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Chemotherapeutic Role of Polyphenols Present in Ocimum sanctum

Khatoon S, Kalam N, Balasubramaniam VR, Shaikh MF, Ansari MT

Anticancer Agents Med Chem, 2022;22(20):3325-3342.
PMID: 35578854 DOI: 10.2174/1871520622666220516142839

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.
Fulltext Channa striatus in inflammatory conditions: A systematic review

Lee VLL, Choo BKM, Norazit A, Noor SM, Shaikh MF

Front Pharmacol, 2022;13:1076143.
PMID: 36545318 DOI: 10.3389/fphar.2022.1076143

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.
Epigenetics in depression and gut-brain axis: A molecular crosstalk

Begum N, Mandhare A, Tryphena KP, Srivastava S, Shaikh MF, Singh SB, et al.

Front Aging Neurosci, 2022;14:1048333.
PMID: 36583185 DOI: 10.3389/fnagi.2022.1048333

Gut-brain axis is a dynamic, complex, and bidirectional communication network between the gut and brain. Changes in the microbiota-gut-brain axis are responsible for developing various metabolic, neurodegenerative, and neuropsychiatric disorders. According to clinical and preclinical findings, the gut microbiota is a significant regulator of the gut-brain axis. In addition to interacting with intestinal cells and the enteric nervous system, it has been discovered that microbes in the gut can modify the central nervous system through metabolic and neuroendocrine pathways. The metabolites of the gut microbiome can modulate a number of diseases by inducing epigenetic alteration through DNA methylation, histone modification, and non-coding RNA-associated gene silencing. Short-chain fatty acids, especially butyrate, are well-known histone deacetylases inhibitors. Similarly, other microbial metabolites such as folate, choline, and trimethylamine-N-oxide also regulate epigenetics mechanisms. Furthermore, various studies have revealed the potential role of microbiome dysbiosis and epigenetics in the pathophysiology of depression. Hence, in this review, we have highlighted the role of gut dysbiosis in epigenetic regulation, causal interaction between host epigenetic modification and the gut microbiome in depression and suggest microbiome and epigenome as a possible target for diagnosis, prevention, and treatment of depression.
Fulltext Preclinical Models for Alzheimer's Disease: Past, Present, and Future Approaches

Akhtar A, Gupta SM, Dwivedi S, Kumar D, Shaikh MF, Negi A

ACS Omega, 2022 Dec 27;7(51):47504-47517.
PMID: 36591205 DOI: 10.1021/acsomega.2c05609

A robust preclinical disease model is a primary requirement to understand the underlying mechanisms, signaling pathways, and drug screening for human diseases. Although various preclinical models are available for several diseases, clinical models for Alzheimer's disease (AD) remain underdeveloped and inaccurate. The pathophysiology of AD mainly includes the presence of amyloid plaques and neurofibrillary tangles (NFT). Furthermore, neuroinflammation and free radical generation also contribute to AD. Currently, there is a wide gap in scientific approaches to preventing AD progression. Most of the available drugs are limited to symptomatic relief and improve deteriorating cognitive functions. To mimic the pathogenesis of human AD, animal models like 3XTg-AD and 5XFAD are the primarily used mice models in AD therapeutics. Animal models for AD include intracerebroventricular-streptozotocin (ICV-STZ), amyloid beta-induced, colchicine-induced, etc., focusing on parameters such as cognitive decline and dementia. Unfortunately, the translational rate of the potential drug candidates in clinical trials is poor due to limitations in imitating human AD pathology in animal models. Therefore, the available preclinical models possess a gap in AD modeling. This paper presents an outline that critically assesses the applicability and limitations of the current approaches in disease modeling for AD. Also, we attempted to provide key suggestions for the best-fit model to evaluate potential therapies, which might improve therapy translation from preclinical studies to patients with AD.
Fulltext Medical Technology: A Systematic Review on Medical Devices Utilized for Epilepsy Prediction and Management

Ong JS, Wong SN, Arulsamy A, Watterson JL, Shaikh MF

Curr Neuropharmacol, 2022;20(5):950-964.
PMID: 34749622 DOI: 10.2174/1570159X19666211108153001

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).
Fulltext Poloxamer 188 (P188), A Potential Polymeric Protective Agent for Central Nervous System Disorders: A Systematic Review

Chen WN, Shaikh MF, Bhuvanendran S, Date A, Ansari MT, Radhakrishnan AK, et al.

