• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Petroselinum crispum extract ameliorates scopolamine-induced cognitive dysfunction: role on apoptosis, inflammation and oxidative stress

    2022-06-23 07:23:14kslnrKarakaogluDilkOzyliSrnfiyYanaragOzlmSaanAsliAyka
    關(guān)鍵詞:配套工程年份樞紐

    G?ksl ?nr*, G?z Karaka?oglu, Dilk Ozyli, Srn E,R fiy Yanarag, Ozlm Saan, Asli Ayka

    a Department of Pharmacology, Faculty of Pharmacy, Fenerbahce University, Istanbul 34758, Turkey

    b Department of Pharmacology, Institude of Health Sciences, Marmara University, Istanbul 34854, Turkey

    c Department of Medical Pathology Techniques, Vocational School of Health Services, Marmara University, Istanbul 34865, Turkey

    d Department of Biochemistry, Faculty of Engineering, Istanbul University?-Cerrahpasa, Istanbul 34320, Turkey

    e Department of Biophysics, Faculty of Medicine, Near East University, Nicosia 99138, Cyprus

    Keywords:

    Petroselinum crispum

    Apoptosis

    Spatial memory

    Recognition memory

    Oxidative stress

    M1 receptor

    A B S T R A C T

    This study was designed to investigate whether Petroselinum crispum (PC) extract has protective effects on the brain in the scopolamine-induced Alzheimer’s disease (AD) rat model. The rats were divided into; control,scopolamine (1 mg/kg, i.p.), galantamine (1.5 mg/kg, i.p.) and PC extract (2 g/kg, p.o.)-treated scopolamine groups. On day 14, the novel object recognition test (NORT) and Morris water maze test (MWMT) were performed and then the rats were sacrificed. Scopolamine-induced cognitive impairments observed in the NORT and MWMT, significantly improved with PC extract and galantamine treatments. Scopolamine reduced M1 receptor expression, Bcl-2/Bax ratio, and glutathione levels in the hippocampus and frontal cortex, while malondialdehyde levels, caspase-3/9 expressions, and acetylcholinesterase (AChE) activity were found to be increased. On the other hand, PC and galantamine treatments reversed these changes. In conclusion, PC extract has shown an ameliorative effect on the spatial and recognition memory, M1 receptor expression,apoptosis, oxidative stress, and increased AChE activity. Thus, it was concluded that PC could prevent AD-like conditions and can be used as a functional food. However, since animal models do not completely mimic those of humans, based on the data obtained in this study, the importance of PC on human AD should be demonstrated in future studies.

    1. Introduction

    Alzheimer’s disease (AD), one of the most important causes of dementia is characterized by impairment in learning ability and memory formation caused by progressive neuronal loss [1].The pathogenesis of AD includes cholinergic synaptic disorder,mitochondrial dysfunction, oxidative damage, and apoptosis in the memory-sensitive brain regions [2-4]. Currently, acetylcholinesterase(AChE) inhibitors such as galantamine, rivastigmine, and donepezil are used which can increase the concentration and effect duration of acetylcholine (ACh) in memory sensitive brain regions, however,these drugs are not adequate to stop the progression of AD [5,6].Thus, research is in progress to develop potent drugs targeting the multiple pathological mechanisms and provide successful treatment of AD in humans.

    It is known that the cholinergic system plays an important role in the regulation of memory function and ACh controls numerous cognitive processes in this system [7]. The subtype of muscarinic receptors (mAChRs) M1has a pivotal role in learning, memory,cognitive functions, and mood [7,8]. Indeed, the blockage of these receptors has been observed to cause memory errors [9].Scopolamine is a non-selective mAChR antagonist that negatively affects learning achievement and memory in animals and humans [10-12]. Scopolamine disrupts short-term novel object recognition memory [13], spatial memory [14], and passive avoidance memory [15]. Scopolamine-induced memory impairment has been reported to be associated with increased brain oxidative stress [12,15-17],apoptosis [4,12,18]and AChE activity [12]. Consequently,scopolamine-induced memory impairment is a useful animal model for investigating antioxidative, AChE inhibition, and anti-apoptotic therapy strategies in AD.

    Parsley (Petroselinum crispum, family Apiaceae, PC) is a green plant with important medicinal properties such as antioxidant [19-24], antiapoptotic [20,21], anti-inflammatory [21], and anti-diabetic [22,23,25].In addition to its high nutritional properties, it is a natural vitamin and mineral source. It contains some antioxidant substances such as flavonoids (apigenin, luteolin), carotenoids, and ascorbic acid [25,26].PC components were found to be prominent suppressors to reactive oxygen species (ROS) in brain and other tissues by stimulating the generation of glutathione synthesis and by increasing cellular antioxidant defense [27]. PC has been reported to have AChE inhibitory activityin vitro[28,29]. Thus, the potential therapeutic benefit of this substance is very important especially for treatment in the early stage of AD [30]. However, the protective effects of PC against the Scopolamine-induced AD rat model are not known.

    Therefore, this study aimed to investigate whether PC has protective effects on the brain in terms of oxidative damage, apoptosis, and cognitive function in the scopolamine-induced AD rat model.

    2. Materials and methods

    2.1 Preparation of PC aqueous extract

    After the leaves of the PC plant harvested from the countryside of Istanbul were thoroughly washed, they were dried in the shade at(20 ± 2) °C for 3 days and then kept in cellophane bags. 100 g of dried PC leaves were extracted with 1 L distilled water and boiled for 30 min. The extract was then filtered, and the filtrate was evaporated, using a rotary evaporator under reduced pressure to dryness (at 45 °C) [22].The gained extract was kept in a dark container at 4 °C until it was used. The PC extract was dissolved in distilled water before the applied to the rats.

    2.2 Animals and conditions

    All protocols were approved by Marmara University Animal Care and Use Committee (no: 25.2019.mar). Wistar albino rats weighing 250-300 g of both sexes (n= 32) provided by Marmara University Experimental Animals Research and Application Center were used. The rats were housed at ambient temperature ((22 ± 2) °C)and of humidity (55 ± 5)% with 12 h : 12 h light-dark. During the experiment, the rats were freely allowed to drink water and standard pellet dietad libitum.

    2.3 Drugs and chemicals

    All chemicals were supplied by Merck KGaA (Darmstadt,Germany) and all antibodies were supplied from Santa Cruz Biotechnology, Inc (Santa Cruz, CA, USA).

    2.4 Experimental design

    After 10 days of habituation, the rats were randomly divided into 4 groups each containing 8 rats. Experimental groups were as follows:Control (C), scopolamine (Scop) and, galantamine (GAL), and PC treated-scopolamine groups.

    To induce AD to the rat model, scopolamine hydrobromide(C17H21NO4·HBr) a mAChRs antagonist was administered at a dose of 1 mg/kg BW, i.p. The dose and duration of scopolamine treatment were based on previous studies [13,31]. Galantamine hydrobromide(C17H21NO3·HBr) an AChE inhibitor was administered at a dose of 1.5 mg/kg BW, i.p. [32]andPC extract was administered 2 g/kg BW orally [22]. An equal volume of physiological saline was given to the control group. All treatments were given at 9 am for 14 days (Fig. 1).

    Fig. 1 An overview of the experimental design.

    2.5 Cognition tests

    To evaluate the cognitive status of rats, the novel object recognition test (NORT) and Morris water maze test (MWMT) were performed respectively at the end of the 14thday (Fig. 1).

    2.5.1 NORT

    The NORT is designed to evaluate short-term recognition memory and the results are affected by both hippocampal and cortical defects [33].The tests were performed in an apparatus and before the test, the rats were handled by the researchers. During all experiments, boxes and objects were wiped with 70% alcohol while passing to the next animal. Habituation, familiarization, and test phases were performed according to a previous study [34]. The evaluation of the results was performed with a comparison of the time spent with the familiar and novel objects. The results were calculated with the formula previously described and the result was expressed as a discrimination index [35,36].

    2.5.2 MWMT

    MWMT was performed after the NORT. MWM is a test for spatial learning and memory study in rodents. MWM test is based on the native reluctance of rats to float [37]. MWM task was performed with a black circular pool with a diameter of 1.2 m and a height of 0.47 m. The apparatus was filled with black coloured 24-25 °C water to 20 cm deep. Coloured cartons were placed on the walls around the pool for the rats to identify the environment. Two main axes of the pool were determined. Each splits the pool in two vertical directions to form an imaginary ‘+’. In this way, the pool was divided into 4 equal quadrants.

    MWM task consists of the training period and probe trial. Each process was recorded with a video camera. The training period was performed in the first 4 days of the experiment. During the training period, an escape platform in the same colour of the water with a 10 cm diameter, was hidden 2 cm under the water and was placed in the middle of one of the quadrants (target quadrant) [38]. Animals were released into the pool from each quadrant with a random sequence. The rats were allowed to swim for 75 s to find the platform.Platform finding times of rats in 75 s were recorded. The animals that cannot find the platform within this period were directed to the platform and their platform finding times were saved as 75 s. They were allowed to observe around on the platform for 20 s. Then the animal was kept in its cage for 60 s before released to the pool again.On the fifth day of the MWM task, the probe trial was performed. By removing the hidden platform, rats were allowed to swim in the pool for 60 s. During this period, how much time was spent on the target quadrant was evaluated.

    2.6 Dissection of the brain tissues

    2.7 Biochemical analysis

    The levels of malondialdehyde (MDA) and reduced glutathione(GSH) expressed as nmol/g and μmol/g in the hippocampal and frontal cortex tissues were measured with the method of Buege and Aust [40], and Beutler [41], respectively. The activity of the AChE responsible for the degradation of ACh was measured in tissue samples using a spectrophotometer with the Ellman method and was expressed as μmol/h/mg protein [42].

    2.8 Immunoblotting analysis

    For the immunoblotting analyses of both brain tissues of the rats, Tris-HCl buffer containing EDTA (1 mmol/L), glycerol (10%),protease inhibitors, NaCl, and DTT (50, 2 mmol/L, respectively)were added to the tissues and then centrifuged for 85 s. After the homogenization using a centrifuge (at 2 000 ×gfor 12 min), they were vortexed for 90 min for incubation with Tris-HCl buffer and 0.05% Triton X-100. The protein content of the samples was determined using the Lowry method [43]. Protein in gels obtained from the loading of samples containing 100 μg protein into electrophoresis was transferred to nitrocellulose membranes [13].After blocking with Tris containing 1% BSA, all membranes were incubated for 12 h with polyclonal primary antibodies [Bax(1:100) (sc-20067), Bcl-2 (1:200) (sc-7382), caspase-3 (1:200)(sc-56053), caspase-9 (1:200) (sc-56076), or M1(1:100)(sc-365966)]at 4 °C. After detection with the desired antibody against the protein of interest, the membranes were incubated with a secondary antibody (anti-goat IgG) (1:1 000) for 1 h at 20 °C.Finally, all membranes were washed with Tris buffer solution. The results were determined by densitometric analysis using the Bio-Rad Molecular Analyst software (free edition, www. totallab.com).

    2.9 Statistical analysis

    Statistical analysis was performed using Graphpad Prism 6.0(Graphpad Software, San Diego, CA, USA). All data are expressed as mean ± standard error (SEM). Biochemical data of groups were analyzed with variance analysis (ANOVA) followed by Tukey multiple comparison tests. The results of NORT and MWMTs were analyzed with the Mann-Whitney U nonparametric test. For all data,P< 0.05 was considered statistically significant.

    3. Results

    3.1 Assessment of scop-induced cognitive deficits in two different tests

    The NORT was performed to evaluate the effect of galantamine and PC extract treatment to impairment in object recognition memory of rats due to scopolamine administration. It was determined that the administration of scopolamine significantly reduced the time spent with the novel object and elevated the time spent with the familiar object, thus reducing the discrimination index of the NORT (P< 0.01;Fig. 2). On the other hand, galantamine andPC treatment reversed the time spent exploring the novel object (P< 0.01).

    Fig. 2 According to NORT, discrimination index of the 4 groups. **P <0.01,compared to control group; ++P < 0.01, compared to Scop group. (n = 8).

    The effect of scopolamine on cognitive impairment was assessed by MWMT which is used to assess spatial memory ability. The comparison of each group according to the 1stand 4thdays is given in Fig. 3a and the comparison between the groups on the test day is given in Fig. 3b. While there was a platform in MWMT from day 1 to day 4, there was no platform in the tank on day 5 of the experiments.No difference in escape latency in all groups was observed on the first training days. When the escape latency of the control group was examined, a significant difference was determined in the 3rdand 4thdays compared to the 1stday of the MWMT (P< 0.05,P< 0.01,respectively; Fig. 3a) however there was no significant difference in escape latency day 1 to day 4 in Scop group. On the other hand,galantamine andPC-treated rats found the platform in a short time,and therefore escape latencies were decreased significantly.

    Fig. 3 Cognitive function assessed by the MWM test of the 4 groups. (a) Mean escape latency time was monitored from day 1 to day 4 in each group. (b) Time spent in the target quadrant was monitored at day 5 in each group. (n = 8). *P < 0.05; **P < 0.01; ***P < 0.001 as compared to the control group; ++P < 0.01 vs Scop group.

    In MWM probe test that was monitored on the 5thday, results showed that the saline-treated Scop group had significantly lower performance(P< 0.05) vs control group (Fig. 3b), but the PC-treated group displayed higher performance and the time spent in the target quadrant was found to be increased significantly compared to the Scop group (P< 0.01).

    Although the galantamine-treated group tended to increase in time spent in the target quadrant, this increase was not statistically different when compared with the Scop group, and there was no significant difference between two treatment groups on the 5thday.

    3.2 Biochemical analysis

    The GSH levels of the hippocampal and frontal cortex tissues were significantly reduced in the Scop group compared to the control group (P< 0.001), but administration of galantamine andPC extract increased this antioxidant in both tissue samples significantly (P< 0.01 or 0.001, Figs. 4a and 4b).

    樞紐及防洪配套工程年運行費按投資2.5%計,后續(xù)灌區(qū)配套工程按其投資4%計,防洪、養(yǎng)殖等配套工程按其投資5%計[2],則正常年份年運行費32.77萬元。

    Fig. 4 The levels of (a-b) GSH, (c-d) MDA and (e-f) AChE activity obtained from the hippocampus and frontal cortex regions of the rats in the 4 groups (n = 8).

    Malondialdehyde levels in the hippocampus and frontal cortex tissues were found to be significantly increased due to scopolamine(P< 0.01), and treatment of galantamine andPCextract significantly(P< 0.05 or 0.01) decreased MDA which were closer to the control levels (Figs. 4c and 4d).

    Scopolamine administration for 14 days caused significant increase in AChE activity (P< 0.01 or 0.001) in the investigated regions, while in galantamine andPC treated groups, the enzyme activities were decreased significantly (P< 0.05 or 0.001; Figs. 4e and 4f).

    3.3 The results of immunoblotting

    We performed immunoblotting experiments in 8 rats per group for the determination of different protein expression levels. The images of the membranes obtained from western blotting assays for each protein are shown in Fig. 5.

    Fig. 5 The representative image of the membranes obtained from western blotting experiments in the Scop-induced AD rat model.

    When evaluating the change of the Bcl-2/Bax ratio in the hippocampus, we found that the Bcl-2/Bax ratio was decreased in the Scop groups compared to the control groups (P< 0.001). In the hippocampal region, the Bcl-2/Bax ratio significantly increased with the administration of galantamine andPC treatment compared to the Scop group (P< 0.001, Fig. 6a).

    Fig. 6 The density of immunoblotting of (a-b) Bcl-2/Bax ratio, (c-d) caspase-9, (e-f) caspase-3 and (g-h) M1 levels of the hippocampus and frontal cortex regions of the rats in the Scop-induced AD rat model (n = 8).

    In the frontal cortex region, it was detected that the levels of the Bcl-2/Bax ratio were found to be decreased in rats treated with scopolamine compared to the control group (P< 0.001). In frontal cortex regions, expression levels of the Bcl-2/Bax ratio were markedly increased in GAL and PC groups compared with the Scop group(P< 0.001, Fig. 6b).

    When we analyzed the expression changes of caspase-9 proteins effective in the apoptosis caspase pathway in the hippocampus, it was found that caspase-9 expression levels were increased in the Scop group compared with the control groups (P< 0.001). When we compared the effect of galantamine andPC treatments on the level of caspase-9 expression compared with the Scop group, we determined that both treatments significantly reduced the caspase-9 expression level compared with the Scop group (P< 0.001, Fig. 6c).

    When the caspase-9 expression was analyzed in the frontal cortex region, it was determined that the caspase-9 expression levels of Scop group rats increased compared to the control groups (P< 0.01). The treatments of galantamine andPC were found to cause the caspase-9 expression levels to increase compared to Scop group (P< 0.001, Fig. 6d).

    In the hippocampus, caspase-3 expressions were markedly elevated in the Scop group compared to the control group (P< 0.001).Galantamine treatment significantly decreased caspase-3 expression levels compared to the Scop group in the same region (P< 0.001).Similar to GAL treatment, it was determined that PC treatment has decreased the level of caspase-3 expression in the hippocampus(P< 0.001, Fig. 6e).

    It was determined that the expressions of caspase-3 were raised in the frontal cortex of rats treated with scopolamine compared to the control group (P< 0.001). Additionally, galantamine treatment led to a significant decrease in caspase-3 expression levels in the frontal cortex region of rats compared with the Scop group (P< 0.001).Moreover, it was determined that PC-treatment was effective in decreasing caspase-3 expression levels in the frontal cortex (P< 0.01,Fig. 6f).

    In the hippocampus, the expression levels of mACh M1subtype was found to be diminished in the rats treated with scopolamine compared to the expression in control rats treated with saline(P< 0.000 1). The expression level of M1was significantly increased in the galantamine treated groups compared to Scop groups(P< 0.001). The M1level was significantly increased in the PC-treated compared to the Scop group (P< 0.000 1, Fig. 6g).

    When M1expression levels were examined in the frontal cortex region, it was determined that the expression level of Scop group diminished markedly compared with the control group (P< 0.001). In the same region, expression levels of M1were markedly raised in the galantamine treated group compared with Scop groups (P< 0.001).The M1level was significantly increased with thePCtreated group compared with the Scop group (P< 0.001, Fig. 6h).

    4. Discussion

    This study reveals a significant increase in the degree of apoptosis, oxidative stress, and AChE activity in the frontal cortex and hippocampus regions of scopolamine-induced cognitive deficient animals. There was also a significant decline in the level of M1receptor expression in the selected brain regions of the rats.The results of the cognitive experiments of this study showed that scopolamine injection resulted in learning and memory impairment in the formation of recognition memory of rats determined with NORT and MWMTs. On the other hand,PCextract has been shown to have an ameliorative effect on apoptosis, oxidative stress, M1receptor expression, and increased AChE activity.

    The NORT was conducted to evaluate the effect of PC on hippocampus-dependent cognitive function. Similar to galantamine, PC extract caused improvement in short term working memory, and these results show that the reduction in scopolamine-induced recognition memory is reversed [44,45]. Although, there is no data in the literature for PC extract treatment on recognition memory function, luteolin an important flavonoid found in the PC, has been shown to improve new object recognition memory in the Ts65Dn mouse model [46]. Thus, the present results indicate for the first time, that PC has an enhancing effect on short term object recognition memory.

    In the MWM experiments, the time spent on the target quadrant is considered a sign of memory rejuvenation. Scopolamine impairs place navigation ability and spatial memory in rats and humans [47,48]and recognition memory in rats [44,45]. Galantamine significantly mitigated the scopolamine-induced reduction of spatial memory in maze tests [49]. The enhancing effects of PC extract on cognitive functions have not been known in the literature. In the present study,scopolamine raised the escape latency in the acquisition phase and declined time spent in the target quadrant in the probe phase meliorated by the treatment with PC extract. Our MWMT results,in which we examined the spatial learning and working memory,indicated that in rats treated with scopolamine, PC extract has significant improvement in spatial memory deficits, similar to galantamine.

    Scopolamine is associated with increased oxidative stress in the hippocampus and frontal cortex [12,50]. GSH a powerful cellular antioxidant clears ROS or free radicals directly, while MDA is one of the end products of fatty acid peroxidation in the membrane. Previous studies have reported that scopolamine caused an increase in MDA levels [13,48,51]and a reduction in GSH levels [13,48,52]in the rat brain. In agreement with previous studies, in the present study, MDA levels were found to be significantly increased while GSH levels were decreased, in the hippocampus and frontal cortex regions with 14 days of scopolamine treatment [53-55]. On the other hand, PC and galantamine treatment in the scopolamine treated rats reversed these changes. In our study, we used galantamine, one of the existing drugs used in AD, as a positive control, because it has been shown to have protective effects on various neurotoxic models in the brain via reducing oxidant damage. Although there is no study about the effects of PC extract in scopolamine-induced AD model, PC has been shown to suppress lipid peroxidation by diminishing MDA and enhancing GSH levels in rats in cisplatin-induced hepatic-cardiac injuries [21]and testicular oxidative stress [20]. Besides, Allam et al. [56],reported that low-dose parsley (P. crispum) juice leads to an increase in GSH levels and decreased oxidative stress when exposed to cadmium in newborn rat brain. Vora et al. [19]indicated that parsley has a protective effect from oxidative damage in the mouse brain on the d-galactose induced oxidative stress model. Taken together, our results indicate that the PC could have a protective effect on scopolamineinduced oxidative injury in the hippocampus and frontal cortex.

    Acetylcholine plays a pivotal role in cognitive function and it is well known that in AD it is reduced. While scopolamine increases AChE’s protein expression level [51,57,58], it reduces ACh level [57]. In agreement with the previous reports, in the current study, scopolamine increasing AChE activity caused cognitive impairment. Accordingly, AChE inhibition is an effective strategy in the early phase of AD [30]. The efficacy of galantamine in AD is accompanied by AChE expression or activity [13,58]. Present results showed that similar to galantamine, PC extract has anti-AChE activity in the hippocampus and frontal cortex, and improve failure caused by a deficiency in the cholinergic system.

    M1is the most expressed muscarinic receptor type in the hippocampus and prefrontal cortex [59]. Jahanshahi et al. [59]showed that M1-neuron density decreased in the entire hippocampal region depending on the dose of scopolamine. Sayyahi et al. [60]reported that M1muscarinic receptor-immunoreactive neurons decreased numerically with scopolamine. Similar to a previous report [13], in our study, the rats who received scopolamine exhibited a significant loss in the level of M1expression in the hippocampus and frontal cortex regions. This result may be related to neuronal oxidative damage or apoptosis caused by scopolamine [4,12,15,17,18]. On the other hand, PC extract increased M1receptor expression and this effect may be due to antioxidant [19-24]and anti-apoptotic [20,21]effects of PC. In a recent study, PC has been shown to protect the number of neurons and dendrite structure in morphine-induced prefrontal cortex damage by reducing oxidative and nitro-oxidative stress [23].

    In our study, Bcl-2/Bax expression ratio was decreased in sensitive brain regions while caspase-3 and caspase-9 increased. These observations indicate the fact that an increase in the pro-apoptotic protein expression could be a cause of mitochondrial dysfunctioninduced neuronal degeneration seen in AD. Demirci et al. [18]demonstrated that scopolamine caused an increase in mitochondrialrelated apoptosis in the brain regions of the rats due to a decrease in mitochondrial function. Previously, it has been reported that active caspase-3 and pro-caspase-9 were increased as well as the ratio of Bax/Bcl-2 after scopolamine treatment [61]. Similarly, the present study con firms that scopolamine causes apoptosis in rat the brain since caspase-3 and 9 expressions were found to be significantly increased.Previously, it has been shown that PC has anti-apoptotic effects on cisplatin-induced hepato-cardiotoxicity in rats [21]. Allam et al. [56]reported that PC juice exhibits remarkable neuronal protection through reducing the rate of chromatolysis and pyknosis in the newborn rat brain. Besides, apigenin, a natural flavonoid found in PC, has been reported to alleviate neuronal apoptosis by decreased Bax and caspase-3, in the brain injury model [62]. Furthermore, Balez et al. [63]suggested that apigenin reduced apoptosis by decreasing caspase-3/7 levels in an induced pluripotent stem cell AD model. Hence, the antiapoptotic effects of PC extract on scopolamine-induced AD model may be due to the existence of various flavonoid compounds, such as apigenin or luteolin. In agreement with previous studies, in this study,we found decreased apoptotic caspase and Bax protein expressions,which represents the anti-apoptotic activity of the PC extract.

    Given our findings, we propose that PC extract has an ameliorative effect on M1receptor expression, apoptosis, oxidative stress, increased AChE activity, and spatial and object recognition memory, in the scopolamine-induced AD rat model. This is possibly through enhancement of antioxidant defence, anti-AChE activity,up-regulation of the M1expression, and anti-apoptotic effect. Thus, it was concluded thatPC prevent AD-like conditions and can be used as a functional food.

    The effect of PC on cognitive functions has not been previously studied. For this reason, the study was first performed on animals and it was investigated whether the PC extract, which is widely consumed as a vegetable, has possible positive effects on memory. On the other hand, since animal models do not completely mimic that of humans the importance of PC as a functional food for human AD is unknown.Thus, the results of this study will shed light on human studies in the future and show that PC preserves memory functions.

    conflict of interest

    The authors report no conflicts of interest.

    Acknowledgment

    The authors received no financial support for the research,authorship, and/or publication of this article.

    猜你喜歡
    配套工程年份樞紐
    港航工程/嘉陵江川境段航運配套工程
    水運工程(2022年9期)2022-09-21 08:09:54
    特殊的一年
    樞紐的力量
    淮安的高鐵樞紐夢
    商周刊(2019年18期)2019-10-12 08:50:56
    樞紐經(jīng)濟的“三維構(gòu)建”
    德陽市地下綜合管廊及配套工程(一期)建設(shè)項目PPP模式應(yīng)用
    建立跨穿南水北調(diào)配套工程管理體系的思考
    什么是閏年?
    一樣的年份
    南寧某綜合配套工程冷熱源方案分析
    不卡一级毛片| 久久草成人影院| 成年免费大片在线观看| 国产精品电影一区二区三区| 黄色成人免费大全| 亚洲片人在线观看| 中国美女看黄片| 97超级碰碰碰精品色视频在线观看| svipshipincom国产片| 最新美女视频免费是黄的| 中文字幕久久专区| 一进一出抽搐gif免费好疼| 国产91精品成人一区二区三区| а√天堂www在线а√下载| e午夜精品久久久久久久| 日日摸夜夜添夜夜添小说| 美女免费视频网站| 久久久国产精品麻豆| 亚洲无线在线观看| 操出白浆在线播放| 欧美极品一区二区三区四区| 久久伊人香网站| 成人欧美大片| 婷婷精品国产亚洲av| 不卡一级毛片| 久久欧美精品欧美久久欧美| 精品电影一区二区在线| 悠悠久久av| 最好的美女福利视频网| 久久久久亚洲av毛片大全| 成人三级黄色视频| 国产免费av片在线观看野外av| 久久中文看片网| 亚洲国产精品sss在线观看| 亚洲av成人精品一区久久| 国产精品久久久久久人妻精品电影| 性色av乱码一区二区三区2| 91久久精品国产一区二区成人 | 中文字幕人妻熟人妻熟丝袜美 | 一本一本综合久久| 免费人成在线观看视频色| 精品一区二区三区视频在线观看免费| 日本精品一区二区三区蜜桃| 在线观看免费午夜福利视频| 欧美日本视频| 亚洲精品日韩av片在线观看 | 99久久精品一区二区三区| 身体一侧抽搐| 综合色av麻豆| x7x7x7水蜜桃| 国产伦在线观看视频一区| 99国产极品粉嫩在线观看| 久久久久久大精品| www国产在线视频色| 欧美高清成人免费视频www| 亚洲精品一卡2卡三卡4卡5卡| 99久久九九国产精品国产免费| 窝窝影院91人妻| 九色国产91popny在线| 男女那种视频在线观看| 一级毛片女人18水好多| 在线观看舔阴道视频| 日本熟妇午夜| 色哟哟哟哟哟哟| 97人妻精品一区二区三区麻豆| 少妇丰满av| 国产精品久久久人人做人人爽| 男女做爰动态图高潮gif福利片| 他把我摸到了高潮在线观看| 国产精品,欧美在线| 长腿黑丝高跟| 极品教师在线免费播放| 乱人视频在线观看| 亚洲aⅴ乱码一区二区在线播放| 日本一二三区视频观看| 中文字幕精品亚洲无线码一区| 少妇的丰满在线观看| 亚洲第一电影网av| 免费观看精品视频网站| 日本熟妇午夜| 手机成人av网站| 国产一区二区三区在线臀色熟女| 亚洲av免费在线观看| 国产高清有码在线观看视频| 国产精品美女特级片免费视频播放器| 人妻久久中文字幕网| 成人一区二区视频在线观看| 成人欧美大片| 日韩国内少妇激情av| 精品电影一区二区在线| 中文字幕人妻丝袜一区二区| 亚洲精品久久国产高清桃花| 法律面前人人平等表现在哪些方面| 看片在线看免费视频| 欧美精品啪啪一区二区三区| 不卡一级毛片| 国内少妇人妻偷人精品xxx网站| 亚洲精品在线美女| 免费看a级黄色片| 亚洲精品美女久久久久99蜜臀| av视频在线观看入口| 女警被强在线播放| 国产成人a区在线观看| 黄色成人免费大全| 无遮挡黄片免费观看| 欧美黑人欧美精品刺激| 欧美一区二区亚洲| 亚洲五月婷婷丁香| 日本黄色片子视频| 午夜福利成人在线免费观看| 久久国产精品人妻蜜桃| 国产色婷婷99| 成人永久免费在线观看视频| 午夜两性在线视频| 大型黄色视频在线免费观看| 少妇丰满av| 欧美成人a在线观看| 人妻久久中文字幕网| 夜夜躁狠狠躁天天躁| 亚洲性夜色夜夜综合| 亚洲av电影在线进入| 午夜精品一区二区三区免费看| 老司机午夜福利在线观看视频| av黄色大香蕉| 18+在线观看网站| 在线观看66精品国产| 人妻夜夜爽99麻豆av| 日本 av在线| 中文字幕熟女人妻在线| 少妇的逼好多水| 天美传媒精品一区二区| 欧美乱妇无乱码| 亚洲av不卡在线观看| 亚洲欧美日韩高清在线视频| 日韩国内少妇激情av| 在线视频色国产色| tocl精华| 一个人看视频在线观看www免费 | 亚洲精品456在线播放app | 欧美乱码精品一区二区三区| 中文字幕人成人乱码亚洲影| 国产欧美日韩一区二区精品| 好看av亚洲va欧美ⅴa在| www日本黄色视频网| 最近最新免费中文字幕在线| 在线国产一区二区在线| 黄色女人牲交| 欧美黑人巨大hd| 国产亚洲av嫩草精品影院| 亚洲欧美精品综合久久99| 久久久久久久午夜电影| 亚洲精品粉嫩美女一区| 听说在线观看完整版免费高清| 两个人视频免费观看高清| 国产真实乱freesex| 国产精品久久电影中文字幕| 熟妇人妻久久中文字幕3abv| 老熟妇仑乱视频hdxx| 国产av不卡久久| 亚洲一区高清亚洲精品| 亚洲电影在线观看av| 欧美日韩中文字幕国产精品一区二区三区| 日韩欧美在线二视频| 成年女人看的毛片在线观看| 一二三四社区在线视频社区8| 俺也久久电影网| 国内精品久久久久久久电影| 琪琪午夜伦伦电影理论片6080| 欧美成人a在线观看| 老司机午夜十八禁免费视频| 亚洲第一电影网av| 国产成+人综合+亚洲专区| 久久精品91蜜桃| 亚洲精品日韩av片在线观看 | 午夜免费激情av| 国产激情偷乱视频一区二区| 国产一区二区在线观看日韩 | 亚洲人成电影免费在线| 人妻丰满熟妇av一区二区三区| 搡老熟女国产l中国老女人| 国产69精品久久久久777片| 日本一本二区三区精品| 午夜日韩欧美国产| 日本成人三级电影网站| 搡老岳熟女国产| 中文字幕人妻丝袜一区二区| 一边摸一边抽搐一进一小说| 午夜视频国产福利| 久久久成人免费电影| 别揉我奶头~嗯~啊~动态视频| 欧美绝顶高潮抽搐喷水| 男女床上黄色一级片免费看| 成人亚洲精品av一区二区| 亚洲一区二区三区色噜噜| 深爱激情五月婷婷| 看免费av毛片| 99久久精品热视频| 狂野欧美激情性xxxx| 久久精品91蜜桃| 少妇裸体淫交视频免费看高清| 午夜久久久久精精品| av天堂在线播放| 在线观看午夜福利视频| 欧美精品啪啪一区二区三区| 一个人免费在线观看的高清视频| 99热这里只有是精品50| 色在线成人网| 在线观看日韩欧美| 小说图片视频综合网站| 91在线精品国自产拍蜜月 | 国产免费av片在线观看野外av| 亚洲成人久久爱视频| 手机成人av网站| 国产成人福利小说| 亚洲精品乱码久久久v下载方式 | 国产高清videossex| 又粗又爽又猛毛片免费看| 欧美激情在线99| 中文字幕久久专区| 又粗又爽又猛毛片免费看| 嫩草影院精品99| 搞女人的毛片| 男女那种视频在线观看| 国产高潮美女av| 91麻豆精品激情在线观看国产| 少妇裸体淫交视频免费看高清| 两人在一起打扑克的视频| 日日夜夜操网爽| 成人av一区二区三区在线看| 麻豆国产97在线/欧美| 亚洲五月婷婷丁香| 老师上课跳d突然被开到最大视频 久久午夜综合久久蜜桃 | 老汉色∧v一级毛片| 欧美日韩综合久久久久久 | 国产99白浆流出| 国产真实伦视频高清在线观看 | av在线蜜桃| 黄色女人牲交| 午夜福利在线观看免费完整高清在 | 国产精品免费一区二区三区在线| 在线观看美女被高潮喷水网站 | 欧美成人a在线观看| 精品久久久久久成人av| 两性午夜刺激爽爽歪歪视频在线观看| 波多野结衣高清无吗| 天堂√8在线中文| 午夜福利视频1000在线观看| 日韩有码中文字幕| 欧美极品一区二区三区四区| 国产99白浆流出| 亚洲av熟女| 亚洲av中文字字幕乱码综合| 国产精品久久久人人做人人爽| 日本撒尿小便嘘嘘汇集6| 亚洲人成网站在线播放欧美日韩| 亚洲av熟女| 亚洲中文日韩欧美视频| 美女黄网站色视频| 国产精品永久免费网站| 五月伊人婷婷丁香| xxxwww97欧美| 一区二区三区高清视频在线| www.www免费av| 两性午夜刺激爽爽歪歪视频在线观看| 天堂√8在线中文| 亚洲国产精品久久男人天堂| 欧美+亚洲+日韩+国产| 俺也久久电影网| 欧美绝顶高潮抽搐喷水| 欧美性猛交╳xxx乱大交人| 国产在线精品亚洲第一网站| 久久这里只有精品中国| 欧美3d第一页| 国产精品综合久久久久久久免费| 国产亚洲av嫩草精品影院| 欧美日韩瑟瑟在线播放| 日韩欧美免费精品| 欧美高清成人免费视频www| 美女高潮喷水抽搐中文字幕| 午夜久久久久精精品| 美女免费视频网站| 两人在一起打扑克的视频| 国产免费一级a男人的天堂| 母亲3免费完整高清在线观看| 欧美乱码精品一区二区三区| 国产精品日韩av在线免费观看| 欧美国产日韩亚洲一区| 国产一区在线观看成人免费| 亚洲欧美激情综合另类| 12—13女人毛片做爰片一| 免费看十八禁软件| 99国产精品一区二区三区| 亚洲av日韩精品久久久久久密| 国产综合懂色| 九九久久精品国产亚洲av麻豆| 两人在一起打扑克的视频| 人妻夜夜爽99麻豆av| 一边摸一边抽搐一进一小说| 黄色成人免费大全| а√天堂www在线а√下载| 欧美高清成人免费视频www| 日本精品一区二区三区蜜桃| 国产又黄又爽又无遮挡在线| 久久精品国产亚洲av香蕉五月| 国产单亲对白刺激| 无遮挡黄片免费观看| 国产成人av教育| 国产一区二区三区视频了| 色精品久久人妻99蜜桃| 99久久九九国产精品国产免费| 亚洲狠狠婷婷综合久久图片| 一级毛片高清免费大全| 国产亚洲欧美在线一区二区| 精品国内亚洲2022精品成人| 十八禁网站免费在线| 亚洲不卡免费看| 亚洲成人精品中文字幕电影| 亚洲一区高清亚洲精品| 亚洲美女黄片视频| 欧美黄色淫秽网站| 久久国产乱子伦精品免费另类| 麻豆国产av国片精品| 伊人久久精品亚洲午夜| 18禁国产床啪视频网站| 男插女下体视频免费在线播放| 亚洲久久久久久中文字幕| 老汉色∧v一级毛片| 亚洲精品国产精品久久久不卡| 欧美3d第一页| 手机成人av网站| 国产蜜桃级精品一区二区三区| 亚洲精品久久国产高清桃花| 亚洲在线观看片| 三级男女做爰猛烈吃奶摸视频| 99精品欧美一区二区三区四区| 欧美色视频一区免费| 9191精品国产免费久久| 午夜福利欧美成人| 99riav亚洲国产免费| 免费人成在线观看视频色| 久久人人精品亚洲av| 天美传媒精品一区二区| 亚洲av免费高清在线观看| 两个人看的免费小视频| 日本免费一区二区三区高清不卡| 老汉色av国产亚洲站长工具| 午夜福利视频1000在线观看| 小蜜桃在线观看免费完整版高清| 搡女人真爽免费视频火全软件 | 色哟哟哟哟哟哟| 日本一二三区视频观看| 午夜福利在线观看免费完整高清在 | 亚洲精华国产精华精| 成人高潮视频无遮挡免费网站| av在线天堂中文字幕| 国产亚洲精品综合一区在线观看| 一个人免费在线观看的高清视频| 欧美乱码精品一区二区三区| 欧美日韩乱码在线| 两性午夜刺激爽爽歪歪视频在线观看| 岛国在线免费视频观看| h日本视频在线播放| 亚洲aⅴ乱码一区二区在线播放| 亚洲va日本ⅴa欧美va伊人久久| 偷拍熟女少妇极品色| 看黄色毛片网站| 国产一区二区在线av高清观看| 天堂网av新在线| 中文字幕人妻丝袜一区二区| 99精品在免费线老司机午夜| 国产亚洲欧美在线一区二区| 亚洲成av人片在线播放无| 一级黄片播放器| 伊人久久大香线蕉亚洲五| av女优亚洲男人天堂| 每晚都被弄得嗷嗷叫到高潮| 成人性生交大片免费视频hd| 又粗又爽又猛毛片免费看| 可以在线观看的亚洲视频| 91久久精品电影网| 国产精品嫩草影院av在线观看 | 久99久视频精品免费| 国产毛片a区久久久久| 亚洲国产欧美人成| 黄色丝袜av网址大全| 久久精品人妻少妇| 欧美zozozo另类| 99精品在免费线老司机午夜| 亚洲精品一区av在线观看| 国产精品久久久久久人妻精品电影| 国产aⅴ精品一区二区三区波| 久久欧美精品欧美久久欧美| 久久久久性生活片| 亚洲精品亚洲一区二区| 成人鲁丝片一二三区免费| 日本与韩国留学比较| 国产69精品久久久久777片| 色在线成人网| 亚洲久久久久久中文字幕| 国产伦精品一区二区三区视频9 | 18禁黄网站禁片免费观看直播| 亚洲欧美精品综合久久99| 久久精品国产自在天天线| 国产精品亚洲av一区麻豆| 一区二区三区高清视频在线| 日本a在线网址| 亚洲av电影在线进入| 亚洲av一区综合| 9191精品国产免费久久| 久久久久久久午夜电影| 午夜久久久久精精品| 97人妻精品一区二区三区麻豆| 国产精华一区二区三区| 亚洲精品一卡2卡三卡4卡5卡| 中文字幕熟女人妻在线| 一级毛片女人18水好多| 搡女人真爽免费视频火全软件 | 亚洲,欧美精品.| 在线观看免费午夜福利视频| 亚洲 欧美 日韩 在线 免费| 免费看美女性在线毛片视频| 欧美大码av| 无遮挡黄片免费观看| 免费人成视频x8x8入口观看| svipshipincom国产片| 国产乱人伦免费视频| 国产精品久久久人人做人人爽| 亚洲欧美日韩卡通动漫| 99精品久久久久人妻精品| 日日夜夜操网爽| 在线天堂最新版资源| 69av精品久久久久久| 午夜福利视频1000在线观看| 国产69精品久久久久777片| 怎么达到女性高潮| 国产男靠女视频免费网站| 欧美色视频一区免费| 国产午夜福利久久久久久| 午夜福利视频1000在线观看| 中文亚洲av片在线观看爽| 18美女黄网站色大片免费观看| 看片在线看免费视频| 琪琪午夜伦伦电影理论片6080| 老师上课跳d突然被开到最大视频 久久午夜综合久久蜜桃 | a级一级毛片免费在线观看| 久久精品国产亚洲av香蕉五月| 三级毛片av免费| 日本成人三级电影网站| 99久久无色码亚洲精品果冻| 国产精品国产高清国产av| 久久久精品欧美日韩精品| 国产精品电影一区二区三区| 久久精品夜夜夜夜夜久久蜜豆| 国产伦人伦偷精品视频| 国产伦一二天堂av在线观看| 丁香欧美五月| www国产在线视频色| 日本与韩国留学比较| 久9热在线精品视频| 熟女电影av网| 99riav亚洲国产免费| 三级男女做爰猛烈吃奶摸视频| 亚洲欧美一区二区三区黑人| 亚洲一区二区三区不卡视频| 哪里可以看免费的av片| 日韩欧美国产在线观看| 男人舔女人下体高潮全视频| 日本在线视频免费播放| 香蕉av资源在线| 成人18禁在线播放| 成人三级黄色视频| 国产视频内射| 两个人的视频大全免费| 熟女人妻精品中文字幕| 成人特级黄色片久久久久久久| 国产伦人伦偷精品视频| 亚洲一区二区三区不卡视频| 亚洲狠狠婷婷综合久久图片| 成人一区二区视频在线观看| 久久中文看片网| 天堂影院成人在线观看| 美女黄网站色视频| 午夜精品一区二区三区免费看| 十八禁网站免费在线| 国产精品电影一区二区三区| 久久久久久大精品| 9191精品国产免费久久| av在线天堂中文字幕| 真人做人爱边吃奶动态| 亚洲av日韩精品久久久久久密| 在线播放国产精品三级| 宅男免费午夜| 观看免费一级毛片| 黄色女人牲交| 亚洲久久久久久中文字幕| 国产精品久久久人人做人人爽| 免费看日本二区| avwww免费| 国产高清videossex| 精品乱码久久久久久99久播| 中文字幕久久专区| 床上黄色一级片| 18+在线观看网站| 日韩欧美 国产精品| 亚洲av免费高清在线观看| 老熟妇仑乱视频hdxx| 夜夜夜夜夜久久久久| 国产不卡一卡二| 日韩欧美国产在线观看| 无遮挡黄片免费观看| 99精品久久久久人妻精品| 麻豆久久精品国产亚洲av| 啪啪无遮挡十八禁网站| 成年版毛片免费区| 中亚洲国语对白在线视频| 欧美区成人在线视频| 精品久久久久久久末码| 国产黄片美女视频| 日韩av在线大香蕉| 欧美日本视频| 色视频www国产| 国产高清视频在线播放一区| 禁无遮挡网站| 变态另类成人亚洲欧美熟女| 99久久无色码亚洲精品果冻| 真实男女啪啪啪动态图| 日本 av在线| 精品久久久久久成人av| eeuss影院久久| 美女高潮的动态| 亚洲国产精品999在线| 欧美日韩一级在线毛片| 欧美最新免费一区二区三区 | 变态另类成人亚洲欧美熟女| 91在线精品国自产拍蜜月 | 我要搜黄色片| 欧美不卡视频在线免费观看| 久久久久久久精品吃奶| 女同久久另类99精品国产91| 久久久色成人| 麻豆成人av在线观看| 毛片女人毛片| 亚洲 国产 在线| 欧美3d第一页| 亚洲片人在线观看| 黄色丝袜av网址大全| 亚洲av成人av| 免费av观看视频| 51午夜福利影视在线观看| 亚洲专区国产一区二区| 国产淫片久久久久久久久 | 免费在线观看影片大全网站| 中文字幕精品亚洲无线码一区| 亚洲精品日韩av片在线观看 | av在线蜜桃| 少妇人妻精品综合一区二区 | 亚洲天堂国产精品一区在线| 久久久成人免费电影| 成人性生交大片免费视频hd| 又黄又爽又免费观看的视频| 69人妻影院| 国产毛片a区久久久久| 国产欧美日韩精品亚洲av| 一级毛片高清免费大全| 久久久精品欧美日韩精品| 熟妇人妻久久中文字幕3abv| 性色av乱码一区二区三区2| 一个人看的www免费观看视频| 国产麻豆成人av免费视频| 国产精品久久久人人做人人爽| 日韩欧美在线乱码| 99riav亚洲国产免费| 精品久久久久久,| 国产色爽女视频免费观看| 欧美性感艳星| 欧美三级亚洲精品| 亚洲av不卡在线观看| 国产亚洲欧美在线一区二区| 在线a可以看的网站| 老司机午夜十八禁免费视频| 日韩欧美一区二区三区在线观看| 免费av观看视频| 男人的好看免费观看在线视频| 99国产极品粉嫩在线观看| 老师上课跳d突然被开到最大视频 久久午夜综合久久蜜桃 | 亚洲国产欧美人成| 欧美最新免费一区二区三区 | 国产高清videossex| 偷拍熟女少妇极品色| 我的老师免费观看完整版| 亚洲人成网站在线播| 久久久精品欧美日韩精品| 精品国产超薄肉色丝袜足j| 亚洲av不卡在线观看| 90打野战视频偷拍视频| 在线天堂最新版资源| 国产v大片淫在线免费观看| 国产亚洲欧美在线一区二区| 国产视频一区二区在线看| 蜜桃亚洲精品一区二区三区| 国产三级黄色录像| 变态另类成人亚洲欧美熟女| 首页视频小说图片口味搜索| 国产成人福利小说| av天堂中文字幕网| www国产在线视频色| 久久久久久国产a免费观看| 亚洲人成网站在线播放欧美日韩| 国产精品久久久久久久久免 | 丝袜美腿在线中文| 亚洲精品在线观看二区| 精品一区二区三区av网在线观看| 99久久无色码亚洲精品果冻| 国产三级在线视频| 国产激情欧美一区二区|