Behavioural impacts of following administration of Ficus carica leaves extract in animal model of acute and chronic unpredictable mild stressed exposed rats.

Stress is described as a noxious stimulus that affects the health of an individual and alters body homeostasis resulting in changes the individual behavioural and metabolic condition. Synthesis of drug from plants has main interest due the significant medicinal values. The recent investigation was designed to examine the pharmacological impacts of Ficus carica leaves extract on stress. In this experiment, the rodents were randomly distributed as (n=6) control rats were kept at standard condition, second group of rats were exposed with different stressors and Third group of rodents was exposed to stress and treated with extract of ficus carica leaves at the dose of 100 mg/kg. Acute behavioural alteration was observed after 7 days and prolonged impact was monitored after the 28 days. The current finding showed that administration of Ficus carica leaves extract produced anxiolytic behaviours and decreased depression like symptoms in CUMS treated rats. It also increased stimulatory, ambulatory, locomotor activity and enhanced spatial working memory and recognition memory in CUMS exposed rats. So, it can be concluded from recent study that leaves of Ficus carica can be utilized as secure drug for curing physiological stress with less side effect profile.

Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials.

Alzheimer's disease (AD) is the common type of dementia and is currently incurable. Existing FDA-approved AD drugs may not be effective for everyone, they cannot cure the disease nor stop its progression and their effects diminish over time. Therefore, the present review aimed to explore the role of natural alternatives in the treatment of AD. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.

Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis.

BACKGROUND: The current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. METHODS: The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC), fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. RESULTS: The binding affinity estimations identified the superior interacting capacity of apigenin over safranal for 5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability and absorbance. In the rodent model, there was a significant increase in the overall mobility time in the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety symptoms after treatment. CONCLUSIONS: Our analyses suggest apigenin and safranal as prospective medication options to treat depression and anxiety.

A new progestin from fungal transformation of norethisterone and its comparative antimicrobial studies.

Fungal transformation of a norethisterone (17α-ethynylestra-4-en-17ß-ol-3-one) (1) by using Macrophomina phaseolina and Paecilomyces variotii was studied. A new metabolite, 17α-hydroxymethyl-androst-4-en-11ß-ol-3-one-17ß-acetate (2) with novel changes and a known metabolite, 17α-ethynylestradiol (3) were obtained from 1 by using M. phaseolina and P. variotii, respectively. Based on various spectroscopic techniques, the structures of both metabolites were characterized. The antimicrobial activities of 1-3 were also evaluated. Compound 1 was found to be moderately active against Salmonella paratyphi while 1-3 were almost inactive against other microorganisms.

Combating effects of Azadirachta indica leaves extract on biochemical and neuropsychological decline observed in diabetes.

Diabetes is a group of metabolic disorder effecting health of wide number of population and cause neuropsychological decline. In the present study, effect of AI leaves extract on neuropsychological behaviors was observed in diabetic rat's model. Rats were divided into 4 groups as control (saline treated healthy rats), positive control (pioglitazone treated diabetic rats), diabetic control (untreated diabetic rats) and AI leaves extract treated diabetic rats. Diabetes was induced by giving 35% fructose for 6 weeks and a single dose of Streptozotocin (40 mg/kg). After 3 weeks of treatment behavioral and biochemical analysis were done. Behavioral results revealed that induction of type 2 diabetes produced anxiety, depression, decreased motor activity and impaired recognition memory in rats. Treatment with AI leaves extract in diabetic rats significantly decreased anxiety, depression, increased motor activity, enhanced recognition memory. Biochemical investigation revealed that AI leaves extract treat diabetes via improving the levels of fasting insulin and HbA1c and a significant decrease in CK and SGPT levels were observed in AI leaves treated diabetic rats. So, AI besides treating diabetes, helps in lowering the risk of co-occurring diabetic diseases and found effective in lowering neuropsychological decline observed in type 2 diabetes.

Exposure to noise augments behavioral deficits in mice: Protective effect of banana peel extract.

