections for GFAP showed strong positive reaction in the processes of astrocytes. Recovery group showed revealed nearly the same as the histological picture as the control group. In conclusion, potassium bromate induces degenerative effects on neurons of cerebral cortex and urtica dioica provide an important neuroprotective effects against these damaging impacts through their antioxidant properties.
The use of herbal drugs may offer great potential opportunities in the prevention and control of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Herbal drugs contain multiple pharmacologically active constituents. The relative amounts and the nature of these constituents vary due to diverse factors viz plant source and plant parts, extraction method, local environmental conditions, storage conditions, adulterations, and contamination which might be accidently or intentionally. After administration, they are put through the processes of absorption, distribution, metabolism, and excretion the same as the modern medicines. When handled by the body, they can show combined effect and get interacted with modern drugs due to various factors including similar transport protein interaction, metabolizing cytochrome P450 enzyme, and different transporter mechanisms. Herb drugs can either induce or inhibit CYP450 enzymes. When herbs are combined with the drugs, either they mimic or oppose the effect of drugs. Many studies worldwide indicate the favorable properties of plant extracts or their bioactive compounds against neurodegenerative disorders, but several clinical concerns have appeared regarding the use of these combinations, which could be due to lack of evidence and scientific support for their effectiveness and safety of the patient
Objective:
The goal of this study is to look into the antiproliferative capabilities of Urtica Dioica (UD) on breast cancer.
Methods:
The cytotoxicity of UD extracts against breast cancer cell lines was investigated. Flow cytometry analyses were used to investigate in vitro apoptosis of breast cancer cells using Annexin V labeling. In vivo tests also performed.
Results:
UD showed cytotoxicity to three cancer cell lines. The number of Annexin-positive cells was higher in UD-treated cell lines than in untreated control cells. When compared to the untreated control group, the rats treated with UD had greater expressions of caspase 3, p53 protein, and TUNEL positive cells. When compared to the control group, Ki-67 expression was reduced in the treatment groups. In vivo tests revealed that, when compared to untreated rats, the mean tumor volume inhibition ratio in the UD group was 38 percent.
Conclusion:
These findings suggest that Urtica Dioica may have antitumoral properties in the treatment of breast cancer.
The potential of plants in the treatment of severe diseases and disorders is well known since Vedic age. Evidences strongly show that most of the ancient medical practitioner’s had utilised the magic of plant based remedies to get maximum therapeutic outcomes. Modern era researchers and scientists are also very well aware of the therapeutic benefits of plants and their extremely low or no side effects as compared to synthetically obtained drug moieties thus most of them are walking in the olden footsteps. This of course is the reason of increasing use of plant based formulations and why now days these formulations are capturing big commercial markets globally. Recently, nanotechnology has also extended its feet to the herbal realm so that maximum advantages can be obtained by the development of nano-based herbal formulations. Keeping all these facts in mind this chapter has been written to highlight the great potential of a plant Urtica dioica which has been neglected and underrated since ages inspite of its well known evidences for the treatment of some severe and life-threatening disease. Numbers of literatures also support the folk and traditional use of this plant for a number of diseases because of its high nutritional value. This chapter includes general introduction, description, chemical constitution, mechanism of action, its use in Alzheimer disease and toxicity aspects of this plant.
Background:
Natural products, whether pure compounds or standardized plant extracts, offer unlimited opportunities for other drug sources due to the unequaled availability of chemical diversity. Stinging Nettle (Urtica dioica) is a unique herbaceous perennial flowering plant with stinging hairs. The leaf extract of nettle was one of the herbal remedies which the experimental, clinical and trials have complemented each other. It is a very well-known plant with a wide historical background use of stems, leaves and roots. It has a long history of use as power sources such as soup or curry, and also used as fiber and a medicinal plant. Urtica dioica has traditionally been used in the control of cardiovascular disorders especially hypertension. The leaf extract of Urtica dioica has been reported to improve glucose homeostasis in vivo. Nettle root could prevent some of the effects of prostatic hyperplasia. Extracts of nettle leaf are used as anti-inflammatory remedies for rheumatoid arthritis. Urtica dioica extract significantly increased the sensitivity of breast cancer cells to paclitaxel. This article aims to review the very wide ranging of pharmacological effects of Urtica dioica extract.
Methods:
Articles on PuBmed between 1980 and 2019.
Results:
Description and critical review of the pharmacological effects of Urtica dioica and other uses.
Conclusion:
The nettle is actually a plant with many qualities and uses. The interest in it is deserved and it is given by other studies and investigations.
This study was conducted to investigate protective effects of Urtica dioica extract on acetylcholinesterase (AChE) activity and the oxidative damage of brain tissues in scopolamine-induced memory impairment model. The rats were treated with (1) saline (control), (2) scopolamine, and (3–5) the plant extract (20, 50, or 100 mg/kg) before scopolamine. The traveled distance and the latency to find the platform in Morris water maze (MWM) by scopolamine-treated group were longer while the time spent in target quadrant was shorter than those of the control. Scopolamine decreased the latency to enter the dark in passive avoidance test. Besides, it also increased AChE activity and malondialdehyde (MDA) concentration in the hippocampal and cortical tissues while decreased thiols content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain (p < 0.01–p <0.001). Treatment by the extract reversed all the effects of scopolamine (p < 0.05–p <0.001). According to the results of present study, the beneficial effects of U. dioica on memory can be attributed to its protective effects on oxidative damage of brain tissue and AChE activity.
Various forms of exercise have been shown to prevent, restore, or ameliorate a variety of brain disorders including dementias, Parkinson’s disease, chronic stress, thyroid disorders, and sleep deprivation, some of which are discussed here. In this review, the effects on brain function of various forms of exercise and exercise mimetics in humans and animal experiments are compared and discussed. Possible mechanisms of the beneficial effects of exercise including the role of neurotrophic factors and others are also discussed.
Large numbers of plants and phytochemicals with potential effects that reduce inflammatory responses or stimulate antioxidant defenses in neural cells have been discovered across the world. They act via downregulation of proinflammatory enzymes through activation of PPARγ; inhibition of PI3K, tyrosine kinases, NF-κB, and c-Jun; modulation of cell survival/cell-cycle genes; and stimulation of antioxidant response-element pathways. Phytochemicals disrupt the Nrf2-Keap1 association, thereby releasing Nrf2, which translocates to the nucleus and upregulates the expression of phase II detoxifying enzymes, such as HO-1 and glutathione S-transferases, which have a protective effect on cells. On compiling the classification of plants that have been reported in the literature to have antineuroinflammatory properties, we discovered that those that have been reported to be effective in antineuroinflammation are not randomly distributed throughout the plant kingdom but are concentrated in a small number of orders, especially Fabales, Lamiales, Rosales, Apiales, and Sapindales. These are the same orders associated with food allergy. We hypothesize that plants that are useful against neuroinflammation are those that are mildly proinflammatory or immunogenic (triggering a host anti-inflammatory response). Knowledge of the orders of plants that are more likely to be effective against neuroinflammation may help in the future discovery of novel phytochemicals. This chapter presents the mechanisms of action, bioavailabilities, and plant orders of origin of phytochemicals, as well as their effects on neuroinflammation, stroke, and Alzheimer's disease.
