ABSTRACT
Neuroinflammation and neuronal apoptosis are central pathogenic consequences associated with Alzheimer's Disease (AD) and Parkinson's Disease (PD). Limonin (LM), a tetracyclic triterpenoid available in citrus fruits, has anti-tumor, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective actions. LM derivative, V-A-4 emerged as a potential neuroprotective drug due to their ability to target multiple molecular pathways intertwined with neuroinflammation and neuronal apoptosis. To date, the treatment of AD and PD is not successful even though the understanding of the mechanism of neuroinflammation and neuronal apoptosis is vast in the literature. Thus, there is an urgent need to identify novel neuroprotective drugs that could target the multiple molecular pathways associated with neuroinflammation and neuronal apoptosis. The various online databases (Google scholar, Pubmed, Scopus) were searched via keywords: limonin, limonin derivatives and neuroprotection. This review highlights the multifunctional nature of LM and derivatives in combating neuroinflammation and neuronal apoptosis by stimulating PI3K/AKT and downregulating TLR4/NF-κB critical pathways. By intervening in the secretion of NO and TNF-α from glial cells, V-A-4 attenuates the damaging cascade of neuroinflammation by suppressing IKK-α and IKK-ß. Furthermore, V-A-4 demonstrates its versatility by suppressing the manifestation of miR-146a and miR-155, both intimately linked to neuroinflammation, this review summarized the activities of LM and its derivatives against AD and PD, with a special focus on V-A-4 as an effective neuroprotective drug. V-A-4's ability to stimulate PI3K/AKT signaling further underscores its neuroprotective effect in combating AD and PD. More in-vitro cell line studies are needed to develop V-A-4 as an upcoming neuroprotective compound.
ABSTRACT
Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by cognitive, motor, and psychiatric symptoms. Despite significant advances in understanding the underlying molecular mechanisms of HD, there is currently no cure or disease-modifying treatment available. Emerging pharmacological approaches offer promising strategies to alleviate symptoms and slow down disease progression. This comprehensive review aims to provide a critical appraisal of the latest developments in pharmacological interventions for HD. The review begins by discussing the pathogenesis of HD, focusing on the role of mutant huntingtin protein, mitochondrial dysfunction, excitotoxicity, and neuro-inflammation. It then explores emerging therapeutic targets, including the modulation of protein homeostasis, mitochondrial function, neuro-inflammation, and neurotransmitter systems. Pharmacological agents targeting these pathways are discussed, including small molecules, gene-based therapies, and neuroprotective agents. In recent years, several clinical trials have been conducted to evaluate the safety and efficiency of novel compounds for HD. This review presents an update on the outcomes of these trials, highlighting promising results and challenges encountered. Additionally, it discusses the potential of repurposing existing drugs approved for other indications as a cost-effective approach for HD treatment. The review concludes by summarizing the current state of pharmacological approaches for HD and outlining future directions in drug development. The integration of multiple therapeutic strategies, personalized medicine approaches, and combination therapies are highlighted as potential avenues to maximize treatment effectiveness.
ABSTRACT
The study by P. D. Yuan et al. titled "Adalimumab Dose Reduction and Withdrawal in Stable Non-Infectious Pediatric Uveitis: An Open-Label, Prospective, Pilot Study" examines dose reduction and withdrawal strategies in managing pediatric uveitis with adalimumab (ADA). The study aims to optimize treatment protocols by minimizing drug exposure while maintaining disease control. However, the open-label design introduces potential bias, and the absence of a control group limits the ability to draw definitive conclusions. The small sample size and short follow-up period further constrain the study's robustness. Methodological refinements, including a randomized controlled trial design with a larger sample size, extended follow-up, detailed adverse event data, standardized tapering protocols, and incorporation of objective outcome measures, are recommended to enhance the reliability and generalizability of the findings. These improvements could significantly inform clinical practice and contribute to the evidence base for pediatric uveitis management.
