Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.
Objective: Hydroxytyrosol (HT), a polyphenol of olive plant is well known for its antioxidant, anti-inflammatory and anti-atherogenic properties. The aim of this systematic search is to highlight the scientific evidence evaluating molecular efficiency of HT in halting the progression of intimal hyperplasia (IH), which is a clinical condition arises from endothelial inflammation. Methods: A systematic search was performed through PubMed, Web of Science and Scopus, based on pre-set keywords which are Hydroxytyrosol OR 3,4-dihydroxyphenylethanol, AND Intimal hyperplasia OR Neointimal hyperplasia OR Endothelial OR Smooth muscles. Eighteen in vitro and three in vitro and in vivo studies were selected based on a pre-set inclusion and exclusion criteria. Results: Based on evidence gathered, HT was found to upregulate PI3K/AKT/mTOR pathways and supresses inflammatory factors and mediators such as IL-1β, IL-6, E-selectin, P-selectin, VCAM-1, and ICAM-1 in endothelial vascularization and functioning. Two studies revealed HT disrupted vascular smooth muscle cells (SMC) cell cycle by dephosphorylating ERK1/2 and AKT pathways. Therefore, HT was proven to promote endothelization and inhibit vascular SMCs migration thus hampering IH development. However, none of these studies described the effect of HT collectively in both vascular endothelial cells (EC) and SMCs in IH ex vivo model. Conclusions: Evidence from this concise review provides an insight on HT regulation of molecular pathways in reendothelization and inhibition of VSMCs migration. Henceforth, we propose effect of HT on IH prevention could be further elucidated through in vivo and ex vivo model.
Increased ASM mass, primarily due to ASM hyperplasia, has been recognized as a hallmark of airway remodeling in asthma. Increased ASM mass is the major contributor to the airway narrowing, thus worsening the bronchoconstriction in response to stimuli. Inflammatory mediators and growth factors released during inflammation induce increased ASM mass surrounding airway wall via increased ASM proliferation, diminished ASM apoptosis and increased ASM migration. Several major pathways, such as MAPKs, PI3K/AKT, JAK2/STAT3 and Rho kinase, have been reported to regulate these cellular activities in ASM and were reported to be interrelated at certain points. This article aims to provide an overview of the signaling pathways/molecules involved in ASM hyperplasia as well as the mapping of the interplay/crosstalk between these major pathways in mediating ASM hyperplasia. A more comprehensive understanding of the complexity of cellular signaling in ASM cells will enable more specific and safer drug development in the control of asthma.
Adolescence is a critical developmental period during which exposure to psychoactive substances like kratom (Mitragyna speciosa) can cause long-lasting deleterious effects. Here, we evaluated the effects of mitragynine, the main alkaloid of kratom, and lyophilised kratom decoction (LKD) on cognitive behaviours and brain metabolite profiles in adolescent rats. Male Sprague-Dawley rats (Postnatal day, PND31) were given vehicle, morphine (5 mg/kg), mitragynine (3, 10, or 30 mg/kg), or LKD (equivalent dose of 30 mg/kg mitragynine) for 15 consecutive days. Later, a battery of behavioural testing was conducted, brain was extracted and metabolomic analysis was performed using LCMS-QTOF. The results showed that mitragynine did not affect the recognition memory in the novel object recognition task. In the social interaction task, morphine, mitragynine, and LKD caused a marked deficit in social behaviour, while in Morris water maze task, mitragynine and LKD only affected reference memory. Metabolomic analysis revealed distinct metabolite profiles of animals with different treatments. Several pathways that may be involved in the effects of kratom exposure include arachidonic acid, pantothenate and CoA, and tryptophan pathways, with several potential biomarkers identified. These findings suggest that adolescent kratom exposure can cause cognitive behavioural deficits that may be associated with changes in the brain metabolite profiles.