The present study was aimed to evaluate the effect of Urtica dioica (UD) extract against chronic unpredictable stress (CUS)-induced associative memory dysfunction and attempted to explore the possible mechanism. Male Swiss albino mice (25–30 g) were divided into six groups, viz. group-I received 0.3% carboxymethyl cellulose and served as control (CTRL), group II was exposed to CUS (21 days) and received vehicle (CUS), group III was subjected to CUS and received Hypericum perforatum extract (350 mg/kg, p.o.) (CUS + HYP), group IV received Hypericum perforatum extract (350 mg/kg, p.o.) (CTRL + HYP); group V was subjected to CUS and received UD extract (50 mg/kg, p.o.) (CUS + UD), group VI received UD extract (50 mg/kg, p.o.) (CTRL + UD). CUS significantly induced body weight loss (p
The aim of this study was to determine the effectiveness of water extract and dried leaves of Urtica dioica in reducing lipid oxidation and color stabilization of cooked sausage. Four variants of sausages were prepared: control (without nettle); sausages with 300 ppm and 600 ppm water extract of nettle; and sausages with dried nettle leaves. TBARS values, color parameters, ORP, pH, aw and sensory attributes of sausages were investigated. The addition of nettle (water extract/dried leaves) did not affect the pH, aw and ORP of the sausages. The addition of nettle water extract (600 ppm) decreased the TBARS value and increased the color stability of sausages during storage. The sensory quality of the samples with added water extract of nettle was greater than that of the remaining samples. This study suggests that water extract of nettle can be used in cooking sausage to reduce lipid oxidation and to increase the stability of color. Practical Applications: Oxidation is a problem encountered in the food industry. The minced meat products are particularly vulnerable to changes in oxidation. Lipids oxidation and oxidation of heme pigments are the main reactions occurring in the meat products during storage and have an effect on their health. The use of natural antioxidants has increased because of the high demand for healthful food products. Many spices and herbs show antioxidant activity. This article deals with the use of Urtica dioica water extract and dried leaves as a functional ingredient in cooked pork sausages.
Exercise is associated with increased metabolic demand, which results in an increased formation of reactive oxygen species (ROS). However, regular exercise appears to decrease the incidence of a wide range of ROS-associated diseases, especially those related to lifestyle, such as cardiovascular diseases and type II diabetes, and also age related conditions such as Alzheimer's diseases and some kind of cancers. The preventive effect of regular exercise, at least in part, is due to oxidative stress-induced adaptation. The oxidative challenge-related adaptive process of exercise is probably not just dependent upon the levels of ROS but primarily on the increase in antioxidant and housekeeping enzyme activities related to oxidative damage repair enzymes. Therefore, the effects of exercise resemble the characteristics of hormesis. In addition, it appears that oxidative challenge-related effects of exercise are systemic. Skeletal muscle, liver, and brain have different metabolic rates and functions during exercise, but the adaptive response is very similar: increased antioxidant/damage repair enzyme activity, lower oxidative damage, and increased resistance to oxidative stress, due to changes in redox homeostasis. Hence, it is likely that the beneficial effects of exercise are due to the ability of exercise to produce increased levels of ROS. A sedentary life, which systemically decreases the body's capability to withstand oxidative challenge, increases the vulnerability to numerous physiological and environmental perturbations. © Springer-Verlag Berlin Heidelberg 2014. All rights are reserved.
Urtica angustifolia (U. angustifolia) is a traditional medicinal material which has anti-inflammatory and detoxification functions. It contains some active ingredient, such as alkaloids, flavonoids and polysaccharides. The objective of this study was to separate and identify alkaloids form it. However, the test of extraction conditions was shown that alkaloids reached the maximum in 1:10 of liquid to material, 85% ethanol concentration, 2h of reflux extraction. The total alkaloids were purified by AB-8 resin column, silica gel column and acid dye experiment successively.In addition, the maximum absorption wavelength of U. angustifolia alkaloid was determined by UV spectrophotometry, followed by their structural identified and analysis for alkaloids by infrared spectroscopy, high performance liquid chromatography and mass spectrometry. It could be concluded that the alkaloids of U. angustifolia which contain monoterpene from incarvillea alkaloids. And its molecular weight and molecular formula had identified.
Context:
The genus Urtica has been known since ancient times. It has known to be useful for the treatment of different human ailments.
Objective:
The present work evaluated the neuropharmacological effects of a hydroalcoholic extract of Urtica circularis (Hicken) Sorarú (Urticaceae). materials and method: The effect on central nervous system of U. circularis hydroalcoholic extract (from leaves and stems) administered by the intraperitoneal route in mice was evaluated by several tests: Pentobarbital- and midazolam-induced hypnosis, open field, hole board, elevated plus-maze and forced swimming. Phytochemical analysis was performed by high-performance liquid chromatography.
Results:
A total of 300 mg/kg i.p. of the extract produced a significant prolongation of pentobarbital- (40 mg/kg i.p.; 60.1 min versus 25.4 min) and midazolam- (50 mg/kg i.v.; 53.4 min versus 25.1 min) induced sleeping time. The extract's administration caused a marked reduction of the head-dipping response (DE50: 373 mg/kg i.p.) in the hole-board test. Urtica circularis extract (DE50: 46 mg/kg i.p.) reduced the spontaneous locomotor activity in the open field test. Flumazenil and atropine significantly antagonized the extract's effect on the locomotor activity. No motor coordination disturbance was observed in the rota rod test at any doses. In the forced swimming test, the extract did not produce any change in the immobility time and it had no significant effects in elevated plus maze test. The phytochemical analysis revealed the presence of chlorogenic acid, vanillic acid, caffeic acid, vicenin-2, p-cumaric acid, ferulic acid, vitexin and isovitexin.
Conclusion:
This study revealed that U. circularis hydroalcoholic extract possesses sedative activity, facilitating GABAergic and cholinergic transmission.
Abstract Reactive oxygen species (ROS) are continuously generated during metabolism. ROS are involved in redox signalling but, in significant concentrations they can greatly elevate oxidative damage leading to neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain a normal redox state in brain and spinal cord cell types. The complex effects of exercise benefit brain function, including functional enhancement as well as preventive and therapeutic roles. Exercise can induce neurogenesis via neurotrophic factors, increase capillarization, decrease oxidative damage, and enhance repair of oxidative damage. Exercise is also effective in attenuating age-associated loss in brain function, which suggests that physical activity-related complex metabolic and redox changes are important for a healthy neural system.
Résumé Cette revue commentée de communications dans le domaine de la plante médicinale (recherche pharmacologique et clinique) a
été élaborée pour son intérêt médical ou pharmaceutique. Elle devrait permettre de faire progresser d’autres études qui aboutiront
à une application thérapeutique. Il est cependant important d’avertir les lecteurs que d’une découverte ou d’une démonstration
pharmacologique ne découle pas immédiatement la justification de l’utilisation médicale.
The objective was to evaluate ovarian functionality and oxidative response in hyperandrogenism-induced polycystic ovary (PCO) and the protective effects of immunomodulator drug (IMOD), an electromagnetically-treated, selenium-based, herbal medicine. Daily oral administration of letrozole (1 mg/kg) for 21 consecutive days induced ovarian cysts in female rats. An effective dose of IMOD (30 mg/kg per day) was given intraperitoneally for 21 days. Biomarkers of ovarian function, serum concentrations of estradiol, progesterone, testosterone, and ovarian prostaglandin-E (PGE), were analyzed. To determine the role of oxidative stress (OS) in hyperandrogenism-induced PCO, concentrations of cellular lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxynitrite (ONOO), and tumor necrosis factor (TNF)-α as a marker of inflammation and apoptosis were measured in serum and ovaries. Letrozole-induced PCO resulted in significant increases in concentrations of lipid peroxidation and peroxynitrite in serum and ovary, but significantly decreased superoxide dismutase, catalase, and glutathione peroxidase. Serum concentrations of testosterone and TNF-α, and ovarian prostaglandin-E were increased (P < 0.001) in animals with cysts versus control, whereas estradiol and progesterone were decreased (P < 0.01 and P < 0.001, respectively). When compared with controls, letrozole induced irregular cycles and PCO characterized by a high incidence of subcapsular ovarian cysts with a diminished granulosa cell layer, luteinized granulosa cells in the cyst wall, significantly more atretic preantral and antral follicles, and absence of CL. There were almost no intact primary, secondary, and tertiary follicles in PCO rats. All end points assessed were significantly improved by IMOD and reached close to normal levels. In conclusion, the present study provided evidence that toxic free radicals and TNF-α were involved in the pathogenesis of PCO; furthermore, IMOD prevented ovarian histopathologic, endocrine, and biochemical alterations induced by hyperandrogenism.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. It is predicted that the incidence of AD will be increased in the future making this disease one of the greatest medical, social, and economic challenges for individuals, families, and the health care system worldwide. The etiology of AD is multifactorial. It features increased oxidative state and deposition of amyloid plaques and neurofibrillary tangles of protein tau in the central cortex and limbic system of the brain. Here we provide an overview of the positive impacts of exercise on this challenging disease. Regular physical activity increases the endurance of cells and tissues to oxidative stress, vascularization, energy metabolism, and neurotrophin synthesis, all important in neurogenesis, memory improvement, and brain plasticity. Although extensive studies are required to understand the mechanism, it is clear that physical exercise is beneficial in the prevention of AD and other age-associated neurodegenerative disorders.
