In vivo protective effects of 6­gingerol in cerebral ischemia involve preservation of antioxidant defenses and activation of anti­apoptotic pathways.

Stroke is an important medical problem in developing countries, characterized by a sudden disruption of blood supply to the brain, either through occlusion or hemorrhage. It is a major cause of neurological impairment, resulting in high medical costs. The present study examined the effect of 6-gingerol on morphological changes, antioxidant defenses, and the anti-apoptotic factors p38 mitogen-activated protein kinase (MAPK) and mitofusin (Mfn)2, in a rat model of focal cerebral ischemia. A total of 60 healthy male Wistar rats were randomly allocated into six groups: Control, right middle cerebral artery occlusion (Rt.MCAO) + vehicle, Rt.MCAO + piracetam, and Rt.MCAO + 6-Gin 5, 10 and 20 mg/kg BW groups. The results indicated that 6-gingerol treatment for a duration of 7 days reverses morphological alterations, enhances catalase and glutathione peroxidase activities, reduces Bax, caspase-3 and MAPK expression, and increases Bcl-xL and Mfn2 expression in the cortex and hippocampus. In conclusion, 6-gingerol demonstrated significant in vivo effectiveness in mitigating pathological changes induced by cerebral ischemia. This beneficial effect is attributed, at least in part, to preservation of antioxidant defenses and activation of anti-apoptotic pathways.

Elastic band resistance combined with modified Thai yoga exercise to alleviate oxidative stress and airway inflammation in type 2 diabetes mellitus.

The objective of this study was to investigate the effects of the combination of elastic band resistance exercise (EBRE) with modified Thai yoga on the alleviation of blood glucose and oxidative stress in type 2 diabetes mellitus (T2DM). Forty-two patients with T2DM were enrolled and allocated to an exercise or control group (n=21/group). The exercise group participated in EBRE combination with modified Thai yoga for 40 min, 5 days/wk, for 12 consecutive weeks. Blood glucose, oxidative stress markers, antioxidants, pulmonary function, respiratory muscle strength, and airway inflammation were measured before and after the 12 weeks. The results showed that the exercise group had a significant reduction in fasting blood glucose and glycated hemoglobin. Moreover, T2DM patients in the exercise group showed a significant reduction in plasma malondialdehyde, while superoxide dismutase and catalase were significantly increased. The exercise group also observed a significant improvement in pulmonary function; forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow, and forced midexpiratory flow as well as respiratory muscle strength. Interestingly, the combination of EBRE with modified Thai yoga markedly improved airway inflammation through the reduction in fractional exhaled nitric oxide. In conclusion, these findings suggest that the combination of EBRE with modified Thai yoga improves blood glucose, oxidative stress, antioxidants, pulmonary function, respiratory muscle strength, and airway inflammation in T2DM patients. Hence, it could be considered as a possible exercise program for T2DM patients.

Ameliorative effects of 6­gingerol in cerebral ischemia are mediated via the activation of antioxidant and anti­inflammatory pathways.

Focal ischemia occurs when an embolus or thrombus occludes an artery, causing the rapid obstruction of cerebral blood flow. Although stroke represents a main cause of disability and mortality in developing countries, therapeutic approaches available for this condition remain very limited. The aim of the present study was to examine the effects of the phytochemical, 6-gingerol, on the brain infarct volume, neuronal loss and on the oxidative stress parameters, cyclooxygenase-2 (COX-2) and interleukin (IL)-6, in an animal model of focal ischemic stroke. Male Wistar rats, weighing 250-300 g, were divided into the following six groups: i) The control; ii) right middle cerebral artery occlusion (Rt.MCAO) + vehicle; iii) Rt.MCAO + piracetam; iv) Rt.MCAO + 6-gingerol (6-Gin) at 5 mg/kg body weight (BW); v) Rt.MCAO + 6-Gin at 10 mg/kg BW; and vi) the Rt.MCAO + 6-Gin at 20 mg/kg BW group. The rats in each group received the vehicle or piracetam or 6-gingerol intraperitoneally for 7 days following Rt.MCAO. The brain infarct volume, neuronal loss and alterations in antioxidant and anti-inflammatory levels were assessed in the cortex and hippocampus. The results revealed that the brain infarct volume, malondialdehyde level and the density ratio of COX-2 and IL-6 to ß-actin were significantly decreased following treatment with 6-gingerol. In addition, neuronal density and superoxide dismutase activity in the cortex and hippocampus were increased. On the whole, the findings of the present study suggest that 6-gingerol exerts antioxidant and anti-inflammatory effects in vivo, which effectively ameliorate the brain damage induced by focal cerebral ischemic strok.

