Pharmacological investigations on efficacy of Phlorizin a sodium-glucose co-transporter (SGLT) inhibitor in mouse model of intracerebroventricular streptozotocin induced dementia of AD type

Author(s):  
Reena Rani ◽  
Amit Kumar ◽  
Amteshwar Singh Jaggi ◽  
Nirmal Singh

Abstract Objectives The study has been commenced to discover the potential of Phlorizin (dual SGLT inhibitor) in streptozotocin induced dementia of Alzheimer’s disease (AD) type. Material and methods Injection of Streptozotocin (STZ) was given via i.c.v. route (3 mg/kg) to induce dementia of Alzheimer’s type. In these animals learning and memory was evaluated using Morris water maze (MWM) test. Glutathione (GSH) and thiobarbituric acid reactive species (TBARS) level was quantified to evaluate the oxidative stress; cholinergic activity of brain was estimated in term of acetylcholinesterase (AChE) activity; and the levels of myeloperoxidase (MPO) were measured as inflammation marker. Results The mice model had decreased performance in MWM, representing impairment of cognitive functions. Biochemical evaluation showed rise in TBARS level, MPO and AChE activity, and fall in GSH level. The histopathological study revealed severe infiltration of neutrophils. In the study, Phlorizin/Donepezil (serving as positive control) treatment mitigate streptozotocin induced cognitive decline, histopathological changes and biochemical alterations. Conclusions The results suggest that Phlorizin decreased cognitive function via its anticholinesterase, antioxidative, antiinflammatory effects and probably through SGLT inhibitory action. It can be conferred that SGLTs can be an encouraging target for the treatment of dementia of AD.

2010 ◽  
Vol 103 (11) ◽  
pp. 1573-1576 ◽  
Author(s):  
Jun Lu ◽  
Di-Feng Ren ◽  
Jian-Zhong Wang ◽  
Hiroo Sanada ◽  
Yukari Egashira

Increasing attention has been paid to Spirulina for its potential clinical uses. The present study investigated the protection by dietary Spirulina platensis against d-galactosamine (d-GalN)- and acetaminophen (APAP)-induced hepatitis in ICR mice. Mice in each group (n 6) were fed with a standard diet (American Institute of Nutrition (AIN)-93G), a positive control diet containing 0·5 % butylated hydroxytoluene (BHT), or a diet containing 3, 6 or 9 % S. platensis for 1 week. On the last day the mice were treated with d-GalN (300 mg/kg body weight, intraperitoneally) or APAP (150 mg/kg body weight, intraperitoneally) and 24 h later the mice were killed. The doses of both 6 and 9 % S. platensis were found to significantly alleviate the increase of serum glutamate oxaloacetoacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities in d-GalN- or APAP-intoxicated mice. The observation was very similar to that of the positive control groups. Two more experiments were carried out to investigate the involvement of thiobarbituric acid-reactive substances (TBARS) and IL-18 in the suppression of 6 % S. platensis on d-GalN- and APAP-induced hepatitis. The significant increase of GOT and GPT activities was found to be accompanied with the elevation of hepatic TBARS level, IL-18 mRNA expression and serum IL-18 concentration, and was significantly alleviated by supplementation with 6 % S. platensis in diets. These results showed that dietary S. platensis could provide a significant protection against d-GalN- and APAP-induced liver injuries, and IL-18 and lipid peroxidation might be involved in the protective influence of S. platensis.


2020 ◽  
Vol 9 (1) ◽  
pp. 43-57
Author(s):  
Jasleen Kaur ◽  
Manish Kumar ◽  
Nitin Bansal

Background: Holarrhena antidysenterica is a deciduous shrub/small-tree having bioactive alkaloids such as conessine, known for astringent, antidysenteric, anthelmintic, stomachic, febrifugal, tonic and anti-acetylcholinesterase properties. Dementia is an age related neurodegenerative syndrome with Alzheimer’s disease, the most prominent cause, which has limited therapeutic options available. Objective: The present study aimed to explore the potential benefits of H. antidysenterica in the management of dementia. Method: Aqueous and methanol extracts of powdered bark of H. antidysenterica were prepared, concentrated and conessine concentration was estimated using High Performance Thin Layer Chromatography (HPTLC) method. Methanol extract of H. antidysenterica (MEHA) was administered at doses 100, 150 and 200 mg/kg (i.p.) to mice (20-30 g) for 14 consecutive days. Scopolamine (Scop; 1 mg/kg) and Lipopolysaccharide (LPS; 250 μg/kg) were given (i.p.) before behavioural trials to induce memory impairment. Learning and memory functions in mice were evaluated. Brain acetylcholinesterase (AChE) activity, glutathione (GSH) and Thiobarbituric Acid Reactive substances (TBARS) levels were estimated. Results: MEHA markedly increased learning and memory of mice. Scop or LPS caused a significant decline of spatial memory in mice, which was attenuated by MEHA (100 and 200 mg/kg). Furthermore, LPS conspicuously increased the lipid peroxidation and compromised antioxidant levels in mice brains. MEHA pre-treatment significantly increased GSH content and decreased TBARS level in the brain of LPS administered mice. AChE activity was significantly decreased by MEHA in the brain of mice. Conclusion: The methanol extract of H. antidysenterica may prove to be a useful remedy in the management of dementia.