Depression is an incapacitating neuropsychiatric disorder. The serotonergic system in the brain plays an important role in the pathophysiology of depression. However, due to delayed and/or poor performance of selective serotonin reuptake inhibitors in treating depressive symptoms, the role of the serotonergic system in depression has been recently questioned further. Evidence from recent studies suggests that increased inflammation and oxidative stress may play significant roles in the pathophysiology of depression. The consequences of these factors can lead to the neuroprogression of depression, involving neurodegeneration, astrocytic apoptosis, reduced neurogenesis, reduced plasticity (neuronal and synaptic), and enhanced immunoreactivity. Specifically, increased proinflammatory cytokine levels have been shown to activate the kynurenine pathway, which causes increased production of quinolinic acid (QA, an N-Methyl-D-aspartate agonist) and decreases the synthesis of serotonin. QA exerts many deleterious effects on the brain via mechanisms including N-methyl-D-aspartate excitotoxicity, increased oxidative stress, astrocyte degeneration, and neuronal apoptosis. QA may also act directly as a pro-oxidant. Additionally, the nuclear translocation of antioxidant defense factors, such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2), is downregulated in depression. Hence, in the present review, we discuss the role of QA in increasing oxidative stress in depression by modulating the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 and thus affecting the synthesis of antioxidant enzymes.
Chamomile (Matricaria chamomilla L.) is a traditional medicinal plant used to treat hay fever, inflammation, muscle spasms, menstrual disorders, insomnia ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids. Dried chamomile flowers have a longer shelf life and the dried extract in form of powder offers much flexibility for new therapeutic formulations as it could be used as a replacement for liquid extract and serve as a shelf-stable ingredient in new applications. This study aims to determine the effect of drying methods, i.e., convection oven-drying at 45 °C, freeze-drying at -50°C, and spray-drying at 140°C at 10.5 and 12 ml/min, respectively) on powder yield, physicochemical properties (moisture content, water activity, and color attributes), and total polyphenol content of chamomile extract powder. Our findings showed that spray-drying conducted at 140°C, 12 ml/min resulted in the lowest yield of powder (16.67%) compared to convection oven-drying (90.17%) and freeze-drying (83.24%). Decreasing the feed flow rate to 10.5 ml/min during spraying caused an increase in powder yield to 26.99%. The moisture content of spray-dried chamomile extract powder obtained at 140°C, 10.5 ml/min was higher (11.00%) compared to that of convection oven-dried (8.50%) and freeze-dried (7.50%). Both convection oven-dried and freeze-dried chamomile extract powder displayed no significant difference (p > 0.05) in moisture content. The higher feed flow rate (12 ml/min) in spray-drying also led to an increase in the moisture content of chamomile extract powder to 12.00%. The higher residual moisture found in the spray-dried samples resulted in partial agglomeration of particles. In terms of water activity, freeze-dried chamomile extract powder was found to have the highest water activity (0.63) compared to that of convection oven-dried (0.52), spray-dried at 140°C, 10.5 ml/min (0.57), and spray-dried at 140°C, 12 ml/min (0.58). Spray-dried and freeze-dried chamomile extract powder with high moisture content and water activity could be highly susceptible to microbial growth. In terms of color attributes, higher drying temperature in spray-drying led to darker, redder, and more yellowish chamomile extract powder that could be caused by heat-induced Maillard reaction and caramelization. Since lower drying temperature was used in both convection oven-drying and freeze-drying, both convection oven-dried (56.94 mg GAE/g powder) and freeze-dried chamomile extract powder (55.98 mg GAE/g powder) were found to have higher total polyphenol content compared to those of spray-dried (42.79-46.79 mg GAE/g powder). The present findings allow us to understand the effect of drying methods on the properties of chamomile extract powder and provide a better drying option to dry chamomile extract. Due to higher powder yield with ideal powder properties such as low moisture content and water activity, desirable color, and high total polyphenol content obtained from convection oven-drying, convection oven-drying was a better option than freeze-drying and spray-drying for drying chamomile extract.
