Search Results (65)

Honey is a natural product of honeybees that has been consumed for centuries due to its nutritional value and potential health benefits. Recent scientific research has focused on its antioxidant capacity, which is linked to a variety of bioactive compounds such as phenolic acids, enzymes (e.g., glucose oxidase, catalase), flavonoids, ascorbic acid, carotenoids, amino acids, and proteins. Together, these components work synergistically to neutralize free radicals, regulate antioxidant enzyme activity, and reduce oxidative stress. This review decisively outlines the antioxidant effects of honey and presents compelling clinical and experimental evidence supporting its critical role in preventing diseases associated with oxidative stress. Honey stands out for its extensive health benefits, which include robust protection against cardiovascular issues, notable anticancer and anti-inflammatory effects, enhanced glycemic control in diabetes, immune modulation, neuroprotection, and effective wound healing. As a recognized functional food and dietary supplement, honey is essential for the prevention and adjunct treatment of chronic diseases. However, it faces challenges due to variations in composition linked to climatic conditions, geographical and floral sources, as well as hive management practices. The limited number of large-scale clinical trials further underscores the need for more research. Future studies must focus on elucidating honey’s antioxidant mechanisms, standardizing its bioactive compounds, and examining its synergistic effects with other natural antioxidants to fully harness its potential. Full article

Vitexin and isovitexin are dietary flavonoids widely distributed in food and medicinal plants. They have attracted increasing attention owing to their diverse pharmacological activities and favorable safety profiles. These compounds exhibit therapeutic potential across multiple biological systems, including the immune, nervous, respiratory, cardiovascular, and endocrine systems, through antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective mechanisms. Although previous reviews have addressed the pharmacological effects of vitexin and isovitexin, most are limited in scope—either focusing solely on vitexin or restricted to specific disease models such as cancer or diabetes. Moreover, some studies are outdated and do not reflect the recent advances in synthetic modification, green extraction technologies, and systems pharmacology. This review aims to provide a comprehensive evaluation of the pharmacological properties, pharmacokinetics, and clinical relevance of vitexin and isovitexin, highlighting their potential in disease prevention and treatment. A literature search was conducted using Web of Science, PubMed, and Google Scholar, with keywords including “vitexin”, “isovitexin”, “disease”, and “mechanism”. Here, we summarize the current research on the pharmacological effects of vitexin and isovitexin in metabolic disorders, inflammatory diseases, cancer, and neurodegenerative conditions, focusing on their molecular mechanisms and therapeutic targets. Furthermore, we discussed their toxicity, bioavailability, pharmacokinetics, and clinical research findings. Vitexin and isovitexin hold promise as therapeutic agents or adjuncts for multiple diseases with potential applications in modern medicine and healthcare. However, their pharmacological mechanisms, clinical efficacy, and potential synergistic effects with other therapeutic agents remain unclear. Further systematic research is needed to clarify molecular targets and optimize their therapeutic applications. Full article

Plants produce an extensive repertoire of secondary metabolites, developed over evolutionary time to support survival. Among these, D-limonene, a monoterpene exuded by citrus fruits, has demonstrated a broad range of pharmacological activities. This review elucidates limonene’s biological versatility, spanning antioxidant, anti-inflammatory, antitumor, antidiabetic, neuroprotective, and gastroprotective domains. Synthesizing data from both preclinical and early-phase clinical research, we explore its molecular mechanisms, ranging from reactive oxygen species mitigation and apoptosis induction to metabolic remodeling and neurotransmitter modulation. Special attention is given to limonene’s emerging role in oncological therapeutics, notably in breast and liver cancers, and its capacity to ameliorate pathophysiological hallmarks of diabetes and neurodegeneration. Its low toxicity and high bioavailability support its potential as a safe adjunct or alternative in phytotherapy. This review advocates for continued investigation into limonene’s translational potential across a spectrum of neoplastic and non-neoplastic diseases. Full article