Extensive research on humans suggests that exercise could have benefits for overall health and cognitive function, particularly in later life. Recent studies using animal models have been directed towards understanding the neurobiological bases of these benefits. It is now clear that voluntary exercise can increase levels of brain-derived neurotrophic factor (BDNF) and other growth factors, stimulate neurogenesis, increase resistance to brain insult and improve learning and mental performance. Recently, high-density oligonucleotide microarray analysis has demonstrated that, in addition to increasing levels of BDNF, exercise mobilizes gene expression profiles that would be predicted to benefit brain plasticity processes. Thus, exercise could provide a simple means to maintain brain function and promote brain plasticity.
α-Linolenic acid and unusual fatty acids of the ω3 and ω6 series play an important role in the modulation of human metabolism.
The presence of these acids in the leaves of several edible wild plants has recently been reported. In this study, six edible
wild species were selected in order to establish the fatty acid compositions in their leaf lipids. Thus, young leaves from
Amaranthus
viridis L.(blet), Chenopodium
album L. (goosefoot), Crithmum
maritimum L. (rock samphire), Plantago
major L. (plantain), Portulaca
oleracea L. (purslane) and Verbena
officinalis L. (vervain) yielded 1.50, 2.20, 3.02, 1.46, 3.81, and 2.28 g of lipids per 100 g dry plant material. Silica gel chromatography
yielded 0.64 g (Plantago
major) to 2.19 g (Crithmum
maritimum) neutral lipids, 0.37 g (Plantago
major) to 1.60 g (Portulaca
oleracea) glycolipids, and 0.26 g (Crithmum
maritimum) to 0.57 g (Verbena
officinalis) phospholipids per 100 g (dry weight). Gas chromatography (GC) showed the major fatty acids to be 18 : 3ω3, 18 : 2ω6 and
16 : 0 in all fractions, with high concentrations of 18 : 3ω3 in the glycolipid fraction. GC-mass spectrometric analyses did
not reveal the presence of unusual fatty acids. Carotenes were found in high concentrations, ranging from 30.5 mg/100 g (Chenopodium
album) to 89.2 mg/100 g (Portulaca
oleracea). The analyzed plants are rich sources of essential fatty acids (18 : 2ω6 and 18 : 3ω3) and also of carotenes.
Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls. These data can be interpreted to indicate that oxidation of cellular proteins may be a critical determinant of brain function. Moreover, it also implies that there is an age-related increase in vulnerability of tissue to oxidation that can be modified by free radical trapping compounds.
We have developed a simplified method for the preparation of liver nuclear extracts to study gene regulation and protein-DNA interactions. This protocol uses conventional laboratory equipment and standard reagents. The liver tissue is homogenized in a low-salt solution at physiological molarity with subsequent adjustment of the molarity and purification of nuclei by density sedimentation. The nuclear extracts are transcriptionally active in a validated cell-free transcription assay and contain functional DNA-binding proteins. This protocol results in the rapid preparation of highly reproducible and active liver nuclear extracts.
The past five years have offered a virtual explosion of information in the field of eukaryotic gene regulation. The natural anticipation that a considerable degree of regulation would be imparted at the level of mRNA synthesis (transcription) has been satisfied. When the polypeptide product of a gene is absent from a eukaryotic cell, its absence is typically due to the fact that its encoding gene is transcriptionally inert. There are important and highly interesting exceptions to this general rule, such as the regulated splicing of transcripts synthesized from the various fruit fly genes that control sexual phenotype. However, many lines of evidence identify transcriptions as the most common and immediate focal point of genetic regulation in eukaryotic cells. As in prokaryotic organisms, transcriptional control in eukaryotes results from an interplay between regulatory DNA sequences and site-specific DNA-binding proteins. Transcription of eukaryotic genes is influenced by various regulatory elements, termed promoters, enhancers, and silencers. These elements, in turn, are composed of discrete DNA sequence motifs, which constitute binding sites for sequence-specific DNA-binding proteins. A major effort is now under way to identify sequence-specific DNA-binding proteins, to match them to their cognate sites within or around eukaryotic genes, and to elucidate how the binding of such proteins results in increased or decreased transcription of the associated gene. This review focuses on recent information regarding the nature of eukaryotic transcriptional regulatory proteins, primarily ones that bind to DNA in a sequence-specific manner. Albeit an exciting time, the past several years have also generated a considerable amount of information that has yet to fall into place. We have chosen to concentrate our discussion on a few examples that illustrate particular concepts. Most of these are cases where considerable biochemical information has been obtained, although many of these systems owe their origins to classical genetic studies. The plethora of information concerning gene regulatory proteins can be largely attributed to several methodological advances that have occurred in the past decade. For example, cell-free extracts have been developed that recapitulate accurate transcription from RNA polymerase II promoters using cloned DNA templates. Also, detection of rare DNA-binding activities in crude cell extracts has become possible due to sensitive DNA protection and gel retardation assays. Finally, purification of these proteins has been expedited by the refinement of sequence-specific DNA affinity chromatography techniques. It would be impossible to cover all of the developments in the diverse field of transcriptional regulators. In particular, we have circumvented two important issues that have recently been reviewed elsewhere: how regulatory proteins communicate information to the transcriptional apparatus via activator domains, and the biochemical events involving RNA polymerase II and ancillary factors that occur during transcriptional initiation. We have instead chosen to begin this review by outlining the basic structural motifs that endow proteins the capacity to bind DNA in a sequence-specific manner, then focus on results and observations that were not necessarily anticipated from precedent studies on bacterial gene regulation. We hope to provide a framework for the consideration of topics that qualify as looming enigmas, and present speculations on the importance of protein:protein interactions. Lastly, we address the problem of how transcriptional regulatory proteins are themselves controlled.
Stroke is the third leading cause of death in the United States, after coronary heart disease and cancer. There are approximately 500,000 cases of stroke each year; of these, 150,000 are fatal.1 Many survivors are left with mental and physical impairment and require assistance with activities of daily living. Twenty-eight percent of patients with stroke are under 65 years of age, and women account for 40 percent of the new cases.2 Blacks in the United States have a rate of mortality due to stroke roughly twice that of whites.3 There are over 3 million patients with stroke alive in the . . .
The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age-related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.