Multiorgan toxicities have been extensively reported in kratom (Mitragyna speciosa Korth) users in Western countries but not in Southeast Asia. Existing literature argued that this discrepancy may be due to underreporting of kratom-related toxicity cases in Southeast Asia. Hence, this case series filled the research gap by clinically assessing the cardiovascular functioning and serum mitragynine level of regular kratom users in its traditional settings in Malaysia. Nine regular kratom users without history of polysubstance use were recruited from the same community via snowball sampling and were subjected to electrocardiogram (ECG) and echocardiogram assessments. Serum mitragynine analysis was also performed by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The mean serum mitragynine level was 10.3 mg/L (SD = 6.9) and ranged from 2.5 mg/L to 22.4 mg/L. Those who consumed an average daily quantity of four or more glasses of brewed kratom juice (p = 0.045) and those who had prolonged QTc intervals (p = 0.017) had significantly higher serum mitragynine level. Echocardiographic findings of all the respondents were normal except one reported left ventricular hypertrophy and another had trivial tricuspid regurgitation with pulmonary artery systolic pressure (PASP) of 10 + 5 mmHg. Regular kratom use without concomitant use of other illicit substances may not provoke any risk of cardiovascular impairment or toxicity except for prolonged QTc interval, which appeared to be dose dependent. However, as this study was limited by a small sample size, future studies with larger sample size are warranted to confirm our findings.
Background: Kratom or Mitragyna speciosa (Korth.) has received overwhelming attention recently due to its alleged pain-relieving effects. Despite its potential therapeutic value, kratom use has been linked to many occurrences of multiorgan toxicity and cardiotoxicity. Accordingly, the current narrative review aimed to provide a detailed account of kratom's adverse cardiovascular effects and cardiotoxicity risk, based on in vitro studies, poison center reports, coroner and autopsy reports, clinical case reports, and clinical studies. Methods: An electronic search was conducted to identify all research articles published in English from 1950 to 2021 using the major research databases, such as Google Scholar, Web of Science, PubMed, Scopus, Mendeley, EMBASE, Cochrane Library, and Medline. We then analyzed the literature's discussion of adverse cardiovascular effects, toxicity, and mortality related to kratom use. Results: Our findings revealed that, although in vitro studies have found kratom preparations' most abundant alkaloid-mitragynine-to cause a prolonged QTc interval and an increased risk of torsades de pointes, a clinical study examining humans' regular consumption of kratom did not report such a risk. However, this latter study did show that regular kratom use could induce an increased QTc interval in a dose-dependent manner. A few case reports also highlighted that kratom consumption is associated with ventricular arrhythmia and cardiopulmonary arrest, but this association could have ensued when kratom was co-administered with another substance. Similarly, analyses of national poison data showed that kratom's most common adverse acute cardiovascular effects include tachycardia and hypertension. Meanwhile, coroner and autopsy reports indicated that kratom's cardiovascular sequelae encompass coronary atherosclerosis, myocardial infarction, hypertensive cardiovascular disease, left ventricular hypertrophy, cardiac arrhythmia, cardiomegaly, cardiomyopathy, focal band necrosis in the myocardium, and myocarditis. Given the available data, we deduced that all cardiac eventualities reported in the literature could have been compounded by polysubstance use and unresolved underlying medical illnesses. Conclusion: Although kratom use has been associated with death and cardiotoxicity, especially at higher doses and when associated with other psychoactive drugs, the dearth of data and methodological limitations reported in existing studies do not allow a definitive conclusion, and further studies are still necessary to address this issue.
Osteoporosis and periodontitis are two major chronic diseases of postmenopausal women. The association between these two diseases are evident through systemic bone loss and alveolar bone loss. Both postmenopausal osteoporosis and periodontitis impose a considerable personal and socioeconomic burden. Biphosphonate and hormone replacement therapy are effective in preventing bone loss in postmenopausal osteoporosis and periodontitis, but they are coupled with severe adverse effects. Phytoestrogens are plant-based estrogen-like compounds, which have been used for the treatment of menopause-related symptoms. In the last decades, numerous preclinical and clinical studies have been carried out to evaluate the therapeutic effects of phytoestrogens including bone health. The aim of this article is to give an overview of the bidirectional interrelationship between postmenopausal osteoporosis and periodontitis, summarize the skeletal effects of phytoestrogens and report the most studied phytoestrogens with promising alveolar bone protective effect in postmenopausal osteoporosis model, with and without experimental periodontitis. To date, there are limited studies on the effects of phytoestrogens on alveolar bone in postmenopausal osteoporosis. Phytoestrogens may have exerted their bone protective effect by inhibiting bone resorption and enhancing bone formation. With the reported findings on the protective effects of phytoestrogens on bone, well-designed trials are needed to better investigate their therapeutic effects. The compilation of outcomes presented in this review may provide an overview of the recent research findings in this field and direct further in vivo and clinical studies in the future.