ABSTRACT
Indole-3-acetic acid (IAA), a protein-bound uremic toxin, has been linked to cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study explores the influence of IAA (125 mg/kg) on cardiovascular changes in adenine sulfate-induced CKD rats. HPLC analysis revealed that IAA-exposed CKD rats had lower excretion and increased circulation of IAA compared to both CKD and IAA control groups. Moreover, echocardiography indicated that CKD rats exposed to IAA exhibited heart enlargement, thickening of the myocardium, and cardiac hypertrophy in contrast to CKD or IAA control group. Biochemical analyses supported the finding that IAA-induced CKD rats had elevated serum levels of c-Tn-I, CK-MB, and LDH; there was also evidence of oxidative stress in cardiac tissues, with a significant decrease in SOD and CAT levels, as well as an increase in MDA levels. The gene expression analysis found significant increases in ANP, BNP, ß-MHC, TNF-α, IL-1ß, and NF-κB levels in IAA-exposed CKD groups in contrast to the CKD or IAA control group. In addition, higher cardiac fibrosis markers, including Col-I and Col-III. The findings of this study indicate that IAA could trigger cardiovascular inflammation and fibrosis in CKD conditions.
ABSTRACT
BACKGROUND: Wound healing pivots on a finely orchestrated inflammatory cascade, critical for tissue repair. Chronic wounds, compounded by persistent inflammation and susceptibility to infection, pose formidable clinical challenges. Nanofiber dressings offer promising avenues for wound care, yet their interaction with inflammation and infection remains elusive. We aim to delineate the inflammatory cascade preceding wound closure and assess Cu@Bbc nanofibers' therapeutic efficacy in mitigating inflammation and combating infection. Their unique attributes suggest promise in modulating inflammation, fostering tissue regeneration, and preventing microbial colonization. Investigating the intricate interplay between nanofiber scaffolds, inflammation, and infection may unveil mechanisms of enhanced wound healing. Our findings could stimulate the development of tailored dressings, urgently needed for effective wound management amidst immune dysregulation, infection, and inflammation. METHODS: In this investigation, we synthesized Cu@Bbc nanofibers, incorporating curcumin and berberine chloride, for wound healing applications. We evaluated their individual and combined antibacterial, anti-biofilm, and antioxidant activities, alongside binding affinity with pro-inflammatory cytokines through molecular docking. Morphological characterization was conducted via SEM, FTIR assessed functional groups, and wettability contact angle measured hydrophobic properties. The physical properties, including tensile strength, swelling behavior, and thermal stability, were evaluated using tensile testing, saline immersion method and thermogravimetric analysis. Biodegradability of the nanofibers was assessed through a soil burial test. Biocompatibility was determined via MTT assay, while wound healing efficacy was assessed with in vitro scratch assays. Controlled drug release and antibacterial activity against MRSA were examined, with in vivo assessment in a zebrafish model elucidating inflammatory responses and tissue remodeling. RESULTS: In this study, the synergistic action of curcumin and berberine chloride exhibited potent antibacterial efficacy against MRSA, with significant anti-mature biofilm disruption. Additionally, the combination demonstrated heightened antioxidant potential. Molecular docking studies revealed strong binding affinity with pro-inflammatory cytokines, suggesting a role in expediting the inflammatory response crucial for wound healing. Morphological analysis confirmed nanofiber quality, with drug presence verified via FTIR spectroscopy. Cu@Bbc demonstrated higher tensile strength, optimal swelling behavior, and robust thermal stability as evaluated through tensile testing and thermogravimetric analysis. Additionally, the Cu@Bbc nanofiber showed enhanced biodegradability, as confirmed by the soil burial test. Biocompatibility assessments showed favorable compatibility, while in vitro studies demonstrated potent antibacterial activity. In vivo zebrafish experiments revealed accelerated wound closure, re-epithelialization, and heightened immune response, indicative of enhanced wound healing. CONCLUSION: In summary, our investigation highlights the efficacy of Cu@Bbc nanofibers, laden with curcumin and berberine chloride, in displaying robust antibacterial and antioxidant attributes while also modulating immune responses and inflammatory cascades essential for wound healing. These results signify their potential as multifaceted wound dressings for clinical implementation.
ABSTRACT
Since the earliest days, people have been employing herbal treatments extensively around the world. The development of phytochemical and phytopharmacological sciences has made it possible to understand the chemical composition and biological properties of a number of medicinal plant products. Due to certain challenges like large molecular weight and low bioavailability, some components of herbal extracts are not utilized for therapeutic purposes. It has been suggested that herbal medicine and nanotechnology can be combined to enhance the benefits of plant extracts by lowering dosage requirements and adverse effects and increasing therapeutic activity. Using nanotechnology, the active ingredient can be delivered in an adequate concentration and transported to the targeted site of action. Conventional therapy does not fulfill these requirements. This review focuses on different skin diseases and nanotechnology-based herbal medicines that have been utilized to treat them.
ABSTRACT
INTRODUCTION: The effectiveness of intracanal medicaments (ICMs) in root canal therapy is critical for successful dental treatments, yet their cytotoxic effects pose significant challenges. This research uses zebrafish embryos and dental pulp stem cells (DPSCs) to identify the optimal concentration that balances antibacterial efficacy with minimal toxicity. AIM: This study aims to address the need for effective ICMs in dentistry by formulating and assessing the embryotoxicity and cytocompatibility of a novel carrageenan-based modified triple antibiotic paste (MTAP) hydrogel at different concentrations (1, 5, and 10 mg/mL) using a zebrafish model and cell culture assay. MATERIALS AND METHODS: The hydrogel was formulated by combining antibiotic solutions (ciprofloxacin, metronidazole, and amoxicillin) with carrageenan and xanthan gum. Zebrafish embryos were exposed to varying concentrations of MTAP hydrogel, chlorhexidine (CHX), calcium hydroxide (CaOH2), and plain carrageenan to assess developmental toxicity, survival rate, heart rate, hatching rate, and macrophage migration. The cytotoxicity against DPSCs was examined within a timeframe of 6, 24, and 72 hours with the use of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay. RESULTS: The analysis revealed developmental toxicity with malformations observed at higher concentrations of MTAP hydrogel, CaOH2, and CHX medicaments, indicating potential toxicity. Significant impacts on survival, heart rate, and hatching rate were noted in the CaOH2 and CHX groups, as well as at higher MTAP hydrogel concentrations, emphasizing the importance of dosage considerations. The neutral red assay confirmed toxicity, with macrophage migration observed in CaOH2, CHX, and higher MTAP hydrogel concentrations. Lower concentrations, particularly at 1 mg/mL, showed no adverse effects on zebrafish embryos and larvae. These findings align with cell viability investigations, which demonstrated that higher antibiotic concentrations resulted in decreased cell proliferation and viability over time. Conversely, at a lower concentration of 1 mg/mL, cell proliferation notably increased after 72 hours. Plain MTAP and CHX exhibited the highest toxicity levels in the MTT assay. CONCLUSION: The study concludes that while higher concentrations of MTAP hydrogel exhibit toxic effects, the hydrogel at 1 mg/mL demonstrates no adverse impact on zebrafish embryos, larvae, and DPSCs. These findings underscore the necessity of optimizing ICM concentrations to balance antibacterial efficacy and minimal cytotoxicity.
ABSTRACT
Environmental pollution, particularly from textile industry effluents, raises concerns globally. The aim of this study is to investigate the hepatotoxicity of Sudan Black B (SBB), a commonly used textile azo dye, on embryonic zebrafish. SBB exposure led to concentration-dependent mortality, reaching 100% at 0.8 mM, accompanied by growth retardation and diverse malformations in zebrafish. Biochemical marker analysis indicated adaptive responses to SBB, including increased SOD, CAT, NO, and LDH, alongside decreased GSH levels. Liver morphology analysis unveiled significant alterations, impacting metabolism and detoxification. Also, glucose level was declined and lipid level elevated in SBB-exposed in vivo zebrafish. Inflammatory gene expressions (TNF-α, IL-10, and INOS) showcased a complex regulatory interplay, suggesting an organismal attempt to counteract pro-inflammatory states during SBB exposure. The increased apoptosis revealed a robust hepatic cellular response due to SBB, aligning with observed liver tissue damage and inflammatory events. This multidimensional study highlights the intricate web of responses due to SBB exposure, which is emphasizing the need for comprehensive understanding and targeted mitigation strategies. The findings bear the implications for both aquatic ecosystems and potentially parallels to human health, underscoring the imperative for sustained research in this critical domain.
