Leveraging AI for the diagnosis and treatment of autism spectrum disorder: Current trends and future prospects.

The integration of artificial intelligence (AI) into the diagnosis and treatment of autism spectrum disorder (ASD) represents a promising frontier in healthcare. This review explores the current landscape and future prospects of AI technologies in ASD diagnostics and interventions. AI enables early detection and personalized assessment of ASD through the analysis of diverse data sources such as behavioural patterns, neuroimaging, genetics, and electronic health records. Machine learning algorithms exhibit high accuracy in distinguishing ASD from neurotypical development and other developmental disorders, facilitating timely interventions. Furthermore, AI-driven therapeutic interventions, including augmentative communication systems, virtual reality-based training, and robot-assisted therapies, show potential in improving social interactions and communication skills in individuals with ASD. Despite challenges such as data privacy and interpretability, the future of AI in ASD holds promise for refining diagnostic accuracy, deploying telehealth platforms, and tailoring treatment plans. By harnessing AI, clinicians can enhance ASD care delivery, empower patients, and advance our understanding of this complex condition.

Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability.

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible for energy production and calcium regulation. This review offers an in-depth examination of the interplay between epilepsy, mitochondrial function, and aging. Many factors might account for the correlation between epilepsy and aging. Mitochondria, integral to cellular energy dynamics and neuronal excitability, perform a critical role in the pathophysiology of epilepsy. The mechanisms linking epilepsy and mitochondria are multifaceted, involving mitochondrial dysfunction, reactive oxygen species (ROS), and mitochondrial dynamics. Mitochondrial dysfunction can trigger seizures by compromising ATP production, increasing glutamate release, and altering ion channel function. ROS, natural byproducts of mitochondrial respiration, contribute to oxidative stress and neuroinflammation, critical factors in epileptogenesis. Mitochondrial dynamics govern fusion and fission processes, influence seizure threshold and calcium buffering, and impact seizure propagation. Energy demands during seizures highlight the critical role of mitochondrial ATP generation in maintaining neuronal membrane potential. Mitochondrial calcium handling dynamically modulates neuronal excitability, affecting synaptic transmission and action potential generation. Dysregulated mitochondrial calcium handling is a hallmark of epilepsy, contributing to excitotoxicity. Epigenetic modifications in epilepsy influence mitochondrial function through histone modifications, DNA methylation, and non-coding RNA expression. Potential therapeutic avenues targeting mitochondria in epilepsy include mitochondria-targeted antioxidants, ketogenic diets, and metabolic therapies. The review concludes by outlining future directions in epilepsy research, emphasizing integrative approaches, advancements in mitochondrial research, and ethical considerations. Mitochondria emerge as central players in the complex narrative of epilepsy, offering profound insights and therapeutic potential for this challenging neurological disorder.

AI-driven innovations in Alzheimer's disease: Integrating early diagnosis, personalized treatment, and prognostic modelling.

Alzheimer's disease (AD) presents a significant challenge in neurodegenerative research and clinical practice due to its complex etiology and progressive nature. The integration of artificial intelligence (AI) into the diagnosis, treatment, and prognostic modelling of AD holds promising potential to transform the landscape of dementia care. This review explores recent advancements in AI applications across various stages of AD management. In early diagnosis, AI-enhanced neuroimaging techniques, including MRI, PET, and CT scans, enable precise detection of AD biomarkers. Machine learning models analyze these images to identify patterns indicative of early cognitive decline. Additionally, AI algorithms are employed to detect genetic and proteomic biomarkers, facilitating early intervention. Cognitive and behavioral assessments have also benefited from AI, with tools that enhance the accuracy of neuropsychological tests and analyze speech and language patterns for early signs of dementia. Personalized treatment strategies have been revolutionized by AI-driven approaches. In drug discovery, virtual screening and drug repurposing, guided by predictive modelling, accelerate the identification of effective treatments. AI also aids in tailoring therapeutic interventions by predicting individual responses to treatments and monitoring patient progress, allowing for dynamic adjustment of care plans. Prognostic modelling, another critical area, utilizes AI to predict disease progression through longitudinal data analysis and risk prediction models. The integration of multi-modal data, combining clinical, genetic, and imaging information, enhances the accuracy of these predictions. Deep learning techniques are particularly effective in fusing diverse data types to uncover new insights into disease mechanisms and progression. Despite these advancements, challenges remain, including ethical considerations, data privacy, and the need for seamless integration of AI tools into clinical workflows. This review underscores the transformative potential of AI in AD management while highlighting areas for future research and development. By leveraging AI, the healthcare community can improve early diagnosis, personalize treatments, and predict disease outcomes more accurately, ultimately enhancing the quality of life for individuals with AD.

