Search Results (5,219)

Curcumin, a plant-derived polyphenolic compound, exhibits diverse pharmacological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and cardiovascular protective effects, and is widely used in food, medicine, and other fields. However, its poor water solubility and easy oxidative degradation limit its extensive application in biomedicine. To solve these problems, a series of biomedical polyurethanes (Cur-PU) with similar molecular weights but different PEG contents were successfully synthesized using HO-PCL-OH and HO-PEG-OH as soft segments and curcumin as a chain extender. The results indicated that increasing the PEG content reduced the T¹_m, T¹_c, and H¹_c of Cur-PU, along with a slower crystallization rate and lower crystallinity. More importantly, a higher PEG content decreased the water contact angle but increased water solubility and water uptake, which, combined with reduced crystallinity, enhanced hydrophilicity, swelling ratio, curcumin release rate, and degradation rate in an enzymatic solution and pH 8.0 buffer. Thus, precise regulation of Cur-PU’s degradation and curcumin release was achieved by controlling the PEG content. Biocompatibility tests confirmed that Cur-PU exhibited excellent antioxidant and antibacterial activities, making it a highly promising biomedical material. Full article

Hesperidin, a flavonoid abundantly found in citrus fruits, has demonstrated a substantial role in the management of various pathogeneses. Furthermore, the wide range of health-promoting properties of hesperidin, including antioxidant, anti-inflammatory, anti-cancerous, hepatoprotective, neuroprotective, nephroprotective, and cardioprotective effects, has been well documented. Additionally, persuasive evidence from both in vivo and in vitro studies highlights its substantial roles in combating obesity, protecting the kidneys, liver, and lung tissue architecture, promoting wound healing, and modulating immune responses. This flavonoid acts as an effective antimicrobial agent against a wide range of microorganisms by inhibiting biofilm formation and disrupting the cell membrane. This review aims to deliver comprehensive insights into the therapeutic potential of hesperidin across different pathogenesis through distinct mechanisms. Moreover, it provides up-to-date evidence on the synergistic properties of this compound with other drugs as well as compounds, and emerging plans to enhance its efficiency in health management through various nanoformulation approaches. Despite its considerable therapeutic potential, the clinical application of hesperidin remains constrained by poor bioavailability, rapid degradation, and dosage-related limitations. Addressing these challenges will require extensive further research to clarify its mechanisms of action, safety profile, and therapeutic efficacy in managing underlying pathogenic conditions. Full article

Although neurons are not productively infected by HIV-1, the envelope glycoprotein gp120, detectable in cerebrospinal fluid independently of active viral replication, gains intraneuronal access via lipid raft-mediated endocytosis, macropinocytosis, and retrograde axonal transport, contributing to persistent neurobiological dysfunction within the central nervous system. Once internalized, gp120 is associated with neuronal dysfunction involving convergent pathways, including excitotoxic calcium dysregulation, mitochondrial and metabolic failure, and inflammatory and senescence-associated amplification. These pathways converge on suppression of CREB and BDNF signaling, dismantling the transcriptional and neurotrophic programs required for synaptic maintenance and cognitive resilience. Extracellular vesicle-mediated dissemination and microRNA reprogramming extend gp120-associated neurobiological effects beyond sites of receptor engagement, while gut-derived metabolites, particularly quinolinic acid, lower the excitotoxic threshold through synergistic activation of NMDA receptors. Together, these mechanisms define HAND as a network disorder in which gp120 contributes to persistent neurocognitive dysfunction beyond active viral replication, identifying convergent therapeutic nodes where combination strategies targeting excitotoxicity, mitochondrial dysfunction, and neuroinflammation offer the most promising path toward durable neuroprotection. Full article

