Effect of ethanolic extract of Zingiber officinale Roscoe on central nervous system activity in mice.

Zingiber officinale Roscoe, commonly known as ginger, is a traditional herb used to treat various disorders. In this study, we evaluated potential pharmacological effects of ethanolic extracts of Z. Officinale with respect to central nervous system (CNS) activity in mice. Role of ethanolic extract of ginger on CNS activity in mice was studied using models of elevated plus maze test, barbiturate-induced sleeping time, tail suspension test, hot-plate and tail-flick test. Ginger extract was administered to mice at single doses of 50 and 200 mg/kg, perorally while diazepam (1 mg/kg), morphine (5 mg/kg) and imipramine (30 mg/kg) intraperitoneally were used as standard drugs. The results showed that the ginger extract at all dose levels significantly exhibited anxiolytic activityincreased the sleeping latency but reduced the sleeping time. Tail suspension test showed that the extract at both the doses was able to induce a significant decrease in the immobility time, similar to imipramine, a recognized antidepressant drug. Tail-flick and hot-plate tests demonstrated antinociceptive property of ginger extract, similar to morphine, a recognized antinociceptive agent. Higher dose level (200 mg/kg) showed better protective effects. Phytochemical screening of ethanolic extract revealed the presence of various phytoconstituents such as phenolic compounds, flavonoids, tannins, anthocyanins, carbohydrates, glycosides, proteins, resins and volatile oils. The possible mechanism by which ginger exhibited the significant beneficial effects on various CNS models in mice could be attributed to its antioxidant potential.

A Comprehensive Review on Molecular Mechanism Involved in Arsenic Trioxide Mediated Cerebral Neurodegenerative and Infectious Diseases.

Arsenic is an environmental toxicant and its toxicity is a global health problem affecting millions of people. Arsenic exposure occurs from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Both cancerous, noncancerous and immunological complications are possible after arsenic exposure. The many other target organs like lungs, thymus, spleen, liver, heart, kidney, and brain. Arsenic-mediated neuro, as well as immunotoxicity, is the main concern of this review. Long-term arsenic exposure can lead to various neurological dysfunctions, which may cause neurobehavioral defects and biochemical impairment in the brain, this might negatively affect one's quality of life in later stages. Arsenic also alters the levels of various neurotransmitters such as serotonin, dopamine and norepinephrine in the brain which produces neurotoxic effects and immunological deficiency. So, it is crucial to understand the neurotoxic mechanism of arsenic trioxide-mediated cerebro neurodegenerative and immunerelated alterations. One of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. This review focuses on the various toxic mechanisms responsible for arsenic-mediated neurobehavioral and immune-related changes. Therefore, this review provides a critical analysis of mitochondrial dysfunctions, oxidative stress, glutamate excitatory, inflammatory and apoptosis-related mechanistic aspects in arsenic-mediated immunotoxicity, neurotoxicity, and neurodegenerative changes.

Targeting the Wnt/ß-catenin cascade in osteosarcoma: The potential of ncRNAs as biomarkers and therapeutics.

Osteosarcoma (OS) is a bone cancer which stems from several sources and presents with diverse clinical features, making evaluation and treatment difficult. Chemotherapy tolerance and restricted treatment regimens hinder progress in survival rates, requiring new and creative therapeutic strategies. The Wnt/ß-catenin system has been recognised as an essential driver of OS development, providing potential avenues for therapy. Non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), are essential in modulating the Wnt/ß-catenin cascade in OS. MiRNAs control the system by targeting vital elements, while lncRNAs and circRNAs interact with system genes, impacting OS growth and advancement. This paper thoroughly analyses the intricate interplay between ncRNAs and the Wnt/ß-catenin cascade in OS. We examine how uncontrolled levels of miRNAs, lncRNAs, and circRNAs lead to an abnormal Wnt/ß-catenin network, which elevates the development, spread, and susceptibility to the treatment of OS. We emphasise the potential of ncRNAs as diagnostic indicators and avenues for treatment in OS care. The review offers valuable insights for academics and clinicians studying OS aetiology and creating new treatment techniques for the ncRNA-Wnt/ß-catenin cascade. Utilising the oversight roles of ncRNAs in the Wnt/ß-catenin system shows potential for enhancing the outcomes of patients and progressing precision medicine in OS therapy.

Regulatory roles of microRNAs in modulating mitochondrial dynamics, amyloid beta fibrillation, microglial activation, and cholinergic signaling: Implications for alzheimer's disease pathogenesis.

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aß) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aß, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease.

A Review on Autism Spectrum Disorder: Pathogenesis, Biomarkers, Pharmacological and Non-Pharmacological Interventions.