Navigating the intersection: Diabetes and Alzheimer's intertwined relationship.

Alzheimer's disease (AD) and Diabetes mellitus (DM) exhibit comparable pathophysiological pathways. Genetic abnormalities in APP, PS-1, and PS-2 are linked to AD, with diagnostic aid from CSF and blood biomarkers. Insulin dysfunction, termed "type 3 diabetes mellitus" in AD, involves altered insulin signalling and neuronal shrinkage. Insulin influences beta-amyloid metabolism, exacerbating neurotoxicity in AD and amyloid production in DM. Both disorders display impaired glucose transporter expression, hastening cognitive decline. Mitochondrial dysfunction and Toll-like receptor 4-mediated inflammation worsen neurodegeneration in both diseases. ApoE4 raises disease risk, especially when coupled with dyslipidemia common in DM. Targeting shared pathways like insulin-degrading enzyme activation and HSP60 holds promise for therapeutic intervention. Recognizing these interconnected mechanisms underscores the imperative for developing tailored treatments addressing the overlapping pathophysiology of AD and DM, offering potential avenues for more effective management of both conditions.

Decoding mitochondrial quality control mechanisms: Identifying treatment targets for enhanced cellular health.

Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.

Modulation of cholesterol metabolism with Phytoremedies in Alzheimer's disease: A comprehensive review.

Alzheimer's disease (AD) is a complex neurological ailment that causes cognitive decline and memory loss. Cholesterol metabolism dysregulation has emerged as a crucial element in AD pathogenesis, contributing to the formation of amyloid-beta (Aß) plaques and tau tangles, the disease's hallmark neuropathological characteristics. Thus, targeting cholesterol metabolism has gained attention as a potential therapeutic method for Alzheimer's disease. Phytoremedies, which are generated from plants and herbs, have shown promise as an attainable therapeutic option for Alzheimer's disease. These remedies contain bioactive compounds like phytochemicals, flavonoids, and polyphenols, which have demonstrated potential in modulating cholesterol metabolism and related pathways. This comprehensive review explores the modulation of cholesterol metabolism by phytoremedies in AD. It delves into the role of cholesterol in brain function, highlighting disruptions observed in AD. Additionally, it examines the underlying molecular mechanisms of cholesterol-related pathology in AD. The review emphasizes the significance of phytoremedies as a potential therapeutic intervention for AD. It discusses the drawbacks of current treatments and the need for alternative strategies addressing cholesterol dysregulation and its consequences. Through an in-depth analysis of specific phytoremedies, the review presents compelling evidence of their potential benefits. Molecular mechanisms underlying phytoremedy effects on cholesterol metabolism are examined, including regulation of cholesterol-related pathways, interactions with Aß pathology, influence on tau pathology, and anti-inflammatory effects. The review also highlights challenges and future perspectives, emphasizing standardization, clinical evidence, and personalized medicine approaches to maximize therapeutic potential in AD treatment. Overall, phytoremedies offer promise as a potential avenue for AD management, but further research and collaboration are necessary to fully explore their efficacy, safety, and mechanisms of action.

An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders.

