Navigating neurological disorders: harnessing the power of natural compounds for innovative therapeutic breakthroughs.

Novel treatments are needed as neurological issues become more frequent worldwide. According to the report, plants, oceans, microorganisms, and animals contain interesting drug discovery compounds. Alzheimer's, Parkinson's, and stroke reviews emphasize neurological disorders' complexity and natural substances' safety. Learn about marine-derived and herbal substances' neuroprotective characteristics and applications. Molecular pathways show these substances' neurological healing effects. This article discusses clinical usage of Bryostatin-1, Fucoidan, Icariin, Salvianolic acid, Curcumin, Resveratrol, etc. Their potential benefits for asthma and Alzheimer's disease are complex. Although limited, the study promotes rigorous scientific research and collaboration between traditional and alternative medical practitioners. Unexplored natural compounds, quality control, well-structured clinical trials, and interdisciplinary collaboration should guide future study. Developing and employing natural chemicals to treat neurological illnesses requires ethical sourcing, sustainability, and public awareness. This detailed analysis covers natural chemicals' current state, challenges, and opportunities in neurological disorder treatment. See also the graphical abstract(Fig. 1).

Investigating the Potential Impact of Air Pollution on Alzheimer's Disease and the Utility of Multidimensional Imaging for Early Detection.

Pollution is ubiquitous, and much of it is anthropogenic in nature, which is a severe risk factor not only for respiratory infections or asthma sufferers but also for Alzheimer's disease, which has received a lot of attention recently. This Review aims to investigate the primary environmental risk factors and their profound impact on Alzheimer's disease. It underscores the pivotal role of multidimensional imaging in early disease identification and prevention. Conducting a comprehensive review, we delved into a plethora of literature sources available through esteemed databases, including Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. Our search strategy incorporated keywords such as "Alzheimer Disease", "Alzheimer's", "Dementia", "Oxidative Stress", and "Phytotherapy" in conjunction with "Criteria Pollutants", "Imaging", "Pathology", and "Particulate Matter". Alzheimer's disease is not only a result of complex biological factors but is exacerbated by the infiltration of airborne particles and gases that surreptitiously breach the nasal defenses to traverse the brain, akin to a Trojan horse. Various imaging modalities and noninvasive techniques have been harnessed to identify disease progression in its incipient stages. However, each imaging approach possesses inherent limitations, prompting exploration of a unified technique under a single umbrella. Multidimensional imaging stands as the linchpin for detecting and forestalling the relentless march of Alzheimer's disease. Given the intricate etiology of the condition, identifying a prospective candidate for Alzheimer's disease may take decades, rendering the development of a multimodal imaging technique an imperative. This research underscores the pressing need to recognize the chronic ramifications of invisible particulate matter and to advance our understanding of the insidious environmental factors that contribute to Alzheimer's disease.

Sub-chronic oral toxicity study of the alkaloid rich fraction from Luffa cylindrica fruit in Sprague-Dawley rats.

The loofah/sponge gourd Luffa cylindrica (L.), a member of the Cucurbitaceae family, is one of the neglected medicinal plants. Traditionally, Luffa cylindrica is prescribed for inducing labor. It has a long history of use in China for the treatment of fever, diabetes, dyspnea, and dysentery. This study investigated the toxicity profile of the alkaloid-rich fraction of Luffa cylindrica (ARF-LC) for the first time in Sprague Dawley rats. A total of 80 rats (40 male and 40 female rats) aged 13 weeks old and weighing 200-220 g were selected for this study. In SD rats, sub-chronic oral toxicity was investigated at doses of 100, 200, and 400 mg/kg/d for a total of 90 days, followed by a 30-day recovery period. The results showed no variation in body weight among the three dose groups compared to the control group. Treatment-related adverse events, such as alterations in hematology and serum biochemistry parameters and the histology of the liver were sporadic in the high-dose rats but within the reference range. However, these changes disappeared after the doses were withdrawn during the recovery period. In conclusion, the "no observed adverse effect level" (NOAEL) of oral administration of ARF-LC in SD rats was considered 400 mg/kg/d and can be studied for its potential in further in vivo chronic investigations.

An Update to Novel Therapeutic Options for Combating Tuberculosis: Challenges and Future Prospectives.