Complete spinal cord lesion leads to profound metabolic abnormalities and striking changes in muscle morphology. Here we assess the effects of electrically stimulated leg cycling (ESLC) on whole body insulin sensitivity, skeletal muscle glucose metabolism, and muscle fiber morphology in five tetraplegic subjects with complete C5-C7 lesions. Physical training (seven ESLC sessions/wk for 8 wk) increased whole body insulin-stimulated glucose uptake by 33+/-13%, concomitant with a 2.1-fold increase in insulin-stimulated (100 microU/ml) 3-O-methylglucose transport in isolated vastus lateralis muscle. Physical training led to a marked increase in protein expression of GLUT4 (378+/-85%), glycogen synthase (526+/-146%), and hexokinase II (204+/-47%) in vastus lateralis muscle, whereas phosphofructokinase expression (282+/-97%) was not significantly changed. Hexokinase II activity was significantly increased, whereas activity of phosphofructokinase, glycogen synthase, and citrate synthase was not changed after training. Muscle fiber type distribution and fiber area were markedly altered compared to able-bodied subjects before ESLC training, with no change noted in either parameter after ECSL training. In conclusion, muscle contraction improves insulin action on whole body and cellular glucose uptake in cervical cord-injured persons through a major increase in protein expression of key genes involved in the regulation of glucose metabolism. Furthermore, improvements in insulin action on glucose metabolism are independent of changes in muscle fiber type distribution.
Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning.
Infection of human epithelial cells with human rhinovirus (HRV)-16 induces rapid production of several proinflammatory cytokines, including IL-8, IL-6, and GM-CSF. We evaluated the role of NF-kappaB in HRV-16-induced IL-8 and IL-6 production by EMSA using oligonucleotides corresponding to the binding sites for NF-kappaB in the IL-6 and IL-8 gene promoters. Consistent with the rapid induction of mRNA for IL-8 and IL-6, maximal NF-kappaB binding to both oligonucleotides was detected at 30 min after infection. NF-kappaB complexes contained p65 and p50, but not c-Rel. The IL-8 oligonucleotide bound recombinant p50 with only about one-tenth the efficiency of the IL-6 oligonucleotide, even though epithelial cells produced more IL-8 protein than IL-6. Neither the potent glucocorticoid, budesonide (10-7 M), nor a NO donor inhibited NF-kappaB binding to either cytokine promoter or induction of mRNA for either IL-8 or IL-6. Sulfasalazine and calpain inhibitor I, inhibitors of NF-kappaB activation, blocked HRV-16-induced formation of NF-kappaB complexes with oligonucleotides from both cytokines, but did not inhibit mRNA induction for either cytokine. By contrast, sulfasalazine clearly inhibited HRV-16 induction of mRNA for GM-CSF in the same cells. Thus, HRV-16 induces epithelial expression of IL-8 and IL-6 by an NF-kappaB-independent pathway, whereas induction of GM-CSF is at least partially dependent upon NF-kappaB activation.
Exercise increases the generation of reactive oxygen and nitrogen species (RONS) and by causing adaptation, could decrease the incidence of RONS-associated diseases. A single bout of exercise, depending upon intensity and duration, can cause an increase in antioxidant enzyme activity, decrease levels of thiols and antioxidant vitamins, and result in oxidative damage as a sign of incomplete adaptation. Increased levels of RONS and oxidative damage are initiators of a specific adaptive response, such as the stimulation of the activation of antioxidant enzymes, thiols, and enhanced oxidative damage repair. Regular exercise has the capability to develop compensation to oxidative stress, resulting in overcompensation against the increased level of RONS production and oxidative damage. Regular exercise causes adaptation of the antioxidant and repair systems, which could result in a decreased base level of oxidative damage and increased resistance to oxidative stress.
Extensive research on humans suggests that exercise could have benefits for overall health and cognitive function, particularly in later life. Recent studies using animal models have been directed towards understanding the neurobiological bases of these benefits. It is now clear that voluntary exercise can increase levels of brain-derived neurotrophic factor (BDNF) and other growth factors, stimulate neurogenesis, increase resistance to brain insult and improve learning and mental performance. Recently, high-density oligonucleotide microarray analysis has demonstrated that, in addition to increasing levels of BDNF, exercise mobilizes gene expression profiles that would be predicted to benefit brain plasticity processes. Thus, exercise could provide a simple means to maintain brain function and promote brain plasticity.
The fluorinated salicylate triflusal has been shown to have a neuroprotective effect after an excitotoxic lesion to the postnatal brain. In this regard, the aim of this study was to elucidate whether neuroprotection was associated with changes in the expression of proinflammatory molecules such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), or cyclooxygenase-2 (COX-2), well-known mediators of oxidative stress and inflammation, mechanisms underlying secondary damage occurring after excitotoxic/ischemic brain injury.
Postnatal day 9 rats received an intracortical injection of N-methyl-D-aspartate followed by oral administration of triflusal (30 mg/kg) 8 hours later. Ten or 24 hours after lesion, animals were killed, and brain sections processed for the immunohistochemical demonstration of IL-1beta, TNF-alpha, iNOS, and COX-2.
Besides a reduction in the neurodegenerative area, triflusal strongly decreased iNOS immunolabeling at both survival times analyzed, attenuating iNOS immunoreactivity in astroglial cells and infiltrated neutrophils. Additionally, a moderate reduction in COX-2, IL-1beta, and TNF-alpha was observed. Triflusal decreased neuronal and microglial COX-2 expression at 10 and 24 hours after lesion and microglial and astroglial expression of IL-1beta and TNF-alpha at 24 hours after lesion. TNF-alpha expression in neuronal cells at 10 hours after lesion was, however, maintained.
This study suggests that triflusal neuroprotection is associated with a decrease of iNOS and other inflammatory mediators and therefore may constitute a good therapeutic agent in pathological situations in which regulation of inflammatory genes constitutes a relevant step in the outcome of the neurodegenerative event.
The effects of two doses (50 and 100 mg/kg body wt given orally for 14 days) of an ethanol-water (80%-20%) extract of Urtica dioica L. and butylated hydroxyanisole (BHA) were investigated, for phase I and phase II enzymes, antioxidant enzymes, lactate dehydrogenase, lipid peroxidation and sulfhydryl groups in the liver of Swiss albino mice (8-9 weeks old). A modulatory effect of two doses and BHA was also observed for the activities of glutathione S-transferase, DT-diaphorase, superoxide dismutase and catalase in the kidney, lung and forestomach, as compared with the control group. The activities of cytochrome b5 (cyt b5), NADH-cytochrome b5 reductase (cyt b5 R), glutathione S-transferase (GST), DT-diaphorase (DTD), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) showed a significant increase in the liver at both dose levels of extract. Both extract-treated showed significantly lower activity of cytochrome P450 (cyt P450), lactate dehydrogenase (LDH), NADPH-cytochrome P450 reductase (cyt P450 R), total sulfhydryl groups (T-SH), nonprotein sulfhydryl groups (NP-SH) and protein-bound sulfhydryl groups (PB-SH). BHA-treated Swiss albino mice showed a notable increase in levels of cyt b5, DTD, T-SH, PB-SH, GPx, GR, and SOD in the liver while, LDH, cyt P450, cyt P450 R, Cyt b5 R, GST, NP-SH, and CAT levels were reduced significantly as compared to control values. The extract was effective in inducing GST, DTD, SOD and CAT activity in the forestomach and SOD and CAT activity in the lung at both dose levels. BHA-treated Swiss albino mice induced DTD, GST and all antioxidative parameters in the kidney, lung and forestomach.
The combined effects of aging and regular physical exercise was investigated on the production of reactive oxygen species (ROS), lipid peroxidation, glutathione status, and the activity of nuclear factor-kappaB (NF-kappaB) in rat liver. A group of 24 male F344 rats was divided into the following categories: adult control (18 months), adult exercised (18 months), and aged control (28 months) and aged exercised (28 months). The ROS formation increased as a function of age and exercise training decreased the rate of ROS formation in the two age groups. Significant positive correlation was found between ROS production and lipid peroxidation (LIPOX). The reduced glutathione (GSH) level was higher and the oxidized glutathione (GSSG) level lower in exercised groups compared with the sedentary controls (P<0.05). An age-associated increase in NF-kappaB activity was attenuated by the regular exercise. The content of p50 and p65 subunits of NF-kappaB increased with age and decreased with exercise training. The content of inhibitory factor-kappaB was inversely related to NF-kappaB activation. Regular exercise-induced adaptive responses, including attenuation of an increase in ROS production, LIPOX level, NF-kappaB activation, and reduced GSH/GSSG ratio, appear to be capable, even in old age, of reducing increases in inflammatory and other detrimental consequences that are often associated with advancing age.