Autistic spectrum disorder (ASD) is a complicated developmental disease characterized by persistent difficulties in social interaction, speech and nonverbal communication, and restricted/ repetitive activities. Our goal is to deliver a step ahead awareness on neurodevelopment in ASD through early behavioral screenings, genetic testing, and detection of various environmental triggers. This would significantly reduce the tally of people with autistic characteristics. As of now, much work is to be done in understanding and treating ASD. Firstly, awareness campaigns must be organized and maintained so that ASD children can be identified and treated feasibly. Secondly, prenatal and prepregnancy environmental risk awareness, including advice against consanguineous marriages, information on optimum mother nutrition, and minimizing pollutants exposure, can be focused. Finally, the extension of genetic screening along with early postnatal monitoring of newborn feeding, nutrition, and eye contact will help in early therapy. People with ASD have strict dietary habits, but they are also more prone to gastrointestinal problems, including diarrhoea, constipation, and sometimes irritable bowel syndrome. Despite significant studies on the symptoms and possible causes of ASD, GI dysfunction is becoming a hot issue of discussion. Dietary strategies can partially help to alleviate both GI and behavioural issues due to the link between gut-microbiota and brain activity. Dietary treatments may be less expensive, easier to administer and have fewer adverse effects than pharmacological interventions. Hence, there is an increasing interest in autistic children's customized diets and supplements. Future studies should look at whether these diets are applicable to diverse people and whether they are practical in various circumstances (areas with fewer resources, lower socioeconomic areas, countries with different dietary restrictions, etc.). The dietary phytochemicals, including curcumin, resveratrol, naringenin, and sulforaphane, have a substantial role as neurotherapeutic agents. These agents can act as an antioxidant, immunomodulator, gut microbiota modulator and Nrf2 activator to provide benefits to ASD patients. Hence an urgent need is to create brain-targeted delivery methods for these dietary phytochemicals and to investigate their therapeutic value in ASD.

Effects of Mangifera indica fruit extract on cognitive deficits in mice.

Mangos are a source of bioactive compounds with potential health-promoting activity. The present work was undertaken to evaluate the ethanolic extract of Mangifera indica L. fruit on cognitive performances. The models used to study the effect on cognitive performances are step down passive avoidance task and elevated plus maze task in mice. Chronic treatment (7 days) of extract and vitamin C significantly (p < 0.05) reversed the aging and scopolamine induced memory deficits in both paradigms. Preliminary phytochemical screening revealed the presence of free sugars, saponins, tannins, and flavonoids. The results suggestthe extract contained pharmacologically active principles that are memory-enhancing in nature.

Central nervous system activity of acute administration of ethanol extract of Punica granatum L. seeds in mice.

Role of ethanolic extract of P. granatum seeds on central nervous system (CNS) in animal models of elevated plus maze test, barbiturate-induced sleeping time, tail suspension test, hot-plate and tail-flick test was studied. P. granatum (PG) extract was administered to young and aged mice at single doses of 100, 250 and 500 mg/kg, perorally while diazepam (1 mg/kg), morphine (5 mg/kg) and imipramine (30 mg/kg) were used intraperitoneally as standard drugs. The results showed that PG extract at all dose levels significantly exhibited the anxiolytic activity. In another study PG extract (250 and 500 mg/kg) significantly increased the sleeping latency and reduced the sleeping time. Tail suspension test showed that PG extract (250 and 500 mg/kg) was able to induce a significant decrease in the immobility time, similar to imipramine, a recognized antidepressant drug. Tail-flick and hot-plate tests exhibited antinociceptive property of PG extract, similar to morphine, a recognized antinociceptive agent. Phytochemical investigation of ethanol extract for the presence of phenolic compounds, flavonoids, tannins, anthocyanins, sugars and saponins was also carried out. Phytochemical screening and measurement of reducing power revealed the CNS activity of ethanol extract of PG seeds may be due to its antioxidative profile.

Effects of adenosine and adenosine A2A receptor agonist on motor nerve conduction velocity and nerve blood flow in experimental diabetic neuropathy.

This study examined the effects of chronic administration of adenosine and CGS 21680 hydrochloride (adenosine A(2A) receptor agonist) on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and histology of sciatic nerve in animal model of diabetic neuropathy. Adenosinergic agents were administered for 2 weeks after 6 weeks of streptozotocin-induced (50 mg/kg i.p.) diabetes in male Sprague-Dawley rats. Significant reduction in sciatic MNCV and NBF were observed after 8 weeks in diabetic animals in comparison with control (non diabetic) rats. Adenosine (10 mg/kg, i.p.) significantly improved sciatic MNCV and NBF in diabetic rats. The protective effect of adenosine on MNCV and NBF was completely reversed by theophylline (50 mg/kg, i.p.), a non-selective adenosine receptor antagonist, suggesting that the adenosine effect was mediated via adenosinergic receptors. CGS 21680 (0.1 mg/kg, i.p.) significantly improved NBF; however, MNCV was not significantly improved in diabetic rats. At a dose of 1 mg/kg, neither MNCV nor NBF was improved by CGS 21680 in diabetic rats. ZM 241385 (adenosine A(2A) receptor antagonist) prevented the effect of CGS 21680 (0.1 mg/kg, i.p.). Histological changes observed in sciatic nerve were partially improved by the adenosinergic agents in diabetic rats. Results of the present study, suggest the potential of adenosinergic agents in the therapy of diabetic neuropathy.