Background/Objectives: Dimethyl trisulfide (DMTS) is a naturally occurring polysulfide with known antioxidant and neuroprotective properties. DMTS is a lipophilic transient receptor potential ankyrin 1 (TRPA1) ligand that reaches the central nervous system (CNS). Its role in the CNS, particularly regarding depression-like behaviour, has yet to be explored. This study investigates the influence of DMTS on stress responses and whether this effect is mediated through the TRPA1 ion channel, known for its role in stress adaptation. Using a mouse model involving three-week exposure, we examined the impact of DMTS on depression-like behaviour and anxiety and identified the involved brain regions. Methods: Our methods involved testing both Trpa1-wild-type and gene-knockout mice under CUMS conditions and DMTS treatment. DMTS was administered intraperitoneally at a dose of 30 mg/kg on days 16 and 20 of the 21-day CUMS protocol—in hourly injections seven times to ensure sustained exposure. Various behavioural assessments—including the open field, marble burying, tail suspension, forced swim, and sucrose preference tests—were performed to evaluate anxiety and depression-like behaviour. Additionally, we measured body weight changes and the relative weights of the thymus and adrenal glands, while serum levels of corticosterone and adrenocorticotropic hormone were quantified via ELISA. FOSB (FBJ murine osteosarcoma viral oncogene homolog B) immunohistochemistry was utilised to assess chronic neuronal activation in stress-relevant brain areas. Results: Results showed that CUMS induces depression-like behaviour, with the response being modulated by the TRPA1 status and that DMTS treatment significantly reduced these effects when TRPA1 channels were functional. DMTS also mitigated thymus involution due to hypothalamic–pituitary–adrenal (HPA) axis dysregulation. Conclusions: Overall, DMTS appears to relieve depressive and anxiety symptoms through TRPA1-mediated pathways, suggesting its potential as a dietary supplement or adjunct therapy for depression and anxiety. Full article

Stroke, the third leading cause of death worldwide, is a major cause of functional disability. Cerebral ischemia causes a rapid elevation of adenosine, the main neuromodulator in the brain. The inhibition of adenosine A2A receptors (A2ARs) has been introduced as a potential target in neurodegenerative disorders involving extracellular adenosine elevation. Istradefylline, a selective A2AR antagonist, has been approved for Parkinson’s disease (PD) adjunctive therapy and showed neuroprotective effects in PD and Alzheimer’s disease. However, the role of A2ARs in post-stroke neuronal damage and behavioral deficits remains unclear. We recently showed that A2AR antagonism prevented the adenosine-induced post-hypoxia synaptic potentiation of glutamatergic neurotransmission following the hypoxia/reperfusion of hippocampal slices. Here, we investigated the potential neuroprotective effects of istradefylline in male Sprague-Dawley rats subjected to pial vessel disruption (PVD) used to model a small-vessel stroke. Rats were treated with either a vehicle control or istradefylline (3 mg/kg i.p.) following PVD surgery for three days. Istradefylline administration prevented anxiety and depressive-like behaviors caused by PVD stroke. In addition, istradefylline significantly attenuated ischemia-induced cognitive impairment and motor deficits. Moreover, istradefylline markedly reduced hippocampal neurodegeneration, as well as GFAP/Iba-1, TNF-α, nNOS, and iNOS levels after PVD, but prevented the downregulation of anti-inflammatory markers TGF-β1 and IL-4. Together, these results suggest a molecular link between stroke and PD and that the anti-PD drug istradefylline displays translational potential for drug repurposing as a neuroprotective agent for cerebral ischemic damage. Full article