Background/Objectives: Alzheimer’s disease (AD) is characterized by amyloid-beta accumulation and neuroinflammation, yet the molecular target of Ginsenoside Rg1 remains elusive. This study aimed to elucidate the neuroprotective mechanism of Ginsenoside Rg1, specifically investigating its interaction with C-C motif chemokine receptor 3 (CCR3). Methods: We utilized 5xFAD transgenic mice and CCR3-overexpressing BV2 microglial cells. Behavioral assessments, enzyme-linked immunosorbent assays, quantitative real-time polymerase chain reaction, molecular docking, and surface plasmon resonance were employed to evaluate cognitive function and molecular pathways. Results: Ginsenoside Rg1 treatment significantly ameliorated spatial learning and memory deficits. Quantitatively, Rg1 reduced cortical amyloid-beta 1–40 levels (p < 0.05) and bound directly to CCR3 with a dissociation constant of 3.599 × 10⁻⁵ mol/L. This inhibition suppressed neuroinflammation and restored neurotrophic factors, including Brain-derived neurotrophic factor. Conclusions: CCR3 is a novel pharmacological target for Ginsenoside Rg1, providing a precise molecular basis for its neuroprotective effects. Future research should focus on clarifying the pharmacokinetic profile and brain bioavailability of Ginsenoside Rg1 to facilitate clinical translation. Full article

Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for neurodegenerative diseases. Metformin has been found to have neuroprotective effect, in addition to antidiabetic function. Our recent studies have identified that metformin ameliorates Cd neurotoxicity via blocking ROS-dependent PP5/AMPK-JNK signaling pathway. Here we further show that metformin protected PC12 cells and primary neurons from Cd-poisoning by mitigating Cd-induced increases in ATG5/LC3-II/p62 levels and autophagosomes. Knockdown of ATG5 dramatically potentiated the inhibitory effects of metformin on Cd-induced LC3-II, cleavage of caspase-3, accumulation of autophagosomes and apoptosis in PC12 cells. Addition of chloroquine (CQ) strengthened the basic and Cd-elevated ATG5/LC3-II/p62 levels, autophagosome accumulation and cell apoptosis, whereas metformin powerfully blocked the events, implying a metformin-promoted autophagic flux-dependent mechanism involved. Further research revealed that metformin prevented Cd-induced autophagic flux impairment and cell apoptosis, which was attributed to restraining Cd inactivation of AMPK. This is supported by the findings that activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα (AMPKα-ca) reinforced the inhibitory effects of metformin on Cd-evoked ATG5/LC3-II/p62/autophagosomes and apoptosis in PC12 cells and/or primary neurons. Taken together, the results indicate that metformin protects neuronal cells from Cd-induced autophagic flux impairment-dependent apoptosis by activating AMPK. Our studies highlight that metformin has a great potential for prevention of Cd toxicity related to neurodegenerative diseases. Full article

This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation—governing membrane excitability, signal transduction, and cellular homeostasis—has emerged as a critical mechanistic basis for their pharmacological effects. Twenty-four representative phytoconstituents are discussed and classified into five major categories based on their structural features: alkaloids, terpenoids, lignans and acetogenins, polyphenols, and other aromatic and conjugated compounds. Across these categories, the reviewed compounds exhibit distinct and often highly specific effects on the amplitude and gating kinetics of multiple ionic currents, including voltage-gated Na⁺ currents (I_Na), delayed-rectifier K⁺ currents (I_K(DR)), M-type K⁺ currents (I_K(M)), hyperpolarization-activated cation currents (I_h), erg-mediated K⁺ currents (I_K(erg)), inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ currents (I_K(Ca)). Alkaloids predominantly suppress voltage-gated K⁺ currents, with notable exceptions such as aconitine, which alters the properties of both I_Na and I_K(DR), thereby contributing to its proarrhythmic toxicity. Terpenoids, including cannabidiol, croton diterpenoids, lutein, thymol, and triptolide, exert multifaceted effects on I_K(M), I_h, inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ channels. Lignans and acetogenins, such as gomisin A, honokiol, sesamin, and squamocin, primarily modulate I_Na, I_h, and I_K(Ca), with several compounds demonstrating strong links between ion-channel modulation and anti-neoplastic or neuroprotective actions. Polyphenolic compounds, including curcumin, eugenol, resveratrol, gastrodigenin, gastrodin, and pterostilbene, display diverse ion-channel targeting profiles, influencing multiple Na⁺ and K⁺ channel subtypes. Other aromatic or conjugated compounds, such as isoplumbagin, plumbagin, and verteporfin, regulate I_K(erg) and I_K(Ca), potentially contributing to both therapeutic efficacy and adverse effects. Collectively, the compound-specific modulation of current amplitude and gating kinetics offers valuable mechanistic insight into the pharmacological and toxicological significance of plant-derived natural products, highlighting the functional role of ion channel evaluation in guiding their therapeutic development and ensuring safety assessment. Full article

The Morus genus comprises several tree species whose fruits are used in human nutrition, while the leaves and roots are used in traditional medicine. The aim of this study was to highlight the antioxidant, cholinesterase inhibitory, and neuroprotective effects of hydroalcoholic extracts from Morus alba (MAE) and Morus nigra (MNE) leaves. RP-UHPLC-PDA analysis of extracts revealed the presence of polyphenols in higher quantities in MNE extract compared to MAE. Both extracts demonstrated antioxidant properties in the hydroxyl radical scavenging and lipid peroxidation inhibition assays. MNE exhibited a superior antioxidant capacity compared to MAE; the IC₅₀ values for the inhibition of plasma lipid oxidation assay were 25.31 ± 2.54 µg/mL for MNE and 29.85 ± 0.97 µg/mL for MAE. Both extracts showed cholinesterase inhibitory activity. The IC₅₀ values for acetylcholinesterase inhibition were 24.34 ± 0.86 µg/mL for MNE and 46.87 ± 2.16 µg/mL for MAE. The inhibitory potency of MNE was comparable to that of galantamine, which was used as standard. Both extracts reversed, in a dose-dependent manner, the scopolamine-induced cognitive impairment and behavioural alterations in scopolamine-treated zebrafish (Danio rerio) as evaluated by the Y-maze test, novel tank diving test, and novel object recognition test. Full article

Background: Intracavernosal platelet-rich plasma (PRP) is increasingly used for erectile dysfunction (ED), despite the absence of standardized biological characterization and clear dose definitions. This systematic review evaluates the clinical efficacy of PRP in ED while integrating emerging immune-centric mechanistic evidence. Methods: Following PRISMA 2020 guidelines, randomized controlled trials (RCTs) and prospective studies (2020–2025) investigating intracavernosal PRP in adult men with ED were identified across major databases. Validated outcomes included International Index of Erectile Function (IIEF-EF or IIEF-5), Erection Hardness Score (EHS), Sexual Encounter Profile (SEP), and penile Doppler parameters. Preclinical data were narratively integrated to contextualize biological plausibility. Results: Fourteen clinical studies met the inclusion criteria (six RCTs, eight prospective cohorts). Across most studies, PRP produced clinically relevant within-patient improvements, and three RCTs demonstrated minimal clinically important difference (MCID) responder rates compared with placebo. However, other trials showed comparable improvements in placebo arms, underscoring substantial contextual effects. Safety was consistently favourable. Marked heterogeneity in blood volume processed (10–120 mL), injected PRP volume (3–12 mL), preparation systems, and session protocols precluded cross-study comparability. Critically, no study reported platelet dose, leukocyte subsets, peripheral blood mononuclear cell (PBMNC) content, or red blood cell contamination. Preclinical models consistently demonstrate that PRP restores erectile function through angiogenic, neuroprotective, and immunomodulatory mechanisms, including CXCL5-mediated monocyte recruitment and M1-to-M2 macrophage polarization. Conclusions: Intracavernosal PRP shows promising short-term efficacy signals and a favourable short-term safety profile in mild-to-moderate vasculogenic ED, but current evidence is limited by profound biological and methodological heterogeneity. PRP should be reconsidered as an immune-regenerative intervention requiring dose-defined, composition-defined, and mechanistically informed randomized trials. Interpretation of these findings is constrained by the absence of formal risk-of-bias assessment for non-randomized studies, substantial clinical and biological heterogeneity across trials, and the lack of standardized PRP characterization. Full article

(1) Different classes of antidepressant drugs have been shown to activate lysophosphatidic acid (LPA) receptors, but their effects on the receptor signaling stimulated by LPA have not been fully investigated. In the present study, we examined the effect of the tricyclic antidepressant amitriptyline on the LPA-induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Rho signaling in C6 glioma cells and cultured rat astrocytes. (2) LPA receptor signaling was investigated by using Western blot and microscopic immunofluorescence assays. Rho activation was determined by a pull-down assay. (3) Amitriptyline potentiated the LPA-induced activation of ERK1/2 signaling, as indicated by the more than additive increases in the phosphorylation/activation of key components of this pathway including fibroblast growth factor 1 receptor, MEK1/2, ERK1/2, Elk-1, and cyclic AMP response element binding protein (CREB). Amitriptyline also enhanced the expression of brain-derived neurotrophic factor (BDNF) elicited by LPA. In contrast, the antidepressant failed to mimic the LPA-induced activation of Rho and Rho-dependent responses, such as the reversal of astrocyte stellation, accumulation of stress fibers, and the phosphorylation of focal adhesion kinase and myosin target subunit of myosin phosphatase isoform 1. Moreover, when combined with LPA, amitriptyline curtailed Rho activation and the Rho-mediated cellular responses. (4) These results demonstrate that in astroglial cells, amitriptyline exerts a balanced action on LPA-activated receptors by enhancing the neuroprotective ERK1/2-CREB-BDNF signaling and dampening the potentially detrimental Rho–ROCK pathway, and suggest that this unique property may contribute to the antidepressant activity of the drug. Full article