Oxidative stress associated with impaired autonomic control and severity of lung function in chronic obstructive pulmonary disease patients.

Oxidative stress has been suggested to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study aimed to investigate a link between malondialdehyde (MDA) levels, pulmonary function, and cardiac autonomic control in patients with COPD. Plasma levels of MDA, heart rate variability, and pulmonary function were measured in 50 clinically stable COPD patients and 50 normal male controls. COPD patients exhibited lower means of the standard deviations of all normal to normal (NN) intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD), and high frequency (HF). Nevertheless, they presented greater low frequency (LF) and low frequency/high frequency ratio (LF/HF ratio) in supine and head-up tilt positions than controls (P<0.001). More-over, a negative correlation between MDA levels with SDNN (P<0.001) and a positive correlation with LF (P<0.01) and LF/HF ratio (P<0.05) were observed in both positions. In COPD patients, plasma MDA levels were 2.3 times greater than controls (4.33±2.03 µM vs. 1.89±0.39 µM, P<0.001), and they were inversely correlated with forced vital capacity, forced expiratory volume in 1 sec, midexpiratory flow, and peak expiratory flow (P<0.001). Our findings suggest a potential role for oxidative stress in impaired cardiac autonomic control and clinical relevance of plasma MDA levels as a predictor of severity of COPD in COPD patients.

Pinostrobin alleviates chronic restraint stress­induced cognitive impairment by modulating oxidative stress and the function of astrocytes in the hippocampus of rats.

Chronic stress has been recognized to induce the alterations of neuronal and glial cells in the hippocampus, and is thus implicated in cognitive dysfunction. There is increasing evidence to indicate that natural compounds capable of exerting neuroprotective and antioxidant activities, may function as potential therapeutic agents for cognitive impairment. The present study examined the neuroprotective effects of pinostrobin from Boesenbergia rotunda (L.) against chronic restraint stress (CRS)-induced cognitive impairment associated with the alterations of oxidative stress, neuronal density and glial fibrillary acidic protein (GFAP) of astrocytes in the hippocampus. For this purpose, male Wistar rats were administered once daily with pinostrobin (20 and 40 mg/kg, per os) prior to exposure to CRS (6 h/day) for 21 days. The cognitive behaviors, the concentration of malondialdehyde, and the activities of superoxide dismutase and catalase were determined. Histologically, the alterations in astrocytic GFAP and excitatory amino acid transporter 2 (EAAT2) in the hippocampus were examined. The results revealed that pinostrobin potentially attenuated cognitive impairment in the Y-maze and in novel object recognition tests, with a reduction in oxidative stress. Furthermore, pinostrobin effectively increased neuronal density, as well as the immunoreactivities of GFAP and EAAT2 in the hippocampus. Taken together, these findings indicate that treatment with pinostrobin alleviates chronic stress-induced cognitive impairment by exerting antioxidant effects, reducing neuronal cell damage, and improving the function of astrocytic GFAP and EAAT2. Thus, pinostrobin may have potential for use as a neuroprotective agent to protect against chronic stress-induced brain dysfunction and cognitive deficits.

Pinostrobin mitigates neurodegeneration through an up-regulation of antioxidants and GDNF in a rat model of Parkinson's disease.

Background: One of the most common neurodegenerative diseases is Parkinson's disease (PD); PD is characterized by a reduction of neurons containing dopamine in the substantia nigra (SN), which leads to a lack of dopamine (DA) in nigrostriatal pathways, resulting in motor function disorders. Oxidative stress is considered as one of the etiologies involved in dopaminergic neuronal loss. Thus, we aimed to investigate the neuroprotective effects of pinostrobin (PB), a bioflavonoid extracted from Boesenbergia rotunda with antioxidative activity in PD. Methods: Rats were treated with 40 mg/kg of PB for seven consecutive days before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. After completing the experiment, the brains including SN and striatum were used for histological studies and biochemical assays. Results: PB treatment demonstrated a reduction of free radicals in the SN as indicated by significantly decreased MDA levels, whereas the antioxidative enzymes (SOD and GSH) were significantly increased. Furthermore, PB treatment significantly increased glial cell line-derived neurotrophic factor (GDNF) immunolabelling which has neurotrophic and neuroprotective effects on the survival of dopaminergic neurons. Furthermore, PB treatment was shown to protect CA1 and CA3 neurons in the hippocampus and dopaminergic neurons in the SN. DA levels in the SN were increased after PB treatment, leading to the improvement of motor function of PD rats. Conclusions: These results imply that PB prevents MPTP-induced neurotoxicity via its antioxidant activities and increases GDNF levels, which may contribute to the therapeutic strategy for PD.

Lotus essential oil improves neurite elongation and facilitates functional recovery after peripheral nerve injury.

Injury to the peripheral nerve may lead to deficits in nerve function. An increase in the levels of free radicals plays a role in inhibition of nerve regeneration following damage. The aim of this study was to investigate the effects of lotus essential oil (LEO) on neurite outgrowth in vitro and nerve regeneration in vivo in a rat model of sciatic nerve crush injury. Gas chromatography-mass spectrometry analysis showed that the principal constituent of LEO was palmitic acid ethyl ester (25.12%). The radical scavenging activity of LEO was evaluated using the DPPH method, and was determined to be IC50=29.01±2.93 µg/ml. LEO-treated sensory neurons exhibited increased neurite outgrowth and upregulated levels of phospho-ERK. Sensory and motor functions were improved in rats treated with 50 and 100 mg/kg LEO, and this was accompanied by an increase in the number of neurons in the dorsal root ganglia, as well as an increase in the nerve axon diameters following nerve injury. Taken together, these results suggests that LEO may serve as a novel pharmacological option for the management of peripheral nerve injury.

The Neuroprotective Effect of Zingiber cassumunar Roxb. Extract on LPS-Induced Neuronal Cell Loss and Astroglial Activation within the Hippocampus.

The systemic administration of lipopolysaccharide (LPS) has been recognized to induce neuroinflammation which plays a significant role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In this study, we aimed to determine the protective effect of Zingiber cassumunar (Z. cassumunar) or Phlai (in Thai) against LPS-induced neuronal cell loss and the upregulation of glial fibrillary acidic protein (GFAP) of astrocytes in the hippocampus. Adult male Wistar rats were orally administered with Z. cassumunar extract at various doses (50, 100, and 200 mg/kg body weight) for 14 days before a single injection of LPS (250 µg/kg/i.p.). The results indicated that LPS-treated animals exhibited neuronal cell loss and the activation of astrocytes and also increased proinflammatory cytokine interleukin- (IL-) 1ß in the hippocampus. Pretreatment with Z. cassumunar markedly reduced neuronal cell loss in the hippocampus. In addition, Z. cassumunar extract at a dose of 200 mg/kg BW significantly suppressed the inflammatory response by reducing the expression of GFAP and IL-1ß in the hippocampus. Therefore, the results suggested that Z. cassumunar extract might be valuable as a neuroprotective agent in neuroinflammation-induced brain damage. However, further investigations are essential to validate the possible active ingredients and mechanisms of its neuroprotective effect.

Effect of Azadirachta indica flower extract on functional recovery of sciatic nerve crush injury in rat models of DM.

Chronic hyperglycemia causes nerves to be more susceptible to compression, which often occurs as a result of hyperglycemia-induced oxidative stress. Oxidative stress impairs nerve function and delays nerve recovery. Azadirachta indica, a herb from Thailand, possesses antioxidant and antidiabetic properties. The aim of the present study was therefore to investigate the effect of A. indica flower extract on the functional recovery of a sciatic nerve crush injury in rat models of diabetes mellitus (DM). Male Wistar rats were randomly assigned into seven groups including the control rats, rats with DM subjected to sham surgery and treated with vehicle, and rats with DM subjected to the crush surgery and treated with vehicle or A. indica flower extract at a dose of 250, 500 or 750 mg/kg animal body weight, or with vitamin C. DM was induced using a single intraperitoneal injection of streptozotocin (55 mg/kg animal body weight). Rats subjected to a sciatic nerve crush injury or sham surgery were orally treated with either vehicle, A. indica flower extract or vitamin C for 21 days. Functional recovery was assessed every 3 days using a walking track analysis, foot withdrawal reflex test and rotarod test. At the end of the study, the rats were sacrificed and their left sciatic nerves were harvested in order to determine malondialdehyde levels, superoxide dismutase activity and axon density. The treatment with A. indica flower extract significantly improved functional recovery, especially motor and sensory functions. The extract significantly decreased malondialdehyde levels, and increased superoxide dismutase activity and axon density. The results of the current study indicate that the mechanism underlying the enhanced functional recovery of the sciatic nerve following treatment with A. indica flower extract may be associated with an antioxidative effect. However, further studies are required to confirm the current results.

Quantitative assessment of microglial morphology and density reveals remarkable consistency in the distribution and morphology of cells within the healthy prefrontal cortex of the rat.

BACKGROUND: Microglial morphology within the healthy brain has been the subject of a number of observational studies. These have suggested that microglia may consist of separate classes, which possess substantially different morphological features. Critically, there have been no systematic quantitative studies of microglial morphology within the healthy brain. METHODS: We examined microglial cells within the adult rat prefrontal cortex. At high magnification, digital reconstructions of cells labelled with the microglial-specific marker ionized calcium-binding adapter molecule-1 (Iba-1) were made in each of the cortical layers. These reconstructions were subsequently analyzed to determine the convex hull area of the cells, their somal perimeter, the length of processes, the number of processes, the extent of process branching and the volume of processes. We additionally examined whether cells' morphological features were associated with cell size or numerical density. RESULTS: Our analysis indicated that while there was substantial variability in the size of cells within the prefrontal cortex, cellular morphology was extremely consistent within each of the cortical layers. CONCLUSIONS: Our results provide quantitative confirmation that microglia are largely homogenous in the uninjured rodent prefrontal cortex.

Chronic stress induces prolonged suppression of the P2X7 receptor within multiple regions of the hippocampus: a cumulative threshold spectra analysis.

A number of studies have identified that mutations in the P2X7 receptor occur with a significantly higher incidence in individuals with major depression. Consistent with these findings, a number of preclinical studies have identified that mice in which the P2X7 receptor has been deleted exhibit a higher level of resilience-like behaviour to acutely aversive situations. At present, however, no studies have examined changes in P2X7 receptor expression in otherwise healthy animals exposed to persistently stressful situations. This is significant as several lines of evidence have demonstrated that it is exposure to persistently aversive, rather than acutely aversive, situations that is associated with the emergence of mood disturbance. Accordingly, the objective of the current study was to examine whether chronic exposure to restraint stress was associated with alterations in the expression of P2X7 within the hippocampal formation. The study involved three principal groups: acute stress (1 session), chronic stress (21 sessions, 1 per day) and a chronic stress with recovery group (21 sessions, 1 per day followed by 7days of no stress) and appropriate control groups. The results of the analysis indicate that all forms of stress, regardless of the duration, provoked a reduction in P2X7 receptor expression. Comparative analysis on normalised data indicated that the magnitude of the P2X7 reduction was significantly greater in the chronic stress relative to the acute stress group. We additionally found that there was a gradual rebound in P2X7 expression, in two of nine regions examined, in animals that were allowed to recover for 7days following the final stress session. Collectively, these findings provide the first evidence that exposure to chronic restraint stress produces a pronounced and relatively persistent suppression of the P2X7 receptor within the hippocampus.

Dynamic structural remodelling of microglia in health and disease: a review of the models, the signals and the mechanisms.

Microglia are unique cells within the central nervous system because of their biophysical independence. As a result of this unusual property the cells must undergo significant structural remodelling in order to engage and connect with other elements within the central nervous system. Efficient remodelling is required for all activities that microglia are involved in ranging from monitoring synaptic information flow through to phagocytosis of tissue debris. Despite the fact that morphological remodelling is a pre-requisite to all microglial activities, relatively little research has been undertaken on the topic. This review examines what is known about how microglia transform themselves during development, under physiological conditions in response to changes in neuronal activity, and under pathological circumstances. Specific attention is given to exploring a variety of models that have been proposed to account for microglial transformation as well as the signals that are known to trigger these transformations.