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The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo (Citrus grandisL. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%),γ-glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli’s risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.

Nitrogen-doped soluble graphene nanosheets (N-wsGNSs) were synthesized using lentil as a natural source of carbon and nitrogen via a simple pyrolysis and oxidation approach. The as-synthesized N-wsGNSs showed remarkable fluorescence emission over the entire visible range, attributed to the high degree of surface passivation due to the introduction of oxygenated functional groups and heteroatom doping. The significant prospect of this approach is to use N-wsGNSs as multifunctional materials for photocatalytic and sensing applications. The as-synthesized N-wsGNSs exhibited high photocatalytic efficiency and could cause almost complete (∼99%) photodegradation of methylene blue (MB) within 75 min under visible light irradiation. Furthermore, a fluorescence “turn-on/-off” probe was designed for the selective sensing of ascorbic acid (AA) with a detection limit of 4 μM. The fluorescence intensity of the N-wsGNSs was selectively quenched by Fe(III) and was recovered by AA. Fe(III) served as both the fluorescence quencher for the N-wsGNSs and the selective recognizer for AA. The results highlight the broad implications of N-wsGNSs for various advanced environmental and biomedical applications.

Plasmalogens are membrane glycerophospholipids with diverse biological functions. Reduced plasmalogen levels have been observed in metabolic diseases; hence, increasing their levels might be beneficial in ameliorating these conditions. Shark liver oil (SLO) is a rich source of alkylglycerols that can be metabolized into plasmalogens. This study was designed to evaluate the impact of SLO supplementation on endogenous plasmalogen levels in individuals with features of metabolic disease. In this randomized, double-blind, placebo-controlled cross-over study, the participants (10 overweight or obese males) received 4-g Alkyrol® (purified SLO) or placebo (methylcellulose) per day for 3 weeks followed by a 3-week washout phase and were then crossed over to 3 weeks of the alternate placebo/Alkyrol® treatment. SLO supplementation led to significant changes in plasma and circulatory white blood cell lipidomes, notably increased levels of plasmalogens and other ether lipids. In addition, SLO supplementation significantly decreased the plasma levels of total free cholesterol, triglycerides, and C-reactive protein. These findings suggest that SLO supplementation can enrich plasma and cellular plasmalogens and this enrichment may provide protection against obesity-related dyslipidemia and inflammation.

Context: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity. Objective: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats. Materials and methods: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods. Results: Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 μM Fe2+) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue. Discussion and conclusion: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.

Statins are the first-line lipid-lowering therapy for reducing cardiovascular disease (CVD) risk. A plasma lipid ratio of two phospholipids, PI(36:2) and PC(18:0_20:4), was previously identified to explain 58% of the relative CVD risk reduction associated with pravastatin, independent of a change in low-density lipoprotein-cholesterol. This ratio may be a potential biomarker for the treatment effect of statins, however, the underlying mechanisms linking this ratio to CVD risk remain unclear. In this study, we investigated the effect of altered cholesterol conditions on the lipidome of cultured human liver cells (Hep3B). Hep3B cells were treated with simvastatin (5 μM), cyclodextrin (20 mg/mL) or cholesterol-loaded cyclodextrin (20 mg/mL) for 48 hours and their lipidomes were examined. Induction of a low-cholesterol environment via simvastatin or cyclodextrin was associated with elevated levels of lipids containing arachidonic acid and decreases in phosphatidylinositol species and the PI(36:2)/PC(18:0_20:4) ratio. Conversely, increasing cholesterol levels via cholesterol-loaded cyclodextrin resulted in reciprocal regulation of these lipid parameters. Expression of genes involved in cholesterol and fatty acid synthesis supported the lipidomics data. These findings demonstrate that the PI(36:2)/PC(18:0_20:4) ratio responds to changes in intracellular cholesterol abundance per se, likely through a flux of the n-6 fatty acid pathway and altered phosphatidylinositol synthesis. These findings support this ratio as a potential marker for CVD risk reduction and may be useful in monitoring treatment response.

