Search

Channa striatus (CS), or snakehead murrel, is an obligate air-breathing freshwater fish. Besides its wound healing properties, CS has also been reported to exhibit anti-inflammatory effects in multiple studies. While there are anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), their long-term use is associated with an increased risk of peptic ulcers, acute renal failure, stroke, and myocardial infarction. Thus, it is essential to look at natural methods such as CS extract. While there is an abundant number of investigative studies on the inflammatory properties of CS, the quality of these studies has not been evaluated effectively. Thus, this review aims to summarise, evaluate, and critically appraise currently available literature regarding the anti-inflammatory properties of CS extract. This is done by performing a search using four databases, namely Google Scholar, Embase via Elsevier, Scopus, and Web of Science, with the following terms: Channa striatus AND inflammation. From our review, CS has been experimentally shown to positively affect inflammatory conditions such as gastric ulcers, dermatitis, osteoarthritis, and allergic rhinitis. Beneficial effects were also found on inflammation in the presence of tuberculosis and in situations that involve inflammation, such as wound healing. While CS clearly has potential for treating inflammatory conditions, much work needs to be done on identifying and isolating the active constituents before exact mechanisms of action can be worked out to develop future anti-inflammatory medications.

Approximately 69 million people worldwide are annually affected by traumatic brain injury (TBI). In Malaysia, the traumatic injury was the leading cause of hospital admission and death, accounting for one in three emergency visits. Among the most recognised complication of TBI is post-traumatic epilepsy (PTE), which is an essential contributor to morbidity and mortality. However, there is a lack of local epidemiological data on PTE in Malaysia. This study aims to describe the incidence and predictors of PTE among TBI patients admitted to a tertiary healthcare centre in Kuala Lumpur, Malaysia. We hypothesised that increases in age, race, and severity of brain injury are among the main potential predictors of PTE. It will also provide evidence that patients with epilepsy following TBI are associated with significant impairment in cognitive performance than TBI patients without epilepsy. An analysis of a two years retrospective cohort will be employed, of which adults with a history of admission for TBI in 2019 and 2020 will be contacted, and the development of epilepsy will be ascertained using a validated tool and confirmed by our neurologists during visits. The patients will then be grouped into two, with PTE and without PTE, and assessed their cognitive performance by clinical psychologists. Given that the management of TBI and PTE patients involves a multidisciplinary team, the findings might be significant to many healthcare providers in determining policy and strategise a better treatment.

Oxidative stress is one of the factors involved in the pathogenesis of several neurodegenerative diseases. It has been reported that a secretory phospholipase A2 known as A2-EPTX-NSm1a has lower cytotoxicity in neuronal cells compared to its crude Naja sumatrana venom. In this study, A2-EPTX-NSm1a was tested for its neuroprotective activity on human neuroblastoma cells (SH-SY5Y) differentiated into cholinergic neurons against oxidative stress induced by hydrogen peroxide (H2O2). H2O2 treatment alone increased the caspase-3 and caspase-8 activities, whereas pre-treatment with A2-EPTX-NSm1a reduced the activity of these apoptosis-associated proteins. Moreover, A2-EPTX-NSm1a protects the morphology and ultrastructure of differentiated SH-SY5Y cells in the presence of H2O2. Oxidative stress increased the number of small mitochondria. Further evaluation showed the size of mitochondria with a length below 0.25 µm in oxidative stress conditions is higher than the control group, suggesting mitochondria fragmentation. Pre-treatment with A2-EPTX-NSm1a attenuated the number of mitochondria in cells with H2O2 Furthermore, A2-EPTX-NSm1a altered the expression of several neuroprotein biomarkers of GDNF, IL-8, MCP-1, TIMP-1, and TNF-R1 in cells under oxidative stress induced by H2O2. These findings indicate that anti-apoptosis with mitochondria-related protection, anti-inflammatory effect, and promote expression of important markers for cell survival may underlie the neuroprotective effect of A2-EPTX-NSm1a in cholinergic rich human cells under oxidative stress, a vital role in the neuronal disorder.

The gut taxonomical profile is one of the contributory factors in maintaining homeostasis within the central nervous system (CNS). Of late, the efficacy of diet as a target of treatment, and how various dietary interventions may modulate gut microbiota differently have been an area of focus in research. The role of ketogenic diet (KD) in particular has been well-established in other diseases like intractable epilepsy due to its postulated effects on gut microbiome modulation, resulting in neuronal stability and prevention of epileptogenesis. Therefore, this systematic review aimed to critically evaluate the current available literature investigating the interplay between the three distinct entities: ketogenic diet, neurodegeneration, and gut microbiota, which may serve as a focus guide for future neurodegenerative diseases (ND) therapeutic research. A comprehensive literature search was performed on three databases; PubMed, Scopus, and Ovid Medline. A total of 12 articles were selected for critical appraisal, after subjecting to the inclusion and exclusion criteria in this study. The selected articles revealed that the hopes of KD as a treatment modality for ND are being ventured into as these individuals are said to acquire gut dysbiosis, primarily through increased colonization of phyla Proteobacteria and Firmicutes. Although positive effects including restoration of healthy gut microbes such as Akkermansia Muciphilia sp., improvement in cognitive functioning and decline in neuro-inflammatory markers were noted, this systematic review also depicted conflicting results such as decrease in alpha and beta species diversity as well as diminution of healthy gut commensals such as Bifidobacteriace. In addition, positive neuromodulation were also observed, notably an increase in cerebral blood perfusion to ventromedial hippocampal region via increased expression of eNOS and clearance of amyloid-beta proteins across the blood-brain-barrier via expression of p-glycoprotein. Neuroprotective mechanisms of ketogenic diet also included downregulation of mTOR expression, to prevention acceleration of pathological diseases such as Alzheimer's. Thus due to this conflicting/contrasting results demonstrated by ketogenic diet, such as a decline in gut species richness, diminution in beneficial microbes and decline cognition unless delivered in an intermittent fasting pattern, further studies may still be required before prior recommendation of a ketogenic diet therapeutic regime in ND patients.

Epilepsy represents a challenge in the management of patients with brain tumors. Epileptic seizures are one of the most frequent comorbidities in neuro-oncology and may be the debut symptom of a brain tumor or a complication during its evolution. Epileptogenic mechanisms of brain tumors are not yet fully elucidated, although new factors related to the underlying pathophysiological process with possible treatment implications have been described. In recent years, the development of new anti-seizure medications (ASM), with better pharmacokinetic profiles and fewer side effects, has become a paradigm shift in many clinical scenarios in neuro-oncology, being able, for instance, to adapt epilepsy treatment to specific features of each patient. This is crucial in several situations, such as patients with cognitive/psychiatric comorbidity, pregnancy, or advanced age, among others. In this narrative review, we provide a rationale for decision-making in ASM choice for neuro-oncologic patients, highlighting the strengths and weaknesses of each drug. In addition, according to current literature evidence, we try to answer some of the most frequent questions that arise in daily clinical practice in patients with epilepsy related to brain tumors, such as, which patients are the best candidates for ASM and when to start it, what is the best treatment option for each patient, and what are the major pitfalls to be aware of during follow-up.

Curcuma longa (Turmeric) is a tropical herbaceous perennial plant of the family Zingiberaceae and contains curcuminoids, sesquiterpenoids and monoterpenoids as its major components. Given the broad range of activities that Curcuma longa possesses and also its use as a traditional epilepsy remedy, this review attempts to systematically review the experimentally proven activities of Curcuma longa and its bioactive components, which are related to the management of epileptic seizures. Using the PRISMA model, five databases (Google Scholar, PubMed, ScienceDirect, SCOPUS and SpringerLink) were searched using the keywords [“Curcuma longa” AND “Epilepsy”] and [“Curcuma longa” AND “Seizures”], leaving 34 articles that met the inclusion criteria. The present systematic review elaborated on the experimentally proven potential of Curcuma longa components, such as an aqueous extract of Curcuma longa itself, Curcuma longa oil and active constituents like curcuminoids and bisabolene sesquiterpenoids found in Curcuma longa with anti-seizure potential. Using human equivalent dose calculations, human treatment parameters were suggested for each component by analysing the various studies in this review. This review also determined that the principal components possibly exert their anti-seizure effect via the reduction of corticosterone, modulation of neurotransmitters signalling, modulation of sodium ion channels, reduction of oxidative DNA damage, reduction of lipid peroxidation, upgregulation of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) mediated inhibition. It is anticipated that this review will help pave the way for future research into the development of Curcuma longa and its neuroactive constituents as potential drug candidates for the management of epilepsy.

Glycyrrhizin (GL) is a well-known pharmacological inhibitor of high mobility group box 1 (HMGB1) and is abundantly present in the licorice root (Glycyrrhiza radix). HMGB1 protein, a key mediator of neuroinflammation, has been implicated in several neurological disorders, including epilepsy. Epilepsy is a devastating neurological disorder with no effective disease-modifying treatment strategies yet, suggesting a pressing need for exploring novel therapeutic options. In the current investigation, using a second hit pentylenetetrazol (PTZ) induced chronic seizure model in adult zebrafish, regulated mRNA expression of HMGB1 was inhibited by pretreatment with GL (25, 50, and 100 mg/kg, ip). A molecular docking study suggests that GL establishes different binding interactions with the various amino acid chains of HMGB1 and Toll-like receptor-4 (TLR4). Our finding suggests that GL pretreatment reduces/suppresses second hit PTZ induced seizure, as shown by the reduction in the seizure score. GL also regulates the second hit PTZ induced behavioral impairment and rescued second hit PTZ related memory impairment as demonstrated by an increase in the inflection ratio (IR) at the 3 h and 24 h T-maze trial. GL inhibited seizure-induced neuronal activity as demonstrated by reduced C-fos mRNA expression. GL also modulated mRNA expression of BDNF, CREB-1, and NPY. The possible mechanism underlying the anticonvulsive effect of GL could be attributed to its anti-inflammatory activity, as demonstrated by the downregulated mRNA expression level of HMGB1, TLR4, NF-kB, and TNF-α. Overall, our finding suggests that GL exerts an anticonvulsive effect and ameliorates seizure-related memory disruption plausibly through regulating of the HMGB1-TLR4-NF-kB axis.

This study was designed to seek the phytochemical analysis, antioxidant, enzyme inhibition, and toxicity potentials of methanol and dichloromethane (DCM) extracts of aerial and root parts ofCrotalaria burhia. Total bioactive content, high-performance liquid chromatography-photodiode array detector (HPLC-PDA) polyphenolic quantification, and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis were utilized to evaluate the phytochemical composition. Antioxidant [including 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH)], 2,2′-azino-bis[3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power assay (FRAP), cupric reducing antioxidant capacity CUPRAC, phosphomolybdenum, and metal chelation assays] and enzyme inhibition [against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, α-amylase, and tyrosinase] assays were carried out for biological evaluation. The cytotoxicity was tested against MCF-7 and MDA-MB-231 breast cell lines. The root-methanol extract contained the highest levels of phenolics (37.69 mg gallic acid equivalent/g extract) and flavonoids (83.0 mg quercetin equivalent/g extract) contents, and was also the most active for DPPH (50.04 mg Trolox equivalent/g extract) and CUPRAC (139.96 mg Trolox equivalent /g extract) antioxidant assays. Likewise, the aerial-methanol extract exhibited maximum activity for ABTS (94.05 mg Trolox equivalent/g extract) and FRAP (64.23 mg Trolox equivalent/g extract) assays. The aerial-DCM extract was noted to be a convincing cholinesterase (AChE; 4.01 and BChE; 4.28 mg galantamine equivalent/g extract), and α-glucosidase inhibitor (1.92 mmol acarbose equivalent/g extract). All of the extracts exhibited weak to modest toxicity against the tested cell lines. A considerable quantities of gallic acid, catechin, 4-OH benzoic acid, syringic acid, vanillic acid, 3-OH-4-MeO benzaldehyde, epicatechin,p-coumaric acid, rutin, naringenin, and carvacrol were quantifiedviaHPLC-PDA analysis. UHPLC-MS analysis of methanolic extracts from roots and aerial parts revealed the tentative identification of important phytoconstituents such as polyphenols, saponins, flavonoids, and glycoside derivatives. To conclude, this plant could be considered a promising source of origin for bioactive compounds with several therapeutic uses.

The US FDA approved Aducanumab in June 2021 as the first Alzheimer's disease (AD) drug under its accelerated approval pathway. It has given some hope to patients suffering from AD around the world. Aducanumab is an antibody that targets one of the well-known key culprits of this disease, known as amyloid-beta (Aβ). The journey of Aducanumab was bumpy, and there are controversies around the rapid approval of this drug AD treatment. This article highlights the potential of Aducanumab in AD, its mode of action and controversies around it.

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and has complicated underlying pathophysiology. Numerous TBI animal models have been developed over the past decade to effectively mimic the human TBI pathophysiology. These models are of mostly mammalian origin including rodents and non‐human primates. However, the mammalian models demanded higher costs and have lower throughput often limiting the progress in TBI research. Thus, this systematic review aims to discuss the potential benefits of non‐mammalian TBI models in terms of their face validity in resembling human TBI. Three databases were searched as follows: PubMed, Scopus, and Embase, for original articles relating to non‐mammalian TBI models, published between January 2010 and December 2019. A total of 29 articles were selected based on PRISMA model for critical appraisal. Zebrafish, both larvae and adult, was found to be the most utilized non‐mammalian TBI model in the current literature, followed by the fruit fly and roundworm. In conclusion, non‐mammalian TBI models have advantages over mammalian models especially for rapid, cost‐effective, and reproducible screening of effective treatment strategies and provide an opportunity to expedite the advancement of TBI research., Traumatic brain injury (TBI) perpetuates lifelong and dynamic effects on health and well‐being. Most of the animal models previously developed to study the TBI pathophysiology were focused mainly on mammalian animal model. Despite of all the contributions that they offered, these mammalian animal models have some drawback such as huge sample size needed and very costly which resulted in lengthy process of preclinical development phase with hindered reproducibility option. Hence, this systematic review gathered all the previous non‐mammalian animal model used in TBI research from January 2010 to December 2019 via 3 search engines which were Embase, Scopus, and PubMed. PRISMA method was chosen to select the research article for the discussion. The result shown on 3 popular species comprised of Danio rerio (zebrafish), Drosophila melanogaster (fruit fly), and Caenorhabditis elegans (roundworm). Criteria that were discussed were mainly on type of animal model, the functional findings, pathophysiological outcomes, and the limitation of the respective models. In conclusion, this non‐mammalian animal model provides more simplistic approach to bridge the knowledge gaps within TBI research and may shorten the preclinical process for the final findings on the outcome prevention and cure.

Epilepsy is a devastating neurological condition characterized by long-term tendency to generate unprovoked seizures, affecting around 1-2 % of the population worldwide. Epilepsy is a serious health concern which often associates with other neurobehavioral comorbidities that further worsen disease conditions. Despite tremendous research, the mainstream anti-epileptic drugs (AEDs) exert only symptomatic relief leading to 30% of untreatable patients. This reflects the complexity of the disease pathogenesis and urges the precise understanding of underlying mechanisms in order to explore novel therapeutic strategies that might alter the disease progression as well as minimize the epilepsy-associated comorbidities. Unfortunately, the development of novel AEDs might be a difficult process engaging huge funds, tremendous scientific efforts and stringent regulatory compliance with a possible chance of end-stage drug failure. Hence, an alternate strategy is drug repurposing, where anti-epileptic effects are elicited from drugs that are already used to treat non-epileptic disorders. Herein, we provide evidence of the anti-epileptic effects of Fingolimod (FTY720), a modulator of sphingosine-1-phosphate (S1P) receptor, USFDA approved already for Relapsing-Remitting Multiple Sclerosis (RRMS). Emerging experimental findings suggest that Fingolimod treatment exerts disease-modifying anti-epileptic effects based on its anti-neuroinflammatory properties, potent neuroprotection, anti-gliotic effects, myelin protection, reduction of mTOR signaling pathway and activation of microglia and astrocytes. We further discuss the underlying molecular crosstalk associated with the anti-epileptic effects of Fingolimod and provide evidence for repurposing Fingolimod to overcome the limitations of current AEDs.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In 2009, the National Trauma Database Malaysia reported that nearly 80% of traumas in the population were caused by road traffic accidents, with 64% of these cases related to TBI. Despite these concerning reports, TBI reporting systems and research are still limited in Malaysia. Thus, this systematic review aimed to identify and evaluate the available literature on TBI in Malaysia in order to uncover the status of TBI research in Malaysia. A comprehensive literature search was performed on four databases (PubMed, Embase, Medline and Scopus) regarding TBI in Malaysia. Critical evaluation of 60 relevant articles after application of inclusion and exclusion criteria have indicated that TBI research in Malaysia may have significant limitations in representing the actual TBI population and was lacking in basic TBI research. Thus, there is a dire need for government and private institutions to provide support for the advancement of TBI reporting and the progression of basic, clinical and translation TBI research in Malaysia. This will create a deeper understanding of TBI, contributing to global TBI knowledge, and advancing the development of efficient interventions for Malaysians with its population heterogeneity taken into consideration.

Neurodegenerative disorders encompass a range of conditions affecting the central nervous system (CNS) in which alterations in the neuronal structure and cellular dysfunction lead to progressive deterioration. Activation of microglia and expression of the inflammatory cytokine interleukin-1 (IL-1) in the CNS have become almost synonymous with neuroinflammation. Additionally, the relentless activation of the IL-1 signalling pathway has been linked with the pathogenesis of various CNS disease states, ranging from Alzheimer disease (AD), Parkinson disease (PD) to amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Moreover, a growing body of evidence has inferred that impeding the IL-1 signalling either pharmacologically or genetically in various CNS disease models could reduce neuroinflammation or delay disease progression. This review will therefore aim to study the role of IL-1 in neurodegenerative diseases and highlight the key aspects that warrant IL-1Ra as a promising target for developing a novel treatment for various CNS conditions.

Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA2 components, there is limited information on the function and activities of PLA2 toxins from the venom. In this study, a secretory PLA2 from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA2 from venoms of other Naja species. The PLA2 activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA2 isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line.

Aducanumab, a human monoclonal antibody, was approved in June of 2021 as the first disease-modifying treatment for Alzheimer’s disease by the United States Food and Drug Administration (U.S. FDA). A substantial proportion of patients with Alzheimer’s disease live in low- and middle-income countries (LMICs), and the debilitating effects of this disease exerts burdens on patients and caregivers in addition to the significant economic strains many nations bear. While the advantages of a disease-modifying therapy are clear in delaying the progression of disease to improve patient outcomes, aducanumab’s approval by the U.S. FDA was met with controversy for a plethora of reasons. This paper will provide precursory insights into aducanumab’s role, appropriateness, and cost-effectiveness in low- and middle-income countries. We extend some of the controversies associated with aducanumab, including the contradicting evidence from the two trials (EMERGE and ENGAGE) and the resources required to deliver the treatment safely and effectively to patients, among other key considerations.

Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA2 components, there is limited information on the function and activities of PLA2 toxins from the venom. In this study, a secretory PLA2 from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA2 from venoms of other Naja species. The PLA2 activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA2 isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line.

Background: The COVID-19 pandemic lockdowns have adversely impacted children on the autism spectrum and their families, especially in Malaysia where this population is often marginalized. The current quantitative research aimed to investigate the impact of the Malaysian COVID-19 lockdown on the behavior and psychological distress of children formally diagnosed with an autism spectrum condition (ASC) as well as the psychological distress and well-being of their parents, in comparison with a typically developing (TD) control group.Methods: The children's ages ranged between 5 and 17 years. The sample included 72 ASC parent-child dyads and 62 TD parent-child dyads. The primary caregiver completed an online survey including the following: demographic and diagnostic information; ASC symptoms; children's inattention, hyperactivity/impulsivity, perceived stress, depression, and anxiety; parents' perceived stress, depression, anxiety, and well-being based on their experience pre- and mid-lockdown (March 18th to June 9th 2020) in Malaysia.Results: Among the ASC group, no significant pre- and mid-lockdown change was found in ASC symptoms (p > 0.05). There were no significant gender differences (boys/girls) in all the child scales. The 2 [diagnosis (ASC, TD)] × 2 [lockdown (pre-lockdown, mid-lockdown)] mixed-model ANOVAs revealed main effects of lockdown on children's attention, hyperactivity/impulsivity, anxiety, and parents' perceived stress, depression, and psychological well-being (p < 0.005). There was a main effect of diagnosis in all child and parent variables, except parents' perceived stress (p >0.005). However, there was no significant interaction effect between diagnosis and lockdown (p >0.005). All child behavior (inattention and hyperactivity/impulsivity) and child psychological distress (anxiety, depression, and perceived stress) were significantly correlated in both the ASC and TD groups (p < 0.005). On the other hand, only some of the parent variables were significantly correlated with child variables (p < 0.0045) in the ASC group while none of the parent variables were significantly correlated with the child variables (p > 0.005) in the TD group.Conclusion: The results provide preliminary evidence indicating negative effects of the Malaysian lockdown on both children on the autism spectrum and TD children, as well as their parents. These quantitative results will be triangulated with the qualitative interview data to provide a holistic understanding of the impact of the pandemic, informing translational policy and practice recommendations.

Low-to-middle income countries (LMICs) in Southeast Asia (SEA) had the highest global traumatic brain injury (TBI). However, post-TBI rehabilitation care may be limited in these countries, thereby contributing to the poorer quality of life (QoL) of patients with TBI. The present systematic review aimed to elucidate the current status of post-TBI rehabilitation care in the LMICs in the SEA region and to discuss the limitations that may hinder the advancement of TBI rehabilitation within this region. A literature search was carried out using five databases (PubMed, Ovid MEDLINE, EMBASE, CINAHL and Scopus), and the final number of articles were selected according to the PRISMA guidelines. This review selected four relevant research articles from Malaysia and Thailand for critical appraisal. These articles showed that the status of post-TBI rehabilitation care in these regions remains unclear based on the scarcity of available literature. Only early rehabilitation care strategies have been discussed in the literature, such as individualised structured cognitive rehabilitation, utilisation of humanoid robots and the implementation of sensory stimulation programs. This review also suggested that TBI rehabilitation improvements may be hindered by a lack of government funding, unequal distribution of care services and reliance on traditional care. Thus, more research into TBI rehabilitation care is significantly needed within the SEA region to overcome these barriers, leading to the preservation of patients’ QoL.

Epilepsy is a debilitating disorder that affects about 70 million people in the world currently. Most patients with epilepsy (PWE) often reported at least one type of comorbid disorder. These may include neuropsychiatric disorders, cognitive deficits, migraine, cardiovascular dysfunction, systemic autoimmune disorders and others. Current treatment strategies against epilepsy-associated comorbidities have been based on targeting each disorder separately with either anti-seizure medications (ASMs), anti-inflammatories or anti-depressant drugs, which have often given inconsistent and ineffective results. Gut dysbiosis may be a common pathological pathway between epilepsy and its comorbid disorders, and thus may serve as a possible intervention target. Therefore, this narrative review aimed to elucidate the potential pathological and therapeutic role of the gut microbiota in adult epilepsy-associated comorbidities. This review noticed a scarcity in the current literature on studies investigating the direct role of the gut microbiota in relation to epilepsy-associated comorbidities. Nevertheless, gut dysbiosis have been implicated in both epilepsy and its associated comorbidities, with similarities seen in the imbalance of certain gut microbiota phyla (Firmicutes), but differences seen in the mechanism of action. Current gut-related interventions such as probiotics have been consistently reported across studies to provide beneficial effects in correcting gut dysbiosis and improving various disorders, independent of epilepsy. However, whether these beneficial effects may translate towards epilepsy-associated comorbidities have yet to be determined. Thus, future studies determining the therapeutic potential of gut microbiota interventions in PWE with epilepsy-associated comorbidities may effectively improve their quality of life.

Extensive studies have been conducted on natural materials due to their unique and biodegradable properties for oral drug delivery. In the current research, we fabricated sodium caseinate nanomicelles (NaCNs) using casein as a natural polymer to develop a controlled-release oral drug delivery system. NaCNs was explored to improve the therapeutic potential of Doxorubicin (DOX) with reduced toxicity in healthy organs. The synthesized and thoroughly characterized DOX-loaded NaCNs were subjected to in vivo anti-tumour evaluation and bio-distribution analysis in a 4T1-induced breast cancer model. Our findings indicated an almost eight-fold reduction in tumour size in the group orally treated with DOX-NaCNs when compared to free DOX. It is plausible that the enhanced anti-tumour effects of oral DOX-NaCNs is related to the controlled release of DOX from the delivery system as well as the longer circulatory time of the drug in the blood, as confirmed by the bio-distribution study, when compared with free DOX and the intravenous formulation of DOX-NaCNs. Additionally, the tumour drug accumulation for the orally administered DOX-NaCNs was 1.27- and 6.8-fold higher than that of the intravenously administered DOX-NaCNs and free DOX, respectively and overall, was 8.34-times higher than the orally administered free DOX. In comparison, the orally administered DOX-NaCNs showed significant reduction in tumour size (5.66 ± 4.36mm3) after the two doses as compared to intravenously administered DOX-NaCNs (10.29 ± 4.86 mm3) on day 17 of the experimental period. Moreover, NaCNs were well tolerated in the mice at a single dose of 2,000 mg/kg in an acute oral toxicity study. Moreover, no significant change in the body weight was observed after treatment with the single dose of NaCNs when compared to the control group. Thus, NaCNs emerge as a safe and non-toxic delivery system with excellent bio-distribution profile and high anti-tumour effects that present as a potential option for oral chemotherapy.

Background: Epilepsy is a devastating neurological disorder that affects nearly 70 million people worldwide. Epilepsy causes uncontrollable, unprovoked and unpredictable seizures that reduce the quality of life of those afflicted, with 1-9 epileptic patient deaths per 1000 patients occurring annually due to sudden unexpected death in epilepsy (SUDEP). Predicting the onset of seizures and managing them may help patients from harming themselves and may improve their well-being. For a long time, electroencephalography (EEG) devices have been the mainstay for seizure detection and monitoring. This systematic review aimed to elucidate and critically evaluate the latest advancements in medical devices, besides EEG, that have been proposed for the management and prediction of epileptic seizures. A literature search was performed on three databases, PubMed, Scopus and EMBASE. Methods: Following title/abstract screening by two independent reviewers, 27 articles were selected for critical analysis in this review. Results: These articles revealed ambulatory, non-invasive and wearable medical devices, such as the in-ear EEG devices; the accelerometer-based devices and the subcutaneous implanted EEG devices might be more acceptable than traditional EEG systems. In addition, extracerebral signalbased devices may be more efficient than EEG-based systems, especially when combined with an intervention trigger. Although further studies may still be required to improve and validate these proposed systems before commercialization, these findings may give hope to epileptic patients, particularly those with refractory epilepsy, to predict and manage their seizures. Conclusion: The use of medical devices for epilepsy may improve patients' independence and quality of life and possibly prevent sudden unexpected death in epilepsy (SUDEP).

Seizures are the outward manifestation of abnormally excessive or synchronous brain activity. While seizures can be somewhat symptomatically managed with anti-epileptic drugs (AEDs), many patients are still refractory to the currently available AEDs. As a result, there is a need to identify new molecules with anti-seizure properties. Curcumin is the principle curcuminoid of Curcuma longa, or colloquially turmeric, and has been experimentally proven to have anti-convulsive properties, but its poor bioavailability has dampened further therapeutic interest. Hence, this study aimed to ask if structural analogues of curcumin with an adequate bioavailability could have an anti-seizure effect in vivo. To do so, we tested these analogues following a multipronged approach combining the use of several zebrafish seizure models (chemically-induced and genetic) and complementary assays (behavioural and brain activity). Overall, from the 68 analogues tested, we found 15 different derivatives that were able to significantly decrease the behavioural hyperactivity induced by pentylenetetrazol. Of those, only a few showed an effect on the hyperactivity phenotype of two genetic models of brain seizures that are the gabra1 and gabrg2 knockouts. Two analogues, CA 80(1) and CA 74(1), were able to significantly alleviate brain seizures of gabrg2-mutant larvae. As a result, these analogues are good candidates as novel anti-seizure agents.

The genetic epidemiology suggests that coronavirus disease 2019 (COVID-19) is most likely transmitted to the human population in November or December 2019, originating from Wuhan and spread entirely by human-to-human transmission. The period of the Chinese New Year holidays is thought to be one of the key periods where a substantial transmission took place within Wuhan. Moreover, the movement of people from Wuhan resulted in massive spread nationally and internationally when people traveled during the holidays.

Epileptic seizures result from excessive brain activity and may affect sensory, motor and autonomic function; as well as, emotional state, memory, cognition or behaviour. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. Medicinal plants are potential candidates for novel AEDs, as many are traditional epilepsy remedies. Malaysia is a megadiverse country, with many endemic plants serving as a large pool of potential candidates for the development of local herbal products. The large variety of flora make Malaysia a prime location for the discovery of medicinal plants with anti-convulsive potential. This review lists 23 Malaysian medicinal plants, of which four are used traditionally to treat epilepsy, without any scientific evidence. A further eight plants have no known traditional anti-epileptic use but have scientific evidence of its anti-epileptic activity. The remaining 11 plants possess both traditional use and scientific evidence. Thus, this review identified several potential candidates for the development of novel AEDs or enhancing current ones; as well as identified an imbalance between traditional use and scientific evidence. In addition, this review also identified several limitations in the reviewed studies and provided additional information to facilitate the design of future studies.

Objective: This research revealed the biochemical outcomes of metabolic dysregulation in serum associated with physiological sickness behavior following lipopolysaccharide (LPS)-induced neuroinflammation in rats, and treatment with Clinacanthus nutans (CN). Verification of 1H NMR analysis of the CN aqueous extract proved the existence of bioactive phytochemical constituents’ in extract. Materials and Methods: Twenty-five rats were subjected to unilateral stereotaxic injection of 10 µL LPS (1 mg/mL), while another ten rats were injected with phosphate-buffered saline (PBS, 10 µL) as control. Then, 29 parameters of rat behavior related to sickness were tracked by a device software (SMART 3.0.1) on days 0 and 14 of CN treatment. The acquired and accumulated data were analyzed using multivariate data analysis with the SIMCA Software package (version 13, Umetrics AB; Umeå, Sweden). The pattern trends of related groups were documented using PCA and OPLS analysis. Results: A similar ameliorated correlation pattern was detected between improvement in physiological sickness behavior and anti-inflammatory biomarkers by the 1H NMR spectra of the sera following treatment with CN (500 and 1000 mg/kg body weight (bw)) and the control drug (dextromethorphan hydrobromide, 5 mg/kg of rats bw) in rats. Here, 21 biomarkers were detected for neuroinflammation. Treatment with the aqueous CN extract resulted in a statistically significant alteration in neuroinflammation metabolite biomarkers, including ethanol, choline, and acetate. Conclusion: This result denotes that the metabolomics approach is a reliable tool to disclose the relationship between central neuroinflammation, and systemic metabolic and physiological disturbances which could be used for future ethno-pharmacological assessments.

The use of metabolomics as a comprehensive tool in the analysis of metabolic profiles in disease progression and therapeutic intervention is rapidly advancing. Yet, a single analytical platform could not be applied to cover the entire spectrum of a biological sample’s metabolome. In the present paper, multi-platform metabolomics approaches were explored to determine the diverse rat sera metabolites extracted from intracerebroventricular lipopolysaccharides (LPS)-induced neuroinflammed rats treated with oral therapeutic interventions of positive drug (dextromethorphan, 5 mg/kg BW); with Clinacanthus nutans (CN) aqueous extract (CNE, 500 mg/kg BW); and with phosphate buffer saline (PBS) as the control group for 14 days. Analyzed by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) techniques, this study depicted the potential of metabolites associated with neuroinflammation and verified by MetDisease. The key observations in the perturbed metabolic pathways that showed ameliorative effects were linked to the class of amino acid and peptide metabolism involving valine, leucine, and isoleucine biosynthesis; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Lipid metabolism of arachidonic acid metabolism, glycerophospholipid metabolism, terpenoid backbone biosynthesis, and glycosphingolipid metabolism were also affected. Current findings suggested that the putative biomarkers, especially lysophosphatidic acid (LPA) and 5-diphosphomevalonic acid from glycerophospholipid and squalene/terpenoid and cholesterol biosynthesis, respectively, showed the ameliorative effects of the drug and CN treatments by controlling cell differentiation and proliferation. Our study proved that the complex and dynamic sera profiling affected during the CN treatment was greatly influenced by the analytical platform selection as integration between the two data yielded a more holistic summary of the metabolite pattern changes. Hence, an evidence-based herb, such as CN, can be used for novel diagnostic tools in the quest for ethnopharmacological studies.

Ocimum sanctum is a sacred herb of India and is commonly known as 'Tulsi' or 'Holy Basil' in regional languages of the country. Various parts of O. sanctum are recognised to have remarkable therapeutic efficacy, and are therefore used in Indian traditional medicine system, Ayurveda. Scientific studies have shown that O. sanctum has a range of pharmacological activities. The presence of a substantial amount of polyphenols in O. sanctum could be the reason for its excellent bioactivity. Polyphenols are used to prevent or treat oncologic diseases due to their anti-cancer effects, which are related to activation of apoptotic signaling, cell cycle arrest, binding ability with membrane receptors, and potential effects on immunomodulation and epigenetic mechanisms. The poor bioavailability of polyphenols restricts their clinical use. The application of nanonization has been implemented to improve their bioavailability, penetrability, and prolong their anticancer action. The present review analyses the recent preclinical studies related to the chemo-preventive and therapeutic potential of polyphenols present in O. sanctum. Moreover, the current article also examines in-depth the biochemical and molecular mechanisms involved in the antineoplastic actions of the considered polyphenols.

Epilepsy is a devastating neurological disorder. Current anti-convulsant drugs are only effective in about 70% of patients, while the rest remain drug-resistant. Thus, alternative methods have been explored to control seizures in these drug-resistant patients. One such method may be through the utilization of fruit phytochemicals. These phytochemicals have been reported to have beneficial properties such as anti-convulsant, anti-oxidant, and anti-inflammatory activities. However, some fruits may also elicit harmful effects. This review aims to summarize and elucidate the anti- or pro-convulsant effects of fruits used in relation to seizures in hopes of providing a good therapeutic reference to epileptic patients and their carers. Three databases, SCOPUS, ScienceDirect, and PubMed, were utilized for the literature search. Based on the PRISMA guidelines, a total of 40 articles were selected for critical appraisal in this review. Overall, the extracts and phytochemicals of fruits managed to effectively reduce seizure activities in various preclinical seizure models, acting mainly through the activation of the inhibitory neurotransmission and blocking the excitatory neurotransmission. Only star fruit has been identified as a pro-convulsant fruit due to its caramboxin and oxalate compounds. Future studies should focus more on utilizing these fruits as possible treatment strategies for epilepsy.

Epilepsy is a debilitating disorder of uncontrollable recurrent seizures that occurs as a result of imbalances in the brain excitatory and inhibitory neuronal signals, that could stem from a range of functional and structural neuronal impairments. Globally, nearly 70 million people are negatively impacted by epilepsy and its comorbidities. One such comorbidity is the effect epilepsy has on the autonomic nervous system (ANS), which plays a role in the control of blood circulation, respiration and gastrointestinal function. These epilepsy-induced impairments in the circulatory and respiratory systems may contribute toward sudden unexpected death in epilepsy (SUDEP). Although, various hypotheses have been proposed regarding the role of epilepsy on ANS, the linking pathological mechanism still remains unclear. Channelopathies and seizure-induced damages in ANS-control brain structures were some of the causal/pathological candidates of cardiorespiratory comorbidities in epilepsy patients, especially in those who were drug resistant. However, emerging preclinical research suggest that neurotransmitter/receptor dysfunction and synaptic changes in the ANS may also contribute to the epilepsy-related autonomic disorders. Thus, pathological mechanisms of cardiorespiratory dysfunction should be elucidated by considering the modifications in anatomy and physiology of the autonomic system caused by seizures. In this regard, we present a comprehensive review of the current literature, both clinical and preclinical animal studies, on the cardiorespiratory findings in epilepsy and elucidate the possible pathological mechanisms of these findings, in hopes to prevent SUDEP especially in patients who are drug resistant.

Epilepsy is a result of unprovoked, uncontrollable, and repetitive outburst of abnormal and excessive electrical discharges, known as seizures, in the neurons. Epilepsy is a devastating neurological condition that affects 70 million people globally. Unfortunately, only two-thirds of epilepsy patients respond to antiepileptic drugs while others become drug resistant and may be more prone to epilepsy comorbidities such as SUDEP. Oxidative stress, mitochondrial dysfunction, imbalance in the excitatory and inhibitory neurotransmitters, and neuroinflammation are some of the common pathologies of neurological disorders and epilepsy. Studies suggests that melatonin, a pineal hormone that governs sleep-wake cycles, may be neuroprotective against neurological disorders and thus may be translated as an antiepileptic as well. Melatonin has been shown to be an antioxidant, antiexcitotoxic, and anti-inflammatory hormone/molecule in neurodegenerative diseases, which may contribute to its antiepileptic and neuroprotective properties in epilepsy as well. In addition, melatonin has evidently been shown to play a regulatory role in the cardiorespiratory system and sleep-wake cycles, which may have positive implications toward epilepsy associated comorbidities, such as SUDEP. However, studies investigating the changes in melatonin release due to epilepsy and melatonin's antiepileptic role have been inconclusive and scarce, respectively. Thus, this comprehensive review aims to summarize and elucidate the potential role of melatonin in the pathogenesis of epilepsy and its comorbidities, in hopes to develop new diagnostic and therapeutic approaches that will improve the lives of epileptic patients, particularly those who are drug resistant.

Embelin is a neuroprotective compound with therapeutic benefit against experimental Alzheimer's disease (AD)-like condition. In the quest of untangling the underlying mechanism behind the neuroprotective effect of Embelin in AD, an

Epilepsy is known as one of the major challenges for medical science. The sudden appearance of a seizure has been a significant health emergency as it may lead to further complications. Although key advancements have been achieved in terms of pharmacological approaches for epilepsy, many issues remain uncertain. Lipid carriers have been at the forefront, especially in neurodegenerative diseases, such as epilepsy, Alzheimer’s, dementia, etc. The blood-brain barrier still appears to be a major impediment in the successful treatment of epileptic seizures. This is mainly due to the limited bioavailability of most anti-convulsant drugs. The present review encompasses the issues underlying the current approach for epilepsy drug treatment and highlights the newer, novel, and more precise drug delivery system to manage seizures. The advantage of using a lipidbased delivery system is its superior absorption in the brain cells. Ample evidence shows that reducing the particle size also infuses the drug easily through the blood-brain barrier. The application of liposomes, polymeric nanoparticles, metallic nanoparticles, and solid lipid nanoparticles for the treatment and management of epilepsy has been highlighted in the present review. This review provides an overview of the current status of the treatment and recent advances in the treatment of epilepsy.

Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of Poly(Ethylene Oxide) (PEO) and poly(propylene oxide) (PPO). Due to its amphiphilic nature and high Hydrophile-Lipophile Balance (HLB) value of 29, P188 is used as a stabilizer/emulsifier in many cosmetics and pharmaceutical preparations. While the applications of P188 as an excipient are widely explored, the data on the pharmacological activity of P188 are scarce. Notably, the neuroprotective potential of P188 has gained a lot of interest. Therefore, this systematic review is aimed at summarizing evidence of neuroprotective potential of P188 in CNS disorders. The PRISMA model was used, and five databases (Google Scholar, Scopus, Wiley Online Library, ScienceDirect, and PubMed) were searched with relevant keywords. The search resulted in 11 articles, which met the inclusion criteria. These articles described the protective effects of P188 on traumatic brain injury or mechanical injury in cells, neurotoxicity, Parkinson’s disease, Amyotrophic lateral sclerosis (ALS), and ischemia/ reperfusion injury from stroke. All the articles were original research in experimental or pre-clinical stages using animal models or in vitro systems. The reported activities demonstrated the potential of P188 as a neuroprotective agent in improving CNS conditions such as neurodegeneration.

Background and aims Diabetic ketoacidosis (DKA) treatment guidelines recommend to initiate potassium-replacement when serum potassium (SK) drops within normal range, and to withhold insulin if SK is below normal. Despite strict recommendations, hypokalemia is frequently observed in DKA. Methods Scientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia. Results Acidosis affects SK and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing SK level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated. Conclusion In light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge.

Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.

Over the decades, various interventions have been developed and utilized to treat epilepsy. However, the majority of epileptic patients are often first prescribed anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as the first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action, including regulation of ion channels, blocking glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one-third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects, which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects, such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggests that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect-free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.

BACKGROUND Incidence of hypokalemia during the management of diabetic ketoacidosis (DKA) is high despite detailed potassium replacement guidelines in its treatment. AIM We aimed to find the role of pH-adjusted potassium (pHK ) in the development of hypokalemia, and their mutual impact on patient outcomes during DKA management. METHODOLOGY Adult DKA patient's admission data of preceding 3 years (2015-2017) were retrospectively clerked. Outcomes of interest were time to develop hypokalemia and to terminate emergency department (ED) care (hours), severity of hypokalemia and hospitalisation length (days). Linear regression was used to determine significant associations/predictors. RESULTS The study was concluded on 85 patients. Hypokalemia was observed in nearly 3/4th of all admissions and occurred by the time of ED care termination. Each 1 mmol/L increase in pHK significantly (a) reduced the degree of hypokalemia by 0.07 mmol/L, (b) delayed time to develop hypokalemia by 4.58 hours, (c) and reduced the ED care time by 1.28 hours. Arterial pH was the other factor significantly delaying time to develop hypokalemia (36.25 hours) and facilitating early discharge from ED (13.86 hours). Moreover, each 1 mmol/L reduction in the degree of hypokalemia increased hospitalisation length by 1.86 days. Though significant, acute kidney injury negligibly increased hospitalisation length by 0.01 days. CONCLUSION pH-adjusted potassium shall be used as a marker for hypokalemia and to initiate potassium replacement instead of measured serum potassium in DKA. Utilising pHK will help to avoid hypokalemia, reduce its severity and shorten ED care which will subsequently reduce hospitalisation length. We expect pHK to improve pharmacoeconomics in the future.

Polyphenolic phytoconstituents have been widely in use worldwide since ages and are categorised as secondary metabolites of plants. The application of polyphenols such as quercetin, resveratrol. curcumin as nutritional supplement has been researched widely. The use of polyphenols, and specifically quercetin for improving the memory and mental endurance have shown significant effects among rats. Even though similar results has not been resonated among human but encouraging preclinical results have encouraged researchers to explore other polyphenols to study the effects as supplements among athletes. The phytopharmacological research has elucidated the use of natural polyphenols to prevent and treat various physiological and metabolic disorders owing to its free radical scavenging properties, anti-inflammatory, anti-cancer and immunomodulatory effects. In spite of the tremendous pharmacological profile, one of the most dominant problem regarding the use of polyphenolic compounds is their low bioavailability. Nanonization is considered as one of the most prominent approaches among many. This article aims to review and discuss the molecular mechanisms of recently developed nanocarrier-based drug delivery systems for polyphenols and its application as drugs and supplements. Nanoformulations of natural polyphenols are bioactive agents, such as quercetin, kaempferol, fisetin, rutin, hesperetin, and naringenin epigalloccatechin-3-gallate, genistein, ellagic acid, gallic acid, chlorogenic acid, ferulic acid, curcuminoids and stilbenes is expected to have better efficacy. These delivery systems are expected to provide higher penetrability of polyphenols at cellular levels and exhibit a controlled release of the drugs. It is widely accepted that natural polyphenols do demonstrate significant therapeutic effect. However, the hindrances in their absorption, specificity and bioavailability can be overcome using nanotechnology.

Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.

Curcuma longa (Turmeric) is a tropical herbaceous perennial plant of the family Zingiberaceae and contains curcuminoids, sesquiterpenoids and monoterpenoids as its major components. Given the broad range of activities that Curcuma longa possesses and also its use as a traditional epilepsy remedy, this review attempts to systematically review the experimentally proven activities of Curcuma longa and its bioactive components, which are related to the management of epileptic seizures. Using the PRISMA model, five databases (Google Scholar, PubMed, ScienceDirect, SCOPUS and SpringerLink) were searched using the keywords ["Curcuma longa" AND "Epilepsy"] and ["Curcuma longa" AND "Seizures"], leaving 34 articles that met the inclusion criteria. The present systematic review elaborated on the experimentally proven potential of Curcuma longa components, such as an aqueous extract of Curcuma longa itself, Curcuma longa oil and active constituents like curcuminoids and bisabolene sesquiterpenoids found in Curcuma longa with anti-seizure potential. Using human equivalent dose calculations, human treatment parameters were suggested for each component by analysing the various studies in this review. This review also determined that the principal components possibly exert their anti-seizure effect via the reduction of corticosterone, modulation of neurotransmitters signalling, modulation of sodium ion channels, reduction of oxidative DNA damage, reduction of lipid peroxidation, upgregulation of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) mediated inhibition. It is anticipated that this review will help pave the way for future research into the development of Curcuma longa and its neuroactive constituents as potential drug candidates for the management of epilepsy.

The exact etiology of Parkinson's disease (PD) remains obscure, although many cellular mechanisms including α-synuclein aggregation, oxidative damage, excessive neuroinflammation, and dopaminergic neuronal apoptosis are implicated in its pathogenesis. There is still no disease-modifying treatment for PD and the gold standard therapy, chronic use of levodopa is usually accompanied by severe side effects, mainly levodopa-induced dyskinesia (LID). Hence, the elucidation of the precise underlying molecular mechanisms is of paramount importance. Fyn is a tyrosine phospho-transferase of the Src family nonreceptor kinases that is highly implicated in immune regulation, cell proliferation and normal brain development. Accumulating preclinical evidence highlights the emerging role of Fyn in key aspects of PD and LID pathogenesis: it may regulate α-synuclein phosphorylation, oxidative stress-induced dopaminergic neuronal death, enhanced neuroinflammation and glutamate excitotoxicity by mediating key signaling pathways, such as BDNF/TrkB, PKCδ, MAPK, AMPK, NF-κB, Nrf2, and NMDAR axes. These findings suggest that therapeutic targeting of Fyn or Fyn-related pathways may represent a novel approach in PD treatment. Saracatinib, a nonselective Fyn inhibitor, has already been tested in clinical trials for Alzheimer's disease, and novel selective Fyn inhibitors are under investigation. In this comprehensive review, we discuss recent evidence on the role of Fyn in the pathogenesis of PD and LID and provide insights on additional Fyn-related molecular mechanisms to be explored in PD and LID pathology that could aid in the development of future Fyn-targeted therapeutic approaches.

Post-traumatic epilepsy (PTE) is one of the detrimental outcomes of traumatic brain injury (TBI), resulting in recurrent seizures that impact daily life. However, the pathological relationship between PTE and TBI remains unclear, and commonly prescribed antiepileptic drugs (AED) are ineffective against PTE. Fortunately, emerging research implicates neuroinflammation, particularly, tumor necrosis factor-α (TNF-α), as the key mediator for PTE development. Thus, this review aims to examine the available literature regarding the role of TNF-α in PTE pathology and, subsequently, evaluate TNF-α as a possible target for its treatment. A comprehensive literature search was conducted on four databases including PubMed, CINAHL, Embase, and Scopus. Articles with relevance in investigating TNF-α expression in PTE were considered in this review. Critical evaluation of four articles that met the inclusion criteria suggests a proportional relationship between TNF-α expression and seizure susceptibilit and that neutralization or suppression of TNF-α release results in reduced susceptibility to seizures. In conclusion, this review elucidates the importance of TNF-α expression in epileptogenesis postinjury and urges future research to focus more on clinical studies involving TNF-α, which may provide clearer insight into PTE prevention, therefore improving the lives of PTE patients.

Lack of disease-modifying therapy against epileptogenesis reflects the complexity of the disease pathogenesis as well as the high demand to explore novel treatment strategies. In the pursuit of developing new therapeutic strategies against epileptogenesis, neurodegenerative proteins have recently gained increased attention. Owing to the fact that neurodegenerative disease and epileptogenesis possibly share a common underlying mechanism, targeting neurodegenerative proteins against epileptogenesis might represent a promising therapeutic approach. Herein, we review the association of neurodegenerative proteins, such as α-synuclein, amyloid-beta (Aβ), and tau protein, with epilepsy. Providing insight into the α-synuclein, Aβ and tau protein-mediated neurodegeneration mechanisms, and their implication in epileptogenesis will pave the way towards the development of new agents and treatment strategies.

Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps.