Cognitive enhancing and antioxidant activity of ethyl acetate soluble fraction of the methanol extract of Hibiscus rosa sinensis in scopolamine-induced amnesia

Objective:

The objective of the present study was to evaluate the cognitive enhancing and antioxidant activity of Hibiscus rosa sinensis.

Materials and Methods:

The learning and memory was impaired by administration of scopolamine (1 mg/kg, i.p.) in mice which is associated with altered brain oxidative status. The object recognition test (ORT) and passive avoidance test (PAT) were used to assess cognitive enhancing activity. Animals were treated with an ethyl acetate soluble fraction of the methanol extract of H. sinensis (25, 50 and 100 mg/kg, p.o).

Results:

The ethyl acetate soluble fraction of the methanol extract of H. sinensis (EASF) attenuated amnesia induced by scopolamine and aging. The discrimination index (DI) was significantly decreased in the aged and scopolamine group in ORT. Pretreatment with EASF significantly increased the DI. In PAT, scopolamine-treated mice exhibited significantly shorter step-down latencies (SDL). EASF treatment showed a significant increase in SDL in young, aged as well as in scopolamine-treated animals. The biochemical analysis of brain revealed that scopolamine treatment increased lipid peroxidation and decreased levels of superoxide dismutase (SOD) and glutathione reductase (GSH). Administration of extract significantly reduced LPO and reversed the decrease in brain SOD and GSH levels. The administration of H. sinensis improved memory in amnesic mice and prevented the oxidative stress associated with scopolamine. The mechanism of such protection of H. sinensis may be due to augmentation of cellular antioxidants.

Conclusion:

The results of the present study suggested that H. sinensis had a protective role against age and scopolamine-induced amnesia, indicating its utility in management of cognitive disorders.     

康寿灵对东莨菪碱痴呆模型大鼠学习记忆的保护作用

目的：观察康寿灵对东莨菪碱诱导的记忆障碍大鼠学习记忆的影响，并探讨其可能的作用机制。方法：各组大鼠分别用生理盐水（正常对照组、模型组）、康寿灵（低、中、高剂量组）和石杉碱甲（阳性对照组）灌胃37d。第31天起进行Morris水迷宫行为测试，连续7d。行为测试结束后，进行大鼠脑组织丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）及ATPase活性测定。结果：预先给予大鼠康寿灵30d可改善东莨菪碱导致的记忆障碍，使大鼠脑组织中抗氧化酶SOD、GSH-Px及ATPase活性升高，而MDA含量降低。结论：康寿灵对东莨菪碱引起的大鼠学习记忆能力障碍有明显保护作用，其作用机制可能与抗氧化作用密切相关。     

Recent Insights into the Involvement of Progranulin in Frontotemporal Dementia

Progranulin is a widely expressed protein that is involved in the regulation of multiple biological processes, including embryogenesis, host defense, and wound repair. In the central nervous system, progranulin is constitutively expressed at modest levels in neurons and microglia, but shows dramatic microglial immunoreactivity in degenerative diseases that exhibit prominent neuroinflammation. In addition to the role that PGRN plays in the periphery, its expression is of critical importance in brain health, as demonstrated by recent discovery that progranulin haploinsufficiency results in familial frontotemporal lobar degeneration. Since progranulin deficiency was first described, there has been an intense ongoing effort to decipher the mysterious role that this protein plays in dementia. This review provides an update on our understanding of the possible neuronal function and discusses the challenging problems related to progranulin expression within genetics, cell biology, and neurodegeneration.     

In vivo investigation of the neuroprotective property of Convolvulus pluricaulis in scopolamine-induced cognitive impairments in Wistar rats

Aim:

To investigate the neuroprotective effect of Convolvulus pluricaulis aqueous extract (AE) against scopolamine (1 mg/kg body weight (bwt))-induced neurotoxicity in the cerebral cortex of male Wistar rats.