Neuroinflammation is the major cause of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Currently available drugs present relatively low efficacy and are not capable of modifying the course of the disease or delaying its progression. Identifying well-tolerated and brain-penetrant agents of plant origin could fulfil the pressing need for novel treatment techniques for neuroinflammation. Attention has been drawn to a large family of flavonoids in citrus fruits, which may function as strong nutraceuticals in slowing down the development and progression of neuroinflammation. This review is aimed at elucidating and summarizing the effects of the flavonoid tangeretin (TAN) in the management of neuroinflammation-mediated neurodegenerative disorders. A literature survey was performed using various resources, including ScienceDirect, PubMed, Google Scholar, Springer, and Web of Science. The data revealed that TAN exhibited immense neuroprotective effects in addition to its anti-oxidant, anti-diabetic, and peroxisome proliferator-activated receptor-γ agonistic effects. The effects of TAN are mainly mediated through the inhibition of oxidative and inflammatory pathways via regulating multiple signaling pathways, including c-Jun N-terminal kinase, phosphoinositide 3-kinase, mitogen-activated protein kinase, nuclear factor erythroid-2-related factor 2, extracellular-signal-regulated kinase, and CRE-dependent transcription. In conclusion, the citrus flavonoid TAN has the potential to prevent neuronal death mediated by neuroinflammatory pathways and can be developed as an auxiliary therapeutic agent in the management of neurodegenerative disorders.

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy.

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy regimen for colorectal, gastric, and breast cancers, cardiotoxicity caused by 5-fluorouracil might affect anywhere from 1.5% to 18% of patients. The precise mechanisms underlying cardiotoxicity associated with CRC treatment are complex and may involve the modulation of various signaling pathways crucial for maintaining cardiac health including TKI ErbB2 or NRG-1, VEGF, PDGF, BRAF/Ras/Raf/MEK/ERK, and the PI3/ERK/AMPK/mTOR pathway, resulting in oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, ultimately damaging cardiac tissue. Thus, the identification and management of cardiotoxicity associated with CRC drug therapy while minimizing the negative impact have become increasingly important. The purpose of this review is to catalog the potential cardiotoxicities caused by anticancer drugs and targeted therapy used to treat colorectal cancer as well as strategies focused on early diagnosing, prevention, and treatment of cardiotoxicity associated with anticancer drugs used in CRC therapy.

Overview on the Polyphenol Avenanthramide in Oats (Avena sativa Linn.) as Regulators of PI3K Signaling in the Management of Neurodegenerative Diseases.

Avenanthramides (Avns) and their derivatives, a group of polyphenolic compounds found abundantly in oats (Avena sativa Linn.), have emerged as promising candidates for neuroprotection due to their immense antioxidant, anti-inflammatory, and anti-apoptotic properties. Neurodegenerative diseases (NDDs), characterized by the progressive degeneration of neurons, present a significant global health burden with limited therapeutic options. The phosphoinositide 3-kinase (PI3K) signaling pathway plays a crucial role in cell survival, growth, and metabolism, making it an attractive target for therapeutic intervention. The dysregulation of PI3K signaling has been implicated in the pathogenesis of various NDDs including Alzheimer's and Parkinson's disease. Avns have been shown to modulate PI3K/AKT signaling, leading to increased neuronal survival, reduced oxidative stress, and improved cognitive function. This review explores the potential of Avn polyphenols as modulators of the PI3K signaling pathway, focusing on their beneficial effects against NDDs. Further, we outline the need for clinical exploration to elucidate the specific mechanisms of Avn action on the PI3K/AKT pathway and its potential interactions with other signaling cascades involved in neurodegeneration. Based on the available literature, using relevant keywords from Google Scholar, PubMed, Scopus, Science Direct, and Web of Science, our review emphasizes the potential of using Avns as a therapeutic strategy for NDDs and warrants further investigation and clinical exploration.

Repurposing Diltiazem for Its Neuroprotective Anti-Dementia Role against Intra-Cerebroventricular Streptozotocin-Induced Sporadic Alzheimer's Disease-Type Rat Model.