Curr Neuropharmacol, 2022;20(4):799-808.
PMID: 34077349 DOI: 10.2174/1570159X19666210528155801

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.
Correction to: Understanding translational research in schizophrenia: A novel insight into animal models

Malik JA, Yaseen Z, Lahari T, Ahmed S, Shaikh MF, Anwar S

Mol Biol Rep, 2023 Apr 06.
PMID: 37024749 DOI: 10.1007/s11033-023-08352-1
Fulltext Editorial: Experimental models of epilepsy and related comorbidities, Volume II

Shaikh MF, Ngadimon IW, Chakraborti A, Abdullah JM, Russo E

Front Pharmacol, 2023;14:1182958.
PMID: 37033657 DOI: 10.3389/fphar.2023.1182958
Fulltext Understanding translational research in schizophrenia: A novel insight into animal models

Malik JA, Yaseen Z, Thotapalli L, Ahmed S, Shaikh MF, Anwar S

Mol Biol Rep, 2023 Apr;50(4):3767-3785.
PMID: 36692676 DOI: 10.1007/s11033-023-08241-7

Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.
Editorial: Ion-channels in epilepsy

Akyuz E, Lazarowski A, de Cabo C, Godlevsky LS, Shaikh MF, Doganyigit Z

Front Neurol, 2023;14:1263539.
PMID: 37638194 DOI: 10.3389/fneur.2023.1263539
Fulltext The Role of Interferon-α in Neurodegenerative Diseases: A Systematic Review

Hui BSM, Zhi LR, Retinasamy T, Arulsamy A, Law CSW, Shaikh MF, et al.

J Alzheimers Dis, 2023;94(s1):S45-S66.
PMID: 36776068 DOI: 10.3233/JAD-221081

BACKGROUND: Neurodegenerative diseases (NDs) impose significant financial and healthcare burden on populations all over the world. The prevalence and incidence of NDs have been observed to increase dramatically with age. Hence, the number of reported cases is projected to increase in the future, as life spans continues to rise. Despite this, there is limited effective treatment against most NDs. Interferons (IFNs), a family of cytokines, have been suggested as a promising therapeutic target for NDs, particularly IFN-α, which governs various pathological pathways in different NDs.
OBJECTIVE: This systematic review aimed to critically appraise the currently available literature on the pathological role of IFN-α in neurodegeneration/NDs.
METHODS: Three databases, Scopus, PubMed, and Ovid Medline, were utilized for the literature search.
RESULTS: A total of 77 journal articles were selected for critical evaluation, based on the inclusion and exclusion criteria. The studies selected and elucidated in this current systematic review have showed that IFN-α may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-α may be displaying its neurotoxic function via various mechanisms such as abnormal calcium mineralization, activation of STAT1-dependent mechanisms, and increased quinolinic acid production.
CONCLUSION: The exact role IFN-α in these neurodegenerative diseases have yet to be determine due to a lack in more recent evidence, thereby creating a variability in the role of IFN-α. Future investigations should thus be conducted, so that the role played by IFN-α in neurodegenerative diseases could be delineated.
Fulltext Neuroinflammation: A Common Pathway in Alzheimer's Disease and Epilepsy

Liew Y, Retinasamy T, Arulsamy A, Ali I, Jones NC, O'Brien TJ, et al.