The study is aimed to evaluate the protective impact of banana peel extract (BPE) following noise induce behavioral deficits in male mice. Animals were separated into two groups (control and test, 12 in each). Control mice were given drinking water, at the same time test group was given BPE (400 mg/kg; oral administration). Animals have received their respective treatment for 14 days. Mice were subdivided (n=6) into unstressed and stressed groups on day 15. Noise stress was given to the respective group for 4-h. Behavioral activities were monitored 24-h after the 4-h noise stress. Forced-swim-test, Elevated-plus-maze and light-dark-activity-box tests were performed for depression/anxiety-like behaviors respectively. Morris-water-maze assessment was used for memory. After behavioral tests animals were sacrificed and brain was detached for biochemical estimations and histopathological studies. In the present study, BPE produced anxiolytic and antidepressant-like effects and enhanced memory. Activity of antioxidant enzymes increased while levels of AChE and MDA decreased in BPE treated animals. Histopathological alterations induced by noise stress were also normalized by BPE. It is concluded that supplementation/administration of banana peel has preventive effects against anxiety, depression and memory impairment via its strong antioxidant potential following NS.

Tryptophan lessens reserpine induced anxiety, depression and memory impairment by modulating oxidative stress and serotonergic activity.

Reserpine (Res)-induced depletion of monoamines and altered neurotransmission and produces oxidative stress. Tryptophan (TRP) regulated the serotonin neurotransmission. Because systemically injected Res induced behavioral deficits and oxidative stress, while, dietary components prevented these adverse effects, we used TRP a pharmacological tool to prevent Res- induced changes in behavior, memory impairments, oxidative stress and regulation of serotonin neurotransmission in rats. Anxiolytic, antidepressant, cognitive functions, lipid peroxidation, antioxidant enzymes serotonin metabolism were studied in Res and vehicle treated animals following administration of 50 and 100 mg/ml/kg of tryptophan. Following administration of TRP [50 and 100mg/ml/kg], Res induced anxiety-and/or depression like behaviors normalized. Res-induced impaired cognitive function and increased acetylcholinesterase activity also improved following administration of TRP at both doses. Res induced increased brains' malondialdehyde (MDA) and decreased antioxidant enzymes activity also normalized by TRP. Res-induced decreased 5-HT metabolism also regulated by administration of TRP at both doses. In conclusion it can be recommended that administration/supplementation of TRP in daily life can aid in battling the anxiety, depression, modulating serotonergic activity and oxidative stress. Study also exhibits the anti-acetylcholinesterase role of TRP which may be possible reason for improved cognition following stress situation.

Biosynthesis of silver nanoparticles from Mukia maderaspatana (L) and their biological activities.

Nanotechnology is a field of science that consists of atoms, molecules and supramolecular molecules that create nanoparticles ranging in size from 1-100nm. Silver nanoparticles are widely used that are considered as effective antimicrobial agents. In this paper, the antioxidant activity of biosynthesized SNPs were analyzed by the DPPPH activity, hydrogen peroxide activity, hydroxyl RSA, TAC, TFC; their results confirmed that the phenolic compounds of this plant peels extracts enhanced the antioxidant and antiglycation activity with respect to silver nanoparticles. Biosynthesized nanoparticles of this plant extracts also showed strong zone of inhibition against the different Xanthomas, Pseudomonas and E. coli. This study concluded that biosynthesized nanoparticles of Mukia maderaspatna (M.M) plant peels extracts have the great biological activities i.e. antiglycation, antioxidant and antibacterial. More research is needed to know the exact dose rate and to compare the different dose combination of the plant with the strong antibiotic agents against these bacteria.

Supplementation of Taurine Insulates Against Oxidative Stress, Confers Neuroprotection and Attenuates Memory Impairment in Noise Stress Exposed Male Wistar Rats.

Noise has always been an important environmental factor that induces health problems in the general population. Due to ever increasing noise pollution, humans are facing multiple auditory and non-auditory problems including neuropsychiatric disorders. In modern day life it is impossible to avoid noise due to the rapid industrialization of society. Continuous exposure to noise stress creates a disturbance in brain function which may lead to memory disorder. Therefore, it is necessary to find preventive measures to reduce the deleterious effects of noise exposure. Supplementation of taurine, a semi essential amino acid, is reported to alleviate psychiatric disorders. In this study noise-exposed (100 db; 3 h daily for 15 days) rats were supplemented with taurine at a dose of 100 mg/kg for 15 days. Spatial and recognition memory was assessed using the Morris water maze and novel object recognition task, respectively. Results of this study showed a reversal of noise-induced memory impairment in rats. The derangements of catecholaminergic and serotonergic levels in the hippocampus and altered brain antioxidant enzyme activity due to noise exposure were also restored by taurine administration. This study highlights the importance of taurine supplementation to mitigate noise-induced impaired memory via normalizing the neurochemical functions and reducing oxidative stress in rat brain.