Materials and Methods:

The study was carried out on male Wistar rats (age matched, weight 250 ± 20 g). The present study investigated cognitive-enhancing property of AE using Elevated plus maze (EPM) (transfer latency [TL]) and Morris water maze (MWM). Besides evaluating the effect of extract on neurochemical enzymes, in vivo antioxidant and free radical scavenging activities were also screened. All the measured parameters were compared with rivastigmine tartrate (1 mg/kg bwt) which was taken as standard.

Results:

Pretreatment of rats with AE (150 mg/kg bwt) significantly reduced scopolamine-induced increase in the TL in EPM, whereas in MWM, administration of extract improved the impairment of spatial memory induced by scopolamine. The activity of acetylcholinesterase (AChE) was significantly inhibited by extract within the cortex and hippocampus. Reduced activities or contents of glutathione reductase, superoxide dismutase, and reduced glutathione within the cortex and hippocampus induced by scopolamine were elevated by the extract. Taken together, it could be postulated that extract may exert its potent-enhancing activity through both anti-AChE and antioxidant action.

Conclusion:

AE possesses neuroprotective potential, thus validating its use in alleviating toxic effects of scopolamine.     

Protective effect of Cnestis ferruginea and its active constituent on scopolamine-induced memory impairment in mice: A behavioral and biochemical study

Abstract

Context: Cnestis ferruginea Vahl ex DC (Connaraceae) (CF) is used in traditional African medicine in the management of CNS disorders. The degeneration and dysfunction of cholinergic neurons is closely associated with the cognitive deficits of Alzheimer’s disease (AD) and oxidative stress has been implicated in its pathogenesis. However, the influence of C. ferruginea on the cholinergic system and oxidative stress parameters has not been explored.

Objective: The present study investigates the effect of methanol root extract of C. ferruginea and its active constituent amentoflavone (CF-2) on memory, oxidative stress and acetylcholinesterase (AChE) activity in scopolamine-induced amnesia.

Materials and methods: Mice were orally treated with CF (25–200?mg/kg), CF-2 (6.25–25?mg/kg) for three days and memory impairment was induced by intraperitoneal injection of scopolamine (3?mg/kg). Memory function was evaluated by passive avoidance and Morris water maze tests. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain after the completion of behavioral studies.

Results: Scopolamine caused memory impairment along with increased AChE activity and oxidative stress in mice brain. Oral administration of CF and CF-2 significantly prevented scopolamine-induced memory impairment, inhibited AChE and enhanced antioxidant enzyme activity in the brain following scopolamine injection as compared to vehicle administration in scopolamine (i.p.)-treated mice that were comparable to the effect of tacrine.

Discussion and conclusion: The study demonstrated that C. ferruginea and its constituent have significant protective effect against scopolamine-induced memory deficits in mice that can be attributed to their antioxidant and antiAChE activity.     

Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia in rats

Amnesia can be induced in rats in the passive avoidance paradigm by administration of scopolamine, a central muscarinic receptor antagonist. Tacrine or galanthamine, inhibitors of acetylcholinesterase, given in conjunction with scopolamine partially reversed the scopolamine-induced deficit in passive avoidance performance. Four so-called cognitive enhancers, all widely used for the treatment of the symptoms associated with mental aging, cerebral insufficiency and senile memory disorder, were investigated in this paradigm. Piracetam, an extract of Ginkgo biloba, dihydroergocristine and a combination of raubasine with dihydroergocristine, all attenuated the amnesia induced by scopolamine. In contrast, nicergoline had no significant effect. Raubasine alone also failed to significantly attenuate scopolamine-induced amnesia, although some doses of raubasine had a non-significant tendency (P<0.10) to reduce the amnesia.     

A preliminary investigation of anticholinesterase activity of some Iranian medicinal plants commonly used in traditional medicine

Background

The aim of this study was to evaluate acetylcholinesterase inhibitory activity of some commonly used herbal medicine in Iran to introduce a new source for management of Alzheimer’s disease. A total of 18 aqueous-methanolic extract (1:1; v/v) from the following plants: Brassica alba, Brassica nigra, Camellia sinensis, Cinchona officinalis, Citrus aurantifolia, Citrus x aurantium, Ferula assafoetida, Humulus lupulus, Juglans regia, Juniperus sabina, Myristica fragrans, Pelargonium graveolens, Pistacia vera, Punica granatum, Rheum officinale, Rosa damascena, Salix alba, and Zizyphus vulgaris were prepared and screened for their acetylcholinesterase inhibitory activity using in vitro Ellman spectrophotometric method.

Results

According to the obtained results, the order of inhibitory activity (IC₅₀ values, μg /ml) of extracts from highest to the lowest was: C. sinensis (5.96), C. aurantifolia (19.57), Z. vulgaris (24.37), B. nigra (84.30) and R. damascena (93.1).

Conclusions

The results indicated and confirmed the traditional use of these herbs for management of central nervous system disorders. C. sinensis showed the highest activity in inhibition of acetylcholinesterase. However, further investigations on identification of active components in the extracts are needed.     

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。     

Differential effects of the neuropeptide galanin on striatal acetylcholine release in anaesthetized and awake rats

1. In the present study the mechanisms were examined by which the neuropeptide galanin modulates the extracellular concentrations of striatal acetylcholine (ACh) in enflurane anaesthetized and in freely moving male rats by use of in vivo microdialysis and high performance liquid chromatography.
2. The perfusion of galanin through the microdialysis probe (0.3 nmol μl⁻¹, flow rate: 2 μl min⁻¹) caused a statistically significant increase in the basal striatal ACh levels in anaesthetized but a decrease in awake animals. No significant effect was revealed after a low dose (0.1 nmol μl⁻¹, flow rate: 2 μl min⁻¹) of galanin perfusion. Both the stimulating and inhibitory effects of galanin on basal ACh release were reversible.
3. The muscarinic antagonist scopolamine (0.1 mg kg⁻¹, subcutaneously (s.c.)) caused a significant increase in ACh release in both anaesthetized and awake animals.
4. The combination of galanin plus scopolamine attenuated the stimulant effect on ACh release caused by scopolamine alone in awake animals.
5. The putative galanin receptor antagonist M35 at 0.3 nmol μl⁻¹ but not at 0.1 nmol μl⁻¹ caused a significant reduction (20%) in ACh release, supporting the view that M35 at higher concentrations behaves as a partial agonist at the galanin receptor. When M35 (0.1 nmol μl⁻¹) was co-infused with galanin (0.3 nmol μl⁻¹) the galanin-evoked decrease in ACh release was completely blocked.
6. Taken together, these results indicate that galanin affects basal ACh release via stimulation of galanin receptors within the striatum. The mechanism involved is dependent on the anaesthesia procedure which may act via enhancement of γ-aminobutyric acid_A (GABA_A) mediated transmission within striatal and/or output neurones. In addition, anaesthesia may also decrease the activity of glutamatergic striatal afferents. The results with M35 indicate that the role of galanin perfused in striatum is permissive in the normal rat. Furthermore, galanin is a potent inhibitory modulator of basal ACh release also in the striatum, as recently was shown in the ventral hippocampus in awake animals.

     

Coadministration of huperzine A and ligustrazine phosphate effectively reverses scopolamine-induced amnesia in rats