Alternariol is a toxic metabolite of Alternaria fungi and studies have shown multiple potential pharmacological effects. To outline the anticancer effects and mechanisms of alternariol and its derivatives based on database reports, an updated search of PubMed/MedLine, ScienceDirect, Web of Science, and Scopus databases was performed with relevant keywords for published articles. The studies found to suggest that this mycotoxin and/or its derivatives have potential anticancer effects in many pharmacological preclinical test systems. Scientific reports indicate that alternariol and/or its derivatives exhibit anticancer through several pathways, including cytotoxic, reactive oxygen species leading to oxidative stress and mitochondrial dysfunction-linked cytotoxic effect, anti-inflammatory, cell cycle arrest, apoptotic cell death, genotoxic and mutagenic, anti-proliferative, autophagy, and estrogenic and clastogenic mechanisms. In light of these results, alternariol may be one of the hopeful chemotherapeutic agents.
Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa. The pharmacological studies reported in vitro, in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N. sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.
With the advent of highly effective plant-based medications with few or no side effects, the use of phytomedicines against complex diseases such as cancer is becoming more widespread. The broadly recognized pentacyclic triterpenes known as boswellic acids (BAs) are derived from the oleogum resin, or frankincense, extracted from the plant species of the genus Boswellia. The frankincense mixture contains various BA types, each having a different potential and helping treat certain cancers. This review focuses on details regarding the traits of the BAs, their roles as anti-cancer agents, the mechanism underlying their activities, and the function of their semi-synthetic derivatives in managing and treating certain cancers. The review also explores the biological sources of BAs, how they are conserved, and how biotechnology might help preserve and improve in vitro BA production. The review concludes that the BAs and their semi-synthetic derivatives are effective against a broad spectrum of cancer cell lines. The detailed information in the review can be helpful for researchers to gain more information about BAs and BA-based medications for efficient and cost-effective cancer treatments.
Momordica species (Family Cucurbitaceae) are cultivated throughout the world for their edible fruits, leaves, shoots and seeds. Among the species of the genus Momordica, there are three selected species that are used as vegetable, and for medicinal purposes, Momordica charantia L (Bitter melon), Momordica foetida Schumach (Bitter cucumber) and Momordica balsamina L (African pumpkin). The fruits and leaves of these Momordica species are rich in primary and secondary metabolites such as proteins, fibers, minerals (calcium, iron, magnesium, zinc), β-carotene, foliate, ascorbic acid, among others. The extracts from Momordica species are used for the treatment of a variety of diseases and ailments in traditional medicine. Momordica species extracts are reputed to possess anti-diabetic, anti-microbial, anthelmintic bioactivity, abortifacient, anti-bacterial, anti-viral, and play chemo-preventive functions. In this review we summarize the biochemical, nutritional, and medicinal values of three Momordica species (M. charantia, M. foetida and M. balsamina) as promising and innovative sources of natural bioactive compounds for future pharmaceutical usage.
