scholarly journals The ApoE-dependent Neuroprotective Effects of Sesamol on Diet-induced Obese Mice: The Role of Gut Microbiota and SCFAs (P06-049-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tian Yuan ◽  
Zhigang Liu ◽  
Xuebo Liu

Abstract Objectives Sesamol, an antioxidant lignan from sesame oil, possesses lipid lowering and neuroprotective bioactivities. Considering the distribution of sesamol in gut is much higher than brain after administration, the present work was aimed to elucidate the systemic protective effects of sesamol on dietary-induced cognitive deficits, and to determine the possible link between gut and brain. Methods Both wildtype and ApoE-/- mice were fed with high-fat diet (HFD) and treated with sesamol (0.05%, w/v) in drinking water for 10 weeks. The cognitive and anxiety behavioral assessment were evaluated by Morris-water maze, Y-maze, and elevated plus maze tests. The synapse ultrastructure was also detected by transmission electron microscope. Moreover, the alteration of gut microbiome and microbial metabolites short chain fatty acids (SCFAs) were also determined by 16S rDNA sequencing and GC, respectively. Results Sesamol prevented HFD-induced bodyweight gain, insulin resistance, and hyperlipidemia. However, the behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype but not ApoE deficient mice. Consistently, sesamol improved synapse ultrastructure and inhibited brain Aβ accumulation in brain in an ApoE-dependent manner. Moreover, sesamol prevented HFD-induced gut barrier damages and systemic inflammation. Sesamol also re-shaped gut microbiome and consequently improved the generation of microbial metabolites short chain fatty acids including acetate, propionate, and butyrate. Conclusions To summarized, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and the beneficial effects of sesamol on gut microbiota/metabolites could be translated into metabolic and neurodegenerative diseases treatment. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China. Supporting Tables, Images and/or Graphs

Author(s):  
Suwathi Ravichandar ◽  
K.A.S. Mohammed Shafeeq ◽  
S. Karpagam Kumara Sundari ◽  
R. Senthamarai

In traditional system of medicine, various parts of Delonix regia have been used for many ailments. The objective of the present study was to evaluate the memory enhancing activity of Ethanolic Extract of Delonix regia leaves (EEDRL) against scopolamine induced amnesia by using Elevated Plus Maze, Y Maze and Morris Water Maze Models. Ethanolic Extract of Delonix regia was prepared then subjected to phytochemical analysis revealed the presence of flavonoids, alkaloids, carbohydrates, tannins, steroids, terpenoids, phenols and saponins. Acute oral toxicity was performed as per OECD guidelines 423. Based on this, two dose levels of EEDRL were chosen as 200 mg/kg and 400 mg/kg for pharmacological screening. Swiss albino mice were divided into five groups of six animals each. EEDRL at a dose levels 200 mg/kg & 400 mg/kg showed increase in inflexion ratio in Elevated Plus Maze, increase in Percentage alterations in Y Maze & decrease in Escape latency in Morris Water Maze Model compared to disease control in dose dependent manner which indicates that the EEDRL reverses the scopolamine induced amnesia in mice. The memory enhancing activity in mice might be due to facilitation of cholinergic transmission. Hence it can be concluded that Delonix regia appears to be a promising candidate for improving memory, and it would be worthwhile to explore the potential of this plant in the management of Alzheimer patient.


Medicina ◽  
2020 ◽  
Vol 56 (3) ◽  
pp. 144
Author(s):  
Humna Malik ◽  
Sana Javaid ◽  
Muhammad Fawad Rasool ◽  
Noreen Samad ◽  
Syed Rizwan Ahamad ◽  
...  