Alzheimer's disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders, has proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured via passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aß) protein expression in rat brain tissues were measured using ELISA kits, Western blotting, and immunostaining techniques. The data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p < 0.05~p < 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg, p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments and ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1ß) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aß protein expression in ICV-STZ-induced brain tissue. Considering the results obtained, DTZ might have a potential therapeutic role in treating and managing AD and related dementia pathologies due to its anti-dementia activity in SAD-type conditions in rats induced by ICV-STZ.

Molecular understanding of ER-MT communication dysfunction during neurodegeneration.

Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed specialized purposes for a very long time. But in recentpast years, scientists have learned that organelles become dynamic and make physical contact. Additionally, Biological processes are regulated by organelles interactions and its alteration play an important role in cell malfunctioning and several pathologies, including neurodegenerative diseases. Mitochondrial-ER contact sites (MERCS) have received considerable attention in the domain of cell homeostasis and dysfunction, specifically in the area of neurodegeneration. This is largely due to the significant role of this subcellular compartment in a diverse array of vital cellular functions, including Ca2+ homeostasis, transport, bioenergetics and turnover, mitochondrial dynamics, apoptotic signaling, ER stress, and inflammation. A significant number of disease-associated proteins were found to physically interact with the ER-Mitochondria (ER-MT) interface, causing structural and/or functional alterations in this compartment. In this review, we summarize current knowledge about the structure and functions of the ER-MT contact sites, as well as the possible repercussions of their alteration in notable neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and fronto-temporal dementia. The constraints and complexities in defining the nature and origin of the highlighted defects in ER-MT communication, as well as their concise contribution to the neurodegenerative process, are illustrated in particular. The possibility of using MERCS as a potential drug target to prevent neuronal damage and ultimately neurodegeneration is the topic of our final discussion.

Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by the dysregulation of cytokines and other immune mediators. JAK/STAT is a classical signal transduction pathway involved in various biological processes, and its dysregulation contributes to the key aspects of AD pathogenesis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate the immune-related inflammatory responses mediated by the JAK/STAT pathway. JAK/STAT-mediated production of cytokines including IL-4, IL-13, IL-31, and TSLP inhibits the expression of important skin barrier proteins and triggers pruritus in AD. The expression of SOCS proteins regulates the JAK-mediated cytokines and facilitates maintaining the skin barrier disruptions seen in AD. STATs are crucial in dendritic-cell-activated Th2 cell differentiation in the skin, releasing inflammatory cytokines, indicating that AD is a Th2-mediated skin disorder. SOCS proteins aid in balancing Th1/Th2 cells and, moreover, regulate the onset and maintenance of Th2-mediated allergic responses by reducing the Th2 cell activation and differentiation. SOCS proteins play a pivotal role in inflammatory cytokine-signaling events that act via the JAK/STAT pathway. Therapies relying on natural products and derived biomolecules have proven beneficial in AD when compared with the synthetic regimen. In this review, we focused on the available literature on the potential natural-product-derived biomolecules targeting JAK/STAT/SOCS signaling, mainly emphasizing the SOCS family of proteins (SOCS1, SOCS3, and SOCS5) acting as negative regulators in modulating JAK/STAT-mediated responses in AD pathogenesis and other inflammatory disorders.

Apigenin Isolated from Carduus crispus Protects against H2O2-Induced Oxidative Damage and Spermatogenic Expression Changes in GC-2spd Sperm Cells.