J Alzheimers Dis, 2023;94(s1):S253-S265.
PMID: 37092226 DOI: 10.3233/JAD-230059

BACKGROUND: Neuroinflammation is an innate immunological response of the central nervous system that may be induced by a brain insult and chronic neurodegenerative conditions. Recent research has shown that neuroinflammation may contribute to the initiation of Alzheimer's disease (AD) pathogenesis and associated epileptogenesis.
OBJECTIVE: This systematic review aimed to investigate the available literature on the shared molecular mechanisms of neuroinflammation in AD and epilepsy.
METHODS: The search included in this systematic review was obtained from 5 established databases. A total of 2,760 articles were screened according to inclusion criteria. Articles related to the modulation of the inflammatory biomarkers commonly associated with the progression of AD and epilepsy in all populations were included in this review.
RESULTS: Only 7 articles met these criteria and were chosen for further analysis. Selected studies include both in vitro and in vivo research conducted on rodents. Several neuroinflammatory biomarkers were reported to be involved in the cross-talk between AD and epilepsy.
CONCLUSION: Neuroinflammation was directly associated with the advancement of AD and epilepsy in populations compared to those with either AD or epilepsy. However, more studies focusing on common inflammatory biomarkers are required to develop standardized monitoring guidelines to prevent the manifestation of epilepsy and delay the progression of AD in patients.
Can endoplasmic reticulum stress observed in the PTZ-kindling model seizures be prevented with TUDCA and 4-PBA?

Doğanyiğit Z, Okan A, Akyüz E, Yılmaz S, Ateş Ş, Taheri S, et al.

Eur J Pharmacol, 2023 Oct 16;960:176072.
PMID: 37852571 DOI: 10.1016/j.ejphar.2023.176072

Epilepsy is a chronic neurological disease with recurrent seizures. Increasing evidence suggests that endoplasmic reticulum (ER) stress may play a role in the pathogenesis of epilepsy. We aimed to investigate the effects of Tauroursodeoxycholic acid (TUDCA) and 4-phenyl-butyric acid (4-PBA), which are known to suppress ER stress, on developed seizures in terms of markers of ER stress, oxidative stress, and apoptosis. The pentylenetetrazole (PTZ) kindling model was induced in Wistar albino rats (n = 48) by administering 35 mg/kg PTZ intraperitoneally (I.P.) every other day for 1 month. TUDCA and 4-PBA were administered via I.P. at a dose of 500 mg/kg dose. ER stress, apoptosis, and oxidative stress were determined in the hippocampus tissues of animals in all groups. Immunohistochemistry, qRT-PCR, ELISA, and Western Blot analyzes were performed to determine the efficacy of treatments. Expressions of ATF4, ATF6, p-JNK1/2, Cleaved-Kaspase3, and Caspase12 significantly increased in PTZ-kindled seizures compared to the control group. Increased NOX2 and MDA activity in the seizures were measured. In addition, stereology analyzes showed an increased neuronal loss in the PTZ-kindled group. qRT-PCR examination showed relative mRNA levels of CHOP. Accordingly, TUDCA and 4-PBA treatment suppressed the expressions of ATF4, ATF6, Cleaved-Caspase3, Kaspase12, NOX2, MDA, and CHOP in TUDCA + PTZ and 4-PBA + PTZ groups. ER stress-induced oxidative stress and apoptosis by reducing neuronal loss and degeneration were also preserved in these groups. Our data show molecularly that TUDCA and 4-PBA treatment can suppress the ER stress process in epileptic seizures.
Fulltext Regulation of gut microbiome by ketogenic diet in neurodegenerative diseases: A molecular crosstalk

Kaviyarasan S, Chung Sia EL, Retinasamy T, Arulsamy A, Shaikh MF

Front Aging Neurosci, 2022;14:1015837.
PMID: 36313018 DOI: 10.3389/fnagi.2022.1015837

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.
Beyond drug discovery: Exploring the physiological and methodological dimensions of zebrafish in diabetes research

Roohi TF, Faizan S, Shaikh MF, Krishna KL, Mehdi S, Kinattingal N, et al.

Exp Physiol, 2024 Jan 27.
PMID: 38279951 DOI: 10.1113/EP091587

Diabetes mellitus is a chronic disease that is now considered a global epidemic. Chronic diabetes conditions include type 1 and type 2 diabetes, both of which are normally irreversible. As a result of long-term uncontrolled high levels of glucose, diabetes can progress to hyperglycaemic pathologies, such as cardiovascular diseases, retinopathy, nephropathy and neuropathy, among many other complications. The complete mechanism underlying diabetes remains unclear due to its complexity. In this scenario, zebrafish (Danio rerio) have arisen as a versatile and promising animal model due to their good reproducibility, simplicity, and time- and cost-effectiveness. The Zebrafish model allows us to make progress in the investigation and comprehension of the root cause of diabetes, which in turn would aid in the development of pharmacological and surgical approaches for its management. The current review provides valuable reference information on zebrafish models, from the first zebrafish diabetes models using genetic, disease induction and chemical approaches, to the newest ones that further allow for drug screening and testing. This review aims to update our knowledge related to diabetes mellitus by gathering the most authoritative studies on zebrafish as a chemical, dietary and insulin induction, and genetic model for diabetes research.
Natural Terpenes Inhibit the Cytopathogenicity of Naegleria fowleri Causing Primary Amoebic Meningoencephalitis in the Human Cell Line Model

Rajendran K, Ahmed U, Meunier AC, Shaikh MF, Siddiqui R, Anwar A

ACS Chem Neurosci, 2023 Dec 06;14(23):4105-4114.
PMID: 37983556 DOI: 10.1021/acschemneuro.3c00258

Naegleria fowleri is one of the free-living amoebae and is a causative agent of a lethal and rare central nervous system infection called primary amoebic meningoencephalitis. Despite the advancement in antimicrobial chemotherapy, the fatality rate in the reported cases is more than 95%. Most of the treatment drugs used against N. fowleri infection are repurposed drugs. Therefore, a large number of compounds have been tested against N. fowleri in vitro, but most of the compounds showed high toxicity. To overcome this, we evaluated the effectiveness of naturally occurring terpene compounds against N. fowleri. In this study, we evaluated the antiamoebic potential of natural compounds including Thymol, Borneol, Andrographolide, and Forskolin againstN. fowleri. Thymol showed the highest amoebicidal activity with IC50/24 h at 153.601 ± 19.6 μM. Two combinations of compounds Forskolin + Thymol and Forskolin + Borneol showed a higher effect on the viability of trophozoites as compared to compounds alone and hence showed a synergistic effect. The IC50 reported for Forskolin + Thymol was 81.30 ± 6.86 μM. Borneol showed maximum cysticidal activity with IC50/24 h at 192.605 ± 3.01 μM. Importantly, lactate dehydrogenase release testing revealed that all compounds displayed minimal cytotoxicity to human HaCaT, HeLa, and SH-SY5Y cell lines. The cytopathogenicity assay showed that Thymol and Borneol also significantly reduced the host cell cytotoxicity of pretreated amoeba toward the human HaCaT cell line. So, these terpene compounds hold potential as therapeutic agents against infections caused by N. fowleri and are potentially a step forward in drug development against this deadly pathogen as these compounds have also been reported to cross the blood-brain barrier. Therefore, an in vivo study using animal models is necessary to assess the efficacy of these compounds and the need for further research into the intranasal route of delivery for the treatment of these life-threatening infections.
Fulltext Zebrafish: A Versatile Animal Model for Fertility Research

Hoo JY, Kumari Y, Shaikh MF, Hue SM, Goh BH

Biomed Res Int, 2016;2016:9732780.
PMID: 27556045 DOI: 10.1155/2016/9732780

The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research.
Fulltext The utilization of small non-mammals in traumatic brain injury research: A systematic review

Zulazmi NA, Arulsamy A, Ali I, Zainal Abidin SA, Othman I, Shaikh MF

CNS Neurosci Ther, 2021 Apr;27(4):381-402.
PMID: 33539662 DOI: 10.1111/cns.13590

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.
Fulltext Nanoparticle-Terpene Fusion: A Game-Changer in Combating Primary Amoebic Meningoencephalitis Caused by Naegleria fowleri

Rajendran K, Ahmed U, Meunier AC, Shaikh MF, Siddiqui R, Anwar A

ACS Omega, 2024 Mar 12;9(10):11597-11607.
PMID: 38497026 DOI: 10.1021/acsomega.3c08844

Pathogenic Naegleria fowleri (N. fowleri) are opportunistic free-living amoebae and are the causative agents of a very rare but severe brain infection called primary amoebic meningoencephalitis (PAM). The fatality rate of PAM in reported cases is more than 95%. Most of the drugs used againstN. fowleri infections are repurposed drugs. Therefore, a large number of compounds have been tested againstN. fowleri in vitro, but most of the tested compounds showed high toxicity and an inability to cross the blood-brain barrier. Andrographolide, forskolin, and borneol are important natural compounds that have shown various valuable biological properties. In the present study, the nanoconjugates (AND-AgNPs, BOR-AgNPs, and FOR-AgNPs) of these compounds were synthesized and assessed against both stages (trophozoite and cyst) ofN. fowleri for their antiamoebic and cysticidal potential in vitro. In addition, cytotoxicity and host cell pathogenicity were also evaluated in vitro. FOR-AgNPs were the most potent nanoconjugate and showed potent antiamoebic activity againstN. fowleriwith an IC50 of 26.35 μM. Nanoconjugates FOR-AgNPs, BOR-AgNPs, and AND-AgNPs also significantly inhibit the viability of N. fowleri cysts. Cytotoxicity assessment showed that these nanoconjugates caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 μg/mL, while also effectively reducing the cytopathogenicity of N. fowleri trophozoites to the HaCaT cells. The outcomes of our experiments have unveiled substantial potential for AND-AgNPs, BOR-AgNPs, and FOR-AgNPs in the realm of developing innovative alternative therapeutic agents to combat infections caused by N. fowleri. This study represents a significant step forward in the pursuit of advanced strategies for managing such amoebic infections, laying the foundation for the development of novel and more effective therapeutic modalities in the fight against free-living amoebae.
Development and Validation of a HPTLC Method for Simultaneous Estimation of L-Glutamic Acid and γ-Aminobutyric Acid in Mice Brain

Sancheti JS, Shaikh MF, Khatwani PF, Kulkarni SR, Sathaye S

Indian J Pharm Sci, 2013 Nov;75(6):716-21.
PMID: 24591747

A new robust, simple and economic high performance thin layer chromatographic method was developed for simultaneous estimation of L-glutamic acid and γ-amino butyric acid in brain homogenate. The high performance thin layer chromatographic separation of these amino acid was achieved using n-butanol:glacial acetic acid:water (22:3:5 v/v/v) as mobile phase and ninhydrin as a derivatising agent. Quantitation of the method was achieved by densitometric method at 550 nm over the concentration range of 10-100 ng/spot. This method showed good separation of amino acids in the brain homogenate with Rf value of L-glutamic acid and γ-amino butyric acid as 21.67±0.58 and 33.67±0.58, respectively. The limit of detection and limit of quantification for L-glutamic acid was found to be 10 and 20 ng and for γ-amino butyric acid it was 4 and 10 ng, respectively. The method was also validated in terms of accuracy, precision and repeatability. The developed method was found to be precise and accurate with good reproducibility and shows promising applicability for studying pathological status of disease and therapeutic significance of drug treatment.

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