Background and Objectives: Ficus benghalensis (FB) is a commonly found tree in Pakistan and its various parts have folkloric importance in managing neurological ailments. In the present study, methanolic extract of its bark has been tested on an experimental animal model to evaluate memory-enhancing, anxiolytic and antidepressant activities to validate the claimed therapeutic potential. Materials and Methods: Methanolic extract of freshly isolated bark was prepared and subjected to preliminary phytochemical studies and gas chromatography–mass spectrometry (GC–MS) analysis for the presence of phytocomponents. To evaluate its effect on spatial learning, passive-avoidance test–step through (PAT-ST), Y-maze and Morris water maze (MWM) tests were carried out. Open-field (OFT) and elevated plus maze (EPM) tests were employed to explore the anti-anxiety potential of FB while a forced swimming test (FST) was utilized to assess its anti-depressant prospective. FB doses of 100, 200 and 300 mg/kg with positive and negative controls given to Sprague Dawley (SD) rats. Results: phytochemical studies showed the presence of various phytoconstituents including alkaloids, flavonoids, terpenes, phenolics and anthraquinones. The presence of synephrine, aspargine, glucose, fructose and fatty acids was revealed by GC–MS analysis. FB administration led to significant improved memory retention when evaluated through passive avoidance (p < 0.05), Y-maze (p < 0.05) and Morris water maze (p < 0.05) tests in a scopolamine model of amnesic rats. When tested by open field and elevated plus maze tests, FB demonstrated anxiety-resolving characteristics (p < 0.05) as animals dared to stay in open areas more than a control group. Mobility time was increased and immobility time was reduced (p < 0.05–0.01) in rats treated with FB, unveiling the anti-depressant importance of F. benghalensis. Conclusion: methanolic extract of F. benghalensis bark furnished scientific proof behind folkloric claims of the memory improving, anxiety-reducing and depression-resolving characteristics of the plant. These activities might be possible due to interaction of its phytoconstituents with serotonergic, glutamatergic, cholinergic and GABAergic systems in the brain.


Drug Research ◽  
2017 ◽  
Vol 67 (07) ◽  
pp. 425-431 ◽  
Author(s):  
Nitin Bansal ◽  
Pushplata Yadav ◽  
Manish Kumar

AbstractRampant production of pro-oxidants and inadequate antioxidant availability in brain exert oxidative stress, which in synergism with impaired glucose metabolism and inflammation leads to neurodegeneration and cognitive deficits. Ellagic acid (EGA) is a phenolic compound present in various fruits and is reported to possess robust antioxidant and anti-inflammatory properties. The present study investigated the effect of EGA administration on streptozotocin (STZ) induced dementia in rats. Bilateral intracerebroventricle (ICV) injection of STZ (3 mg/kg) was given to Wistar rats (200 g) on day 1 and 3. EGA (17.5 and 35 mg/kg) was administered orally to rats for 28 days daily. The spatial memory of rats was quantified by using Morris water maze and elevated plus maze. Brain TBARS, GSH and TNF-α were also measured. Administration of EGA prevented the induction of STZ-ICV triggered cognitive deficits as evident by a significant (p<0.05) reduction in mean escape latency during acquisition trial and increased (p<0.05) time spent in target quadrant during retrieval trial in Morris water maze test, and reduction (p<0.05) in transfer latency in elevated plus maze test. Furthermore, both the doses of EGA attenuated STZ-ICV induced rise in brain TBARS as well as TNF-α and simultaneously enhanced the GSH content. Thus, EGA ameliorated STZ-induced dementia by probably restoring the balance between cellular pro-oxidants and anti-oxidants in brain of rats.


2020 ◽  
Vol 16 ◽  
Author(s):  
Dang Kim Thu ◽  
Dao Thi Vui ◽  
Nguyen Thi Ngoc Huyen ◽  
Nguyen Thi Thanh Binh ◽  
Nguyen Thi Huyen ◽  
...  

Background: Huperzia phlegmaria has been used for the treatment of neurological disorder. Alkaloids are main bioactive compounds found in Huperzia phlegmaria. We aimed to investigate the acetylcholinesterase (AChE) inhibitory activity in vitro of Huperzia phlegmaria alkaloid extract (HpAE) and protective effects on mice which were induced cognitive deficits by scopolamine. Methods: AChE inhibitory activity and kinetic inhibition mechanism was investigated by Ellman's assay. Mice were administrated orally HpAE (30 mg/kg and 60 mg/kg) for fourteen days, and injected scopolamine at a dose of 1 mg/kg intraperitoneally for four days to induce cognitive impairment. The Y-maze and the Morris water maze were used for evaluating the memory behaviors. Acetylcholine (ACh) levels and AChE activity were measured in brain tissue. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, and malondialdehyde (MDA) groups were also evaluated in the mouse brain tissues. Results: Our data showed that HpAE had the strong AChE inhibitory activity with an IC50 value of 5.12 ± 0.48 μg/mL in a concentration-dependent manner. Kinetic inhibition analysis demonstrated that HpPAE inhibited AChE followed the mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 4.37 ± 0.35 µg/mL. Scopolamine induced the cognitive impairment in Morris Water Maze and Y-maze test along with reduced brain levels of ACh and antioxidant enzyme and increased AChE activity in mouse brain tissues. Treatment with HpAE at both dose (30 mg/kg and 60 mg/kg) decreased the SCP-induced cognitive impairment in both behavioral tests along with decreased acetylcholinesterase activity and MDA level, and increased ACh level and antioxidant enzyme in mouse brain tissues. Conclusion: Our results suggested that the HpAE at both dose (30 mg/kg and 60 mg/kg) may be used for prevent and treatment of Alzheimer’s disease.


Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2036 ◽  
Author(s):  
Kaichi Yoshizaki ◽  
Masato Asai ◽  
Taichi Hara

Obesity is characterized by massive adipose tissue accumulation and is associated with psychiatric disorders and cognitive impairment in human and animal models. However, it is unclear whether high-fat diet (HFD)-induced obesity presents a risk of psychiatric disorders and cognitive impairment. To examine this question, we conducted systematic behavioral analyses in C57BL/6J mice (male, 8-week-old) fed an HFD for 7 weeks. C57BL/6J mice fed an HFD showed significantly increased body weight, hyperlocomotion in the open-field test (OFT) and Y-maze test (YMZT), and impaired sucrose preference in the sucrose consumption test, compared to mice fed a normal diet. Neither body weight nor body weight gain was associated with any of the behavioral traits we examined. Working memory, as assessed by the YMZT, and anxiety-like behavior, as assessed by the elevated plus maze test (EPMT), were significantly correlated with mice fed an HFD, although these behavioral traits did not affect the entire group. These results suggest that HFD-induced obesity does not induce neuropsychiatric symptoms in C57BL/6J mice. Rather, HFD improved working memory in C57BL/6J mice with less anxiety, indicating that an HFD might be beneficial under limited conditions. Correlation analysis of individual traits is a useful tool to determine those conditions.


2019 ◽  
Vol 10 (12) ◽  
pp. 7973-7982 ◽  
Author(s):  
Yi Wan ◽  
Wenfeng Tong ◽  
Renke Zhou ◽  
Jie Li ◽  
Jihong Yuan ◽  
...  

A diet with higher animal-based fat consumption is likely to be associated with moderately unfavorable impacts on gut microbial diversity, community, and regulation of fecal short-chain fatty acids.


Author(s):  
Pratap Kumar Sahu ◽  
Mishra Sk ◽  
Rout K ◽  
Prusty Sk

<p>ABSTRACT<br />Objective: To evaluate the nootropic activity of methanolic extract of pre-shodhit and shodhit Semecarpus anacardium (SA) nuts and to observe the<br />effect of shodhana on nootropic activity of SA.<br />Methods: Spatial learning and working memory was considered for evaluation. The parameters used were spontaneous alternation behavior<br />(Y-maze), number of correct responses (radial maze), and transfer latency in day 1 (elevated plus maze). Scopolamine, an anticholinergic drug, was<br />used to induce cognitive deficit. % inhibition of acetylcholine esterase (AChE) was measured in vitro.<br />Results: Both pre-shodhit and shodhit drug reversed the scopolamine-induced a decrease in percentage spontaneous alternation behavior in Y-maze<br />and number of correct responses in radial maze. Scopolamine-induced increase in transfer latency in elevated plus maze was significantly decreased<br />by pre-shodhit drug only. Shodhit drug has no significant effect on transfer latency. Both pre-shodhit and shodhit drug showed dose-dependent<br />inhibition of AChE activity in vitro. Pre-shodhit drug showed a more nootropic activity than shodhit drug.<br />Conclusion: Methanolic extract of the nuts of S. anacardium possesses nootropic activity which may be attributed to inhibition of cholinesterase<br />activity. Shodhana of the nuts decreases nootropic activity.<br />Keywords: Semecarpus anacardium, Acetylcholine esterase, Shodhana, Nootropic.</p>


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