Nuclear factor-kappaB (NF-kappaB) is a major transcription factor that plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The dysregulation of NF-kappaB is associated with many disease states such as AIDS, atherosclerosis, asthma, arthritis, cancer, diabetes, inflammatory bowel disease, muscular dystrophy, stroke, and viral infections. Recent evidence also suggests that the dysfunction of NF-kappaB is a major mediator of some human genetic disorders. Appropriate regulation and control of NF-kappaB activity, which can be achieved by gene modification or pharmacological strategies, would provide a potential approach for the management of NF-kappaB related human diseases. This review summarizes the current knowledge of the physiological and pathophysiological functions of NF-kappaB and its possible role as a target of therapeutic intervention
The study of free radical reactions is not an isolated and esoteric branch of science. A knowledge of free radical chemistry and biochemistry is relevant to an understanding of all diseases and the mode of action of all toxins, if only because diseased or damaged tissues undergo radical reactions more readily than do normal tissues. However it does not follow that because radical reactions can be demonstrated, they are important in any particular instance. We hope that the careful techniques needed to assess the biological role of free radicals will become more widely used.
Twenty healthy volunteers ingested for 21 days 2 capsules b.i.d. of an IDS 23/1 containing nettle leaf extract (Rheuma-Hek). Before and after 7 and 21 days the basal and the lipopolysaccharide (LPS) stimulated tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1 β) and interleukin-6 (IL-6) concentrations were measured ex vivo. In vitro the effects of IDS 23/1 on the release of these cytokines were determined. Additionally basal interleukin-4 (IL-4) and interleukin-10 (IL-10) levels were recorded. Orally taken the test drug has ex vivo no effect on basal levels of TNF-α, IL-1β, IL-4, IL-6 or IL-10 which were always below detection limits. After 7 and 21 days ingestion ex vivo a decrease of LPS stimulated TNF-α release of 14.6 and 24.0%, respectively, was observed. IL-1 β was reduced for 19.2 and 39.3%. In vitro IDS 23/1 added to whole blood resulted in an exceeded inhibition of LPS stimulated TNF-α and IL-1 β secretion which correlated with the duration of the drug ingestion. Using the highest tested IDS 23/1 concentration the inhibition reached 50.5 (day 0) to 79.5% (day 21) for TNF-α and 90.0 (day 0) to 99.2% (day 21) for IL-1 β, respectively. IDS 23/1 induced a pronounced release of IL-6 in absence of LPS only in vitro. The detected IL-6 concentrations were comparable to those after LPS stimulation, additive effects could not be observed. The absence of detectable IL-6 concentrations in whole blood ex vivo after oral ingestion of the tested drug as well as the differences in the inhibition patterns for TNFα and IL-1β ex vivo and ex vivo in vitro suggest that the extract contains different pharmacological effective compounds with varying bioavailabilities.
Upon leaving an elevated runway to enter a darkened chamber, male Wistar rats were given a single electric shock of .12, .25, or .50 ma. for 1, 3, or 9 sec. Retention trials, during which latency to enter the darkened chamber and defecation were recorded, were given immediately (30 sec.) or 3, 24, or 48 hr. after the shock trial. Latency and defecation were directly related to both the intensity and duration of the electric shock. No interaction between shock intensity and duration was observed. Reponse latency was inversely related to the retention interval. Although there was more defecation during the 3-hr test than during the immediate retention test, this could be interpreted as a recency effect rather than incubation of fear. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The long-term behavioural effects of prenatal chronic anaemic hypoxia were investigated in young (5 months old), late adult (19 months) and aged Wistar rats (23–26 months). Sodium nitrite (2 g/l) offered in the drinking water during the second half of pregnancy served to evoke prenatal hypoxia. In parallel to nitrite treatment the Ca2+ channel blocker nimodipine (10 mg/kg) or vehicle alone was administered intragastrically once daily. Open-field activity, intermale social behaviour, learning ability in a black–white discrimination paradigm and fear-induced emotionality were assessed at different ages. Plasma corticosterone response to novelty stress was measured by blood sampling through chronic venous canulas at the age of 28 months. The nitrite-exposed 5-month-old offspring started exploration in a novel open-field with considerable delay. This delayed start-latency was augmented in 19- and 23-month-old rats, pointing to exaggerated suppression of behavioural arousal. Nitrite-induced hypoxia decreased the duration of social interactions during ageing. Aged rats exposed to nitrite were unable to learn a black–white discrimination but showed a normal generalized conditioned fear response (immobility) to the test situation as a whole. The conditioned fear-induced vocalization was more frequent among hypoxic aged animals. The aged hypoxic rats displayed a prolonged plasma corticosterone stress response and had higher adrenal weight than their controls. The abnormal open-field, social, learning and emotional behaviours, as well as the altered plasma corticosterone response, were prevented by prenatal nimodipine treatment.
Moderate daily exercise is known to be beneficial to health, reducing risks of a number of age-related disorders. Molecular mechanisms that bring about these effects are not clear. In contrast, it has been claimed that some types of prolonged physical exertion are detrimental to health because active oxygen species are generated excessively by enhanced oxygen consumption. Using two age groups of rats, young (4 week) and middle aged (14 months), we investigated the effects of long-term swimming training on the oxidative status of phospholipids, proteins, and DNA. The concentration of thiobarbituric acid reactive substances and 4-hydroxynonenal protein adducts did not differ in the gastrocnemius muscle between exercised and nonexercised animals in the two age groups. The extent of carbonylation in a protein of molecular weight around 29 KDa and the amount of 8-hydroxydeoxyguanosine in nuclear DNA were smaller (p < .05) in the exercised rats than in the sedentary animals. Activities of DT-diaphorase (C1: 29.3 ± 1.9; C2: 36.1 ± 2.6; E1: 27.2 ± 1.3; C2: 33.4 ± 2.9 nmol/mg protein) and proteasome, a major proteolytic enzyme for oxidatively modified proteins were significantly higher in the exercised animals of both age groups (p < .05). The adaptive response against oxidative stress induced by moderate endurance exercise constitutes a beneficial effect of exercise.
The biochemical mechanisms by which regular exercise significantly benefits health and well being, including improved cognitive function, are not well understood. Four-week-old (young) and 14-month-old (middle aged) Wistar rats were randomly assigned to young control and young exercised, middle-aged control and middle-aged exercised groups. Exercise groups were exposed to a swimming regime of 1 h a day, 5 days a week for 9 weeks. The passive avoidance test showed that middle-aged exercised rats had significantly (P<0.05) better short- (24 h) and long-term (72 h) memory than aged-matched control rats. Conditioned pole-jumping avoidance learning was improved markedly in both age groups by exercise. Brain thiobarbituric acid-reactive substances and 8-hydroxy-2′deoxyguanosine content in the DNA did not change significantly, while the protein carbonyl levels decreased significantly (P<0.05) in both exercised groups. This decrease was accompanied by an increase in the chymotrypsin-like activity of proteasome complex in the exercised groups, whereas trypsin-like activity did not differ significantly between all groups. The DT-diaphorase activity increased significantly (P<0.05) in the brain of young exercised animals. These data show that swimming training improves some cognitive functions in rats, with parallel attenuation of the accumulation of oxidatively damaged proteins.
The study of free radical reactions is not an isolated and esoteric branch of science. A knowledge of free radical chemistry and biochemistry is relevant to an understanding of all diseases and the mode of action of all toxins, if only because diseased or damaged tissues undergo radical reactions more readily than do normal tissues. However it does not follow that because radical reactions can be demonstrated, they are important in any particular instance. We hope that the careful techniques needed to assess the biological role of free radicals will become more widely used.
Aging and cancer share a number of characteristics. This has led to the hypothesis that species' differences in longevity may be governed in part by the same mechanisms as those processes governing species' differences in their age-dependent probability of developing cancer. Much evidence has indicated that beta-carotene and retinol may be important natural anticarcinogens. Accordingly, they also may be important antiaging agents. This possibility has been tested by determining if a positive correlation exists between the concentration of carotenoids and retinol in serum and brain tissue with the maximal life-span potential of mammalian species. The results show a significant positive correlation for the carotenoids but not for retinol. These results suggest that the carotenoids may be biologically active as protective agents against cancer and as longevity determinants. Retinol appears to be less important in these functions.
The effects of vitamin A and some carotenoids (beta-carotene, beta-cryptoxanthin, zeaxanthin, lutein, capsorubin, capsanthin, capsanthol and lycopene) were studied (a) on the development of acute gastric mucosal lesions produced by topical application of 0.6 M HCl and (b) on gastric secretion in 4-h pylorus-ligated rats. It was found (a) that vitamin A, beta-carotene, beta-cryptoxanthin, zeaxanthin and lutein significantly inhibited the development of gastric mucosal lesions produced by 0.6 M HCl, while capsorubin, capsanthin, capsanthol and lycopene failed to prevent the development of such lesions; and (b) that vitamin A, beta-carotene, beta-cryptoxanthin, zeaxanthin and lutein, i.e., the carotenoids which exerted a cytoprotective effect, had no inhibitory effect on gastric acid secretion in 4-h pylorus-ligated rats. The possible relationship between chemical structure and gastric cytoprotection is discussed.
The purpose of this investigation was to determine whether any alterations in antioxidant enzyme activities and levels of glutathione (GSH) in brain regions occurred following exercise training. Sprague-Dawley rats were given exercise training on a treadmill for 7.5 weeks and sacrificed 18 h after the last exercise along with the sedentary control rats. Different brain regions-cerebral cortex (CC), brainstem (BS), corpus striatum (CS), and hippocampus (H)-were isolated; GSH, oxidized glutathione (GSSG), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined. The exercise training increased SOD activity significantly (130% of sedentary control) in BS and in CS. SOD activity in H was the lowest of all four brain regions. Different brain regions showed GSH-Px activity in decreasing order for CS < BS < CC < H. GSH levels were 43% less in BS than CC and CS. The ratio of GSH/GSSG significantly increased from 6.8 to 8.3 in CC, and from 9.4 to 13.5 in BS as a result of exercise training. Different brain regions contained different activities of antioxidant enzymes, as well as GSH and GSSG levels, which were preferentially altered as a result of exercise training to cope with oxidative stress.
NF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling, and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins. In vertebrates, five distinct DNA binding subunits are currently known which might extensively heterodimerize, thereby forming complexes with distinct transcriptional activity, DNA sequence specificity, and cell type- and cell stage-specific distribution. The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates. I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes. An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus. Other I kappa B proteins are rather involved in terminating NF-kappa B's activity in the nucleus. The intracellular events that lead to the inactivation of I kappa B, i.e. the activation of NF-kappa B, are complex. They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells' redox status. Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, acute phase response, and radiation damage. The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes.
In the current study the neuroprotective effect of the L-type calcium channel antagonist nimodipine in rat brain was investigated in N-methyl-D-aspartate-induced neuronal degeneration in vivo. In the present model NMDA was unilaterally injected in the magnocellular nucleus basalis and the neurotoxic impact assessed by measuring cortical cholinergic fibre loss as a percentage of fibre density of the intact control hemisphere. This procedure proved to be a reproducible model in which the degree of damage was almost linearly proportional to the NMDA dose. Neuroprotection by nimodipine was determined in a number of conditions. First, the effect of nimodipine treatment in adult animals starting two weeks prior to neurotoxic injury was compared with neuroprotection provided by perinatal treatment of the mother animals with the calcium antagonist. Surprisingly, the degree of protection was in both cases similar, yielding almost 30% reduction of fibre loss. The neuroprotective effect in adulthood of perinatal nimodipine treatment may be explained by developmentally enhanced calcium binding proteins or persistent developmental changes in calcium channel characteristics. Protection by nimodipine was also investigated in aged, 26 month old rats. Compared to young adult cases, aged animals proved to be less vulnerable to NMDA exposure, while nimodipine application was more potent, thus yielding a reduction of nearly 50% in nerve fibre damage induced by NMDA infusions. Possible mechanisms of differential calcium influx in the various experimental conditions will be discussed.
The present study investigated the effects of nucleus basalis magnocellularis (NBM) lesions in young (3 months), adult (9 months), and aged (24 months) rats by injections of either NMDA or AMPA upon performance of a delayed alternation task on a T maze. During phase 1 of testing, the interchoice interval (ICI) was 5 s and each rat was given 10 trials per day during phase 2, the ICI was 30 s across 10 trials per day; during phase 3, the ICI was 5 s across 20 trials per day. Analyses of variance revealed (a) a significant effect of age during phase 1 (i.e., 24-month-old rats performed worse than 3-month-old rats); (b) a significant effect of age and lesion in phase 2 (i.e., the lesions impaired choice accuracy equally in all age groups when the ICIs were 30 s); (c) a significant effect of age and lesions, and a significant interaction in phase 3 (i.e., young rats were more impaired by the lesions than were aged rats.
Neuroprotection against excitotoxicity by a combined therapy with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the L-type Ca2+ channel blocker nimodipine was examined using an in vivo rat model of NMDA-induced neurodegeneration. Attention was focused on the neuroprotective potential of this combined drug treatment before and after NMDA-exposure. NMDA was unilaterally injected in the magnocellular nucleus basalis (MBN). Neuronal damage was assessed 12 days after the NMDA-injection by measuring the reduction of cholinergic cortical fibres that originate from the MBN neurons. In controls that received no drug treatment, NMDA-exposure damaged MBN neurons such that 66% of the cholinergic terminals were lost in the ipsilateral parietal cortex. Pretreatment with a nimodipine diet (860 ppm) combined with application of MK-801 (5 mg/kg i.p.) before NMDA-exposure reduced fibre loss by 89% thereby providing a near complete neuroprotection. Combined therapy of MK-801 (5 mg/kg i.p.) and nimodipine (15 mg/kg i.p.) 8 min after NMDA-infusion reduced neuronal injury by 82%, while the same combination given 2 h after the excitotoxic treatment still yielded a 66% protection against neurotoxic damage invoked by NMDA. In conclusion, the present data show that a dual blockade of NMDA-channels and voltage-dependent calcium channels (VDCC's) up to 2 h after NMDA-exposure is able to provide a significant protection against NMDA-neurotoxicity.