Diet supplements of banana fruit pulp mitigates repeated noise stress induced behavioral deficits and oxidative stress.

The current study was designed to determine the outcome of banana fruit pulp (BFP) on repeated noise stress exposure (NSE)-induced behavioral deficits and oxidative stress in male mice. BFP (600mg/kg b.w) was administered orally once daily for 2 weeks prior exposure to noise stress. Mice were exposed to NS for 4 h after administration of BFP for 2 weeks. Control mice were administered drinking water and similar treatment as given to test animals. At the end of the treatment behavioral changes were monitored. Animals were sacrificed following behavioral assessment and the brain and plasma samples were collected for biochemical analysis. Repeated NS-induced behavioral deficits (anxiety and depression), impaired learning and memory and produced oxidative stress. Administration of BFP inhibited NS-induced behavioral deficits (anxiolytic and antidepressant effects) and improved cognitive abilities. Brain lipid per oxidation was also decreased with concomitant increase of antioxidant enzyme activities. Repeated noise stress increased plasma corticosterone levels. A significant decrease of plasma corticosterone was observed on unstressed BFP treated animals while this decrease was comparable in stressed + BFP animals. Decreased levels of acetylcholinesterase in BPF+NS treated animals indicated increased cholinergic function which improves learning and memory. Repeated oral administration of BFP induced cognitive improving ability, anti-stress effect and potentiated antioxidant defence mechanism in both control and NS mice. Thus, it is suggested that dietary supplementation of BFP has a curative effect against NS-induced psychiatric and cognitive related disorders which merits deliberation and additional appraisal.

Effect of lithium chloride on d-galactose induced organs injury: Possible antioxidative role.

The aging process is concerned with oxidative stress and causing malfunction of various organs such as the liver, kidney and heart. Lithium (Li) salts have shown anti-manic, anti-suicidal, and antioxidant properties. The current study is aimed to evaluate the possible inhibitory effects of various doses (10, 20 & 40mg/ml/kg) of Lithium chloride (LiCl) on D-galactose (D-gal)-produced aging model and explore the underlying mechanism. In the study 40 male rats were randomly alienated into 8 groups i.e. saline, LiCl (10, 20 & 40mg/ml/kg), D-gal and D-gal+LiCl (10, 20 & 40 mg/ml/kg). D-gal was given at a dosage of 300mg/ml/kg$ and animals received their respective treatment for 6 weeks [intraperitoneally (I.P), once daily]. After 2 weeks animals were decapitated and organs (liver, kidney, and heart) were removed for antioxidant assays. Blood was also collected for biochemical parameters. LiCl substantially decreased oxidative strain marker and increased enzymatic antioxidants in the liver, kidney, and heart of D-gal treated rats. LiCl also decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), creatine, urea, CK-MB, triglyceride, cholesterol, low-density lipoprotein (LDL) and increased high-density lipoprotein (HDL) in D-gal treated animals. High dose (80mg/ml/kg) of LiCl observed as the most effective dose against D-gal induced alterations. These finding LiCl inhibits D-gal induced liver, kidney and heart damages via its antioxidant potential.

Spirulina platensis (Blue-green algae): A miracle from sea combats the oxidative stress and improves behavioral deficits in an animal model of Schizophrenia.

Spirulina platensis (blue-green algae) is a nutritional supplement. It constitutes of high content of protein, antioxidants, various phytopigments and possesses neuroprotective activities. Schizophrenia (SZ) is recognized as a neuropsychiatric disorder in humans with a reduced lifespan followed with impairments in social as well as vocational functioning. Major psychotic symptoms of SZ cluster into three categories: positive, negative and cognitive dysfunctions. Dizocilpine recognized as one of the best drugs to mimic full spectrum of SZ can develop an animal model of the disorder. Various antipsychotics are considered as approved treatment therapy for the psychotic symptoms of SZ but they also exert adverse effects. Thus, there is an excessive need for novel treatment(s) with negligible adverse effects. Present study was designed to evaluate the neuroprotective effects of spirulina in ameliorating the psychosis- like symptoms in dizocilpine-induced rat model of SZ. Spirulina was tested at the dose of 180 mg/kg. Results showed that administration of spirulina improved behavioral deficits and combated the oxidative damage evident by a significant reduction in lipid peroxidation and increase in antioxidant level. Thus, from present findings it may be suggested that spirulina can be used as a therapy for preventive or therapeutic measures.