Subject(s)
Azo Compounds , Liver , Water Pollutants, Chemical , Zebrafish , Animals , Azo Compounds/toxicity , Water Pollutants, Chemical/toxicity , Liver/drug effects , Liver/metabolism , Liver/pathology , Larva/drug effects , Coloring Agents/toxicity , Chemical and Drug Induced Liver Injury/etiology , NaphthalenesABSTRACT
BACKGROUND: Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations. METHODS: We synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells. RESULTS: ZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53. CONCLUSIONS: This approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice.
Subject(s)
Alkaloids , Apoptosis , Benzodioxoles , Biofilms , Mouth Neoplasms , Piperidines , Polyunsaturated Alkamides , Zinc Oxide , bcl-2-Associated X Protein , Humans , Alkaloids/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/drug effects , Benzodioxoles/pharmacology , Biofilms/drug effects , Cell Line, Tumor , KB Cells , Metal Nanoparticles/therapeutic use , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Mouth Neoplasms/drug therapy , Mouth Neoplasms/pathology , Nanoparticles , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/drug effects , X-Ray Diffraction , Zinc Oxide/pharmacologyABSTRACT
The growing concern about pollution and toxicity in aquatic as well as terrestrial organisms is predominantly caused due to waterborne exposure and poses a risk to environmental systems and human health. This study addresses the co-toxic effects of cadmium (Cd) and ketoprofen (KPF), representing heavy metal and pharmaceutical discharge pollutants, respectively, in aquatic ecosystems. A 96-h acute toxicity assessment was conducted using zebrafish embryos. The results indicated that high dosages of KPF (10, 15, and 100 µg/mL) and Cd (10 and 15 µg/mL) reduced survivability and caused concentration-dependent deformities such as scoliosis and yolk sac edema. These findings highlight the potential defects in development and metabolism, as evidenced by hemolysis tests demonstrating dose-dependent effects on blood cell integrity. Furthermore, this study employs adult zebrafish for a 42-day chronic exposure to Cd and KPF (10 and 100 µg/L) alone or combined (10 + 10 and 100 + 100 µg/L) to assess organ-specific Cd and KPF accumulation in tissue samples. Organ-specific accumulation patterns underscore complex interactions impacting respiratory, metabolic, and detoxification functions. Prolonged exposure induces reactive oxygen species formation, compromising antioxidant defense systems. Histological examinations reveal structural changes in gills, gastrointestinal, kidney, and liver tissues, suggesting impairments in respiratory, osmoregulatory, nutritional, and immune functions. This study emphasizes the importance of conducting extensive research on co-toxic effects to assist with environmental risk assessments and safeguard human health and aquatic ecosystems.