Testicular oxidative stress is one of the most common factors underlying male infertility. Welted thistle, Carduus crispus Linn., and its bioactive principles are attracting scientific interest in treating male reproductive dysfunctions. Here, the protective effects of apigenin isolated from C. crispus against oxidative damage induced by hydrogen peroxide (H2O2) and dysregulation in spermatogenesis associated parameters in testicular sperm cells was investigated. Cell viabilities, ROS scavenging effects, and spermatogenic associated molecular expressions were measured by MTT, DCF-DA, Western blotting and real-time RT-PCR, respectively. A single peak with 100% purity of apigenin was obtained in HPLC conditions. Apigenin treated alone (2.5, 5, 10 and 20 µM) did not exhibit cytotoxicity, but inhibited the H2O2-induced cellular damage and elevated ROS levels significantly (p < 0.05 at 5, 10 and 20 µM) and dose-dependently. Further, H2O2-induced down-regulation of antioxidant (glutathione S-transferases m5, glutathione peroxidase 4, and peroxiredoxin 3) and spermatogenesis-associated (nectin-2 and phosphorylated-cAMP response element-binding protein) molecular expression in GC-2spd cells were attenuated by apigenin at both protein and mRNA levels (p < 0.05). In conclusion, our study showed that apigenin isolated from C. crispus might be an effective agent that can protect ROS-induced testicular dysfunctions.

Cordycepin from Medicinal Fungi Cordyceps militaris Mitigates Inflammaging-Associated Testicular Damage via Regulating NF-κB/MAPKs Signaling in Naturally Aged Rats.

Inflammaging in male reproductive organs covers a wide variety of problems, including sexual dysfunction and infertility. In this study, the beneficial effects of cordycepin (COR), isolated from potential medicinal fungi Cordyceps militaris, in aging-associated testicular inflammation and serum biochemical changes in naturally aged rats were investigated. Male Sprague Dawley rats were divided into young control (YC), aged control (AC), and COR (5, 10, and 20 mg/kg) treated aged rat groups. Aging-associated serum biochemical changes and inflammatory parameters were analyzed by biochemical assay kits, Western blotting, and real-time RT-PCR. Results showed a significant (p < 0.05) alteration in the total blood cell count, lipid metabolism, and liver functional parameters in AC group when compared with YC group. However, COR-treated aged rats ameliorated the altered biochemical parameters significantly (p < 0.05 and p < 0.01 at 5, 10, and 20 mg/kg, respectively). Furthermore, the increase in the expression of inflammatory mediators (COX-2, interleukin (IL)-6, IL-1ß, and tissue necrosis factor-alpha) in aged rat testis was significant (p < 0.05) when compared with YC group. Treatment with COR at 20 mg/kg to aged rats attenuated the increased expression of inflammatory mediators significantly (p < 0.05). Mechanistic studies revealed that the potential attenuating effects exhibited by COR in aged rats was mediated by regulation of NF-κB activation and MAPKs (c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38) signaling. In conclusion, COR restored the altered serum biochemical parameters in aged rats and ameliorated the aging-associated testicular inflammation proving the therapeutic benefits of COR targeting inflammaging-associated male sexual dysfunctions.

Cordycepin mitigates spermatogenic and redox related expression in H2O2-exposed Leydig cells and regulates testicular oxidative apoptotic signalling in aged rats.

CONTEXT: Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable agent with immense health benefits. OBJECTIVE: The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H2O2)-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 µg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR. RESULTS: COR treatment (1, 5, and 10 µg/mL) significantly (p < 0.05 ∼ p < 0.001) inhibited the H2O2-induced decrease in the percentage of viable cells (from 63.27% to 71.25%, 85.67% and 93.97%, respectively), and reduced the malondialdehyde (MDA) content (from 4.28 to 3.98, 3.14 and 1.78 nM MDA/mg protein, respectively). Further, the decreased antioxidant enzymes (glutathione-S-transferase mu5, glutathione peroxidase 4 and peroxiredoxin 3), spermatogenesis-related factors (nectin-2 and inhibin-α) and testosterone levels in H2O2-exposed TM3 cells were significantly (p < 0.05 ∼ p < 0.001) ameliorated by COR. In aged rats, COR (20 mg/kg) restored the altered enzymatic and non-enzymatic antioxidative status and attenuated the apoptotic p53 and Bax/Bcl-2 expression significantly (p < 0.05). CONCLUSION: COR might be developed as a potential agent against ageing-associated and oxidative stress-induced male infertility.