All human clinical trials evaluating neuroprotective therapeutics in cerebral ischemia have failed, casting a pall over the field which has not recovered. Numerous methodological issues in the performance of these trials were identified, with the result that current trials are now subject to higher degrees of rigor and transparency. Advances in re-canalization technologies now offer the hope that adjunctive neuroprotection can improve patient outcome. The evaluation of neuroprotection in preclinical animal models has also suffered from methodological issues, which has also been addressed, resulting in an improved performance of studies. This leaves the question of how to actually pick the most appropriate neuroprotective therapy for translation. Given the current limitations in resources, and the numerous strategies that have been proposed to take advantage of clinical and preclinical methodological improvements, we suggest that in vitro studies involving subjecting the most sensitive cells—neurons—to oxygen–glucose deprivation (OGD) can be used to resolve among the many possibilities. Specifically, a large body of evidence shows that successive increases in OGD durations (spanning the lethal/supra-lethal continuum) require increasingly ‘strong’ drugs and combinations to adequately protect neurons (criteria not met in clinical trials). Notably, as the OGD duration is lengthened, NMDA receptor (NMDAR) antagonists of increasing potency and dose are required to match this increasing severity. Under supra-lethal OGD conditions, cocktails composed of anti-excitotoxic antagonists with maximal potency and dose are required to achieve neuroprotection. We propose that this approach can serve as a strategy—a neuroprotective framework—to prioritize among the many possibilities that exist for neuroprotective therapeutics for translation. Specifically, utilize the OGD continuum to compare within-, between- and outside-classes of drugs, first alone and then in combinations, to identify the most efficacious drugs (‘head-to-head’ competitions to identify the ‘last man standing’). While the current state of knowledge strongly suggests that anti-excitotoxic approaches are required, this framework allows the integration of testing established and new therapeutics alike. This framework should include new technologies such as multi-electrode arrays (MEAs), which allow the evaluation of adverse effects of drugs alone, as well as if a drug truly provides functional neuroprotection, and not just survival. The neuroprotective framework provides a comprehensive strategy to eliminate ineffectual treatments, leaving only those modalities with the highest therapeutic index to be prioritized for translation. Full article

Background/Objectives: Dexmedetomidine, an alpha-2 adrenergic agonist, has gained significant attention for its sedative, analgesic, and anxiolytic properties in paediatric anaesthesia. This review explores its pharmacokinetics and pharmacodynamics, perioperative applications and efficacy, and safety profile in paediatric patients. Findings: Dexmedetomidine has emerged as a highly effective adjunct in paediatric anaesthesia, offering significant advantages across various perioperative settings. It reduces the need for other anaesthetics and opioids, leading to smoother recoveries with lower postoperative pain and agitation. Studies highlight its role in enhancing procedural sedation, improving patient cooperation, and providing superior analgesia in neuraxial and general anaesthesia. Its neuroprotective properties and stable haemodynamic profile make it particularly valuable in the perioperative and critical care settings. Conclusions: Dexmedetomidine has shown a favourable safety and efficacy profile in paediatric anaesthesia when doses are carefully titrated within the ranges recommended in the literature. While its use remains off-label in paediatric populations, increasing clinical experience and evidence support its integration into perioperative protocols. Full article

Palmitoylethanolamide (PEA) is an endogenous lipid mediator belonging to the N-acyl-ethanolamine family, widely recognized for its multifaceted effects on neuroprotection, chronic pain management, and immune modulation. As a naturally occurring compound, PEA plays a crucial role in maintaining homeostasis under conditions of cellular stress and inflammation. Its pharmacological effects are primarily mediated through peroxisome proliferator-activated receptor-alpha (PPAR-α) activation, alongside indirect modulation of cannabinoid receptors CB1 and CB2, as well as interactions with novel targets such as GPR55 and TRPV1. These molecular mechanisms underpin its broad therapeutic potential, particularly in the management of neuroinflammatory and neurodegenerative disorders, pain syndromes, and immune dysregulation. A major advancement in PEA research has been the development of ultramicronized palmitoylethanolamide (umPEA), which significantly enhances its bioavailability and therapeutic efficacy by facilitating better tissue absorption and interaction with key molecular pathways. Preclinical and clinical studies have demonstrated that umPEA is particularly effective in reducing neuroinflammation, stabilizing mast cells, and enhancing endocannabinoid system activity, making it a promising candidate for integrative approaches in neuropsychiatric and chronic inflammatory diseases. Given its well-established safety profile, umPEA represents an attractive alternative or adjunct to conventional anti-inflammatory and analgesic therapies. This communication provides a comprehensive overview of the mechanisms of action and therapeutic applications of both PEA and umPEA, emphasizing their emerging role in clinical practice and personalized medicine. Full article