Twenty healthy volunteers ingested for 21 days 2 capsules b.i.d. of an IDS 23/1 containing nettle leaf extract (Rheuma-Hek). Before and after 7 and 21 days the basal and the lipopolysaccharide (LPS) stimulated tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) concentrations were measured ex vivo. In vitro the effects of IDS 23/1 on the release of these cytokines were determined. Additionally basal interleukin-4 (IL-4) and interleukin-10 (IL-10) levels were recorded. Orally taken the test drug has ex vivo no effect on basal levels of TNF-alpha, IL-1 beta, IL-4, IL-6 or IL-10 which were always below detection limits. After 7 and 21 days ingestion ex vivo a decrease of LPS stimulated TNF-alpha release of 14.6 and 24.0%, respectively, was observed. IL-1 beta was reduced for 19.2 and 39.3%. In vitro IDS 23/1 added to whole blood resulted in an exceeded inhibition of LPS stimulated TNF-alpha and IL-1 beta secretion which correlated with the duration of the drug ingestion. Using the highest tested IDS 23/1 concentration the inhibition reached 50.5 (day 0) to 79.5% (day 21) for TNF-alpha and 90.0 (day 0) to 99.2% (day 21) for IL-1 beta, respectively. IDS 23/1 induced a pronounced release of IL-6 in absence of LPS only in vitro. The detected IL-6 concentrations were comparable to those after LPS stimulation, additive effects could not be observed. The absence of detectable IL-6 concentrations in whole blood ex vivo after oral ingestion of the tested drug as well as the differences in the inhibition patterns for TNF-alpha and IL-1 beta ex vivo and ex vivo in vitro suggest that the extract contains different pharmacological effective compounds with varying bioavailabilities.
The dihydropyridine receptor (DHPR) and ryanodine receptor (RYR1) are needed for excitation-contraction coupling in skeletal muscle. Previous studies from this laboratory have shown DHPR-RYR1 uncoupling in 33-month-old Fischer 344 x Brown Norway F1 (F344BNF1) rats fed ad libitum. The purpose of the present study is to determine whether caloric restriction prevents age-related impairments in skeletal muscle function and expression of DHPR and RyR1. Bundles of soleus and extensor digitorum longus (EDL) were studied from rats fed ad libitum and on 60 percent caloric restriction. Significant differences were found in peak twitch or tetanic tension between the ad libitum and calorie-restricted groups in soleus and EDL muscles. A significant increase in the expression of DHPR and RyR1 was observed in caloric restricted rats. These results show that calorie restriction preserves the mechanical properties of aging hind-limb skeletal muscle and maintains the level of DHPR and RyR1 in aged F344BNF1 rats fed ad libitum.
Previous results from our laboratory indicate that two nights of voluntary wheel running upregulates brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. In order to investigate the time-course of the BDNF response and to examine how physical activity preferentially activates particular transcriptional pathways, the effects of 6 and 12 h of voluntary wheel running on BDNF and exons I-IV mRNA expression were investigated in rats. Hippocampal full-length BDNF mRNA expression was rapidly influenced by physical activity, showing significant increases in expression levels as soon as 6 h of voluntary wheel running. Moreover, there was a strong positive correlation between distance run and BDNF mRNA expression. Exon I mRNA expression was significantly upregulated after 6 h of running and was maintained or enhanced by 12 h of voluntary running. Exon II had a slower time-course and was significantly upregulated after 12 h, selectively in the CA1 hippocampal region. Exon III and Exon IV showed no significant increase in expression level after 6 or 12 h of running in the paradigm studied. It is significant that the rapid neurotrophin response is demonstrated for a physiologically relevant stimulus, as opposed to the extreme conditions of seizure paradigms. Furthermore, exercise-induced upregulation of BDNF may help increase the brain's resistance to damage and neurodegeneration that occurs with aging.
Activation of transcription factor NF-kappaB is elevated in several chronic inflammatory diseases and is responsible for the enhanced expression of many proinflammatory gene products. Extracts from leaves of stinging nettle (Urtica dioica) are used as antiinflammatory remedies in rheumatoid arthritis. Standardized preparations of these extracts (IDS23) suppress cytokine production, but their mode of action remains unclear. Here we demonstrate that treatment of different cells with IDS23 potently inhibits NF-kappaB activation. An inhibitory effect was observed in response to several stimuli, suggesting that IDS23 suppressed a common NF-kappaB pathway. Inhibition of NF-kappaB activation by IDS23 was not mediated by a direct modification of DNA binding, but rather by preventing degradation of its inhibitory subunit IkappaB-alpha. Our results suggests that part of the antiinflammatory effect of Urtica extract may be ascribed to its inhibitory effect on NF-kappaB activation.
It is remarkable that neurons are able to survive and function for a century or more in many persons that age successfully. A better understanding of the molecular signaling mechanisms that permit such cell survival and synaptic plasticity may therefore lead to the development of new preventative and therapeutic strategies for age-related neurodegenerative disorders. We all know that overeating and lack of exercise are risk factors for many different age-related diseases including cardiovascular disease, diabetes and cancers. Our recent studies have shown that dietary restriction (reduced calorie intake) can increase the resistance of neurons in the brain to dysfunction and death in experimental models of Alzheimer's disease, Parkinson's disease, Huntington's disease and stroke. The mechanism underlying the beneficial effects of dietary restriction involves stimulation of the expression of 'stress proteins' and neurotrophic factors. The neurotrophic factors induced by dietary restriction may protect neurons by inducing the production of proteins that suppress oxyradical production, stabilize cellular calcium homeostasis and inhibit apoptotic biochemical cascades. Interestingly, dietary restriction also increases numbers of newly-generated neural cells in the adult brain suggesting that this dietary manipulation can increase the brain's capacity for plasticity and self-repair. Work in other laboratories suggests that physical and intellectual activity can similarly increase neurotrophic factor production and neurogenesis. Collectively, the available data suggest the that dietary restriction, and physical and mental activity, may reduce both the incidence and severity of neurodegenerative disorders in humans. A better understanding of the cellular and molecular mechanisms underlying these effects of diet and behavior on the brain is also leading to novel therapeutic agents that mimick the beneficial effects of dietary restriction and exercise.
Dendritic cells are important antigen presenting cells that play a role in the initiation of rheumatoid arthritis (RA). The stinging nettle leaf extract IDS 30 (Hox alpha) has been recommended for adjuvant therapy of rheumatic diseases. We investigated the immunomodulating effect of IDS 30 extract on the maturation of hematopoietic dendritic cells.
Human dendritic cells were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin 4 (IL-4). Dendritic cell maturation was induced by keyhole limped hemocyanin (KLH). Dendritic cell phenotype was characterized by flow cytometric analysis; dendritic cell cytokine production was measured by ELISA. The ability of dendritic cells to activate naive autologous T cells was evaluated by mixed leukocyte reaction.
IDS 30 prevented the maturation of dendritic cells, but did not affect their viability. IDS 30 reduced the expression of CD83 and CD86. It increased the expression of chemokine receptor 5 and CD36 in a dose dependent manner. The secretion of tumor necrosis factor-alpha was reduced. Application of IDS 30 to dendritic cells in culture caused a high endocytosis of dextran and a low capacity to stimulate T cell proliferation.
Our in vitro results showed the suppressive effect of IDS 30 on the maturation of human myeloid dendritic cells, leading to reduced induction of primary T cell responses. This may contribute to the therapeutic effect of IDS 30 on T cell mediated inflammatory diseases like RA.
COTMAN, C.W., and C. ENGESSER-CESAR. Exercise enhances and protects brain function. Exerc. Sport Sci. Rev., Vol. 30, No. 2, pp. 75–79, 2002. Physical activity, in the form of voluntary wheel running, induces gene expression changes in the brain. Animals that exercise show an increase in brain-derived neurotrophic factor, a molecule that increases neuronal survival, enhances learning, and protects against cognitive decline. Microarray analysis of gene expression provides further support that exercise enhances and supports brain function.