Epilepsy is a chronic brain disease afflicting around 70 million global population and is characterized by persisting predisposition to generate epileptic seizures. The precise understanding of the etiopathology of seizure generation is still elusive, however, brain inflammation is considered as a major contributor to epileptogenesis. HMGB1 protein being an initiator and crucial contributor of inflammation is known to contribute significantly to seizure generation via activating its principal receptors namely RAGE and TLR4 reflecting a potential therapeutic target. Herein, we evaluated an anti-seizure and memory ameliorating potential of an anti-HMGB1 monoclonal antibody (mAb) (1, 2.5 and 5 mg/kg, I.P.) in a second hit Pentylenetetrazol (PTZ) (80 mg/kg, I.P.) induced seizure model earlier stimulated with Pilocarpine (400 mg/kg, I.P.) in adult zebrafish. Pre-treatment with anti-HMGB1 mAb dose-dependently lowered the second hit PTZ-induced seizure but does not alter the disease progression. Moreover, anti-HMGB1 mAb also attenuated the second hit Pentylenetetrazol induced memory impairment in adult zebrafish as evidenced by an increased inflection ration at 3 and 24 h trail in T-maze test. Besides, decreased level of GABA and an upregulated Glutamate level was observed in the second hit PTZ induced group, which was modulated by pre-treatment with anti-HMGB1 mAb. Inflammatory responses occurred during the progression of seizures as evidenced by upregulated mRNA expression of HMGB1, TLR4, NF-κB, and TNF-α, in a second hit PTZ group, which was in-turn downregulated upon pre-treatment with anti-HMGB1 mAb reflecting its anti-inflammatory potential. Anti-HMGB1 mAb modulates second hit PTZ induced changes in mRNA expression of CREB-1 and NPY. Our findings indicates anti-HMGB1 mAb attenuates second hit PTZ-induced seizures, ameliorates related memory impairment, and downregulates the seizure induced upregulation of inflammatory markers to possibly protect the zebrafish from the incidence of further seizures through via modulation of neuroinflammatory pathway.
Epilepsy is a neuronal disorder associated with several neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Despite having more than 20 anti-epileptic drugs (AEDs), they only provide a symptomatic treatment. As well as, currently available AEDs also displayed cognitive alterations in addition to retarding seizure. This leads to the need for exploring new molecules that not only retard seizure but also improve cognitive impairment. Embelin (EMB) is a benzoquinone derivative which has already demonstrated its pharmacological potentials against arrays of neurological conditions. The current study developed a chronic kindling model in adult zebrafish by using repeated administration of small doses of pentylenetetrazole (PTZ) and a single dose of Kainic acid (KA) to investigate the associated memory impairment. This has been done by using the three-axis maze which is a conventional method to test the learning ability and egocentric memory in zebrafish. As well as, the ameliorative potential of EMB has been evaluated against chronic epilepsy-related memory alterations. Moreover the expression level of pro-inflammatory genes such as C-C motif ligand 2 (CCL2), toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interferon-γ (IFN-γ) were evaluated. The level of several neurotransmitters such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamate (Glu) was evaluated by liquid chromatography-mass spectrometry (LC-MS). The results showed that daily dose of PTZ 80 mg/kg for 10 days successfully induces a kindling effect in zebrafish, whereas the single dose of KA did not. As compared to control, the PTZ and KA group demonstrates impairment in memory as demonstrated by the three-axis maze. The PTZ group treated with a series of EMB doses (ranging from 0.156 to 0.625 mg/kg) was found to have retarded seizure as well as significantly reduces epilepsy-induced memory alteration. In addition, EMB treatment reduces the expression of inflammatory markers implicating its anti-inflammatory potential. Moreover, levels of GABA, Ach, and glutamate are increased in EMB administered group as compared to the PTZ administered group. Overall, findings demonstrate that EMB might be a potential candidate against chronic epilepsy-related cognitive dysfunction as EMB prevents the seizures, so we expect it to prevent the associated neuroinflammation and learning deficit.