Drug repurposing is an ongoing and clever strategy that is being developed to eradicate tuberculosis amid challenges, of which one of the major challenges is the resistance developed towards antibiotics used in standard directly observed treatment, short-course regimen. Surpassing the challenges in developing anti-tuberculous drugs, some novel host-directed therapies, repurposed drugs, and drugs with novel targets are being studied, and few are being approved too. After almost 4 decades since the approval of rifampicin as a potent drug for drugsusceptible tuberculosis, the first drug to be approved for drug-resistant tuberculosis is bedaquiline. Ever since the urge to drug discovery has been at a brisk as this milestone in tuberculosis treatment has provoked the hunt for novel targets in tuberculosis. Host-directed therapy and repurposed drugs are in trend as their pharmacological and toxicological properties have already been researched for some other diseases making the trial facile. This review discusses the remonstrance faced by researchers in developing a drug candidate with a novel target, the furtherance in tuberculosis research, novel anti-tuberculosis agents approved so far, and candidates on trial including the host-directed therapy, repurposed drug and drug combinations that may prove to be potential in treating tuberculosis soon, aiming to augment the awareness in this context to the imminent researchers.

Effect of Per and Poly-Fluoroalkyl Substances on Pregnancy and Child Development.

BACKGROUND: Childhood obesity is significantly influenced by maternal exposure to Per- and Poly-Fluoroalkyl Substances (PFAS) during pregnancy. PFAS exposure occurs through the Peroxisome Proliferator-Activated Receptor (PPAR-γ) receptor, leading to increased fat deposition and profound health effects in child growth and development. Despite ongoing investigations, the relationship between maternal serum PFAS concentration and child obesity requires further exploration. OBJECTIVE: This study aimedto review the possible effects of Per and poly-fluoroalkyl substances exposure and their mechanism in overweight/obese children from pregnant ladies. METHODS: A detailed literature survey was conducted using online databases, including Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. The study focused on the diverse effects of PFAS on maternal and child health, with particular emphasis on neurological complications. RESULTS: Child growth development depends upon breastfeeding and placenta health, which is disrupted by PFAS exposure, ultimately destroying the body mass index of the child. Neurotoxicity testing utilized the SH-SY5Y human-derived cell line as an in vitro model, revealing PFAS-induced increases in adipocyte number, reduced cell size, altered lipid conglomeration, increased adiposity, and changes in liver function. in vivo studies in mice and human cell lines indicated PPAR-γ and ER-α activation, leading to adiposity and weight gain through Estrogen signaling and Lipid metabolism. PFAS concentrations positively correlated in maternal sera, analyzed by liquid chromatography/quadrupole mass spectrometry. CONCLUSION: PFAS, with a long half-life of 3.5-8.5 years, is commonly found in the serum of pregnant women, crossing the placenta barrier. This exposure disrupts placental homeostasis, negatively impacting mechanisms of action and potentially leading to deterioration in pregnancy and child health. Further research is needed to comprehensively understand the complex interplay between PFAS exposure and its implications for maternal and child well-being.

Alzheimer's disease: the role of extrinsic factors in its development, an investigation of the environmental enigma.

In the realm of Alzheimer's disease, the most prevalent form of dementia, the impact of environmental factors has ignited intense curiosity due to its substantial burden on global health. Recent investigations have unveiled these environmental factors as key contributors, shedding new light on their profound influence. Notably, emerging evidence highlights the detrimental role of various environmental contaminants in the incidence and progression of Alzheimer's disease. These contaminants encompass a broad spectrum, including air pollutants laden with ozone, neurotoxic metals like lead, aluminum, manganese, and cadmium, pesticides with their insidious effects, and the ubiquitous presence of plastics and microplastics. By meticulously delving into the intricate web connecting environmental pollutants and this devastating neurological disorder, this comprehensive chapter takes a deep dive into their involvement as significant risk factors for Alzheimer's disease. Furthermore, it explores the underlying molecular mechanisms through which these contaminants exert their influence, aiming to unravel the complex interactions that drive the pathogenesis of the disease. Additionally, this chapter proposes potential strategies to mitigate the detrimental effects of these environmental contaminants on brain health, with the ultimate goal of restoring and preserving typical cognitive function. Through this comprehensive exploration, we aim to enhance our understanding of the multifaceted relationship between neurotoxins and Alzheimer's disease, providing a solid foundation for developing innovative in-vivo models and advancing our knowledge of the intricate pathological processes underlying this debilitating condition.

Ozone-induced neurotoxicity: In vitro and in vivo evidence.

