Ascorbic acid attenuates cognitive impairment and brain oxidative stress in ovariectomized mice

Background

Menopause is associated with increased oxidative stress and memory impairment. Based on the antioxidant property of ascorbic acid (AA), It’s effect on cognitive function, the serum level of the brain-derived neurotrophic factor (BDNF) and the activity of antioxidant enzymes within the brain in ovariectomized (OVX) mice was investigated.

中药海龙抗D-半乳糖诱导衰老小鼠学习记忆损伤作用研究

目的 研究中药海龙对D-半乳糖诱导衰老小鼠学习记忆损伤的影响及其作用机制。方法 采用高效液相色谱（HPLC）技术测定海龙中抗学习记忆损伤有效成分二十二碳六烯酸（DHA）含量;腹腔注射D-半乳糖(D-gal)制备衰老小鼠模型,以Morris水迷宫实验及蛋白免疫印迹法等,对小鼠学习记忆能力、海马组织氧化损伤相关生化指标及蛋白表达进行检测,探究海龙对衰老小鼠学习记忆损伤的保护作用及其机制。结果 HPLC结果显示,海龙中DHA含量为7.761 3 mg/g（以生药计）,约占总成分的47%;Morris水迷宫实验结果显示,海龙可减少学习记忆损伤小鼠逃避潜伏期时间,增加小鼠目标象限游泳时间、游泳路程占比、穿台次数,改善小鼠学习记忆损伤;此外,海龙可激活衰老小鼠海马组织AKT/FOXO1/SOD2信号通路,上调氧化应激通路相关蛋白表达,降低衰老小鼠海马组织氧化损伤程度改善小鼠学习记忆损伤。结论 本研究发现海龙富含二十二碳六烯酸,具有改善D-半乳糖诱导衰老小鼠学习记忆损伤的作用,并初步阐明其作用机制与抗氧化相关,为中药海龙抗学习记忆损伤研究提供了实验依据。     

欧洲越桔提取物对小鼠眼内氧化应激状态的影响

欧洲越桔属于杜鹃花科越桔亚科植物,富含花色苷类化合物.该类化合物具有抗癌[1]、抗氧化[2,3],改善视力疲劳[4]、缓解糖尿病及高血压性视网膜病变[5]等方面的效果.已有研究表明束缚应激 (restraint tress) 下小鼠眼内存在氧化应激[6],然而花色苷对束缚应激下眼内氧化应激状态影响的研究未见报道.     

Effect of Morus alba L. (mulberry) leaves on anxiety in mice

Objective:

The aim of the present work is to evaluate the anxiolytic effect of a methanolic extract of Morus alba L. leaves in mice.

Materials and Methods:

The hole-board test, elevated plus-maze paradigm, open field test, and light/dark paradigm were used to assess the anxiolytic activity of the methanolic extract of M. alba L. Morus alba extract (50, 100, and 200 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were administered 30 min before the tests.

Results:

The results showed that the methanolic extract of M. alba significantly increased the number and duration of head poking in the hole-board test. In the elevated plus-maze, the extract significantly increased the exploration of the open arm in similar way to that of diazepam. At a dose of 200 mg/kg i.p. the extract significantly increased both the time spent in and the entries into the open arm by mice. Further, in the open field test, the extract significantly increased rearing, assisted rearing, and number of squares traversed, all of which are demonstrations of exploratory behavior. In the light/dark paradigm, the extract produced significant increase in time spent in the lighted box as compared to vehicle. The spontaneous locomotor activity count, measured using an actophotometer, was significantly decreased in animals pretreated with M. alba extract, indicating a remarkable sedative effect of the plant.

Conclusion:

The results of the present study suggest that a methanolic extract of M. alba leaves may possess an anxiolytic effect.     

Inhibitory effect of aqueous extract of different parts of unripe pawpaw (Carica papaya) fruit on Fe2+-induced oxidative stress in rat pancreas in vitro

Abstract

Context: Carica papaya L. (Caricaceae) is widespread throughout tropical Africa; it is cultivated for its fruits and it is eaten in various ways.

Objective: This study sought to investigate the inhibitory effect of the aqueous extract of different parts of unripe pawpaw fruit on Fe²⁺-induced lipid peroxidation in rat’s pancreas in vitro.

Materials and methods: The aqueous extract of the unripe pawpaw fruit parts; peel (PG), seed (SG), flesh (FG), flesh with peel (FPG) and a combination of equal amount of all parts (CG) were prepared, the total phenolic content and the antioxidant activities of the extracts were then evaluated using various spectrophotometric methods.

Result: PG had the highest total phenol content (1.24?mg GAE/g), flavonoid content (0.63?mg QUE/g), reducing power (7.07?mg AAE/g) and Fe²⁺ chelating ability while the SG had the highest 1,1-diphenyl-2-picrylhydrazyl radical scavenging ability. Furthermore, all the extracts caused a significant decrease (p?<?0.05) in the malondialdehyde contents in the pancreas with SG (IC₅₀?=?4.25?mg/mL) having the highest inhibitory effect on Fe²⁺-induced lipid peroxidation.

Discussion and conclusion: This protective effect of the extracts on Fe²⁺-induced lipid peroxidation in rat pancreas could be attributed to their phenolic compounds and, the possible mechanism may be through their antioxidant activities. However, the effect of combination of different parts of unripe pawpaw fruit in equal amount (w/w) on the inhibition of Fe²-induced lipid peroxidation in rat pancreas exhibited additive properties.     

油酰乙醇胺对东莨菪碱诱导小鼠认知功能损伤的保护作用

目的 探讨油酰乙醇胺对东莨菪碱诱导小鼠认知功能损伤的保护作用。方法 将小鼠随机分为6组：对照组、模型组、多奈哌奇组（阳性药,3 mg·kg^-1）和油酰乙醇胺低、中、高剂量（50、100、200 mg·kg^-1）组,每组6只。在ig给药4周后,除对照组外,各组ip 3 mg·kg^-1的东莨菪碱建立阿尔茨海默病（AD）模型。避暗、跳台行为学实验检测小鼠记忆功能; ELISA法检测小鼠海马和大脑皮层中乙酰胆碱（Ach）和乙酰胆碱酯酶（AChE）水平;HE染色观察小鼠大脑皮层及海马损伤。结果 与对照组比较,模型组的避暗潜伏期显著缩短、避暗错误次数显著增加（P<0.001）;大脑皮层、海马的Ach水平显著减少（P<0.01、0.001）,AChE活性显著升高（P<0.001）;模型组的小鼠脑组织形态结构不均匀,组织细胞呈弥散状,提示组织存在病变。与模型组比较,各给药组的避暗潜伏期显著升高、避暗错误次数显著减少（P<0.01）;油酰乙醇胺给药组的小鼠大脑皮层、海马组织Ach水平显著升高（P<0.05、0.01）,AChE活性显著降低（P<0.01、0.001）;小鼠脑组织形态结构病理改变减轻。结论 油酰乙醇胺对东莨菪碱诱导学习记忆障碍模型小鼠的认知功能具有改善作用,其作用机制可能与调节胆碱能系统功能、促进神经细胞存活有关。     

The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats

The favorable pharmacological profile exhibited by piracetam stimulated the synthesis of related compounds potentially endowed with a higher nootropic potency. The antiamnesic and procognitive activity of DM232 (unifiram), a new compound structurally related to piracetam, was investigated. Mouse passive avoidance and rat Morris water maze and Social learning tests were employed. DM232 (0.001–1 mg kg^?1 i.p. – 0.01–0.1 1 mg kg^?1 p.o.) prevented amnesia induced by scopolamine (1.5 mg kg^?1 i.p.), mecamylamine (20 mg kg^?1 i.p.), baclofen (2 mg kg^?1 i.p.), and clonidine (0.125 mg kg^?1 i.p.). Furthermore, The antiamnesic effect of the investigated compound was comparable to that exerted by well‐known nootropic drugs such as piracetam (30–100 mg kg^?1 i.p.), aniracetam (100 mg kg^?1 p.o.), rolipram (30 mg kg^?1 p.o.), and nicotine (5 mg kg^?1 i.p). DM232 (0.1 mg kg^?1 i.p.) was also able to prevent amnesia induced by scopolamine (0.8 mg kg^?1 i.p.) in the rat Morris watermaze test. In the rat social learning test, DM232 (0.1 mg kg^?1 i.p.) injected in adults rats reduced the duration of active exploration of the familiar partner in the second session of the test. DM232, similarly to piracetam, reduced the duration of hypnosis induced by pentobarbital. At the highest effective doses, the investigated compound did not impair motor coordination (rota rod test), nor modified spontaneous (Animex). These results indicate DM232 (unifiram) as a novel cognition enhancer, strictly related to piracetam‐like compounds, able to ameliorate memory impairment at doses about 1,000 times lower than the most active available nootropic compounds. Drug Dev. Res. 56:23–32, 2002. © 2002 Wiley‐Liss, Inc.     

Naringin alleviates cognitive impairment,mitochondrial dysfunction and oxidative stress induced by d-galactose in mice

Role of mitochondrial dysfunction and oxidative stress has been well documented in aging and related disorders such as Alzheimer’s disease. Bioflavonoids have been reported to have a therapeutic potential against several age related processes. Bioflavonoids are being used as a neuroprotectants in the treatment of various neurological disorders including aging. Therefore, present study has been conducted in order to explore the possible role of naringin against d-galactose induced cognitive dysfunction, oxidative damage and mitochondrial dysfunction in mice. Chronic administration of d-galactose (100 mg/kg) for 6 weeks significantly impaired cognitive performance (both in Morris water maze and elevated plus maze), locomotor activity, oxidative defense and mitochondrial complex (I, II and III) enzymes activities as compared to sham group. Six weeks naringin (40 and 80 mg/kg) treatment significantly improved cognitive performance, oxidative defense and restored mitochondria complex enzyme activities as compared to control (d-galactose). Naringin treatment significantly attenuated acetylcholine esterase activity in d-galactose treated mice. In conclusion, present study highlights the potential role of naringin against d-galactose induced cognitive impairment, biochemical and mitochondrial dysfunction in mice.     

Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice

Oxidative stress is a major factor implicated in the degeneration of cholinergic neurons in Alzheimer's disease. Presently, cholinesterase inhibitors are the mainstay of therapy for Alzheimer's disease. However, the potential of cholinesterase inhibitors as antioxidants, an important aspect for neuroprotection, has not been properly investigated. Therefore, the present study was designed to investigate the influence of antidementia drugs, tacrine and donepezil, on biochemical markers of oxidative stress, glutathione (GSH) and malondialdehyde (MDA), and acetylcholinesterase activity in the brain in a streptozotocin-induced experimental model of dementia in mice. Intracerebral (i.c.) injection of streptozotocin at a dose of 0.5 mg/kg on 1st and 3rd days caused significant deficits in memory function, as evaluated in a passive avoidance test and Morris Water Maze (spatial memory) test 14 days after the 1st dose. Mice were treated with tacrine and donepezil at a dose of 5 mg/kg orally in separate groups. Both tacrine- and donepezil-treated mice showed a significant improvement of the streptozotocin (i.c.)-induced memory impairment. Streptozotocin (i.c.) administration caused a significant decrease in GSH and increase in MDA as compared to control, indicating a state of oxidative stress in the brain of streptozotocin (i.c.) amnesic mice. Treatment of streptozotocin (i.c.) amnesic mice with tacrine or donepezil did not cause significant changes in GSH and MDA levels in the brain as compared to control. Streptozotocin amnesic mice had raised acetylcholinesterase activity in the brain while there was a significant decrease in brain acetylcholinesterase activity in tacrine- and donepezil-treated streptozotocin (i.c.) mice. Thus, results indicate that tacrine and donepezil, beside inhibition of acetylcholinesterase, may also suppress oxidative stress.     

长苞凹舌兰提取物对亚急性衰老小鼠学习记忆和凋亡相关蛋白表达的影响

目的研究长苞凹舌兰提取物(CE)能否改善衰老小鼠的学习记忆能力,及其与神经元凋亡的关系。方法ipD-半乳糖120mg·kg-1·d-1和亚硝酸钠90mg·kg-1·d-1连续60d建立衰老模型,从d47开始igCE2.5,5,10mg·kg-1·d-1,连续14d。跳台实验检测小鼠的学习记忆能力;免疫组化染色测定海马内Bcl-2,半胱氨酸天冬氨酸蛋白酶-3(cas-pase-3)和Bax凋亡相关蛋白的阳性细胞数,并用图像分析系统进行灰度扫描。结果CE明显改善衰老小鼠的学习记忆能力,跳台实验的潜伏期明显延长,错误次数显著减少。衰老小鼠脑中Bcl-2阳性神经元减少,caspase-3和Bax阳性神经元增多。CE可抑制这些凋亡相关蛋白的阳性细胞数改变,从而可能阻断凋亡级联反应的发生。结论CE可增强衰老小鼠的学习记忆能力,其机制可能与抑制神经元凋亡有关。     

健脑益智胶囊对衰老小鼠大脑学习记忆功能减退的作用机制研究

目的：研究健脑益智胶囊（JNYZ）对老年小鼠学习记忆能力的药理作用及其作用机制。方法：将40只老年小鼠,随机分为4组：老年组、JNYZ低、中、高剂量组（2.5,5.0,10.0 g·kg^-1）,另设10只4月龄小鼠作为青年对照组。连续灌胃给予健脑益智胶囊治疗60 d。治疗结束后采用Morris水迷宫法测试小鼠的学习记忆能力,免疫组化法检测海马组织中Bax的表达,透射电镜观察神经细胞及其突触的超微结构,生化法和放射免疫法分别测定脑组织中的乙酰胆碱（Ach）含量、胆碱酯酶（AChE）活性和胆碱乙酰转移酶（ChAT）活性,免疫印迹法分析大脑组织中突触素的表达水平。结果：与老年组相比,JNYZ 3个剂量组均可明显提高老年小鼠学习记忆能力（P<0.05,P<0.01,P<0.01）,显著升高治疗组大脑组织中的乙酰胆碱含量、ChAT活性（P<0.01,P<0.01,P<0.01）和降低脑组织AChE活性（P<0.05或P<0.01）,并能明显减少海马神经细胞中Bax的蛋白表达水平,对老年小鼠大脑神经细胞和突触结构有明显的保护作用,并能有效地提高突触素在大脑组织中的表达水平。结论：JNYZ能够改善和提高老年小鼠的学习记忆能力,可能与它抑制神经细胞凋亡、增强中枢神经系统神经递质和改善神经细胞超微结构等作用有密切的相关性。     

孕酮对东莨菪碱所致记忆损伤小鼠的作用及机制

目的观察孕酮对东莨菪碱所致记忆损伤小鼠的作用及机制。方法东莨菪碱(1mg·kg-1,ip)造成小鼠记忆损伤模型,利用被动逃避实验评价小鼠记忆成绩,并测定给药后24h小鼠皮质和海马胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的活性。结果在被动逃避实验中,东莨菪碱造成小鼠记忆损伤,孕酮(1、10mg·kg-1,sc)预处理能减少跳台错误次数(P<0.05),延长跳台潜伏期(P<0.01)和避暗潜伏期(P<0.01)。东莨菪碱增加皮质和海马AChE活性,降低ChAT活性,孕酮(1mg·kg-1,sc)预处理抑制皮质和海马AChE活性的增加(P<0.01),升高皮质(P<0.05)和海马(P<0.01)ChAT活性。结论孕酮可以改善东莨菪碱所致记忆损伤,机制可能与其抑制皮质和海马AChE活性、升高ChAT活性有关。     

Effects of yam tuber protein,dioscorin, on attenuating oxidative status and learning dysfunction in d-galactose-induced BALB/c mice

The yam tuber is a traditional Chinese medicine used in long-term treatment as a juvenescent substance. The purified yam tuber’s major water-soluble protein, dioscorin, and its protease hydrolysates have been reported to have several biological activities. In this study, d-galactose (Gal) was subcutaneously injected into the dorsal necks of BALB/c mice daily for 10 weeks (Gal group) to induce oxidative stress. By the fifth week, 20 or 80 mg dioscorin/kg was orally administered daily combined with a daily Gal injection until the end of the study. The plasma malondialdehyde (MDA) level and advanced glycation end-products obtained after dioscorin oral administrations were lower compared to the Gal group. In addition, the latency and swimming distance in the mice that received dioscorin administration were significantly improved compared to the Gal group in the Morris water maze. Dioscorin administration resulted in higher GSH levels and oxygen radical antioxidant capacity (ORAC) activity and lower MDA and inducible nitric oxide synthase (iNOS) levels in the brain compared to mice in the Gal group. These elevated antioxidant activities following oral administration of yam dioscorin in vivo may reflect traditional juvenescent uses with the potential for anti-aging treatments.     

急性阿片处理对学习记忆功能的影响

阿片长期处理能够造成动物对阿片产生顽固性的病理性记忆,表明学习记忆参与了阿片依赖过程。阿片本身对动物的学习记忆过程也能产生明显的影响。基于不同的研究模型和不同的给药方案,阿片可能分别对记忆形成、巩固和再现过程表现出抑制或促进作用,其作用的复杂性反映了阿片受体及其与多种非阿片受体间相互作用的多样性。尽管目前仍有争论,但有关这方面的研究已经取得了较大进展。     

黄芪总提取物抗衰老作用的实验研究

目的 研究黄芪总提取物 (totalextractofastragalus,TEA)延缓衰老的作用机理。方法采用小鼠D_半乳糖 (D_galactose,D_gal)人工衰老模型和自然衰老模型(17mon),从氧自由基代谢方面进行研究。结果TEA(40mg·kg-1·d-1ig×10wk)可明显降低D_gal衰老小鼠过高的MDA含量 ,上调其过低的抗氧化酶 (GSHPX、Mn_SOD)活性和GSH/GSSG比值。TEA(40mg·kg-1·d -1ig×3mon)对17mon小鼠亦有类似作用。结论TEA对D_gal衰老小鼠和由中年期(14mon)进入老前期 (17mon)小鼠的自然衰老进程有明显的延缓作用 ,可能与其抗氧化作用有关     

Tunisian radish extract (Raphanus sativus) enhances the antioxidant status and protects against oxidative stress induced by zearalenone in Balb/c mice

Radish (Raphanus sativus) is a food plant known worldwide. From antiquity it has been used in folk medicine as a natural drug against many toxicants. Zearalenone (zen) is a non-steroidal estrogenic mycotoxin present in corn and food mixture for farm animals and it is hepatotoxic, hematotoxic, immunotoxic, nephrotoxic and genotoxic. The objectives of the present study were to assess the biological activity of radish extract and to evaluate the protective role of radish extract against the toxicity of zen in female Balb/c mice. Animals were divided into seven groups and treated orally for 10 days as follows: a control, an olive oil group, groups treated with radish extract alone (5, 10 and 15 mg kg(-1) b.w.), a group treated with zen (40 mg kg(-1) b.w.) and a group treated with zen plus the lowest dose of radish extract. The results indicate that radish extract improved the antioxidant status and had no significant effects on hematological and biochemical parameters tested or histology of the liver and kidney. Treatment with zen results in a significant increase in ALT, AST, ALP, BILT, BILD, CRE accompanied with significant changes in most of hematological parameters and the antioxidant enzyme activities, co-treatment of zen and the radish extract results in a significant reestablishment of hematological, serum biochemical parameters, and the histology of the liver and kidney. These findings suggest that radish extract is safe and can be overcome or, at least, significantly diminish zen effects.     

小鼠暂时性脑缺血引起学习记忆障碍模型的制备及人参皂甙的保护作用

人参皂甙是人参的主要有效成分。本文在建立小鼠脑缺血再灌注导致学习记忆障碍模型的基础上，用跳台、避暗两种实验方法观察了人参皂甙对小鼠脑缺血再灌注后学习记忆功能的保护作用。结果显示小鼠脑缺血再灌注可以导致学习记忆障碍，而人参皂甙（１０，１００ｍｇ·ｋｇ－１，ｐｏ）可以对这种记忆障碍起到保护作用。     

大黄酚对小鼠记忆障碍的作用及其机制分析

目的　研究大黄酚对AlCl3致急性衰老模型小鼠记忆障碍的保护作用及其机制分析。方法　以AlCl3(60mg·kg- 1 sc,7d)造成小鼠记忆障碍模型 ,采用小鼠避暗试验和跳台试验 ,观察大黄酚 (1 0、1、0 1mg·kg- 1 ip ,1 5d)对记忆障碍模型小鼠的保护作用 ,并于d 1 6对各剂量组小鼠进行脑组织超氧化物歧化酶 (SOD)活性及血浆和脑组织谷胱甘肽过氧化物酶 (GSH px)活性测定。 结果　大黄酚各个剂量组均能明显改善AlCl3所致被动回避性记忆障碍 ,增加SOD和GSH px活性。 结论　大黄酚对AlCl3致急性衰老小鼠记忆障碍有保护作用 ,其作用机制可能是通过增强抗氧化酶GSH px和SOD活性 ,清除氧自由基对中枢神经系统神经细胞的损伤     

Effect of Spirulina platensis ingestion on the abnormal biochemical and oxidative stress parameters in the pancreas and liver of alloxan-induced diabetic rats

Context: Previous studies have shown that Spirulina platensis Gomont (Phormidiaceae) (SP) extract has beneficial effects on many disease conditions. The putative protective effects of SP were investigated in diabetic rats.

Objective: The current study investigates the antioxidant effects of SP in diabetic Wistar rats.

Materials and methods: Alloxan monohydrate (150?mg/kg body weight) was intraperitoneally administrated to induce diabetes. An aqueous suspension of SP powder in distillate water (10% w/v) was administrated orally by gavage (1?mL/day) for 50?days. Histopathological, biochemical and antioxidant analyses were performed. Glycemia, liver function and HOMA-IR were assessed using Spinreact and ELISA kits.

Results: SP exhibited high-antioxidant activity. The IC₅₀ values of the SP aqueous extract were 70.40 and 45.69?mg/L compared to those of the standard antioxidant BHT, which were 27.97 and 19.77?mg/L, for the DPPH and ABTS tests, respectively. The diabetic animals showed a significant increase in glycaemia (from 4.05 to 4.28?g/L) and thiobarbituric acid reactive substances (50.17?mmol/g protein) levels. Treatment with SP significantly reduced glycaemia by 79% and liver function markers [glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT) and alkaline phosphatase (Alk-p)]) by 25, 36 and 20%, respectively, compared to that of the controls. There was a significant increase in superoxide dismutase (48%), total antioxidant status (43%), glutathione peroxidase (37%) and glutathione reductase (16%) in the diabetic rats treated with SP.

Discussion and conclusion: These results showed that SP has high antioxidant activity, free radical scavenging, antihyperglycemic and hepatoprotective effects in diabetes.