In the present study, whether coadministration of huperzine A (HA) and ligustrazine phosphate (LP) could effectively improve the memory deficits in association with ameliorating cholinergic impairment and oxidative stress in the scopolamine-induced amnesia rats was assessed. The effects of treatment with Coa [HA (0.14 mg/kg, i.g.) and LP (110 mg/kg, i.g.)] on amnesia were investigated in Morris water maze. Furthermore, the effects on the activities of acetylcholinesterase (AChE) and antioxidant enzymes within the cerebral cortex and hippocampus were evaluated, and the lipid peroxidation product malondialdehyde (MDA) was also analyzed. As a result, coadministration of HA and LP for 10 consecutive days could markedly reverse the scopolamine-induced learning and memory impairment determined by the Morris water maze test. Moreover, AChE activity was significantly inhibited, and superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities were significantly increased with a remarkable reduction in the level of MDA. In conclusion, coadministration of HA and LP effectively prevented cholinergic impairment and oxidative damage, thereby resulting in improvement of spatial learning memory in rats induced by scopolamine. The results suggested that coadministration of HA and LP might offer a novel poly-therapeutic drug regimen for preventing Alzheimer's disease (AD).     

Donepezil in Alzheimer's disease: an evidence-based review of its impact on clinical and economic outcomes

INTRODUCTION: Donepezil is indicated for the symptomatic treatment of mild to moderate Alzheimer's disease. It is a specific and reversible inhibitor of acetylcholinesterase (AChE); by increasing levels of available acetylcholine, donepezil may compensate for the loss of functioning cholinergic brain cells. AIMS: This review evaluates the clinical impact of donepezil by assessing randomized controlled and open-label naturalistic trials, as well as observational studies. A broad perspective is gained of its effectiveness on various outcomes. EVIDENCE REVIEW: There is strong evidence that donepezil has efficacy against the three major domains of Alzheimer's disease symptoms, namely functional ability, behavior, and cognition. The strongest evidence is for improvement or less deterioration in global outcomes and cognition in the short to medium term. There is limited evidence that improved global outcomes are maintained in the long term and clear evidence to support long-term maintenance of cognitive benefits. Also, donepezil appears to maintain function in the long term and there is some level 1 and 2 evidence of improved or limited deterioration in behavior or mood in the short to medium term. Despite donepezil's effects on major symptoms of Alzheimer's disease, its impact on patients' quality of life has not been consistently demonstrated, perhaps reflecting the difficulty of assessing this aspect in this patient population. Donepezil may also lessen caregiver burden. Donepezil has some effect on markers of brain function, but more data are needed to confirm a neuroprotective effect. There is limited and conflicting evidence that long-term donepezil treatment delays time to institutionalization. There is some evidence that donepezil may be cost effective, especially when unpaid caregiver costs are considered. Donepezil is generally safe and well tolerated. CLINICAL VALUE: AChE inhibitors are the only agents recommended for the treatment of cognitive decline in patients with mild to moderate Alzheimer's disease. Donepezil is more effective than placebo and is well tolerated in improving the major symptoms of this disease. Improvements are usually modest, although stabilization of cognitive and functional symptoms with donepezil can also be considered an important clinical outcome. Donepezil may lessen caregiver burden. Donepezil may also be cost effective, especially when unpaid caregiver costs are considered. More data are required from randomized controlled trials with long-term follow-up to confirm its cost effectiveness and impact on quality of life, disease progression, and time to institutionalization.     

Improved metabolic status and insulin sensitivity in obese fatty (fa/fa) Zucker rats and Zucker Diabetic Fatty (ZDF) rats treated with the thiazolidinedione,MCC-555

1. We examined the effect of chronic (21 days) oral treatment with the thiazolidinedione, MCC-555 ((±)-5-[{6-(2-fluorbenzyl)-oxy-2-naphy}methyl]-2,4-thiazolidinedione) on metabolic status and insulin sensitivity in obese (fa/fa) Zucker rats and Zucker Diabetic Fatty (ZDF) rats which display an impaired glucose tolerance (IGT) or overt diabetic symptoms, respectively.
2. MCC-555 treatment to obese Zucker rats (10 and 30 mg kg⁻¹) and diabetic ZDF rats (10 mg kg⁻¹) reduced non-esterified fatty acid concentrations in both rat strains and reduced plasma glucose and triglyceride concentrations in the obese Zucker rats. Liver glycogen concentrations were significantly increased by chronic MCC-555 treatment in both obese Zucker rats (30 mg kg⁻¹ day⁻¹) and diabetic ZDF rats (10 mg kg⁻¹ day⁻¹), as compared with vehicle-treated lean and obese rats and there was a significant increase in hepatic glycogen synthase activity in MCC-555-treated diabetic ZDF rats as compared to vehicle-treated controls.
3. During a euglycaemic hyperinsulinaemic clamp, MCC-555-treated obese Zucker rats and diabetic ZDF rats required significantly higher glucose infusion rates to maintain stable glucose concentrations (2.01±0.19 mg min⁻¹ and 6.42±1.03 mg min⁻¹, respectively) than vehicle-treated obese controls (0.71±0.17 mg min⁻¹ and 2.09±0.71 mg min⁻¹; P<0.05), demonstrating improved insulin sensitivity in both Zucker and ZDF rats. MCC-555 treatment also enhanced insulin-induced suppression of hepatic glucose production in ZDF rats as measured using infusions of [6-³H]-glucose under clamp conditions.
4. In conclusion, we have demonstrated that MCC-555 improves metabolic status and insulin sensitivity in obese Zucker and diabetic ZDF rats. MCC-555 may prove a useful compound for alleviating the metabolic disturbances and IGT associated with insulin resistance in man.

     

Meserine对胆碱酯酶活性及东莨菪碱诱导痴呆小鼠学习记忆的影响

目的：考察新型胆碱酯酶抑制剂Meserine对胆碱酯酶活性及东莨菪碱（Scopolamine）诱导的胆碱能障碍痴呆模型小鼠学习记忆的影响。方法：选取小鼠脑匀浆、血浆、人源重组AChE（rHuAChE）为体外酶源,测定Meserine抑制AChE／BuChE的活性、选择性及酶动力学。通过鼻腔给药后检测脑部AChE活性和ACh浓度评价Meserine对小鼠脑内胆碱能系统的调节。选用避暗及水迷宫实验考察Meserine对痴呆模型小鼠学习记忆功能的影响。结果：Meserine对AChE和BuChE都具有较好的抑制活性,IC50分别为（65．2±3．2）nmol／L和（86．7±4．9）nmol／L,并对rHuAChE呈现非竞争性抑制。经鼻给药Meserine可显著抑制脑内AChE活性、升高ACh水平,且二者变化的时程具有一致性,给药15min后,AChE抑制活性最强（26．9％）,ACh浓度最高（1269．0ng／g）。行为学实验结果显示,经鼻给药Meserine（10μg／kg）能显著改善东莨菪碱诱导的痴呆模型小鼠的工作记忆及空间学习能力,较模型组具有统计学差异（P〈0．OlVS东莨菪碱组）。结论：上述结果提示Meserine为强效非竞争性胆碱酯酶抑制剂,经鼻给药Meserine可通过调节脑内胆碱能系统有效改善东莨菪碱诱导的痴呆模型小鼠的学习记忆功能。     

Antidiabetic activity of Cassia occidentalis (Linn) in normal and alloxan-induced diabetic rats

Objective:

To evaluate the hypoglycemic activity of various extracts, petroleum ether, chloroform and aqueous extract of Cassia occidentalis in normal and alloxan-induced diabetic rats.

Materials and Methods:

Petroleum ether, chloroform and aqueous extract of whole plant of Cassia occidentalis were orally tested at the dose of 200 mg/kg for hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, changes in body weight, serum cholesterol, triglyceride and total protein levels, assessed in the ethanol extract-treated diabetic rats, were compared with diabetic control and normal animals. Histopathological observations during 21 days treatment were also evaluated.

Results:

Aqueous extract of C. occidentalis produced a significant reduction in fasting blood glucose levels in the normal and alloxan-induced diabetic rats. Apart from aqueous extract, petroleum ether extract showed activity from day 14 and chloroform extract showed activity from 7 days. Significant differences were observed in serum lipid profiles (cholesterol and triglyceride), serum protein, and changes in body weight by aqueous extract treated-diabetic animals, when compared with the diabetic control and normal animals. Concurrent histopathological studies of the pancreas of these animals showed comparable regeneration by extract which were earlier necrosed by alloxan.

Conclusion:

Aqueous extract of C. occidentalis exhibited significant antihyperglycemic activity in normal and alloxan-induced diabetic rats. They also showed improvement in parameters like body weight and serum lipid profiles as well as histopathological studies showed regeneration of β-cells of pancreas and so might be of value in diabetes treatment.     

Removal of Toxin (Tetrodotoxin) from Puffer Ovary by Traditional Fermentation

The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented “Nukazuke” and “Kasuzuke” ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (I_Na) recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in “Nukazuke” and “Kasuzuke” ovaries decreased to 1/50–1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes” fresh muscle that is normally eaten. It was concluded that the fermented “Nukazuke” and “Kasuzuke” ovaries of puffer fish T. Stictonotus are safe and harmless as food.     

Neuroprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) in CNS Disorders: Mechanistic and Therapeutic Insights

Neurological disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), epilepsy, traumatic brain injury (TBI), depression, and anxiety are responsible for thousands of deaths worldwide every year. With the increase in life expectancy, there has been a rise in the prevalence of these disorders. Age is one of the major risk factors for these neurological disorders, and with the aged population set to rise to 1.25 billion by 2050, there is a growing concern to look for new therapeutic molecules to treat age-related diseases. Caffeic acid phenethyl ester (CAPE) is a molecule obtained from a number of botanical sources, such as the bark of conifer trees as well as propolis which is extracted from beehives. Though CAPE remains relatively unexplored in human trials, it possesses antioxidant, anti-inflammatory, antimitogenic, and anti-cancer activities, as shown by preclinical studies. Apart from this, it also exhibits tremendous potential for the treatment of neurological disorders through the modulation of multiple molecular pathways and attenuation of behavioural deficits. In the present article, we have reviewed the therapeutic potential of CAPE and its mechanisms in the treatment of neurological disorders.     

Antiovulatory and abortifacient effects of Areca catechu (betel nut) in female rats

Objectives:

To study the antiovulatory and abortifacient effects of ethanolic extract of Areca catechu in female rats.

Materials and Methods:

For antiovulatory effect, ethanolic extract of A. catechu at 100 and 300 mg/kg doses was administered orally for 15 days. Vaginal smears were examined daily microscopically for estrus cycle. Rats were sacrificed on 16^th day. Ovarian weight, cholesterol estimation, and histopathological studies were done. Abortifacient activity was studied in rats at 100 and 300 mg/kg doses administered orally from 6^th to 15^th day of pregnancy. Rats were laparotomised on 19^th day. The number of implantation sites and live fetuses were observed in both horns of the uterus.

Results:

The extract of A. catechu showed a significant decrease in the duration of estrus at 100 mg/kg (P = 0.015) and 300 mg/kg doses (P = 0.002) as compared with control. Metestrus phase was also significantly reduced at 100 mg/kg (P = 0.024) and 300 mg/kg doses (P = 0.002). There was a significant increase in proestrus (P < 0.001) phase. However, diestrus phase was unchanged. Histopathological study of the ovaries showed mainly primordial, primary, and secondary follicles in the test groups as compared to control. There was also a significant (P = 0.002) decrease in ovarian weight and a significant (P = 0.021) increase in ovarian cholesterol level at 100 mg/kg dose. In the study to evaluate abortifacient effect, the mean percentage of abortion with 100 and 300 mg/kg doses were 75.5% and 72.22%, respectively, which was significantly (P = 0.008 and P = 0.006, respectively) increased when compared with control.

Conclusion:

The ethanolic extract of A. catechu at doses of 100 and 300 mg/kg has antiovulatory and abortifacient effects.     

Aqueous and hydroalcoholic extracts of Black Maca (Lepidium meyenii) improve scopolamine-induced memory impairment in mice.

Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4,000 and 4,500 m altitude in the central Peruvian Andes, particularly in Junin plateau. Previously, Black variety of Maca showed to be more beneficial than other varieties of Maca on learning and memory in ovariectomized mice on the water finding test. The present study aimed to test two different doses of aqueous (0.50 and 2.00 g/kg) and hydroalcoholic (0.25 and 1.00 g/kg) extracts of Black Maca administered for 35 days on memory impairment induced by scopolamine (1mg/kg body weight i.p.) in male mice. Memory and learning were evaluated using the water Morris maze and the step-down avoidance test. Brain acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities in brain were also determined. Both extracts of Black Maca significantly ameliorated the scopolamine-induced memory impairment as measured in both the water Morris maze and the step-down avoidance tests. Black Maca extracts inhibited AChE activity, whereas MAO activity was not affected. These results indicate that Black Maca improves scopolamine-induced memory deficits.     

Peptidase activities in rats treated chronically with N(omega)-nitro-L-arginine methyl ester (L-NAME)

The chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension. This inhibition of NO production results in activation of the renin-angiotensin system, with increased activity of the carboxypeptidase angiotensin I-converting enzyme (ACE). Since chronic NO inhibition increases ACE activity, we hypothesized that this inhibition could also affect the activities of other peptidases involved in cardiovascular functions. To test this possibility, we examined the activities of aminopeptidase M (APM), dipeptidyl peptidase IV (DPP IV), metalloendopeptidase 24.15 (MEP 24.15) and neutral endopeptidase 24.11 (NEP 24.11) in rat brain, heart, kidney, liver, lung and thoracic aorta. Male Wistar rats were treated chronically with L-NAME (80mgkg(-1) per day) administered in the drinking water for 4 weeks and their organs then removed and processed for the determination of peptidase activities. Treatment with L-NAME did not significantly alter the activities of the four peptidases in brain, heart, kidney, liver and lung. In contrast, in aorta, the activity of APM was slightly but significantly reduced whereas those of DPP IV and MEP 24.15 were markedly enhanced; NEP 24.11 was not detected in this tissue. Immunoblotting for DPP IV and MEP 24.15 showed increased expression in aortic tissue. Neither L-NAME (1-100microM) nor the NO donors sodium nitroprusside and 3-morpholinosydnonimine (SIN-1; 1-100microM) had any consistent effect on the activity of recombinant MEP 24.15 or renal DPP IV. The importance of MEP 24.15 in peptide metabolism was confirmed in pentobartibal-anesthetized rats pretreated with the MEP 24.15 inhibitor N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA2), which significantly potentiated the hypotensive response to bradykinin. The altered peptidase activities seen in aorta may contribute to modulating vascular responses in this model of hypertension.     

C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside

Neurodegenerative diseases are characterized by the increasing dysfunction and death of neurons, resulting in progressive impairment of a person’s mobility and/or cognition. Protein misfolding and aggregation are commonly hypothesized to cause neurotoxicity and, eventually, neuronal degeneration that are associated with these diseases. Emerging experimental evidence, as well as recent findings from human studies, reveal that the C-terminus of Hsp70 Interacting Protein (CHIP), or STIP1 Homology and U-box containing Protein 1 (STUB1), is a quality control protein involved in neurodegeneration. Here, we review evidence that CHIP interacts with and plays a role in regulating proteins implicated in the pathogenesis of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and polyglutamine diseases, including Huntington’s disease and spinocerebellar ataxias. We also review clinical findings identifying mutations in STUB1 as a cause of both autosomal recessive and autosomal dominant forms of cerebellar ataxia. We propose that CHIP modulation may have therapeutic potential for the treatment of multiple neurodegenerative diseases.