Plasmalogens or alkenylphospholipids are a sub-class of glycerophospholipids with numerous biological functions and are thought to have protective effects against metabolic disease. Dietary supplementation with alkylglycerols (AKGs) has been shown to increase endogenous plasmalogen levels, however effective modulation of different molecular plasmalogen species has not yet been demonstrated. In this study, the effects of an orally-administered AKG mix (a mixture of chimyl, batyl and selachyl alcohol at a 1:1:1 ratio) on plasma and tissue lipids, including plasmalogens, was evaluated. Mice on a Western-type diet were treated with either an AKG mix or vehicle (lecithin) for 1, 2, 4, 8 and 12 weeks. Treatment with the AKG mix significantly increased the total plasmalogen content of plasma, liver and adipose tissue as a result of elevations in multiple plasmalogen species with different alkenyl chains. Alkylphospholipids, the endogenous precursors of plasmalogens, showed a rapid and significant increase in plasma, adipose tissue, liver and skeletal muscle. A significant accumulation of alkyl-diacylglycerol and lyso-ether phospholipids was also observed in plasma and tissues. Additionally, the dynamics of plasmalogen-level changes following AKG mix supplementation differed between tissues. These findings indicate that oral supplementation with an AKG mix is capable of upregulating and maintaining stable expression of multiple molecular plasmalogen species in circulation and tissues.

Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, biologically stable in the environment and bio-accumulate in the tissues of aquatic animals as well as wildlife and humans. The toxicity of perfluorooctane sulfonate were tested at 1, 3 and 5mg/L concentrations on the juvenile tilapia, Oreochromis niloticus after 7, 15, 30, 45 and 60 days of exposure. The hematological parameters revealed that with the increase in concentrations and exposure time the total count of the RBC, WBC and hemoglobin content were significantly (p

AlthoughCitrus macroptera(Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract ofCitrus macroptera(EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase,γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested thatC. macropterafruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

The current study aimed to investigate the ameliorative effects of two types of mushrooms, Ganoderma lucidum (GL) and Auricularia polytricha (AP), against carbofuran- (CF) induced toxicity in rats. Male Wistar rats (n=42) were divided into six equal groups. The rats in the negative control group received oral administration of CF at 1 mg/kg with the normal diet for 28 days. The treatment groups received oral administration of ethanolic extract of GL or AP at 100 mg/kg followed by coadministration of CF at 1 mg/kg with the normal diet for the same experimental period, respectively. In the CF alone treated group, there were significant decreases in the erythrocytic and thrombocytic indices but increases in the concentrations of the total leukocytes, including the agranulocytes. A significant increase in all of the liver function biomarkers except albumin, in lipid profiles except high-density lipoprotein, and in the kidney function markers occurred in the negative control group compared to the rats of the normal control and positive control groups. The coadministration of mushroom extracts significantly ameliorated the toxic effects of the CF. The GL mushroom extract was more efficacious than that of the AP mushroom, possibly due to the presence of high levels of phenolic compounds and other antioxidants in the GL mushroom.

Sundarban honey is one of the most renowned and popular types of honey from Bangladesh. This study was undertaken to investigate the antioxidant and DNA damage inhibition potentials of Sundarban honey. The estimated polyphenol, flavonoid, ascorbic acid, reducing sugar and protein contents in the investigated honey were found to be 593.96 ± 13.71 mg GAEs/kg, 50.00 ± 0.00 mg CEs/kg, 117.04 ± 1.05 mg/kg, 60.58 ± 3.23 g/100 g and 6.43 ± 0.12 mg/g, respectively. Some phenolics including gallic acid, pyrogallol, vanillic acid and trans-Cinnamic acid, as well as three flavonoids, naringin, rutin and quercetin, were identified and quantified by high performance liquid chromatography. Sundarban honey was found to possess protective activity against hydrogen peroxide and UV irradiation-induced damage to pBR322. The DNA protection activity of honey corresponded to its antioxidant potential and exhibited dose-dependent effects. Practical Application: Sundarban honey, a wild multifloral honey produced by Apis dorsata bees is one of the most renowned types of honey from Bangladesh and confers protection against oxidative stress-induced liver and kidney damage. This honey can a be very good source of natural antioxidant which particularly contains some phenolic compounds including gallic, vanillic and trans-Cinnamic acids as well as three flavonoids (naringin, rutin and quercetin). Sundarban honey can protect against oxidative DNA damage and consecutive illness.

Honey is a popular natural food product with a very complex composition mainly consisting of both organic and inorganic constituents. The composition of honey is strongly influenced by both natural and anthropogenic factors, which vary based on its botanical and geographical origins. Although minerals and heavy metals are minor constituents of honey, they play vital role in determining its quality. There are several different analytical methods used to determine the chemical elements in honey. These methods are typically based on spectroscopy or spectrometry techniques (including atomic absorption spectrometry, atomic emission spectrometry, inductively coupled plasma mass spectrometry, and inductively coupled plasma optical emission spectrometry). This review compiles available scientific information on minerals and heavy metals in honey reported from all over the world. To date, 54 chemical elements in various types of honey have been identified and can be divided into 3 groups: major or macroelements (Na, K, Ca, Mg, P, S, Cl), minor or trace elements (Al, Cu, Pb, Zn, Mn, Cd, Tl, Co, Ni, Rb, Ba, Be, Bi, U, V, Fe, Pt, Pd, Te, Hf, Mo, Sn, Sb, La, I, Sm, Tb, Dy, Sd, Th, Pr, Nd, Tm, Yb, Lu, Gd, Ho, Er, Ce, Cr, As, B, Br, Cd, Hg, Se, Sr), and heavy metals (trace elements that have a specific gravity at least 5 times higher than that of water and inorganic sources). Chemical elements in honey samples throughout the world vary in terms of concentrations and are also influenced by environmental pollution.

In this study, the antioxidant potential of Citrus macroptera fruit was compared between its pulp (CMPU) and peel (CMPE). The biochemical effects of an ethanol extract of CMPU were investigated on major organs, including the liver, kidney and pancreas. Male wistar rats (n = 24) were randomly divided into four groups, including Group I (control), Group II (250 mg kg), Group III (500 mg kg) and Group IV (1000 mg kg) and they were administered the extract for 28 days. The CMPE contained higher amounts of total polyphenols (620.91±7.75 mg), flavonoids (508.33±5.49 mg), tannins (585.99±4.46 mg) and protein (4.00±0.14 g) compared to the pulp (291.06±10.14, 145.02±0.36, 526.08±3.32 mg/100 g and 2.89±0.32 g/100 g, respectively). Similarly, CMPE also exhibited higher 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity and Ferric Reducing Antioxidant Power (FRAP) values than CMPU. However, the ascorbic acid content was higher in CMPU (120.83±0.0019 mg/100 g) than CMPE. In vivo studies confirmed that CMPU possessed a significant lipid lowering activity that occurred in a dose dependent manner and that it caused beneficial changes in several other biochemical parameters. Additionally, a significant diminution of lipid peroxidation in liver and kidney tissues was observed. It was concluded that C. macroptera possesses high antioxidant potential and is relatively safe. Its protective effects against various chronic diseases that are associated with oxidative stress should be further investigated.

The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases (MMPs) has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the interaction of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neurological function and brain edema were significantly alleviated, cerebral infarct volume was significantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were significantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was -37.848672 kJ/mol and -36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These findings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

Increases in the incidence of cardiovascular disease (CVD) have aroused strong interest in identifying antioxidants from natural sources for use in preventive medicine. Citrus macroptera (C. macroptera), commonly known as "Satkara", is an important herbal and medicinal plant reputed for its antioxidant, nutritious and therapeutic uses. The aim of the present study was to investigate the cardio-protective effects of ethanol extracts of C. macroptera peel and pulp against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats (n=36) were pre-treated with peel and pulp extracts (500mg/kg) for 45days. They received a challenge with ISO (85mg/kg) on the 44th and 45th days. Our findings indicated that subcutaneous injection of ISO induced severe myocardial injuries associated with oxidative stress, as confirmed by elevated lipid peroxidation (LPO) and decreased cellular reduced glutathione (GSH) and anti-peroxidative enzymes, including glutathione peroxidase, glutathione reductase and glutathione-S-transferase, compared with levels observed in control animals. Pre-treatment with C. macroptera peel and pulp extracts prior to ISO administration however, significantly improved many of the investigated biochemical parameters, i.e., cardiac troponin I, cardiac marker enzymes, lipid profile and oxidative stress markers. The fruit peel extract showed stronger cardio-protective effects than the pulp extract. The biochemical findings were further confirmed by histopathological examinations. Overall, the increased endogenous antioxidant enzyme activity against heightened oxidative stress in the myocardium is strongly suggestive of the cardio-protective potential of C. macroptera.

The study reports on major and trace elements as well as antioxidant properties of honey samples from Bangladesh. Four major cationic elements, seven trace elements, and three heavy metals were determined in the 12 honey samples using atomic absorption spectrophotometer. Nutritional values in these honey samples were further investigated according to their antioxidant properties. The content of major elements was in the range of 62.75–616.58, 579.48–2219.43, 69.42–632.25, and 0.13–1.20 mg/kg for sodium, potassium, magnesium, and calcium, respectively. The trace elements varied in the range of 0.41–28, 0.12–3.54, 1.54–2.85, 0.29–0.59, 0.02–0.35, and 0.01–0.06 mg/kg for iron, zinc, copper, nickel, cobalt, and cadmium, respectively. Among the heavy metals, only lead (0.17–2.19 mg/kg) was detected. The results of antioxidant analysis based on phenolics, flavonoids, ascorbic acid, reducing sugar, and proteins (as nonphenolic antioxidants) revealed that multifloral raw honey samples contain significantly higher levels of reducing agents than monofloral and commercial brand honeys. The study provides a useful insight on the minerals, heavy metals, and antioxidant properties of honey samples commonly consumed in Bangladesh and found to be rich source of antioxidants and minerals. Some samples might pose some risk to the health due to lead contamination.

This study was undertaken to investigate the toxicological profile of a methanolic extract ofGarcinia pedunculatafruit in rats by conducting hematological, biochemical, and histopathological examinations. Long Evans rats were divided into four groups, each with 6 animals, and were treated with three oral doses (250, 500, and 1000 mg/kg) once daily for 21 days. The extract did not cause significant changes in body and relative organ weight, percent water content, or hematological parameters at any administered doses. However, a significant dose-dependent positive effect in serum lipid profile and all atherogenic indices including the cardiac risk ratio, Castelli’s risk index-2, and the atherogenic coefficient were observed. Significant increases in the levels of iron and decreases in serum alkaline phosphatase, alanine transaminase, and lactate dehydrogenase activities and the levels of serum glucose were noted when the extract was administered at the highest dose (1000 mg/kg). Histopathological examination of the target tissues further confirmed that the extract was safe and had no observed toxicological features. Our study indicates thatG. pedunculatafruit is nontoxic, has the potential to be effective against atherosclerosis, and may be used as a hepatoprotectant. The fruit extract is also beneficial to those with iron deficiency and hyperglycemia.

The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract ofGarcinia pedunculata(GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions.

Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P < 0.01) reduction in cerebral infarct volume and potentiation of the intrinsic antioxidant status. High-performance liquid chromatography of brain cortex and striatum revealed changes in extracellular concentrations of neurotransmitters which were found to be 0.519 ± 0.44 pmole/mg (GABA); 1.18 ± 0.28 pmole/mg (glutamate), and 0.63 ± 0.21 pmole/mg (serotonin), respectively. Hydroxyl radical (·OH) adduct of salicylate in the frontal cortex and striatum in control, untreated, and treated groups was found to be 0.261 ± 0.06, 0.68 ± 0.52, and 0.401 ± 0.68 pmole/mg, respectively. After stroke, the extracellular level of glutamate in rat brain increases continuously as compared to that of control group. However, piroxicam administration in stroke rat significantly reduced (P < 0.05) elevated extracellular cerebral glutamate. This indicates that piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism.

An intervention to reduce brain injury before, during, or after an ischemic injury irrespective of the cause remains an exciting prospect. Increasing evidences suggest that the excessive activation of calcium-dependent neutral proteases, calpains, could play a key role in the pathology of cerebral ischemia. Targeting calcium-activated proteolysis could, therefore, be an alternative strategy for protecting neurons against post-ischemic injury. In addition, blood brain barrier (BBB) breakdown after stroke is linked to the up-regulation of metalloproteinases (MMPs) and inflammation. MMPs are zinc-dependent endopeptidases which are capable of degrading many types of extracellular matrix proteins and are also involved in the process of tissue remodeling in various pathologic conditions. Previous studies suggest that MMPs, in particular MMP-2 and MMP-9, are deleterious in the brain after stroke. In acute stage after ischemic stroke, the effects of MMP activity is correlated to the degradation of neurovascular matrix and opening of the BBB which promotes vasogenic edema and results in neurological deficits. Hence, calpain and MMPs are considered to be a potential drug target to develop novel therapeutics against cerebral ischemia. To explore such, we have tried to study the interaction of Piroxicam with calpain and MMPs by exploring molecular docking studies. The in silico studies revealed that Piroxicam occupied the active site of μ-calpain, MMP-2, and MMP-9. The binding energy of the complexes was −5.27, −9.75, and −6.47 kcal/mol for μ-calpain, MMP-2, and MMP-9, respectively. On the basis of these in silico studies collectively, we hypothesize for the first time that Piroxicam might have a strong potential to inhibit μ-calpain, MMP-2, and MMP-9 concomitantly which can be explored as a potent therapeutic target for treating cerebral ischemia in future.

The effect of chemical hypoxia, i.e., KCN-induced hypoxia on protein kinase C (PKC) translocation and cell injury was well reported. It has been well documented that activation of PKC is regulated by calcium and unsaturated free fatty acids which are actively involved in the phosphorylation of various cellular proteins, thereby initiating a variety of physiologic as well as cellular processes. The involvement of PKC has been reported in the regulation of neuronal excitability, neurotransmitter release, cellular proliferation, and gene expression. PKC can affect Ca2+ homeostasis by increasing the activity of Na+/Ca2+ exchanger and Ca2+-ATPase. These effects are most probably neuroprotective since they promote Ca2+ sequestration, thereby decreasing free cytosolic Ca2+ level. On the other side, PKC-mediated phosphorylation of NMDA receptor increases the probability of the channel opening and reduces the Mg2+ block increasing the channel’s conductivity. It has been proposed that sustained elevation of free cytosolic Ca2+ levels could result in prolonged activation of PKC which, in turn, may decrease neuronal energy due to excessive utilization of ATP by the activated enzyme. However, all known protein kinase inhibitors target the ATP-binding site. Owing to this reason, search for strong natural inhibitors that selectively target the protein kinase domains continues to be a daunting challenge. Past studies reiterated that quercetin being a dietary flavonoid of plant origin which has antioxidant, anti-inflammatory properties, and capability to cross the blood brain barrier. The binding energy of quercetin with PKCθ was −9.28 kcal/mol. Thus, we hypothesized that Quercetin, a plant-originated natural polyphenolic compound that can act as a neuroprotective agent in chemical hypoxia-induced injury due to its inhibitory effects on PKC. The aim of our proposed hypothesis is to find out a successful modality of effective natural and dietary compound for the treatment of chemical hypoxia available till date. Hence, we have tried to put forward a hypothesis on the basis of our in silico studies which involves the clue for regulation of PKC by quercetin.

Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP) has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO-) induced myocardial infarction in rats. Male Wistar rats (n=32) were pretreated orally with an ethanol extract of MP (100 mg/kg/day) for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

We investigated the protective role ofWithania somniferaleaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats.

Owing to the intricate and multifaceted pathology of cerebral stroke, multiple drug therapy had long been suggested for effective stroke treatment. Therefore, the development of a potential new combination of drug is necessitated which can bring about desirable improved neuroprotection targeting different pathways against ischemic stroke. In this context, we hypothesize the combination effect of Piroxicam, a Non steroidal anti inflammatory drug with Ifenprodil, a NR2b selective NMDAR antagonist in animal model of cerebral ischemia. A few past studies have enumerated the neuroprotective roles of Piroxicam and Ifenprodil administered in singlet against cerebral ischemia in animal model, hence we hypothesized that by using Piroxicam and Ifenprodil in combination would provide additive neuroprotection than either of the agents used alone. In this article, we discuss our hypothesis regarding the possibility of Piroxicam and Ifenprodil as a potent combination which may have a positive therapeutic role in treatment of cerebral ischemia through its anti-inflammatory, anti-apoptotic and anti-oxidative characteristics of Piroxicam with Ifenprodil which has been proved to have neuroprotective, anticonvulsant and antinociceptive effects and has potentials for the treatment of several neuropsychiatric disorders, such as Parkinson's disease alcoholism and drug addiction.

Cerebral ischemia is associated with altered neuronal mechanics leading to dynamic reshaping of neuronal structures, giving rise to a cascade of biological pathways leading to many deleterious consequences and cognitive deficits. Memory and learning specifically are mediated by neurotransmitter release from vesicles clustered at the synapse. Mechanical tension is an important factor governing the amount of vesicular neurotransmitter release in response to an action potential. Neuroinflammation in cerebral ischemia leads to altered mechanical/physical forces on neurons which gives rise to abnormal mechanical tension along the neuron resulting in neurotransmitter imbalance leading to cognitive dysfunction. We consider the possibility that modulation of mechanical forces on neurons may be a therapeutic strategy to help prevent cognitive deficit in cerebral ischemia. Here we show how NSAIDs may act as candidate pharmacological molecules which have the ability to inhibit neuroinflammation and which can alter neuronal mechanics by their COX-2 inhibiting property.

A neuroprotective strategy through a combination therapy is always being superior to any other singular therapeutic interventions, as these acts through a multifauceted approach within the brain during cerebral ischemia. Therefore, the development of a potential new combination of drug is necessitated which can bring about desirable improved neuroprotection targeting different pathways against ischemic stroke. Numerous past studies have enumerated the neuroprotective roles of minocycline and magnesium administered in single against cerebral ischemia in animal model hence we hypothesized that by using magnesium with minocycline in combination would provide additive neuroprotection than either of the agents used alone. In this article, we discuss our hypothesis regarding the possibility of minocycline and magnesium as a potent combination which may have a positive therapeutic role in treatment of cerebral ischemia through its anti-inflammatory, anti-apoptotic and anti-oxidative characteristics with magnesium contributing as a regulator of increased calcium influx.

Erratum to ‘‘An in silico strategy to explore neuroprotection by quercetin in cerebral ischemia: A novel hypothesis based on inhibition of matrix metalloproteinase (MMPs) and acid sensing ion channel 1a (ASIC1a)’’ [Med. Hypotheses 79 (1) (2012) 76–81] Anand Kumar Pandey , Sharad Verma , Pallab Bhattacharya , Sudip Paul , Abha Mishra , Ranjana Patnaik a,⇑ a School of Biomedical Engineering, Institute of Technology, Banaras Hindu University, Varanasi 221005, India b School of Biochemical Engineering, Institute of Technology, Banaras Hindu University, Varanasi 221005, India