Epilepsy is a common neurological disorder characterized by seizures which result in distinctive neurobiological and behavioral impairments. Not much is known about the causes of epilepsy, making it difficult to devise an effective cure for epilepsy. Moreover, clinical studies involving epileptogenesis and ictogenesis cannot be conducted in humans due to ethical reasons. As a result, animal models play a crucial role in the replication of epileptic seizures. In recent years, non-mammalian models have been given a primary focus in epilepsy research due to their advantages. This systematic review aims to summarize the importance of non-mammalian models in epilepsy research, such as in the screening of anti-convulsive compounds. The reason for this review is to integrate currently available information on the use and importance of non-mammalian models in epilepsy testing to aid in the planning of future studies as well as to provide an overview of the current state of this field. A PRISMA model was utilized and PubMed, Springer, ScienceDirect and SCOPUS were searched for articles published between January 2007 and November 2017. Fifty-one articles were finalized based on the inclusion/exclusion criteria and were discussed in this review. The results of this review demonstrated the current use of non-mammalian models in epilepsy research and reaffirmed their potential to supplement the typical rodent models of epilepsy in future research into both epileptogenesis and the treatment of epilepsy. This review also revealed a preference for zebrafish and fruit flies in lieu of other non-mammalian models, which is a shortcoming that should be corrected in future studies due to the great potential of these underutilized animal models.
Purpose of the research: Epilepsy is a continuous process of neurodegeneration categorized by an enduring tendency to generate uncontrolled electrical firing known as seizures causing involuntary movement all over the body. Cognitive impairment and behavioral disturbances are among the more alarming co-morbidities of epilepsy. Anti-epileptic drugs (AEDs) were found to be successful in controlling epilepsy but are reported to worsen cognitive status in patients. Embelin (EMB) is a benzoquinone derived from the plant Embelia ribes and is reported to have central nervous system (CNS) activity. This study aims to evaluate the effectiveness of EMB against pentylenetetrazole (PTZ) induced acute seizures and its associated cognitive dysfunction. This was done via docking studies as well as evaluating neurotransmitter and gene expression in the zebrafish brain. The principal results: Behavioral observations showed that EMB reduced epileptic seizures and the T-maze study revealed that EMB improved the cognitive function of the fish. The docking study of EMB showed a higher affinity toward gamma-aminobutyric acid (GABAA) receptor as compared to the standard diazepam, raising the possibility of EMB working via the alpha subunit of the GABA receptor. EMB was found to modulate several genes, neurotransmitters, and also neuronal growth, all of which play an important role in improving cognitive status after epileptic seizures. Healthy zebrafish treated with EMB alone were found to have no behavioral and biochemical interference or side effects. The immunohistochemistry data suggested that EMB also promotes neuronal protection and neuronal migration in zebrafish brains. Major Conclusions: It was perceived that EMB suppresses seizure-like behavior via GABAA receptor pathway and has a positive impact on cognitive functions. The observed effect was supported by docking study, T-maze behavior, neurotransmitter and gene expression levels, and immunohistology study. The apparatus such as the T-maze and seizure scoring behavior tank were found to be a straightforward technique to score seizure and test learning ability after acute epileptic seizures. These research findings suggest that EMB could be a promising molecule for epilepsy induced learning and memory dysfunction.
Orthosiphon stamineus (OS) or Orthosiphon aristatus var. aristatus (OAA) is commonly known as cat's whiskers or "misai kucing". It is an herbaceous shrub that is popular in many different traditional and complementary medicinal systems. Its popularity has been justified by the plethora of studies that have shown that the secondary metabolites of the plant has effects that range from anti-inflammatory and gastroprotective to anorexic and antihypertensive. As such, OS could also be a potential treatment for Central Nervous System (CNS) disorders. However, a cohesive synthesis of the protective actions of OS was lacking. This systematic review was therefore commenced to elaborate on the various protective mechanisms of OS in the CNS. The PRISMA model was used and five databases (Google Scholar, SCOPUS, SpringerLink, ScienceDirect, and PubMed) were searched with relevant keywords to finally identify four articles that met the inclusion criteria. The articles described the protective effects of OS extracts on Alzheimer's disease, epilepsy, learning and memory, oxidative stress, and neurotoxicity. All the articles found were experimental or preclinical studies on animal models or in vitro systems. The reported activities demonstrated that OS could be a potential neuroprotective agent and might improve CNS conditions like neurodegeneration, neuroinflammation, and oxidative stress.
Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs.