Damage In PC12 Cells Research Articles

Macathiohydantoin L, a Novel Thiohydantoin Bearing a Thioxohexahydroimidazo [1,5-a] Pyridine Moiety from Maca (Lepidium meyenii Walp.).

Five new thiohydantoin derivatives (1–5) were isolated from the rhizomes of Lepidium meyenii Walp. NMR (1H and 13C NMR, 1H−1H COSY, HSQC, and HMBC), HRESIMS, and ECD were employed for the structure elucidation of new compounds. Significantly, the structure of compound 1 was the first example of thiohydantoins with thioxohexahydroimidazo [1,5-a] pyridine moiety. Additionally, compounds 2 and 3 possess rare disulfide bonds. Except for compound 4, all isolates were assessed for neuroprotective activities in corticosterone (CORT)-stimulated PC12 cell damage. Among them, compound (−)-3 exhibited moderate neuroprotective activity (cell viability: 68.63%, 20 μM) compared to the positive control desipramine (DIM) (cell viability: 88.49%, 10 μM).

LINC00665 knockdown protects against cerebral ischemia-reperfusion injury.

LINC00665 has been reported to participate in several human diseases. However, the role of LINC00665 in cerebral ischemia-reperfusion (CI/R) is still unknown. This study is designed to investigate the role of LINC00665 in rats with CI/R injury. We established middle cerebral artery occlusion/ reperfusion (MCAO/R) rats model in vivo. PC12 cells treated with oxygen-glucose deprivation/reperfusion (OGD/R) were used to establish in vitro I/R model. RT-qPCR assay was adopted to assess the mRNA expression of LINC00665 and miR-744-5p. MTT assay was used to determine cell viability. The protein expression of Bax and Bcl-2 were detected by Western blot assay. The relationship between LINC00665 and miR-744-5p was confirmed by dual luciferase reporter assay and RNA immunoprecipitation (RIP). In this study, we found that LINC00665 was sharply up regulated in MCAO/R rats and PC12 cells treated with I/R. Functionally, LINC00665 knockdown attenuated oxidative damage in PC12 cells treated with I/R. Moreover, LINC00665 knockdown promoted cell viability, while inhibited cell apoptosis in PC12 cells treated with I/R. In addition, miR-744-5p was confirmed to be a target of LINC00665. LINC00665 knockdown was validated to project CI/R injury by sponging miR-744-5p expression.

Protein hydrolysates from Pleurotus geesteranus obtained by simulated gastrointestinal digestion exhibit neuroprotective effects in H2 O2 -injured PC12 cells.

Neurodegenerative diseases are considered to be among the diseases most threatening to human beings. Increasing evidence shows that antioxidant hydrolysates/peptides with neuroprotective effects may relieve neurodegenerative diseases. However, related research in mushrooms, one of the richest sources of antioxidant hydrolysates/peptides, is in its infancy. Therefore, the in vitro neuroprotective effects of protein hydrolysates from Pleurotus geesteranus were researched in this study. Proteins were extracted from P. geesteranus and then hydrolyzed by simulated gastrointestinal digestion. The neuroprotective effects of the protein hydrolysates were evaluated by H2 O2 -injured PC12 cells. The hydrolysates showed a superior antioxidative ability and had a higher abundance of hydrophobic amino acids (e.g., leucine, alanine, and phenylalanine). Neither cytotoxicity nor the increase of ROS in PC12 cells was observed under treatment with the hydrolysates. However, pre-treatment with the hydrolysates in PC12 cells, which were then injured by H2 O2 , markedly attenuated ROS generation and enhanced the activities and mRNA expression of the endogenous antioxidant enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)), leading to a 26.68% increase in cell viability. The hydrolysates exhibited strong neuroprotective activity in H2 O2 -injured PC12 cells, possibly by reducing ROS generation and enhancing the activity of the antioxidant enzymatic system. PRACTICAL APPLICATIONS: Antioxidant hydrolysates with neuroprotection were obtained from Pleurotus geesteranus proteins by simulating gastrointestinal digestion, which exhibited an excellent pre-protective effect in oxidatively damaged PC12 cells. Further study showed that hydrolysates pre-protection may exert antioxidant activities not only as an exogenous antioxidant to scavenge ROS but also as a gene regulator to modulate the endogenous antioxidant enzymes gene expression. These results indicated that the potential of antioxidant peptides, derived from P. geesteranus through gastrointestinal digestion, could serve as a source of bioactive molecules in the prevention, relief or even treatment of neurodegenerative disorders.

Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: in vitro and in vivo biological activities against Alzheimer's disease.

Alzheimer's disease (AD) is now ranked as the third leading cause of death after heart disease and cancer. There is no definite cure for AD due to the multi-factorial nature of the disease, hence, multi-target-directed ligands (MTDLs) have attracted lots of attention. In this work, focusing on the efficient cholinesterase inhibitory activity of tacrine, design and synthesis of novel arylisoxazole-tacrine analogues was developed. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assay confirmed high potency of the title compounds. Among them, compounds 7l and 7b demonstrated high activity toward AChE and BChE with IC50 values of 0.050 and 0.039μM, respectively. Both compounds showed very good self-induced Aβ aggregation and AChE-induced inhibitory activity (79.4 and 71.4% for compound 7l and 61.8 and 58.6% for compound 7b, respectively). Also, 7l showed good anti-BACE1 activity with IC50 value of 1.65µM. The metal chelation test indicated the ability of compounds 7l and 7b to chelate biometals (Zn2+, Cu2+, and Fe2+). However, they showed no significant neuroprotectivity against Aβ-induced damage in PC12 cells. Evaluation of in vitro hepatotoxicity revealed comparable toxicity of compounds 7l and 7b with tacrine. In vivo studies by Morris water maze (MWM) task demonstrated that compound 7l significantly reversed scopolamine-induced memory deficit in rats. Finally, molecular docking studies of compounds 7l and 7b confirmed establishment of desired interactions with the AChE, BChE, and BACE1 active sites.

Preparation, structural characterization and neuroprotective effects of polysaccharides from the pericarp of Zanthoxylum bungeanum Maxim against H2O2-induced oxidative damage in PC12 cells

The pericarp of Zanthoxylum bungeanum Maxim (PZM) is one of eight fascinating condiments and also used as a traditional herbal medicine to treat a variety of diseases. In this study, ultrasound-assisted extraction (UAE) was applied for the extraction of polysaccharides from PZM (PPZM) and the extraction conditions were optimized by response surface methodology (RSM). The obtained PPZM yield (2.60 ± 0.06%) was closely agreed with the predicted value (2.58%), and the optimal extraction conditions obtained were: liquid to solid ratio of 32 mL/g, extraction time of 42 min, and extraction temperature of 61 °C. PPZM was determined to be composed of mannose (Man), rhamnose (Rha), galacturonic acid (GalA), glucose (Glu), galactose (Gal), arabinose (Ara) with a molar ratio of 4.93: 5.03: 71.01: 16.01: 24.87: 18.79, and the average molecular weight (Mw) of PPZM was 1.72 × 105 Da. Typical polysaccharide characteristics were determined by fourier transform infrared spectroscopy (FT-IR). PPZM exhibited remarkable antioxidant activities in vitro. More importantly, PPZM effectively protected adrenal phaeochromocytoma PC12 cells against H2O2-induced damage by inhibiting the release of lactate dehydrogenase (LDH) and malondialdehyde (MDA), increasing the level of superoxide dismutase (SOD), and inhibiting abnormal apoptosis. Further experiments indicated that the anti-apoptotic effects of PPZM were closely related to down-regulating the expressions of Bax and Caspase-3, and up-regulating the expression of Bcl-2. Therefore, PPZM can be used as the source of natural antioxidants and neuroprotective agents.

Neuroprotective Activities of Constituents from Phyllosticta capitalensis, an Endophyte Fungus of Loropetalum chinense var. rubrum.

One new dioxolanone derivative, guignardianone G (1) and twelve known compounds (2-13) were isolated from the 95 % ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Among these known compounds, isoaltenuene (3), brassicasterol (7), 5,6-epoxyergosterol (8), citreoanthrasteroid A (9), demethylincisterol A (10), and chaxine C (11) were reported from Phyllosticta sp. for the first time. The structure of 1 was elucidated by 1D- and 2D-NMR experiments and HR-ESI-MS data analysis, and its absolute configuration was established through the comprehensive use of the methods of modified Mosher methods, calculations of ECD spectra and optical rotation values. The neuroprotective activity of compounds (1-9, 11-13) were evaluated on PC12 cells damage induced by glutamate, and compounds 9 and 12 showed potential neuroprotective activities with half effective concentration (EC50 ) of 24.2 and 33.9 μM, respectively.

Discovery of eudesmane-type sesquiterpenoids with neuroprotective effects from the roots of Chloranthus serratus

Seven eudesmane-type sesquiterpenoids, including three pairs of racemic compounds (1a–3a and 1b–3b) and a sesquiterpenoid lactone (4), were obtained from the roots of Chloranthus serratus. The structures of these sesquiterpenoids were characterized based on spectroscopic analyses, ECD calculations, and X-ray diffraction experiment. Neuroprotection assays of the isolated eudesmane-type sesquiterpenoids were conducted on H2O2 damaged PC12 cells. At the concentration of 10 μM, compounds 1b and 4 increased cell viability from 54.8 ± 3.3% to 76.8 ± 2.3 and 72.7 ± 8.2%, respectively.

Piceatannol alleviate ROS-mediated PC-12 cells damage and mitochondrial dysfunction through SIRT3/FOXO3a signaling pathway.

Oxidative stress-associated mitochondrial dysfunction has been identified as a major mechanism in multiple neurodegenerative diseases. This study aims to investigate the cytoprotective effects of piceatannol on ROS-mediated PC-12 cells damage and related mitochondrial dysfunction. Piceatannol treatment could significantly attenuate PC-12 cells oxidative damage and ROS-mediated cells apoptosis. Moreover, pretreatment with piceatannol effectively decreased mitochondrial membrane depolarization, cleaved-caspase 3, and increased Bcl-2 and Bcl-2/Bax compared with control H2 O2 group. Meanwhile, piceatannol treatment improved mitochondrial respiration function which led to an enhancement in the maximal respiration and spare respiratory capacity. Further mechanisms analysis showed that the protein expression of SIRT3 and its downstream protein FOXO3a were significantly increased after piceatannol addition in a dose-dependent manner. Whereas the cytoprotective role of piceatannol was markedly abolished by the SIRT3 inhibitor 3-TYP, suggesting that SIRT3/FOXO3a signaling pathway played a vital role in mediating the neuronal cytoprotective effects of piceatannol. PRACTICAL APPLICATIONS: The results of our study provide a novel insight that piceatannol could be potentially used as a promising bioactive component against oxidative damage and neurocyte apoptosis. The findings may provide theoretical basis for brain health of piceatannol consumption in some extent.

Protective effect of dexmedetomidine on neuronal hypoxic injury through inhibition of miR-134.

To explore the mechanism of dexmedetomidine (DEX)-mediated miR-134 inhibition in hypoxia-induced damage in PC12 cells. Hydrogen peroxide (H2O2)-stimulated PC12 cells were divided into control, H2O2, DEX + H2O2, miR-NC/inhibitor + H2O2, and miR-NC/ mimic + DEX + H2O2 groups. Cell viability and apoptosis were assessed by the 3-(4,5-dimethylthiazol(-2-y1)-2,5-diphenytetrazolium bromide (MTT) assay and Annexin V-FITC/PI staining, while gene and protein expression levels were detected by qRT-PCR and western blotting. Reactive oxygen species (ROS) levels were tested by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and malondialdehyde (MDA) content was determined with a detection kit. DEX treatment decreased H2O2-elevated miR-134 expression. H2O2-induced PC12 cell damage was improved by DEX and miR-134 inhibitor; additionally, cell viability was increased, while cell apoptosis was reduced. In addition, both DEX and miR-134 inhibitor reduced the upregulated expression of cleaved caspase-3 and increased the downregulated expression of Bcl-2 in H2O2-induced PC12 cells. However, compared to that in the DEX + H2O2 group, cell viability in the mimic + DEX + H2O2 group was decreased, and the apoptotic rate was elevated with increased cleaved caspase-3 and decreased Bcl-2 expression. Inflammation and oxidative stress were increased in H2O2-induced PC12 cells but improved with DEX or miR-134 inhibitor treatment. However, this improvement of H2O2-induced inflammation and oxidative stress induced by DEX in PC12 cells could be reversed by the miR-134 mimic. DEX exerts protective effects to promote viability and reduce cell apoptosis, inflammation, and oxidative stress in H2O2-induced PC12 cells by inhibiting the expression of miR-134.

Bioactive anti-aging agents and the identification of new anti-oxidant soybean peptides

Degenerative diseases associated with aging could be attributed primarily to the deleterious effects of free radicals on cell constituents and connective tissues. The aim of this study was to compare the anti-aging effects of soybean (PHS), oyster (PHO), and sea cucumber (PHH) protein hydrolysates and then isolate and characterize the responsible anti-aging peptides of the most effective hydrolysate that could allow for the further development of anti-aging bioactive ingredients. Protein hydrolysates were prepared from the three natural products using Alcalase for the enzymatic hydrolysis. D-galactose-induced specific pathogen-free (SPF) Kunming mice were used to explore the anti-aging effects of the three hydrolysates. The results showed that the three protein hydrolysates all had a significant impact on reversing D-galactose-induced aging-associated learning and memory impairments and oxidative stress in the order PHS > PHO > PHH. Consistent with the activity in vivo, PHS also showed the strongest DPPH scavenging activity among the three hydrolysates. Consequently, PHS was further purified using DEAE-52 ion exchange resin into three fractions (Fa, Fb and Fc), of which Fa showed the highest antioxidative activity. Fa was subsequently purified using G-15 gel filtration chromatography. Using LC-MS/MS, two peptides, Trp-Pro-Lys (WPK) and Ala-Tyr-Leu-His (AYLH), were identified as the active components of the purified fraction. In vitro antioxidant analysis showed that the peptides strongly alleviated H2O2-induced oxidative damage in PC12 cells. The results suggested that PHS and its constituent peptides could be potentially effective antioxidant agents in functional foods or nutraceuticals for aging-related learning and memory impairments and oxidative stress.

Antioxidants and the Battle for the Brain: Antioxidant Effectiveness Against a Beta-amyloid Challenge

ObjectivesThe objective of this study was to determine the protective effects of antioxidants against oxidative damage in PC12 cells when treated with beta-amyloid (BA), a common source of reactive oxygen species (ROS) in older adult brains. MethodsPC12 cells (2 × 105 cells/mL) were treated with secoisolariciresinol diglucoside (SDG, 50 or 100 μM) or control antioxidants, superoxide dismutase (SOD, 100 U/mL) or catalase (100 U/mL), for 2 hours, then treated with 10 μM BA for 24 hours. After antioxidant and BA treatments, ROS and lactate dehydrogenase (LDH) were measured using assay kits. Differences in ROS and LDH between control (no antioxidant and BA treatments) and experimental groups were analyzed by Student’s t-tests. ResultsCells treated with BA without an antioxidant treatment showed a significant reduction in LDH (p < 0.01) when compared to the control, but did not differ in ROS. Cells treated with BA and catalase showed no significant difference in LDH. LDH and ROS were significantly reduced in BA and SOD treated cells (p < 0.01 and < 0.05, respectively) compared to the control. However, LDH or ROS in both SOD and catalase treated cells, either with or without BA treatment, was not different compared to the control. BA and SDG (50 μM or 100 μM) treated cells showed significant reductions in ROS, but no significant difference in LDH compared to the control. ConclusionsAn antioxidant, SDG, found in flaxseed shows promise for reducing oxidative stress in cells. Funding SourcesThe authors gratefully acknowledge funding provided by North Dakota State University’s College of Human Sciences and Education.

Resveratrol against 6-OHDA-induced damage of PC12 cells via PI3K/Akt.

ObjectiveOur previous in vivo study found that resveratrol (Res), which is a phytoalexin, attenuated 6-hydroxydopamine (6-OHDA)-induced motor dysfunction by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in rats. Therefore, we further explored the protective effect of Res on 6-OHDA-induced damage to PC12 cells in vitro with respect to the PI3K/Akt signaling pathway.MethodsWe incubated PC12 cells with 75 μM 6-OHDA for 24 h, and Res was then added at a final concentration of 25 μM; the protective effect was examined via MTT and lactate dehydrogenase (LDH) assays. In addition, the PI3K inhibitor LY294002 was used to investigate the potential mechanism. JC-1 staining was used to detect the mitochondrial membrane potential (MMP), and western blotting (WB) was used to detect the phosphorylation of Akt-Ser473.ResultsCompared with that in the control, the cell viability, total superoxide dismutase (SOD) activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly decreased, while the leakage rate of LDH was increased. And after treatment with 25 μM Res, the cell viability, total SOD activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly increased compared with those of the control cells, while the leakage rate of LDH was decreased. These effects of Res were antagonized by LY294002.ConclusionsRes ameliorates 6-OHDA-induced damage to PC12 cells via activation of the PI3K/Akt signaling pathway.

Effects of Ecklonia cava Extract on Neuronal Damage and Apoptosis in PC-12 Cells against Oxidative Stress.

Marine algae (seaweed) encompass numerous groups of multicellular organisms with various shapes, sizes, and colors, and serve as important sources of natural bioactive substances. The brown alga Ecklonia cava Kjellman, an edible seaweed, contains many bioactives such as phlorotannins and fucoidans. Here, we evaluated the antioxidative, neuroprotective, and anti-apoptotic effects of E. cava extract (ECE), E. cava phlorotannin-rich extract (ECPE), and the phlorotannin dieckol on neuronal PC-12 cells. The antioxidant capacities of ECPE and ECE were 1,711.5 and 1,050.4 mg vitamin C equivalents/g in the ABTS assay and 704.0 and 474.6 mg vitamin C equivalents/g in the DPPH assay, respectively. The dieckol content of ECPE (58.99 mg/g) was approximately 60% higher than that of ECE (36.97 mg/g). Treatment of PC-12 cells with ECPE and ECE increased cell viability in a dose-dependent manner. Intracellular oxidative stress in PC-12 cells due to ECPE and ECE decreased dose-independently by up to 63% and 47%, respectively, compared with the stress control (323%). ECPE reduced the production of the pro-apoptotic proteins Bax and caspase-3 more effectively than ECE. Early and late apoptosis in PC-12 cells were more effectively decreased by ECPE than ECE treatments. From the results obtained in this study, we concluded that ECPE, which is rich in phlorotannins, including the marker compound dieckol, may be applied to the development of functional materials for improving cognition and memory.

Metal-Free α-C(sp3)-H Aroylation of Amines via a Photoredox Catalytic Radical-Radical Cross-Coupling Process.

Here we describe an unprecedented metal-free C(sp3)-H aroylation of amines via visible-light photoredox catalysis, which provides a straightforward route for the construction of a useful α-amino aryl ketone skeleton. Additionally, a number of selected products exhibit good biological activity for protecting PC12 cell damage, which shows that this skeleton has the potential to become a new neuroprotective agent. Finally, a series of mechanism experiments indicate that this transformation undergoes a photoredox catalytic radical-radical cross-coupling pathway.

Illilanceolide A, a unique seco-prezizaane sesquiterpenoid with 5/5/6 tricyclic scaffold from the fruits of Illicium lanceolatum A. C. Smith

A unique seco-prezizaane sesquiterpenoid with 5/5/6 tricyclic skeleton, illilanceolide A (1), and two rare 10,14-cycloseco-prezizaane sesquiterpenoids, 2-oxo-6-dehydroxyneoanisatinic acid (2) and 3,4-anhydro-2-oxo-6-dehydroxyneoanisatinic acid (3), together with two known sesquiterpenoids, were isolated from the fruits of Illicium lanceolatum. Their structures and absolute configurations were elucidated on the basis of extensive 1H, 13C, and 2D NMR, and HRESIMS data, as well as single-crystal X-ray diffraction analysis. Compounds 2–4 enhanced the neurite outgrowth of NGF-mediated PC12 cells at a concentration of 10 μM with differentiation rates of 13.33%, 10.90%, and 11.76%, respectively. Moreover, compounds 2–4 were found to exhibit moderate neuroprotective effect against MPP+-induced PC12 cell damage.

Hydroazulene Diterpenes from a Dictyota Brown Alga and Their Antioxidant and Neuroprotective Effects Against Cerebral Ischemia-Reperfusion Injury.

Five new diterpenes, including four new hydroazulenes, (8R,11R)-8,11-diacetoxypachydictyol A (1), (8R*,11R*)-6-O-acetyl-8-acetoxy-11-hydroxypachydictyol A (2), (8R*,11S*)-8-acetoxy-11-hydroxypachydictyol A (3), and (8R*,11S*)-6-O-acetyl-8,11-dihydroxypachydictyol A (4), and a secohydroazulene derivative, named 7Z-7,8-seco-7,11-didehydro-8- acetoxypachydictyol A (5), were isolated from a South China Sea collection of a Dictyota sp. nov. brown alga, together with five known analogues (6-10). Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. All compounds showed potent antioxidant effects against H2O2-induced oxidative damage in neuron-like PC12 cells at a low concentration of 2 μM. The antioxidant property of dictyol C (9) was associated with activation of the Nrf2/ARE signaling pathway; it also showed neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in a rat model of transient middle cerebral artery occlusion. As such, hydroazulene diterpenes could serve as lead structures for the development of novel neuroprotective agents against CIRI.

Protective effects of Lavandula stoechas L. methanol extract against 6-OHDA-induced apoptosis in PC12 cells

Ethnopharmacological relevanceParkinson's disease (PD) is a neurodegenerative disorder associated with oxidative stress-induced neuronal damage and death. In European and Persian Traditional Medicine, aerial parts (leaves, stems, and flowers) of Lavandula stoechas L. have been widely used for treating neurodegenerative disorders including PD.Aim of the study: Herein, the protective effects of L. stoechas methanol extract were investigated on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and oxidative damage in PC12 cells. Materials and methodsThe cells were pretreated with a standardized L. stoechas methanol extract (2.5–20 μg/mL) for 24 h and exposed to 6-OHDA (200 μM) thereafter. The cell viability percentage was determined by AlamarBlue test. Intracellular reactive oxygen species (ROS) production was determined by a fluorimetric method using 2′,7′-dichlorodihydrofluorescein diacetate and cellular apoptosis was assessed by the fluorescent probe propidium iodide test. Finally, the expression of proteins involved in apoptosis pathway (Phospho SAPK/JNK, SAPK/JNK, p44/42 MAPK (ERK1/2) and Poly ADP ribose polymerase (PARP)) was measured via Western blot analysis. ResultsTreatment of PC12 cells with 6-OHDA could significantly increase cytotoxicity, ROS level, and cell apoptosis. Pretreatment of PC12 cells with the extract could significantly decrease 6-OHDA cytotoxicity, ROS production, (2.5 and 5 μg/mL) and cell apoptosis (5 μg/mL). Western blot analysis showed that 6-OHDA exposure could increase the expression of proteins involved in apoptosis signaling, while pretreatment with L. stoechas (5 μg/mL) reduced apoptotic proteins. ConclusionsThe present study demonstrated that L. stoechas, which has been traditionally used in Persian Medicine for treating CNS diseases, is a valuable source of active compounds with neuroprotective, anti-oxidant, and anti-apoptotic activity.

Four new resorcinol derivatives with neuroprotective activities from Xylaria nigripes

Four new resorcinol derivatives, namely (−)/(+)-xylarinig A (1), as well as xylarinigs B (2) and C (3), were isolated from the ethyl acetate extracts of the solid fermentation of Xylaria nigripes. Their structures were established by comprehensive spectroscopic analysis combined with electronic circular dichroism (ECD) calculations. Compound 1 is an optical mixture, and was resoluted into optical pure enatiomers (+)-1 and (−)-1 by chiral HPLC. The neuroprotective effects of 1–3 against the damage of PC12 cells induced by oxygen and glucose deprivation (OGD) were evaluated.

Neuronal Apoptosis Preventive Potential of Sophocarpine via Suppression of Aβ-Accumulation and Down-Regulation of Inflammatory Response.

In the current study sophocarpine was investigated in vitro for prevention of β-amyloid induced PC12 neuronal cell damage. Exposure to β-amyloid caused a dose-dependent suppression in growth of PC12 cells with maximum reduction at 10 μM. Sophocarpine pre-treatment reversed suppressive effect of β-amyloid (10 μM) on PC12 cell growth in concentration-based manner. In sophocarpine pre-treated PC12 cells the β-amyloid mediated PGE2 level elevation was attenuated significantly at 0.25-2 μM doses. Moreover, in sophocarpine pretreated PC12 cells the β-amyloid mediated promotion of COX-2 level was also inhibited. Sophocarpine pre-treatment attenuated iNOS expression in β-amyloid exposed PC12 cells at 0.25-2 μM doses. Pre-treatment of PC12 cells with sophocarpine suppressed NO-species generation induced by β-amyloid exposure. In sophocarpine pretreated PC12 cells elevation of nuclear NF-κB expression induced by β-amyloid was significantly inhibited. In summary, sophocarpine prevents reduction of PC12 cell growth induced by β-amyloid exposure via inhibition of inflammatory processes. The preventive effect of sophocarpine on β-amyloid induced PC12 cell damage is associated with inhibition of NF-κB nuclear translocation. Therefore, sophocarpine may be used for treatment of neurological disorders like Alzheimer's disease.

Neuroprotective effects of Actinidia eriantha cv. Bidan kiwifruit on amyloid beta-induced neuronal damages in PC-12 cells and ICR mice

The positive effects of Actinidia eriantha cv. Bidan extract (AEE) were investigated in terms of improvement in Aβ1-42-induced cognitive impairment. AEE was shown to have neuroprotective effects, such as reduction in intracellular reactive oxygen species levels and suppression of apoptotic cell death, in neuron-like PC-12 cells. Results of the in vivo experiment showed that AEE at 200 and 1,000 mg/kg body weight/day, and even at 50 mg/kg body weight/day, reduced impairments in learning and spatial memory in Aβ1-42-treated ICR mice. Furthermore, the endogenous antioxidant systems (SOD, CAT, and GSH/GSSG) in the mouse brain tissue significantly (p < 0.05) increased by AEE administration compared with the group treated with only Aβ1-42. In the analysis of UPLC-Q-TOF mass spectrometry, caffeic acid derivatives such as caffeoylquinic acids were identified in AEE. These results suggest that the Bidan kiwifruit is a good source of antioxidant phenolics that hold the potential to improve cognitive function.