Prosopis africana exerts neuroprotective activity against quaternary metal mixture-induced memory impairment mediated by oxido-inflammatory response via Nrf2 pathway.

The beneficial effects of Prosopis africana (PA) on human health have been demonstrated; however, its protective effects against heavy metals (HM) are not yet understood. This study evaluated the potential neuroprotective effects of PA in the cerebral cortex and cerebellum. To accomplish this, we divided 35 albino Sprague Dawley rats into five groups. Group I did not receive either heavy metal mixture (HMM) or PA. Group II received a HMM of PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg) orally for a period of two months. Groups III, IV, and V received HMM along with PA at doses of 500, 1000, and 1500 mg/kg, respectively. PA caused decreased levels of HM accumulation in the cerebral cortex and cerebellum and improved performance in the Barnes maze and rotarod tests. PA significantly reduced levels of IL-6 and TNF-α. PA increased concentrations of SOD, CAT, GSH, and Hmox-1 and decreased the activities of AChE and Nrf2. In addition, levels of MDA and NO decreased in groups III, IV, and V, along with an increase in the number of live neurons. In conclusion, PA demonstrates a complex neuroprotective effect with the potential to alleviate various aspects of HM-induced neurotoxicity.

Exploring the Neuroprotective Potential of Desmodium Species: Insights into Radical Scavenging Capacity and Mechanisms against 6-OHDA-Induced Neurotoxicity.

In this study, we collected seven prevalent Taiwanese Desmodium plants, including three species with synonymous characteristics, in order to assess their antioxidant phytoconstituents and radical scavenging capacities. Additionally, we compared their inhibitory activities on monoamine oxidase (MAO) and 6-hydroxydopamine (6-OHDA) auto-oxidation. Subsequently, we evaluated the neuroprotective potential of D. pulchellum on 6-OHDA-induced nerve damage in SH-SY5Y cells and delved into the underlying neuroprotective mechanisms. Among the seven Desmodium species, D. pulchellum exhibited the most robust ABTS radical scavenging capacity and relative reducing power; correspondingly, it had the highest total phenolic and phenylpropanoid contents. Meanwhile, D. motorium showcased the best hydrogen peroxide scavenging capacity and, notably, D. sequax demonstrated remarkable prowess in DPPH radical and superoxide scavenging capacity, along with selective inhibitory activity against MAO-B. Of the aforementioned species, D. pulchellum emerged as the frontrunner in inhibiting 6-OHDA auto-oxidation and conferring neuroprotection against 6-OHDA-induced neuronal damage in the SH-SY5Y cells. Furthermore, D. pulchellum effectively mitigated the increase in intracellular ROS and MDA levels through restoring the activities of the intracellular antioxidant defense system. Therefore, we suggest that D. pulchellum possesses neuroprotective effects against 6-OHDA-induced neurotoxicity due to the radical scavenging capacity of its antioxidant phytoconstituents and its ability to restore intracellular antioxidant activities.

Evaluation of the neuroprotective effect of antipsychotics by serum quantification of protein S100B.

OBJECTIVE: This research delves into the intricate interplay between antipsychotic medications and neuroprotection focusing on the S100B protein-a central player in the regulation of neuroapoptotic activity. METHOD: Blood samples were collected to assess serum S100B protein levels using an immunoassay of immunoelectrochemiluminescence. The first two samples were collected with a 3-month interval between each, and the third sample was obtained 6 months after the previous one. Changes in S100B protein levels throughout the study were assessed using Friedman's ANOVA test. This was followed by the Wilcoxon signed-rank test with Bonferroni correction to account for multiple comparisons. RESULTS: This study involved 40 patients diagnosed with severe mental disorders (34 schizophrenia, 4 schizoaffective disorder, 1 bipolar disorder, and 1 borderline personality disorder). These patients had been receiving antipsychotic treatment for an average duration of 17 years. The results revealed that the S100B protein remained within physiological levels (median values 39.0 ng/L for the first sample, median values 41.0 ng/L for the second sample, and median values 40.5 ng/L for the third sample) with no significant changes (p = 0.287), with all anti-psychotic medicaments values consistently below 50 ng/L, a lower value compared to maximum range of 105 ng/L. Importantly, there were no significant differences in S100B protein levels between patients on monotherapy and those on combination antipsychotic therapy (p = 0.873), suggesting that combination therapy did not increase neuroapoptotic activity. CONCLUSIONS: These findings provide compelling evidence for the potential neuroprotective effects of long-term antipsychotic treatment in individuals with severe mental disorders. By maintaining physiological levels of the S100B protein, antipsychotic medications may help protect against neuronal damage and dysfunction. This research contributes valuable insights into the neuroprotective mechanisms of antipsychotic drugs, enhancing our understanding of their potential benefits in the treatment of severe mental disorders.

Neuroprotective potential of solanesol against tramadol induced zebrafish model of Parkinson's disease: insights from neurobehavioral, molecular, and neurochemical evidence.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and subsequent depletion of dopamine in the striatum. Solanesol, an alcohol that acts as a precursor to coenzyme Q10, possesses potential applications in managing neurological disorders with antioxidant, anti-inflammatory, and neuromodulatory potential. In this study, a zebrafish model was employed to investigate the effects of solanesol in tramadol induced PD like symptoms. Zebrafish were administered tramadol injections (50 mg/kg) over a 20-day period. Solanesol was administered at doses of 25, 50, and 100 mg/kg, three hours prior to tramadol administration from day 11 to day 20. Behavioral tests assessing motor coordination were conducted on a weekly basis using open field and novel diving tank apparatus. On day 21, the zebrafish were euthanized, and brain tissues were examined for markers of oxidative stress, inflammation, and neurotransmitters level. Chronic tramadol treatment resulted in motor impairment, reduced antioxidant enzyme levels, enhanced release of proinflammatory cytokines in the striatum, and disrupted neurotransmitter balance. However, solanesol administration mitigated these effects and exhibited a neuroprotective effect against neurodegenerative alterations in the zebrafish model of PD. This was evident through improvements in behavior, modulation of biochemical markers, attenuation of neuroinflammation, restoration of neurotransmitters level, and enhancement of mitochondrial activity. The histopathological study also confirmed that solanesol dose dependently restored neuronal cell density which confirmed its neuroprotective potential. Further investigations are required to elucidate the underlying mechanisms of solanesol neuroprotective effects and evaluate its efficacy in human patients.

Neuroprotective effects: Solanesol has shown significant neuroprotective effects in a zebrafish model of Parkinson's disease induced by chronic tramadol usage.Improved behavioral performance: Administration of solanesol resulted in improved motor coordination in the open field test (OFT) and novel diving apparatus in the tramadol-induced zebrafish model of PD.Decreased inflammation: Solanesol treatment significantly reduced pro-inflammatory cytokine levels in the tramadol-induced zebrafish model of PD, indicating its anti-inflammatory properties.Restored oxidative parameters: Solanesol administration restored oxidative stress parameters, as well as catecholamine and neurotransmitter levels in the tramadol-induced zebrafish model of PD.Histopathological improvement: Solanesol administration prevented histopathological alterations induced by tramadol, indicating its ability to protect against neuronal damage in the zebrafish model of PD.

Unlocking longevity with GLP-1: A key to turn back the clock?

Traditionally known for managing blood sugar, GLP-1, a gut hormone, is emerging as a potential key to both lengthening lifespan and combating age-related ailments. While widely recognized for its role in blood sugar control, GLP-1 is increasingly recognized for its diverse effects on various biological pathways beyond glucose metabolism. Research across organisms and humans suggests that activating GLP-1 receptors significantly impacts cellular processes linked to aging. Its ability to boost mitochondrial function, enhance cellular stress resistance, and quell inflammation hints at its wider influence on aging mechanisms. This intricate interplay between GLP-1 and longevity appears to act through multiple pathways. One key effect is its ability to modulate insulin sensitivity, potentially curbing age-related metabolic issues like type 2 diabetes. Its neuroprotective properties also make it a promising candidate for addressing age-related cognitive decline and neurodegenerative diseases. Furthermore, preclinical studies using GLP-1 analogs or agonists have shown promising results in extending lifespan and improving healthspan in various model organisms. These findings provide a compelling rationale for exploring GLP-1-based interventions in humans to extend healthy aging. However, despite the exciting therapeutic prospects of GLP-1 in promoting longevity, challenges remain. Determining optimal dosages, establishing long-term safety profiles, and investigating potential adverse effects require comprehensive clinical investigations before we can confidently translate these findings to humans. This article emphasises the wide applicability of GLP-1.

Quercetin improves the protection of hydroxysafflor yellow a against cerebral ischemic injury by modulating of blood-brain barrier and src-p-gp-mmp-9 signalling.

Protection of the structural and functional integrity of the blood-brain barrier (BBB) is crucial for treating ischemic stroke (IS). Hydroxysafflor yellow A (HSYA) and quercetin (Quer), two main active components in the edible and medicinal plant Carthamus tinctorius L., have been reported to exhibit neuroprotective effects. We investigated the anti-IS and BBB-protective properties of HSYA and Quer and the underlying mechanisms. They decreased neurological deficits in middle cerebral artery occlusion (MCAO) mice, while their combination showed better effects. Importantly, HSYA and Quer ameliorated BBB permeability. Their effects on reduction of both EB leakage and infarct volume were similar, which may contribute to improved locomotor activities. Moreover, HSYA and Quer showed protective effects for hCMEC/D3 monolayer against oxygen-glucose deprivation. Src, p-Src, MMP-9, and P-gp were associated with ingredients treatments. Furthermore, molecular docking and molecular dynamics simulations revealed stable and tight binding modes of ingredients with Src and P-gp. The current study supports the potential role of HSYA, Quer, and their combination in the treatment of IS by regulating BBB integrity.

Integrated Transcriptomic and Proteomic Study of the Mechanism of Action of the Novel Small-Molecule Positive Allosteric Modulator 1 in Targeting PAC1-R for the Treatment of D-Gal-Induced Aging Mice.

Small-molecule positive allosteric modulator 1 (SPAM1), which targets pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R), has been found to have a neuroprotective effect, and the underlying mechanism was explored in this study. First, using a D-galactose (D-gal)-induced aging mouse model, we confirmed that SPAM1 improves the structure of the hippocampal dentate gyrus and restores the number of neurons. Compared with D-gal model mice, SPAM1-treated mice showed up-regulated expression of Sirtuin 6 (SIRT6) and Lamin B1 and down-regulated expression of YinYang 1 (YY1) and p16. A similar tendency was observed in senescent RGC-5 cells induced by long-term culture, indicating that SPAM1 exhibits significant in vitro and in vivo anti-senescence activity in neurons. Then, using whole-transcriptome sequencing and proteomic analysis, we further explored the mechanism behind SPAM1's neuroprotective effects and found that SPAM is involved in the longevity-regulating pathway. Finally, the up-regulation of neurofilament light and medium polypeptides indicated by the proteomics results was further confirmed by Western blotting. These results help to lay a pharmacological network foundation for the use of SPAM1 as a potent anti-aging therapeutic drug to combat neurodegeneration with anti-senescence, neuroprotective, and nerve regeneration activity.

An anthocyanin-rich extract from Zea mays L. var. ceratina alleviates neuronal cell death caused by hydrogen peroxide-induced cytotoxicity in SH-SY5Y cells.

The incidence of dementia is rising, with neuronal cell death from oxidative stress and apoptosis recognized as a significant contributor to its development. However, effective strategies to combat this condition are lacking, necessitating further investigation. This study aimed to assess the potential of an anthocyanin-rich extract from Zea mays L. var. ceratina (AZC) in alleviating neuronal cell death.Neurotoxicity was induced in SH-SY5Y cells using hydrogen peroxide (H2O2) at a concentration of 200 µM. Cells were pretreated with varying doses (31.25 and 62.5 µg/mL) of AZC. Cell viability was assessed using the MTT assay, and molecular mechanisms including reactive oxygen species (ROS) levels, antioxidant enzyme activities (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)), malondialdehyde (MDA) levels for oxidative stress, and the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), cAMP response element-binding protein (CREB), and apoptotic factors (B-cell lymphoma 2 (Bcl-2), caspase 3) were explored.Results showed that AZC significantly improved cell viability, reduced ROS production and MDA levels, and downregulated caspase 3 expression. It enhanced CAT, SOD, and GSH-Px activities, activated ERK1/2 and CREB, and upregulated Bcl-2 expression. These findings support the neuroprotective effects of AZC, suggesting it activates ERK1/2, leading to CREB activation and subsequent upregulation of Bcl-2 expression while suppressing caspase 3. AZC may mitigate neuronal cell death by reducing ROS levels through enhanced scavenging enzyme activities.In conclusion, this study underscores the potential of AZC as a neuroprotective agent against neuronal cell death. However, further investigations including toxicity assessments, in vivo studies, and clinical trials are necessary to validate its benefits in neuroprotection.

Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aß), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aß and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aß. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.

Curcumin nanogel and its efficacy against oxidative stress and inflammation in rat models of ischemic stroke.

Aim: The study was designed to develop and analyze curcumin nanoparticles. Methods: Curcumin nanoparticles were formulated and evaluated. Their efficacy in protecting against brain damage was investigated in a rat model of ischemic stroke, considering motor function, muscle strength and antioxidant enzyme activity. Results: Curcumin nanoparticles displayed a zeta potential of -55 ± 13.5 mV and an average particle size of 51.40 ± 21.70 nm. In ischemic stroke rat models, curcumin nanoparticle treatment significantly improved motor functions, and muscle strength and increased the activities of antioxidant enzymes like glutathione peroxidase, glutathione, glutathione S-transferase, superoxide dismutase and catalase, reducing oxidative stress and inflammation. Conclusion: Curcumin nanoparticles showed significant neuroprotective effects in ischemic stroke models.

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Dihydropashanone Isolated from Lindera erythrocarpa, a Potential Natural Product for the Treatment of Neurodegenerative Diseases.

Lindera erythrocarpa, a flowering plant native to eastern Asia, has been reported to have neuroprotective activity. However, reports on the specific bioactive compounds in L. erythrocarpa are finite. The aim of this study was to investigate the anti-neuroinflammatory and neuroprotective effects of the compounds isolated from L. erythrocarpa. Dihydropashanone, a compound isolated from L. erythrocarpa extract, was found to have protected mouse hippocampus HT22 cells from glutamate-induced cell death. The antioxidant and anti-inflammatory properties of dihydropashanone in mouse microglial BV2 and HT22 cells were explored in this study. The results reveal that dihydropashanone inhibits lipopolysaccharide-induced inflammatory response and suppresses the activation of nuclear factor (NF)-κB in BV2 cells. In addition, dihydropashanone reduced the buildup of reactive oxygen species in HT22 cells and induced activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling pathway in BV2 and HT22 cells. Our results suggest that dihydropashanone reduces neuroinflammation by decreasing NF-κB activation in microglia cells and protects neurons from oxidative stress via the activation of the Nrf2/HO-1 pathway. Thus, our data suggest that dihydropashanone offers a broad range of applications in the treatment of neurodegenerative illnesses.

Gold Nanoparticles in Neurological Diseases: A Review of Neuroprotection.

This review explores the diverse applications of gold nanoparticles (AuNPs) in neurological diseases, with a specific focus on Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The introduction highlights the pivotal role of neuroinflammation in these disorders and introduces the unique properties of AuNPs. The review's core examines the mechanisms by which AuNPs exert neuroprotection and anti-neuro-inflammatory effects, elucidating various pathways through which they manifest these properties. The potential therapeutic applications of AuNPs in AD are discussed, shedding light on promising avenues for therapy. This review also explores the prospects of utilizing AuNPs in PD interventions, presenting a hopeful outlook for future treatments. Additionally, the review delves into the potential of AuNPs in providing neuroprotection after strokes, emphasizing their significance in mitigating cerebrovascular accidents' aftermath. Experimental findings from cellular and animal models are consolidated to provide a comprehensive overview of AuNPs' effectiveness, offering insights into their impact at both the cellular and in vivo levels. This review enhances our understanding of AuNPs' applications in neurological diseases and lays the groundwork for innovative therapeutic strategies in neurology.

The Neuroprotective Effects of BMSC-Derived Exosomes against Glutamate-Induced HT22 Cell Cytotoxicity.

Many central nervous system diseases are closely related to nerve damage caused by dysregulation of the endogenous neurotransmitter glutamate. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) play an important role in improving injury and regeneration functions. However, its mechanism remains unknown. Therefore, the aim of this study is to investigate whether and how BMSC-Exos improve neurotoxicity caused by glutamate and to fill the gap in the literature. In this study, glutamate-treated HT22 cells were first exposed to mouse-derived BMSC-Exos at different concentrations to observe their effects on HT22 apoptosis. Next, we treated glutamate-treated HT22 cells with mouse-derived BMSC-Exos. We then inhibited the PI3K/Akt/mTOR signaling pathways using the PI3K/Akt inhibitor and the mTOR inhibitor, respectively, and observed the protective effect of mouse-derived BMSC-Exos on HT22 cells treated with glutamate. Our results show that BMSC-Exos reduced apoptosis triggered by glutamate stimulation, increased cell vitality, and decreased the levels of proapoptotic proteins while increasing the levels of anti-apoptotic proteins. The protective effect of BMSC-Exos was weakened when PI3K/Akt inhibitor and mTOR inhibitor were added. To sum up, we draw the following conclusions: BMSC-Exos can reduce neuronal apoptosis and apoptosis-related protein expression after glutamate stimulation by regulating the PI3K/Akt/mTOR signaling pathway.

Structure characterization of polysaccharides from Cistanche deserticola and their neuroprotective effects against oxidative stress in slow transit constipation mice.

Oxidative stress-induced enteric neuropathy is an important factor in slow transit constipation (STC). Cistanche deserticola crude polysaccharides (CDCP) are natural antioxidants with various biological activities. We prepared CDCP through water-extract and alcohol-precipitation methods. The structural characteristics of CDCP were analyzed by infrared spectroscopy and methylation analysis. The results showed that CDCP was primarily composed of (1 â†’ 4)-linked glucans with minor amounts of pectic polysaccharides. Different doses of CDCP (100, 200, and 400 mg/kg) were administered to loperamide-induced STC mice to explore the therapeutic effects of CDCP. Compared with the untreated group, CDCP treatment significantly improved constipation symptoms, relevant gut-regulating peptides levels, colonic pathological damage, and colonic myenteric nerons injury. CDCP enhanced the antioxidant capacity by decreasing Malondialdehyde (MDA) content, increasing Superoxide Dismutase (SOD) activity and Reduced Glutathione (GSH) content. CDCP significantly reduced oxidative stress-induced injury by preserving mitochondrial function in the colonic myenteric plexus. Furthermore, the neuroprotective effects of CDCP might be associated with the Nrf2/Keap1 pathway. Thus, our findings first revealed the potential of CDCP to protect the colonic myenteric plexus against oxidative stress-induced damage in STC, establishing CDCP as promising candidates for natural medicine in the clinical management of STC.

Synthesis, biological activity evaluation and mechanism analysis of new ganglioside GM3 derivatives as potential agents for nervous functional recovery.

Neuronal regenerative ability is vital for the treatment of neurodegenerative diseases and neuronal injuries. Recent studies have revealed that Ganglioside GM3 and its derivatives may possess potential neuroprotective and neurite growth-promoting activities. Herein, six GM3 derivatives were synthesized and evaluated their potential neuroprotective effects and neurite outgrowth-promoting activities on a cellular model of Parkinson's disease and primary nerve cells. Amongst these derivatives, derivatives N-14 and 2C-12 demonstrated neuroprotective effects in the MPP + model in SH-SY5Y cells. 2C-12 combined with NGF (nerve growth factor) induced effecially neurite growth in primary nerve cells. Further action mechanism revealed that derivative 2C-12 exerts neuroprotective effects by regulating the Wnt signaling pathway, specifically involving the Wnt7b gene. Overall, this study establishes a foundation for further exploration and development of GM3 derivatives with neurotherapeutic potential.

Active compounds from Calendula officinalis flowers act via PI3K and ERK signaling pathways to offer neuroprotective effects against Parkinson's disease.

Calendula officinalis flowers, associated with diverse biological effects, could be utilized as functional food ingredients to play a crucial role in human health. In this study, we examined the anti-PD activity of C. officinalis flower extracts and investigated their bioactive compounds and molecular mechanisms based on LC-MS/MS assay, bioinformatic exploration and in vitro treatment of SH-SY5Y cells. C. officinalis extracts exhibited significant positive effects on the length and fluorescence density of the dopaminergic neuron region in zebrafish larvae. At 10 µg/mL, the extract restored the length to 96.54% and fluorescence density to 87.77% of the control values, which was equivalent to the effect of a positive drug, indicating the extract's powerful potential to alleviate PD symptoms. Five active compounds, including chlorogenic acid, 3,4-dicaffeoylquinic acid (DA), rutin, isorhamnetin 3-O-glucoside (IG) and calenduloside E (CE) were identified in extracts by LC-QTOF-MS/MS. Hsp90α, PI3K and ERK were revealed as core targets of DA, IG and CE in relation to anti-PD activity. The compounds docked deeply within the pocket region of Hsp90α protein, and their binding energies (∆G b) were -6.93 kcal/mol (DA), -6.51 kcal/mol (IG) and -3.03 kcal/mol (CE), respectively. Subsequently, they concurrently activated the PI3K/Akt signaling pathway and inhibited the ERK signaling pathway, thereby preventing neuronal death and alleviating neuronal degeneration. These compounds from C. officinalis could be potent nutraceutical agents with protective properties that may shield dopaminergic neurons against the damage caused by PD. Our findings provide a basis for utilizing the C. officinalis flowers in functional foods.

Harnessing the neuroprotective effect of oral administration of benfotiamine in MPTP induced Parkinson's disease in rats.

The study was performed to evaluate the neuroprotective effects of Benfotiamine (BFT) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in rats. The rats were given daily doses of BFT (100 mg/kg, 200 mg/kg) through oral administration for 42 days. The rats were given a single bilateral dosage of MPTP (0.1 mg/nostril) intranasally once before the drug treatment to induce PD. On day 42, the animals were subjected to various behavioral paradigms. Post-treatment with BFT for 42 days significantly improved the motor and nonmotor fluctuations of MPTP. The results demonstrated that treatment with BFT ameliorated MPTP-induced disorders in behavior, body balance, and dopamine levels in the mid-brain. Among the post-treated groups, a high dose of BFT was the most effective treatment. Mean values are indicated in ±SEM, n = 5***(p < 0.001) when compared with the vehicle control, n = 5 ### (p < 0.001) when compared with the disease control; (p < 0.001) when compared with the BFT per se; (p < 0.001) when compared with the low dose of BFT; (p < 0.001) when compared with the high dose of BFT. Our finding suggests that BFT contributed to superior antioxidant, and anti-inflammatory and could be a novel therapeutic method for PD management. In conclusion, BFT could be a potential drug candidate for curbing and preventing PD.

Protective Effects of Repetitive Transcranial Magnetic Stimulation Against Streptozotocin-Induced Alzheimer's Disease.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation under investigation for treatment of a wide range of neurological disorders. In particular, the therapeutic application of rTMS for neurodegenerative diseases such as Alzheimer's disease (AD) is attracting attention. However, the mechanisms underlying the therapeutic efficacy of rTMS have not yet been elucidated, and few studies have systematically analyzed the stimulation parameters. In this study, we found that treatment with rTMS contributed to restoration of memory deficits by activating genes involved in synaptic plasticity and long-term memory. We evaluated changes in several intracellular signaling pathways in response to rTMS stimulation; rTMS treatment activated STAT, MAPK, Akt/p70S6K, and CREB signaling. We also systematically investigated the influence of rTMS parameters. We found an effective range of applications for rTMS and determined the optimal combination to achieve the highest efficiency. Moreover, application of rTMS inhibited the increase in cell death induced by hydrogen peroxide. These results suggest that rTMS treatment exerts a neuroprotective effect on cellular damage induced by oxidative stress, which plays an important role in the pathogenesis of neurological disorders. rTMS treatment attenuated streptozotocin (STZ)-mediated cell death and AD-like pathology in neuronal cells. In an animal model of sporadic AD caused by intracerebroventricular STZ injection, rTMS application improved cognitive decline and showed neuroprotective effects on hippocampal histology. Overall, this study will help in the design of stimulation protocols for rTMS application and presents a novel mechanism that may explain the therapeutic effects of rTMS in neurodegenerative diseases, including AD.

Quercetin plays a neuroprotective role in inhibiting mitochondrial apoptosis by mediating JNK signaling pathway / 中国药理学通报

Aim To study the mechanism of quereetin (Que) inhibiting mitochondrial damage induced by Aβ

A pair of new chromone enantiomers from Xylaria nigripes.

A pair of new chromone derivative enantiomers, (+)-xylarichromone A (1a) and (-)-xylarichromone A (1b), were isolated from the solid fermentation of Xylaria nigripes. The planar structure of 1 was determined by extensive NMR spectroscopic data, and its absolute configuration was assigned by comparison the ECD spectra with the known chromone derivatives. Compound 1 was the first chromone derivative reported from this medicinal fungus. The neuroprotective effects of 1 against oxygen and glucose deprivation (OGD) induced pheochromocytoma-12 cells (PC12) injury was investigated.