Together with cities in higher-income nations, it is anticipated that the real global ozone is rising in densely populated areas of Asia and Africa. This review aims to discuss the possible neurotoxic pollutants and ozone-induced neurotoxicity: in vitro and in vivo, along with possible biomarkers to assess ozone-related oxidative stress. As a methodical and scientific strategy for hazard identification and risk characterization of human chemical exposures, toxicological risk assessment is increasingly being implemented. While traditional methods are followed by in vitro toxicology, cell culture techniques are being investigated in modern toxicology. In both human and rodent models, aging makes the olfactory circuitry vulnerable to spreading immunological responses from the periphery to the brain because it lacks the blood-brain barrier. The ozone toxicity is elusive as it shows ventral and dorsal root injury cases even in the milder dose. Its potential toxicity should be disclosed to understand further the clear mechanism insights of how it acts in cellular aspects. Human epidemiological research has confirmed the conclusions that prenatal and postnatal exposure to high levels of air pollution are linked to behavioral alterations in offspring. O3 also enhances blood circulation. It has antibacterial action, which may have an impact on the gut microbiota. It also activates immunological, anti-inflammatory, proteasome, and growth factor signaling Prolonged O3 exposure causes oxidative damage to plasma proteins and lipids and damages the structural and functional integrity of the mitochondria. Finally, various studies need to be conducted to identify the potential biomarkers associated with ozone and the brain.

Structure of the Blood Brain Barrier and its Role in the Transporters for the Movement of Substrates across the Barriers.

For the brain to operate normally and to develop with structural integrity in addition to neuronal function, blood-brain barrier present in brain capillaries serves as a vital barrier mechanism. In addition to the transport barrier created by membranes, transporters, and vesicular processes, the structure and function of the BBB are summarised. The physical barrier is created by endothelial tight junctions. The permeability and transport of molecules between extracellular fluid and plasma are constrained by the presence of tight junctions between neighbouring endothelial cells. Each solute must pass through both membranes in the luminal and abluminal divisions. The functions of the neurovascular unit are described, with special emphasis on the pericytes, microglia, and astrocyte endfeet. The luminal membrane contains five separate facilitative transport mechanisms, each of which is exclusive to a few substrates. Nevertheless, the import of big-branched and aromatic neutral amino acids is facilitated by two key carriers (System L and y+) in the plasma membrane. It is asymmetrically present in both membranes. The sodium pump Na+/K+-ATPase is highly expressed in the abluminal membrane, where many Na+ dependent transport mechanisms move amino acids against its concentration gradient. The trojan horse strategy, which uses molecular tools to bind the medication and its formulations, is also preferred in drug delivery. The BBB's cellular structure, the transport systems unique to each substrate, and the necessity to identify transporters with changes that assist the transfer of various medications have all been changed in the current work. Nevertheless, to rule out the BBB passage for the new class of neuroactive medications, the mixing of traditional pharmacology and nanotechnology needs to be focused on outcomes that show promise.

Diagnostic Dilemmas and Current Treatment Approaches in Latent Onset Autoimmune Diabetes in Adults: A Concise Review.

Latent Onset Autoimmune Diabetes in Adults (LADA) is an autoimmune disorder between T1DM and T2DM and is often misdiagnosed as T2DM due to its late-onset. The disease is characterized by ß-cell failure and slow progression to insulin dependence. Early diagnosis is significant in limiting disease progression. C-peptide levels and autoantibodies against ß-cells are the most critical diagnostic biomarkers in LADA. The review aims to provide an overview of the biomarkers used to diagnose LADA, and the following treatment approaches. We have summarized LADA's pathophysiology and the autoantibodies involved in the condition, diagnostic approaches, and challenges. There are clear shortcomings concerning the feasibility of autoantibody testing. Finally, we have explored the treatment strategies involved in the management of LADA. In conclusion, the usual management includes treatment with metformin and the addition of low doses of insulin. Newer oral hypoglycaemic agents, such as GLP-1RA and DPP-4 inhibitors, have been brought into use. Since the disease is not entirely understood at the research level and in clinical practice, we hope to encourage further research in this field to assess its prevalence. Large randomized controlled trials are required to compare the efficacy of different available treatment options.

Bisphenol A exposure links to exacerbation of memory and cognitive impairment: A systematic review of the literature.

This systematic-review probes the deleterious outcome of Bisphenol A (BPA) exposure on cognition/memory by scrutinizing the extant preclinical studies on this focus, to promote apprehension about this environmental toxin among the general population with a long-term goal to build a plastic (BPA)-free future. Bibliographic databases, including Scopus, ProQuest, PubMed, Google Scholar, DOAJ, and ScienceDirect were searched for preclinical reports assessing the impact of BPA exposure on memory/cognition. The review protocol has been published in PROSPERO with the registration number CRD42022333965. The SYRCLE's RoB tool was implemented to assess the risk of bias in the retrieved reports. The review finally comprehended 22 reports. Results of 22 reports compositely suggest that maternal exposure to BPA raises the likelihood of the fetus enduring neuro-developmental dysfunction, which may manifest as memory/cognitive decline. BPA impairs memory and cognition by binding to estrogen receptors, inhibiting ERK-CREB-BDNF signaling pathway, altering the expression of synaptic proteins, impairing the morphology of pyramidal neurons in the hippocampus, dysregulation of thyroid hormones, and altering the neurotransmitter levels.