Persea americana seeds improve glycosylation and dyslipidemia in fructose-fed streptozotocin-injected type 2 diabetic male rats.

This work explored the in-vitro phytochemical contents and antidiabetic activity of crude seeds powder of Persea americana (CSSPa) and their in-vivo biochemical effects on glycated hemoglobin, lipid profile and other parameters in type 2 diabetic rats (fructose-STZ model). There were 2 groups of over night fasted rats, control (normal diet) and diabetic (35% Fructose for 6 weeks followed with injection (i.p.) of streptozotocin (STZ) (40mg/kg bw). Diabetic group was further divided into diabetic control, positive control (pioglitazone 15mg) and test (CSSPa 500mg) groups. After the appropriate treatments in each group for 2 weeks fasting glucose level (FGL), serum lipids, insulin, alanine aminotransferase (ALT), creatine Kinase (CK) & uric acid were determined. CSPPa showed presence of alkaloids, flavonoids, phenols etc and potent antidiabetic activity with IC50 13.23±0.76µM. CSPPa treatment showed a significant (p<0.01) decline in lipid profile, while HDL showed significant increase (p<0.01) in test group as compared with positive and diabetic control groups. The serum ALT, CK, uric acid, bilirubin & fasting glucose (fbg) showed significant improvements in test group (p<0.01). Coronary risk index (CRI), Fasting insulin resistance index (FIRI), Percent glycemic change (PGC) and HbA1c values also significantly (p<0.01) improved.

Antidepressant-like deliverables from the sea: evidence on the efficacy of three different brown seaweeds via involvement of monoaminergic system.

Brown seaweeds exhibit several health benefits in treating and managing wide array of ailments. In this study, the antidepressant-like effect of methaolic extracts from Sargassum swartzii (SS), Stoechospermum marginatum (SM), and Nizamuddinia zanardinii (NZ) was examined in forced swimming test (FST), in rats. Oral administration of SS, SM, and NZ extract (30-60 mg/kg) exhibited antidepressant-like activity in FST by reducing immobility time as compared to control group, without inducing significant change in ambulatory behavior in open field test. In order to evaluate the involvement of monoaminergic system, rats were pretreated with the inhibitor of brain serotonin stores p-chlorophenylalanin (PCPA), dopamine (SCH23390 and sulpiride), and adrenoceptor (prazosin and propranolol) antagonists. Rats receiving treatment for 28 days were decapitated and brains were analyzed for monoamine levels. It may be concluded that the extracts of SS, SM, and NZ produces antidepressant-like activity via modulation of brain monoaminergic system in a rat model.

Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

Enhancement in spatial and recognition memory functions following long term oral administration of ginger extract in rats.

Ginger (Zingiber Officinale) is known over the centuries for its medicinal properties and has been used worldwide as health supplement and for treatment of several diseases. The purpose of this study was to evaluate the effects of whole ginger extract administration on spatial and recognition memory using experimental animal models. The antimicrobial properties of ginger extract against various pathogenic fungal and bacterial species were also examined. Aqueous extract of ginger at a dose of 500 mg/kg was orally administered to test rats and water was orally given to control rats for 6 weeks. Water Maze task (WM) was used to assess spatial memory and recognition memory of rats was evaluated by the Novel Object Recognition (NOR) task. Time spent with novel object was significantly increased in ginger treated rats as compared to control animals in novel object recognition task exhibiting enhanced recognition memory in ginger treated rats. Ginger treated rats exhibited significantly enhanced both short term memory and long term memory as evidenced by decrease in time to reach the hidden platform 1h and 24 h after training as compared to control rats. Short term memory functions of ginger treated rats were more enhanced than long term memory functions. Our findings suggest that ginger consumption may lead to an improvement in spatial and recognition memory. Significant activity of aqueous ginger extract was observed against pathogenic bacteria as well as fungal species. It is therefore suggested in this study that ginger extract can be used in microbial infections and as a memory enhancing drug in various memory disorders.

Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats.

Development of AD like symptoms following co-administration of AlCl3 and D-gal in rats: A neurochemical, biochemical and behavioural study.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with neurochemical and neurobehavioural alterations. Aluminium (Al) is considered as a contributing factor in the etiology of several neurodegenerative disorders like AD. D-galactose (D-gal) is a physiological nutrient but over supply induces some neurochemical and biochemical changes that exacerbate natural aging process. In this study, we aimed to develop AD animal model by co-administration of Al and D-gal in rats. Male albino Wistar rats were intraperitoneally injected with AlCl3 and D-gal at a dose of 150mg/kg and 300mg/kg respectively for one week. After one week rats were subjected to behavioural analysis. After behavioural analysis rats were decapitated to remove their brain. Biochemical and neurochemical analysis were conducted in whole brain. AlCl3+D-gal significantly induced depressive and anxious behaviour in rats. Rats cognitive abilities were also significantly impaired following AlCl3 and D-gal co-administration. AlCl3+D-gal significantly altered antioxidant enzyme activities and biogenic amine levels in whole brain. A marked increase in brain lipid peroxidation and acetylcholinesterase activity was found in test rats. These findings suggest that co-administration of AlCl3 and D-gal for one week could induce AD like symptoms and may be used to develop AD animal model.

Enriched environment palliates nicotine-induced addiction and associated neurobehavioral deficits in rats.

This study was designed to investigate the role of enriched environment in preventing and/or reducing the neurobehavioral deficits produced after nicotine administration in albino Wistar rats. Equal numbers of rat in two groups were either placed in social environment (control group) or social along with physically enriched environment for four weeks before the administration of nicotine. Exposure to different environmental conditions was followed by the intraperitoneal injection of nicotine at the dose of 0.6 mg/kg for seven consecutive days during which addictive behavior was monitored using conditioned placed preference paradigm. Behavioral responses to locomotor activity, anxiety and retention of short term memory were investigated in control and nicotine injected groups exposed to different environments. Results of this study showed that the rats pre-exposed to physical along with social enrichment exhibited a decrease in drug seeking behavior, hyper locomotion, anxiogenic effects along with improvement of working memory as compared to control and nicotine injected groups that were kept in social environment alone. This behavioral study suggests that the exposure to physical enrichment along with socialization in young age can later reduce the chances of compulsive dependence on nicotine and related neurobehavioral deficits.

Dizocilpine induced psychosis-like behavior in rats: A possible animal model with full spectrum of schizophrenia.

Schizophrenia (SZ) is categorized as neuropsychiatric disorder with reduced lifespan and significant impairments in social and vocational functioning. One of the best proposed pharmacological animal models is dizocilpine, as it can mimic the full spectrum of schizophrenic disorder including positive and negative symptoms along with cognitive deficits. Dizocilpine is N-methyl-D-aspartate (NMDA) receptor antagonist known to induce hyper-locomotion and stereotyped behavior in rodents. Present study was designed to develop an animal model of SZ via intraperitoneal administration of dizocilpine in rats (100-150g) at a dose of 0.3 mg/kg for eight days. For the evaluation of positive symptoms, hyperlocomotor behavior was monitored. Negative symptoms were assessed by sucrose preference test (SPT) and social interaction test (SIT). Moreover, Cognitive deficits were evaluated by novel object recognition test (NORT). After behavioral assessments animals were decapitated for further evaluation of biochemical and neurochemical estimations. Present findings revealed that dizocilpine injected rats exhibited significant hyperlocomotor behavior, depressive symptoms and cognitive deficits. Results are further strengthened with a marked increase in lipid per oxidation (LPO) in brain and a decline in reduced glutathione (GSH) levels. Biogenic amine levels (Dopamine, DA; 5-hydroxytryptamine, 5-HT) were also significantly increased and decreased respectively. Thus, present findings suggest that dizocilpine can be used as one of the best drug to develop psychosis-like symptoms in rats and to develop an animal model following a short-term study.