Researchers have long focused on the accumulation of amyloid beta (Aβ) peptides in the brain as a primary pathological hallmark driving cognitive decline. This study investigated the neuroprotective effects of Rosa rugosa (RR) root extract and its key bioactive constituent, oleamide, against amyloid beta (Aβ)-induced neurotoxicity. Initially, an ethanolic extract of RR root was screened via in vitro assays to assess antioxidant and cytoprotective potential in rat pheochromocytoma cells. Subsequent fractionation, open-column chromatography, and preparatory thin-layer chromatography led to the isolation of oleamide, confirmed by gas chromatography–mass spectrometry and ¹H/¹³C nuclear magnetic resonance analyses. In vivo experiments using intracerebroventricularly injected Aβ in male mice demonstrated that both RR root extract and oleamide significantly improved cognitive performance in the Y-maze and passive avoidance tests. Additionally, oleamide restored acetylcholine levels and reduced malondialdehyde concentrations in brain tissue, indicating mitigation of oxidative stress and support of cholinergic function. No significant toxicity was observed, as evidenced by stable serum transaminase levels and unaltered body or brain weights. These findings highlight oleamide’s potential to protect against Aβ-driven pathology through multiple mechanisms, including reduced lipid peroxidation and improved neurotransmission. Further investigations into oleamide’s molecular targets and synergy with existing therapies may advance its development as a novel candidate for Alzheimer’s disease prevention or adjunct treatment. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain–gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD. Full article

Background and Objectives: Peripheral nerve injuries often result in significant functional impairment, and complete recovery remains challenging despite surgical interventions. Polyethylene glycol (PEG) has shown promise in nerve repair by facilitating axonal fusion and inhibiting Wallerian degeneration. This study investigates the biochemical, histopathological, and electrophysiological effects of PEG 3350 in a sciatic nerve injury model. Materials and Methods: Thirty adult male Wistar rats were divided into three groups: a control group, a surgery and saline group, and a surgery and PEG 3350 treatment group. Sciatic nerve transection was performed, and PEG 3350 was administered intraperitoneally for 12 weeks. Electromyography (EMG) and the inclined plane test assessed functional recovery. Sciatic nerve tissues were analyzed histologically and biochemically, including nerve growth factor (NGF), heat shock protein 70 (HSP-70), and malondialdehyde (MDA) levels. Results: PEG 3350 significantly improved electrophysiological parameters, reducing compound muscle action potential (CMAP) latency and increasing CMAP amplitude compared to the saline group (p < 0.05). Functional recovery, assessed by the inclined plane test, showed a significant improvement in the PEG-treated group (p < 0.01). Biochemical analysis revealed increased NGF and HSP-70 levels, suggesting enhanced neuroprotection and regeneration. Histopathological analysis demonstrated reduced fibrosis and increased axonal density in the PEG group compared to controls. PEG 3350 enhances nerve regeneration by improving electrophysiological function, promoting axonal repair, and increasing neurotrophic factor expression. Conclusions: These findings suggest PEG as a potential adjunct therapy for peripheral nerve injuries. Future research should explore the optimal administration protocols and combined therapeutic strategies for maximizing recovery. Full article

Neurological disorders are defined by a deterioration or disruption of the nervous system’s structure and function. These diseases, which include multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and schizophrenia, are caused by intricate pathological processes that include excitotoxicity, neuroinflammation, oxidative stress, genetic mutations, and compromised neurotrophic signaling. Although current pharmaceutical treatments relieve symptoms, their long-term efficacy is limited due to adverse side effects and weak neuroprotective properties. However, when combined with other neuroprotective drugs or adjunct therapy, they may offer additional benefits and improve treatment outcomes. Phytochemicals have emerged as attractive therapeutic agents due to their ability to regulate essential neurotrophic pathways, especially the brain-derived neurotrophic factor (BDNF) signaling cascade. BDNF is an important target for neurodegenerative disease (ND) treatment since it regulates neuronal survival, synaptic plasticity, neurogenesis, and neuroprotection. This review emphasizes the molecular pathways through which various phytochemicals—such as flavonoids, terpenoids, alkaloids, and phenolic compounds—stimulate BDNF expression and modulate its downstream signaling pathways, including GSK-3β, MAPK/ERK, PI3K/Akt/mTOR, CREB, and Wnt/β-catenin. This paper also highlights how phytochemical combinations may interact to enhance BDNF activity, offering new therapeutic options for ND treatment. Despite their potential for neuroprotection, phytochemicals face challenges related to pharmacokinetics, blood–brain barrier (BBB) permeability, and absorption, highlighting the need for further research into combination therapies and improved formulations. Clinical assessment and mechanistic understanding of BDNF-targeted phytotherapy should be the main goals of future studies. The therapeutic efficacy of natural compounds in regulating neurotrophic signaling is highlighted in this review, providing a viable approach to the prevention and treatment of NDs. Full article