Perspectives of ozone induced neuropathology and memory decline in Alzheimer's disease: A systematic review of preclinical evidences.

This systematic review aims to discover the plausible mechanism of Ozone in A.D., to boost translational research. The main focus of our review lies in understanding the effects of ozone pollution on the human brain and causing degenerative disease. Owing to the number of works carried out as preclinical evidence in association with oxidative stress and Alzheimer's disease and the lack of systematic review or meta-analysis prompted us to initiate a study on Alzheimer's risk due to ground-level ozone. We found relevant studies from PubMed, ScienceDirect, Proquest, DOAJ, and Scopus, narrowing to animal studies and the English language without any time limit. The searches will be re-run before the final analysis. This work was registered in Prospero with Reg ID CRD42022319360, followed the PRISMA-P framework, and followed the PICO approach involving Population, Intervention/Exposure, Comparison, and Outcomes data. Bibliographic details of 16 included studies were studied for Exposure dose of ozone, duration, exposure, and frequency with control and exposure groups. Primary and secondary outcomes were assessed based on pathology significance, and results were significant in inducing Alzheimer-like pathology by ozone. In conclusion, ozone altered oxidative stress, metabolic pathway, and amyloid plaque accumulation besides endothelial stress response involving mitochondria as the critical factor in ATP degeneration, caspase pathway, and neuronal damage. Thus, ozone is a criteria pollutant to be focused on in mitigating Alzheimer's Disease pathology.

Anthocyanin as a therapeutic in Alzheimer's disease: A systematic review of preclinical evidences.

BACKGROUND: The aim of this systematic review is to ponder the possible mechanism of action of anthocyanin in Alzheimer's disease (AD), to prompt the development of anthocyanin-based dietary supplementation or therapeutic intervention for AD and to explore the natural sources of anthocyanins. METHODS: Electronic bibliographic databases such as PubMed, ScienceDirect, Proquest, DOAJ, Scopus, and Google Scholar were searched for preclinical studies probing the efficacy of anthocyanin on AD. The search strategy included no time limit, but was restricted to English. The review protocol is registered on PROSPERO, registration no. CRD42021272972. The systematic review followed the PICO approach for inclusion of reports. All the reports were appraised for risk of bias using the SYRCLE's RoB tool. RESULTS: Bibliographic details of the article, animal strain/weight/age, induction model, anthocyanin source, type of anthocyanin, dose, route of administration, duration, and the outcome measures were extracted from 12 retrieved reports explicitly. The implication of food-based anthocyanin in acute and long-term cognition and Aß mediated neurodegeneration appears alluring. Majority of the studies comprehended in this review had moderate methodological quality. DISCUSSION: Efficacy of anthocyanin in alleviating oxidative stress, reactive astrogliosis, cholinergic dysfunction, apoptosis, synaptotoxicity, neuroinflammation, tau hyperphosphorylation, dysregulated membrane potential, neuronal extracellular calcium, dysfunctional amyloidogenic pathway, and cognitive deficits in various rodent models of AD is manifested compositely in 12 studies.

Junk food-induced obesity- a growing threat to youngsters during the pandemic.

INTRODUCTION: Obesity has been declared an epidemic that does not discriminate based on age, gender, or ethnicity and thus needs urgent containment and management. Since the third wave of COVID-19 is expected to affect children the most, these children and adolescents should be more cautious while having junk foods, during covid situations due to the compromise of Immunity in the individuals and further exacerbating the organ damage. METHODOLOGY: A PAN India survey organized by the Centre for Science and Environment (CSE) among 13,274 children between the ages 9-14 years reported that 93% of the children ate packed food and 68% consumed packaged sweetened beverages more than once a week, and 53% ate these products at least once in a day. Almost 25% of the School going children take ultra-processed food with high levels of sugar, salt, fat, such as pizza and burgers, from fast food outlets more than once a week. Children and adolescents who consume more junk food or addicted to such consumption might be even more vulnerable during the third wave, which will significantly affect the younger category. CONCLUSION: There is an urgent need to spread awareness among children and young adults about these adverse effects of junk food. There is no better time than now to build a supportive environment nurturing children and young adults in society and promising good health.