Erythromycin-induced genotoxicity and hepatotoxicity in mice pups treated during prenatal and postnatal period.

The main aim of this study was to investigate the oxidative stress, genotoxicity and cytotoxicity of erythromycin (EMC) in pups of treated dams in gestation as well as the lactation period (LP). The two doses of EMC were compared using intraperitoneal (i.p.) route in two different periods, that is, in gestation period and in the LP. The rationale behind selection of i.p. route is because of the fact that EMC gets degrades in acidic pH of the stomach. The doses of EMC used were clinically equivalent dose (CED; EMC 14.2 mg/kg, i.p.) and a lower dose (EMC 10 mg/kg, i.p.) than CED. EMC toxicities in mice pups were evaluated using various parameters such as micronucleus (MN) test in peripheral blood and bone marrow, malondialdehyde (MDA) assay, glutathione (GSH reduced) assay and histopathological assessment in liver tissue. The CED of EMC led to a significant increase in MDA and decreased in GSH concentration in pups' liver tissue in both gestation and LPs and also to a significant increase in MN frequency in both peripheral blood and bone marrow cells of pups. There were no significant toxicities at a lower dose than CED. There were also some chronic findings with liver histopathological examination at CED. It is thus concluded that EMC accentuates the oxidative stress, cytotoxicity and DNA damage in pups of their postnatal life; hence, EMC should be avoided in the pregnancy and also in the LP.

Estimation of total phenolic content, in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa oleifera.

OBJECTIVE: To evaluate and compare the antioxidant potential and anti-inflammatory activity of ethanolic extract of flowers of Moringa oleifera (M. oleifera) grown in Oman. METHODS: Flowers of M. oleifera were collected in the month of December 2012 and identified by a botanist. Alcoholic extract of the dry pulverized flowers of M. oleifera were obtained by cold maceration method. The ethanolic flower extract was subjected to preliminary phytochemical screening as the reported methods. Folin-Ciocalteu reagent was used to estimate total phenolic content. DPPH was used to determine in-vitro antioxidant activity and anti-inflammatory activity of flowers was investigated by protein denaturation method. RESULTS: Phytochemical analysis of extract showed presence of major classes of phytochemicals such as tannins, alkaloids, flavonoids, cardiac glycosides etc. M. oleifera flowers were found to contain 19.31 mg/g of gallic acid equivalent of total phenolics in dry extract but exhibited moderate antioxidant activity. The anti-inflammatory activity of plant extract was significant and comparable with the standard drug diclofenac sodium. CONCLUSIONS: The results of our study suggest that flowers of M. oleifera possess potent anti-inflammatory activity and are also a good source of natural antioxidants. Further study is needed to identify the chemical compounds responsible for their anti-inflammatory activity.

Nanoparticles-mediated drug delivery approaches for cancer targeting: a review.

Cancer has become the leading cause of death among different populations of the world. The treatment is limited to chemotherapy, radiation, and surgery. Selective targeting to the tumor cells is possible by nanoparticles-based drug delivery system. It maximizes the drug concentration at the desired target and protects the surrounding healthy tissues at the same time. To improve the targeting potential of the anticancer drugs, nanoparticles were optimized for the size and surface characteristics to enhance their circulation time and targeting efficiency. Passive targeting involves surface modification with polyethylene glycol to avoid its elimination by natural body defense mechanism. Active targeting involves chemical interaction with certain antigen, receptors, and genes which are over expressed during progression of disease. In addition, the article highlights recent developments in "smart"-stimulus-responsive-drug carriers designed to enhance the localization and efficacy of therapeutic payloads as compared with free drug. Enhanced targeting potential, imaging, and controlled release of drugs or therapeutic molecules could be possible through multi-functional nanocarrier. Such multi-faceted, versatile nanocarriers and drug delivery systems promise a substantial increase in the efficacy of diagnostic and therapeutic applications in pharmaceutical sciences.

Protective effects of Punica granatum seeds extract against aging and scopolamine induced cognitive impairments in mice.

Dementia is one of the age related mental problems and characteristic symptom of various neurodegenerative diseases including Alzheimer's disease. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. Many studies have shown that certain phenolic antioxidants attenuate neuronal cell death induced by oxidative stress. The present work was undertaken to assess the effect of ethanolic extract of Punica granatum seeds on cognitive performance of aged and scopolamine treated young mice using one trial step-down type passive avoidance and elevated plus maze task. Aged or scopolamine treated mice showed poor retention of memory in step-down type passive avoidance and in elevated plus maze task. Chronic administration (21 days) of Punica granatum extract and vitamin C significantly (p < 0.05) reversed the age induced or scopolamine induced retention deficits in both the paradigms. Punica granatum extract also significantly lowered lipid peroxidation level and increased antioxidant glutathione level in brain tissues. Punica granatum preparations could be protective in the treatment of cognitive disorders such as dementia and Alzheimer's disease.