A total of 27 extracts from non-cultivated and weedy vegetables traditionally consumed by ethnic Albanians (Arbëreshë) in the Vulture area (southern Italy) were tested for their free radical scavenging activity (FRSA) in the DPPH (1,1-diphenyl-2-picrylhydrazil radical) screening assay, for their in vitro non-enzymatic inhibition of bovine brain lipid peroxidation and for their inhibition of xanthine oxidase (XO). In both antioxidant assays strong activity was shown for Leopoldia comosa (bulbs, syn.: Muscari comosum) and Centaurea calcitrapa (young whorls). In the lipid peroxidation assay, extracts from leaves of Origanum heracleoticum, Urtica dioica and Tordylium apulum showed a remarkable inhibitory activity (> 50%), too. In the case of Leopoldia comosa and Origanum heracleoticum this activity was comparable to quercetin (at a concentration of 50 microM) and Rhodiola rosea extract. Extracts from non-cultivated Cichorium intybus, Chondrilla juncea and Stellaria media showed strong in vitro inhibition of xanthine oxidase, with an activity higher than that of a reference extract from Ledum groenlandicum. These findings suggest that weedy vegetables may be useful antioxidants of interest in the prevention of ageing related diseases, CNS disorders and as potential sources of phytomedicines against hyperuricaemia and gout.
Lesions in the nervous system induce rapid activation of glial cells and under certain conditions additional recruitment of granulocytes, T-cells and monocytes/ macrophages from the blood stream triggered by upregulation of cell adhesion molecules, chemokines and cytokines. Hematogenous cell infiltration is not restricted to infectious or autoimmune disorders of the nervous system, but also occurs in response to cerebral ischemia and traumatic lesions. Neuroinflammation can cause neuronal damage, but also confers neuroprotection.
Granulocytes occlude vessels during reperfusion after transient focal ischemia, while the functional role of T-cells and macrophages in stroke development awaits further clarification. After focal cerebral ischemia neurotoxic mediators released by microglia such as the inducible nitric oxide synthase (leading to NO synthesis) and the cytokines interleukin-1ß (IL-ß) and tumor necrosis factor-a (TNF-α) are upregulated prior to cellular inflammation in the evolving lesion and functionally contribute to secondary infarct growth as revealed by numerous pharmacological experiments and by use of transgenic animals. On the other hand, cytokine induction remote from ischemic lesions involves NMDA-mediated signalling pathways and confers neuroprotection. After nerve injury T cells can rescue CNS neurons. In the peripheral nervous system neuroinflammation is a prerequisite for successful regeneration that is impeded in the CNS. In conclusion, there is increasing evidence that neuroinflammation represents a double edged sword. The opposing neurotoxic and neuroprotective properties of neuroinflammation during CNS injury provide a rich and currently unexplored set of research problems.
The levels of different reactive species, especially those of nitric oxide and peroxynitrite, were determined in streptozotocin-induced diabetic rat tissues, before the development of histopathological damages. Significantly higher steady state free radical concentrations were found in the liver 3 weeks after the onset of diabetes compared to age-matched control groups. Increased nitric oxide levels in diabetic vasculature and kidney decreased the production of detectable reactive oxygen species. High peroxynitrite generation suggested the onset of processes characteristic to premature aging of the endothelium. According to the histopathological results, there were no signs of late complications in the tissues up to 7 weeks after induction of diabetes. These results support the idea that oxidative stress is increased at a very early stage of diabetes and, in particular, that high levels of nitric oxide and peroxynitrite could play a decisive role in the development of late complications in the diabetic vasculature and kidney.
We examined the expression of TNF-alpha within the substantia nigra pars reticulata (SNR) following intrastriatal injection of quinolinic acid (QA) and studied the effect of rolipram, a TNF-alpha-inhibitor, on the secondary neuronal damage. QA (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. After survival of 1, 3 or 10 days, the animals were sacrificed and immunohistochemical staining with an antibody against TNF-alpha was performed. From day 1 to day 10 after striatal QA injection TNF-alpha positive cells were observed within ipsilateral substantia nigra which were neither present on the contralateral side nor in sham-operated controls. Double labeling with antibodies against TNF-alpha and NeuN, keratan sulfate proteoglycan or GFAP displayed a good overlap between TNF-alpha and NeuN, which suggests that TNF-alpha positive cells are neurons. For the pharmacological approach, three groups of QA rats were treated intraperitoneally with either solvent (n=5), the NMDA receptor antagonist MK 801 (4 mg/kg, n=6) or the TNF-alpha inhibitor rolipram (0.3 mg/kg, n=6), which was started 24 h after QA-injection and continued with daily applications for 14 days. The amount of striatal damage did not differ between the three groups. The number of intact neurons within the ipsilateral substantia nigra of the solvent treated group was reduced by approximately 30% compared to the contralateral side. Both MK 801 and rolipram ameliorated this secondary damage and reduced the number of TNF-alpha positive cells. The observed association between expression of TNF-alpha and secondary neuronal damage within the substantia nigra induced by intrastriatal QA application might hint towards an involvement of this cytokine in transneuronal degeneration.
N-Methyl-d-aspartate (NMDA)-induced striatal excitotoxicity is mediated by nitric oxide (NO) but the role of inflammatory mechanisms and inducible nitric oxide synthase (iNOS) induction is not clear. Unilateral intrastriatal administration of NMDA to rats resulted in the loss of intrinsic striatal neurones and the degeneration of NADPH-diaphorase positive interneurones within 24 h. NMDA administration caused activation of glial fibrillary acidic protein positive astroglial cells and MAC-1 ir microglia. Marked iNOS immunoreactivity was expressed within both astroglial and microglial cells and there was marked cellular labelling for 3-nitrotyrosine (3-NT). One month following the NMDA lesion, administration of (+)-amphetamine (AMPH) produced a circling response in rats. Pre-treatment of rats with the iNOS inhibitor aminoguanidine (AG) decreased the extent of NMDA-induced striatal cell loss at 24 h and reduced 3-NT expression but was without effect on glial cell activation. AG pre-treatment also prevented the onset of rotation to AMPH at 30 days following NMDA lesioning. NMDA administration unexpectedly caused a loss of tyrosine hydroxylase immunoreactive (TH-ir) fibres in the striatum at 24 h and at 30 days the number of TH-ir cells were decreased in the substantia nigra. The loss of nigral cells was prevented by AG pre-treatment. This study demonstrates a role for iNOS induction in NO-mediated NMDA excitotoxicity to rat striatum and suggests that inflammatory mechanisms play a key role in this process.
Cerebral deposition of beta-amyloid (Abeta) peptides is an invariant pathological hallmark in brains of patients with Alzheimer's disease (AD) and transgenic mice coexpressing familial AD-linked APP and PS1 variants. We now report that exposure of transgenic mice to an "enriched environment" results in pronounced reductions in cerebral Abeta levels and amyloid deposits, compared to animals raised under "standard housing" conditions. The enzymatic activity of an Abeta-degrading endopeptidase, neprilysin, is elevated in the brains of "enriched" mice and inversely correlated with amyloid burden. Moreover, DNA microarray analysis revealed selective upregulation in levels of transcripts encoded by genes associated with learning and memory, vasculogenesis, neurogenesis, cell survival pathways, Abeta sequestration, and prostaglandin synthesis. These studies provide evidence that environmental enrichment leads to reductions in steady-state levels of cerebral Abeta peptides and amyloid deposition and selective upregulation in levels of specific transcripts in brains of transgenic mice.
A large amount of aging individuals show diminished cognitive and endocrine capabilities. The main brain areas involved in these changes are the hippocampus and hypothalamus, two regions possessing high plasticity and implicated in cognitive and endocrine functions, respectively. Among neurotrophins (considered as genuine molecular mediators of synaptic plasticity), brain-derived neurotrophic factor (BDNF) exhibits in adult rats, the highest concentrations in the hippocampus and hypothalamus. Most of neuronal effects of BDNF are mediated through high-affinity cell surface BDNF tyrosine kinase receptors (TrkB). Different TrkB isoforms are issued by alternative splicing of mRNA encoding for TrkB (trkB mRNA) generating at least three different TrkB receptors with different signaling capabilities. The goal of this study was to examine simultaneously the expression (mRNAs and proteins) of BDNF and its three specific receptors, in the hippocampus and hypothalamus throughout lifespan in rats.