Potential Nutrients from Natural and Synthetic Sources Targeting Inflammaging-A Review of Literature, Clinical Data and Patents.

Inflammaging, the steady development of the inflammatory state over age is an attributable characteristic of aging that potentiates the initiation of pathogenesis in many age-related disorders (ARDs) including neurodegenerative diseases, arthritis, cancer, atherosclerosis, type 2 diabetes, and osteoporosis. Inflammaging is characterized by subclinical chronic, low grade, steady inflammatory states and is considered a crucial underlying cause behind the high mortality and morbidity rate associated with ARDs. Although a coherent set of studies detailed the underlying pathomechanisms of inflammaging, the potential benefits from non-toxic nutrients from natural and synthetic sources in modulating or delaying inflammaging processes was not discussed. In this review, the available literature and recent updates of natural and synthetic nutrients that help in controlling inflammaging process was explored. Also, we discussed the clinical trial reports and patent claims on potential nutrients demonstrating therapeutic benefits in controlling inflammaging and inflammation-associated ARDs.

Coriandrum sativum attenuates microglia mediated neuroinflammation and MPTP-induced behavioral and oxidative changes in Parkinson's disease mouse model.

Coriandrum sativum Linn. (family: Umbelliferae; C. sativum), is a potential herb widely used as a spice and traditional medicine. In the present work, the effects of C. sativum fruit extract (CSE), against lipopolysaccharide (LPS)-stimulated BV-2 microglia-mediated neuroinflammation in vitro and 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) animal model in vivo was investigated. LPS-stimulated increase in nitric oxide (NO), inducible NO synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor-alpha were significantly (p < 0.05 ~ p < 0.001) inhibited by CSE (25, 50 and 100 µg/mL) in BV-2 microglial cells. Further, CSE inhibited the LPS-induced nuclear factor of kappa-beta activation and IκB-α phosphorylation in BV-2 microglia. In vivo studies, CSE (100, 200 and 300 mg/kg) ameliorated the MPTP (25 mg/kg, i.p.)-induced changes in locomotor, cognitive and behavior functions evaluated by rotarod, passive avoidance and open field test significantly (p < 0.05 ~ p < 0.001). The MPTP-induced changes in brain oxidative enzyme levels such as superoxide dismutase, catalase, and lipid peroxidation were significantly (p < 0.01 and p < 0.001 at 200 and 300 mg/kg, respectively) restored with CSE treatment. High-performance thin-layer chromatography fingerprinting analysis of CSE exhibited several distinctive peaks with quercetin and kaempferol-3O-glucoside as identifiable compounds. In conclusion, our study indicated that CSE attenuated neuroinflammatory processes in LPS-stimulated microglia in vitro and restored the MPTP-induced behavioral deficits and brain oxidative enzyme status in vivo proving its therapeutic potential in the treatment of neuroinflammatory and oxidative stress-mediated neurodegeneration seen in PD.

Mitigating Effect of Lindera obtusiloba Blume Extract on Neuroinflammation in Microglial Cells and Scopolamine-Induced Amnesia in Mice.

Lindera obtusiloba Blume (family, Lauraceae), native to Northeast Asia, has been used traditionally in the treatment of trauma and neuralgia. In this study, we investigated the neuroinflammatory effect of methanol extract of L. obtusiloba stem (LOS-ME) in a scopolamine-induced amnesia model and lipopolysaccharide (LPS)-stimulated BV2 microglia cells. LOS-ME downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, inflammatory cytokines, and inhibited the phosphorylation of nuclear factor kappa-B (NF-ĸB) and extracellular signal-regulated kinase (ERK) in LPS-stimulated BV2 cells. Male C57/BL6 mice were orally administered 20 and 200 mg/kg of LOS-ME for one week, and 2 mg/kg of scopolamine was administered intraperitoneally on the 8th day. In vivo behavioral experiments (Y-maze and Morris water maze test) confirmed that LOS-ME alleviated cognitive impairments induced by scopolamine and the amount of iNOS expression decreased in the hippocampus of the mouse brain. Microglial hyper-activation was also reduced by LOS-ME pretreatment. These findings suggest that LOS-ME might have potential in the treatment for cognitive improvement by regulating neuroinflammation.