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article

Coenzyme Q10 (CoQ10), a natural antioxidant produced by the human body, has strong anti-inflammatory properties, reduces oxidative stress, and improves mitochondrial function. It is also known for its strong neuroprotective effects. With age, endogenously produced CoQ10 levels decline, contributing to the development of chronic diseases, including eye disorders. Irreversible ocular diseases that result in blindness present a significant challenge in contemporary medicine, as no fully effective cure exists; current treatments primarily aim to decelerate disease progression, manage symptoms, and preserve residual vision. Our study reviews research on the use of CoQ10 in eye diseases like age-related macular degeneration (AMD), retinitis pigmentosa (RP), and glaucoma, which can cause permanent vision loss and are linked to oxidative stress and mitochondrial dysfunction. This article explores whether CoQ10 can be a safe and effective addition to treatment for these conditions. We also outline directions for future research and explain how CoQ10 functions in the studies discussed in this review. Full article

Neurodegenerative disorders (NDs), such as Alzheimer’s and Parkinson’s diseases (AD and PD), despite having different main neuropathological hallmarks, share several interconnected aetiologic mechanisms and lack effective disease-modifying treatments. The multifactorial nature of these diseases has encouraged the development of new drugs such as multi-target-directed ligands (MTDLs). In this work, an anti-AD drug (rivastigmine, RIV) was fused and conjugated with a series of antioxidant scaffolds to obtain a small library of RIV–antiox hybrids. In addition to inhibitory activity towards both cholinesterases, these hybrids exhibited radical scavenging activity, inhibition of Aβ aggregation, and neuroprotection against cell death induced in AD models. The relevant anti-AD properties already found for these hybrids challenged us to also assess their capacity to modulate and interfere with ROS-associated harmful dysfunctions, namely in the dysregulation of biometal ions (Fe³⁺, Cu²⁺, and Zn²⁺) and upregulation of monoamine oxidases (MAOs). In particular, the capacity of the hybrids for metal chelation and inhibition of Cu-induced Aβ aggregation and MAO isoforms was evaluated, as well as their neuroprotection capacity in cell models of PD. Overall, some of these RIV hybrids appear as lead compounds for the development of novel multifunctional agents against NDs. Full article

Glucagon-like peptide-1 (GLP-1) and dual GIP/GLP-1 receptor agonists, originally introduced for the management of type 2 diabetes mellitus and obesity, are increasingly recognized for their broader actions within the central nervous system, with emerging implications in neuropsychiatry and neurodegeneration. This review integrates current preclinical and clinical evidence, emphasizing their pharmacodynamic profile, central receptor distribution, and the molecular pathways linking metabolic signaling to neural function. Evidence suggests that GLP-1 receptor activation across key brain regions involved in energy balance and reward modulates multiple neurotransmitter systems, including dopamine and serotonin, as well as glutamatergic and GABAergic transmission, thereby influencing behavior, affective processes, and cognitive function. In parallel, these agents exhibit neuroprotective properties through improved neuronal insulin sensitivity, attenuation of neuroinflammatory pathways, and support of neuroplasticity, alongside effects on limiting pathological protein aggregation. Dual GIP/GLP-1 agonism may further potentiate these central actions through complementary metabolic and synaptic mechanisms. Although pharmacovigilance data have identified isolated neuropsychiatric adverse events, current clinical evidence does not support a consistent causal association. Collectively, incretin-based therapies represent a promising translational approach at the interface of metabolic and neuropsychiatric disorders, warranting further investigation into their long-term central safety, therapeutic efficacy, and clinical relevance. Full article