ABSTRACT
BACKGROUND: Antimicrobial resistance has surged due to widespread antimicrobial drug use, prompting interest in biosynthesizing nanoparticles from marine-derived actinomycetes extracellular metabolites, valued for their diverse bioactive compounds. This approach holds promise for addressing the urgent need for novel antimicrobial agents. The current study aimed to characterize novel bioactive compounds from unexplored biodiversity hotspots, halophilic Streptomyces sp. isolated from mangrove sediment in the Pichavaram region, India. METHODS AND RESULTS: Streptomyces rochei SSCM102 was conclusively identified through morphological and molecular characterization. Synthesis of silver nanoparticles (AgNPs) from Streptomyces rochei SSCM102 was characterized using various techniques, including UV-Vis, XRD, SEM, EDX, and FT-IR. The UV-Vis spectrum of the reduced AgNPs exhibited a prominent peak at 380 nm, confirming the AgNPs. The UV-Vis spectrum confirmed the synthesis of AgNP, and SEM analysis revealed a cubic morphology with sizes ranging from 11 to 21 nm. The FTIR spectrum demonstrated a shift in frequency widths between 626 cm-1 and 3432 cm-1. The EDX analysis substantiated the presence of metallic silver, evident from a strong band at 1.44 keV. The synthesized AgNPs exhibited antibacterial efficacy against human pathogens Escherichia coli (64 ± 0.32 µg/ml), Klebsiella pneumoniae (32 ± 0.16 µg/ml), and Pseudomonas aeruginosa (16 ± 0.08 µg/ml) by MIC and MBC values of 128 ± 0.64 (µg/ml), 64 ± 0.32 (µg/ml) and 32 ± 0.16 (µg/ml), respectively. Additionally, at a concentration of 400 µg/ml, the AgNPs displayed a 72% inhibition of DPPH radicals, indicating notable antioxidant capacity. The LC50 value of 130 µg/mL indicates that the green-synthesized AgNPs have lower toxicity by Brine Shrimp Larvae assay. CONCLUSION: The study's novel approach to synthesizing eco-friendly silver nanoparticles using Halophilic Streptomyces rochei SSCM102 contributes significantly to the field of biomedical research and drug development. By demonstrating potent antibacterial properties and aligning with sustainability goals, these nanoparticles offer promising avenues for novel antibacterial therapies.
Subject(s)
Anti-Bacterial Agents , Geologic Sediments , Metal Nanoparticles , Microbial Sensitivity Tests , Silver , Streptomyces , Streptomyces/metabolism , Silver/chemistry , Silver/pharmacology , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Geologic Sediments/microbiology , Green Chemistry Technology/methods , Spectroscopy, Fourier Transform Infrared/methods , India , Bacteria/drug effectsABSTRACT
BACKGROUND: The development of cost-effective, simple, environment-friendly biographene is an area of interest. To accomplish environmentally safe, benign culturing that has advantages over other methods to reduce the graphene oxide (GO), extracellular metabolites from actinobacteria associated with mushrooms were used for the first time. METHODS: Bactericidal effect of GO against methicillin-resistant Staphylococcus aureus, antioxidant activity, and hydroxyapatite-like bone layer formation, gene expression analysis and appropriate biodegradation of the microbe-mediated synthesis of graphene was studied. RESULTS: Isolated extracellular contents Streptomyces achromogenes sub sp rubradiris reduced nano-GO to graphene (rGO), which was further examined by spectrometry and suggested an efficient conversion and significant reduction in the intensity of all oxygen-containing moieties and shifted crystalline peaks. Electron microscopic results also suggested the reduction of GO layer. In addition, absence of significant toxicity in MG-63 cell line, intentional free radical scavenging prowess, liver and kidney histopathology, and Wistar rat bone regeneration through modulation of OPG/RANKL/RUNX2/ALP pathways show the feasibility of the prepared nano GO. CONCLUSIONS: The study demonstrates the successful synthesis of biographene from actinobacterial extracellular metabolites, its potential biomedical applications, and its promising role in addressing health and environmental concerns.
Subject(s)
Bone Regeneration , Graphite , Osteoprotegerin , RANK Ligand , Rats, Wistar , Graphite/pharmacology , Animals , Bone Regeneration/drug effects , Rats , RANK Ligand/metabolism , Osteoprotegerin/metabolism , Humans , Biocompatible Materials/pharmacology , Core Binding Factor Alpha 1 Subunit/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Actinobacteria/metabolism , Anti-Bacterial Agents/pharmacology , Antioxidants/metabolism , Antioxidants/pharmacology , Signal Transduction/drug effectsABSTRACT
Oxidative stress and the accumulation of misfolded proteins in the brain are the main causes of Parkinson's disease (PD). Several nanoparticles have been used as therapeutics for PD. Despite their therapeutic potential, these nanoparticles induce multiple stresses upon entry. Selenium (Se), an essential nutrient in the human body, helps in DNA formation, stress control, and cell protection from damage and infections. It can also regulate thyroid hormone metabolism, reduce brain damage, boost immunity, and promote reproductive health. Selenium nanoparticles (Se-NPs), a bioactive substance, have been employed as treatments in several disciplines, particularly as antioxidants. Se-NP, whether functionalized or not, can protect mitochondria by enhancing levels of reactive oxygen species (ROS) scavenging enzymes in the brain. They can also promote dopamine synthesis. By inhibiting the aggregation of tau, α-synuclein, and/or Aß, they can reduce the cellular toxicities. The ability of the blood-brain barrier to absorb Se-NPs which maintain a healthy microenvironment is essential for brain homeostasis. This review focuses on stress-induced neurodegeneration and its critical control using Se-NP. Due to its ability to inhibit cellular stress and the pathophysiologies of PD, Se-NP is a promising neuroprotector with its anti-inflammatory, non-toxic, and antimicrobial properties.
ABSTRACT
Over the last three decades, neurodegenerative diseases (NDs) have increased in frequency. About 15% of the world's population suffers from NDs in some capacity, which causes cognitive and physical impairment. Neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Parkinson's disease, Alzheimer's disease, and others represent a significant and growing global health challenge. Neuroinflammation is recognized to be related to all NDs, even though NDs are caused by a complex mix of genetic, environmental, and lifestyle factors. Numerous genes and pathways such as NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide, and COX are involved in triggering brain immune cells like astrocytes and microglia to secrete inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. In AD, the binding of Aß with CD36, TLR4, and TLR6 receptors results in activation of microglia which start to produce proinflammatory cytokines and chemokines. Consequently, the pro-inflammatory cytokines worsen and spread neuroinflammation, causing the deterioration of healthy neurons and the impairment of brain functions. Gene therapy has emerged as a promising therapeutic approach to modulate the inflammatory response in NDs, offering potential neuroprotective effects and disease-modifying benefits. This review article focuses on recent advances in gene therapy strategies targeting neuroinflammation pathways in NDs. We discussed the molecular pathways involved in neuroinflammation, highlighted key genes and proteins implicated in these processes, and reviewed the latest preclinical and clinical studies utilizing gene therapy to modulate neuroinflammatory responses. Additionally, this review addressed the prospects and challenges in translating gene therapy approaches into effective treatments for NDs.
Subject(s)
Genetic Therapy , Neurodegenerative Diseases , Neuroinflammatory Diseases , Humans , Genetic Therapy/methods , Genetic Therapy/trends , Neurodegenerative Diseases/therapy , Neurodegenerative Diseases/genetics , Neuroinflammatory Diseases/therapy , AnimalsABSTRACT
The escalating focus on ageing-associated disease has generated substantial interest in the phenomenon of cognitive impairment linked to diabetes. Hyperglycemia exacerbates oxidative stress, contributes to ß-amyloid accumulation, disrupts mitochondrial function, and impairs cognitive function. Existing therapies have certain limitations, and apigenin (AG), a natural plant flavonoid, has piqued interest due to its antioxidant, anti-inflammatory, and anti-hyperglycemic properties. So, we anticipate that AG might be a preventive medicine for hyperglycemia-associated amnesia. To test our hypothesis, naïve zebrafish were trained to acquire memory and pretreated with AG. Streptozotocin (STZ) was administered to mimic hyperglycemia-induced memory dysfunction. Spatial memory was assessed by T-maze and object recognition through visual stimuli. Acetylcholinesterase (AChE) activity, antioxidant enzyme status, and neuroinflammatory genes were measured, and histopathology was performed in the brain to elucidate the neuroprotective mechanism. AG exhibits a prophylactic effect and improves spatial learning and discriminative memory of STZ-induced amnesia in zebrafish under hyperglycemic conditions. AG also reduces blood glucose levels, brain oxidative stress, and AChE activity, enhancing cholinergic neurotransmission. AG prevented neuronal damage by regulating brain antioxidant response elements (ARE), collectively contributing to neuroprotective properties. AG demonstrates a promising effect in alleviating memory dysfunction and mitigating pathological changes via activation of the Nrf2/ARE mechanism. These findings underscore the therapeutic potential of AG in addressing memory dysfunction and neurodegenerative changes associated with hyperglycemia.