2-Hydroxy-4-Methylbenzoic Anhydride Inhibits Neuroinflammation in Cellular and Experimental Animal Models of Parkinson's Disease.

Microglia-mediated neuroinflammation is one of the key mechanisms involved in acute brain injury and chronic neurodegeneration. This study investigated the inhibitory effects of 2-hydroxy-4-methylbenzoic anhydride (HMA), a novel synthetic derivative of HTB (3-hydroxy-4-trifluoromethylbenzoic acid) on neuroinflammation and underlying mechanisms in activated microglia in vitro and an in vivo mouse model of Parkinson's disease (PD). In vitro studies revealed that HMA significantly inhibited lipopolysaccharide (LPS)-stimulated excessive release of nitric oxide (NO) in a concentration dependent manner. In addition, HMA significantly suppressed both inducible NO synthase and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in LPS-stimulated BV-2 microglia cells. Moreover, HMA significantly inhibited the proinflammatory cytokines such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in LPS-stimulated BV-2 microglial cells. Furthermore, mechanistic studies ensured that the potent anti-neuroinflammatory effects of HMA (0.1, 1.0, and 10 µM) were mediated by phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) in LPS-stimulated BV-2 cells. In vivo evaluations revealed that intraperitoneal administration of potent neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg, four times a 1 day) in mice resulted in activation of microglia in the brain in association with severe behavioral deficits as assessed using a pole test. However, prevention of microglial activation and attenuation of Parkinson's disease (PD)-like behavioral changes was obtained by oral administration of HMA (30 mg/kg) for 14 days. Considering the overall results, our study showed that HMA exhibited strong anti-neuroinflammatory effects at lower concentrations than its parent compound. Further work is warranted in other animal and genetic models of PD for evaluating the efficacy of HMA to develop a potential therapeutic agent in the treatment of microglia-mediated neuroinflammatory disorders, including PD.

Phosphoinositide 3-kinase inhibitor AS605240 ameliorates streptozotocin-induced Alzheimer's disease like sporadic dementia in experimental rats.

The quest for chemical entities able to curb the action of the phosphoinositide 3-kinase, (PI3K)/protein kinase B (AKT) signaling pathways is evolving as a potential therapeutic strategy for the treatment and/or prevention of neurodegenerative disorders including Alzheimer's disease (AD). In this study, the effects of a PI3K inhibitor, AS605240 on cognitive dysfunction and antioxidative defense parameters against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced rat model of sporadic AD was evaluated. ICV administration of a single dose of STZ (3 mg/kg) was performed to induce behavioral and biochemical changes in rats using the stereotaxic technique. Animals were administered with varying doses of AS605240 (5, 10 and 15 mg/kg) orally, 1 h before ICV-STZ on day 1 and continued once daily for four weeks. The behavioral parameters (passive avoidance and Morris water maze), antioxidative defense parameters, amyloid-beta (Aß) protein expression by Western blotting and immunostaining technique were estimated in brain tissue. AS605240 dose-dependently and significantly (p < 0.05 and p < 0.01 and p < 0.001) improved ICV-STZ-induced cognitive impairment and attenuated the altered antioxidative related parameters including superoxide dismutase, lipid peroxidation, glutathione and nitrite levels. Further, the increased Aß protein expression levels in brain tissue were markedly restored with AS605240 treatment. In conclusion, our study demonstrated that AS605240 exhibited immense potential in attenuating STZ-induced sporadic AD features in rats and may be developed as a therapeutic agent in the treatment and management of sporadic AD.