Background/Objectives: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.g., Lavandula dentata L., are rich in phenolic compounds and may provide neuroprotective and anti-inflammatory benefits. However, limited research evaluates their effectiveness in modulating neuroinflammation and histopathological changes in epilepsy models. Therefore, the current study hypothesized that treating Lavandula dentata L. extract or essential oils may reduce neuroinflammatory responses and mitigate histopathological changes in the brain, providing a natural alternative or adjunct therapy for epilepsy management. Methods: Five groups of male Wistar rats were used: control, pilocarpine-treated epileptic, valproic acid (VPA-treated epileptic), L. dentata extract, and essential oils. Numerous electrolyte levels, monoamine levels, neurotransmitter levels, and the mRNA expression of specific gate channel subtypes were evaluated in homogenate brain tissue. Additionally, histological changes in various brain regions were investigated. Results: The investigation revealed that the extract and essential oils obtained from L. dentata L. exhibited the ability to improve the modulation of electrolytes and ions across voltage- and ligand-gated ion channels. Furthermore, it was revealed that they could decrease neuronal excitability by facilitating repolarization. Moreover, L. dentata’s oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusions: The present work confirms that the extract and essential oils of L. dentata L. have different activities to ameliorate the progression of histopathological alterations. Therefore, when used in conjunction with other AEDs, the extract and essential oils of L. dentata can slow the progression of epileptogenesis. Full article

Flavonoids are naturally occurring polyphenolic compounds known for their extensive range of biological activities. This review focuses on the inhibitory effects of flavonoids on acetylcholinesterase (AChE) and their potential as therapeutic agents for cognitive dysfunction. AChE, a serine hydrolase that plays a crucial role in cholinergic neurotransmission, is a key target in the treatment of cognitive impairments due to its function in acetylcholine hydrolysis. Natural polyphenolic compounds, particularly flavonoids, have demonstrated significant inhibition of AChE, positioning them as promising alternatives or adjuncts in neuropharmacology. This study specifically examines flavonoids such as quercetin, apigenin, kaempferol, and naringenin, investigating their inhibitory efficacy, binding mechanisms, and additional neuroprotective properties, including their antioxidant and anti-inflammatory effects. In vitro, in vivo, and in silico analyses reveal that these flavonoids effectively interact with both the active and peripheral anionic sites of AChE, resulting in increased acetylcholine levels and the stabilization of cholinergic signaling. Their mechanisms of action extend beyond mere enzymatic inhibition, as they also exhibit antioxidant and anti-amyloidogenic properties, thereby offering a multifaceted approach to neuroprotection. Given these findings, flavonoids hold considerable therapeutic potential as modulators of AChE, with implications for enhancing cognitive function and treating neurodegenerative diseases. Future studies should prioritize the enhancement of flavonoid bioavailability, evaluate their efficacy in clinical settings, and explore their potential synergistic effects when combined with established therapies to fully harness their potential as neurotherapeutic agents. Full article

In regenerative medicine, mesenchymal stem cells (MSCs) have shown their importance and potential in tissue reconstruction and immune system modification. However, such cells’ potential is often diminished by factors such as oxidative stress, immune rejection, and inadequate engraftment. This review highlights the role of molecular hydrogen (H₂) and cold atmospheric plasma (CAP) as adjunct therapies to improve the effectiveness of MSC therapy. H₂ has strong antioxidative and anti-inflammatory actions as it quenches reactive oxygen species and positively stimulates the Nrf2 pathway that promotes MSC survival and life. CAP, being a modulated source of ROS and RNS, also assists MSCs by altering the cellular redox balance, thus facilitating cellular adaptation, migration, and differentiation. H₂ and CAP in conjunction with each other assist in establishing an ambience favorable for promoting MSCs’ survival and growth abilities, and reduce the healing time in various pathways such as wound, neuroprotection, and ischemia. Besides these concerns, this review also covers the best administration routes and doses of H₂ and CAP together with MSCs in therapy. This study informs on a novel dual method aimed at improving the outcome of MSC therapy while adding several molecular targets and relevant clinical uses concerning these therapies. Research of the future has to deal with bettering these protocols so that the therapeutic benefits can be maximized without long-term implications for clinical applications. Full article