Author(s):  
CHITRA V ◽  
MANASA K ◽  
EVELYN SHARON S ◽  
SHATABDI CHOUDHURY

Objective: The objective of this study was to evaluate the protective effect of Hemidesmus indicus against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model. Methods: A total of 18 male Swiss Albino mice were divided into three groups (n=6). Hydroalcoholic concentrate of H. indicus (HAHI) at 200 and 400 mg/kg dosages, 30 min before the MPTP (20 mg/kg, intraperitoneal organization) treatment, was regulated for 7 days, and behavioral assessment was made by rotarod test, grip strength test, locomotor activity, and catatonia behavioral study. Appraisal of cell reinforcement catalysts, such as thiobarbituric acid reactive substance (TBARS), superoxide dismutase, catalepsy, glutathione (GSH) peroxidase, and GSH, were also assessed to screen the neurotoxicity incited by MPTP. Results: In the present investigation, the neuroprotective impacts of the hydroalcoholic concentrate of H. indicus were assessed, Which is known for its monoamine oxidiase activity, stimulant, anti-convulsant activity and a section of it is used as nerve tonic Frozen at 8 degree C. The cell viability analysis and IC50 determination in SH-SY5Y neuroblastoma cell lines were performed by MTT assay, and neuronal red uptake assay and HAHI were found to have a significant IC50 value in SH-SY5Y cells. Conclusion: The outcomes demonstrated that HAHI essentially enhanced the behavioral studies, striatal neurotransmitter content, and antioxidant status in a dose-dependent manner lessened TBARS level.


2011 ◽  
Vol 14 (3) ◽  
pp. 443-448 ◽  
Author(s):  
N. Kurhalyuk ◽  
H. Tkachenko ◽  
K. Pałczyńska

Resistance of erythrocytes from Brown trout (Salmo trutta m. trutta L.) affected by ulcerative dermal necrosis syndrome In the present work we evaluated the effect of ulcerative dermal necrosis (UDN) syndrome on resistance of erythrocytes to haemolytic agents and lipid peroxidation level in the blood from brown trout (Salmo trutta m. trutta L.). Results showed that lipid peroxidation increased in erythrocytes, as evidenced by high thiobarbituric acid reactive substance (TBARS) levels. Compared to control group, the resistance of erythrocytes to haemolytic agents was significantly lower in UDN-positive fish. Besides, UDN increased the percent of hemolysated erythrocytes subjected to the hydrochloric acid, urea and hydrogen peroxide. Results showed that UDN led to an oxidative stress in erythrocytes able to induce enhanced lipid peroxidation level, as suggested by TBARS level and decrease of erythrocytes resistance to haemolytic agents.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
María Guadalupe Prado-Ochoa ◽  
Víctor Hugo Abrego-Reyes ◽  
Ana María Velázquez-Sánchez ◽  
Marco Antonio Muñoz-Guzmán ◽  
Patricia Ramírez-Noguera ◽  
...  

Female and male Wistar rats were used to determine the subchronic oral toxicities of two new ethyl-carbamates with ixodicidal activities (ethyl-4-bromphenyl-carbamate and ethyl-4-chlorphenyl-carbamate). The evaluated carbamates were administered in the drinking water (12.5, 25 and 50 mg/kg/day) for 90 days. Exposure to the evaluated carbamates did not cause mortality or clinical signs and did not affect food consumption or weight gain. However, exposure to these carbamates produced alterations in water consumption, hematocrit, percentages of reticulocytes, plasma proteins, some biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, cholinesterase, and creatinine activities), thiobarbituric acid reactive substances, and the relative weight of the spleen. Histologically, slight pathological alterations were found in the liver that were consistent with the observed biochemical alterations. The nonobserved adverse effect levels (NOAELs) of the evaluated carbamates were 12.5 mg/kg/day for both the female and male rats. The low severity and reversibility of the majority of the observed alterations suggest that the evaluated carbamates have low subchronic toxicity.


2021 ◽  
Vol 18 ◽  
Author(s):  
Sobia Manzoor ◽  
Ayesha Khan ◽  
Beena Hasan ◽  
Shamim Mushtaq ◽  
Nikhat Ahmed

Background: Oxidative damage contributes to the pathophysiology of schizophrenia (SZ). Redox imbalance may lead to increased lipid peroxidation, which produces toxic aldehydes like 4-hydroxynonenal (4-HNE) ultimately leading to oxidative stress. Conversely, implications of oxidative stress points towards an alteration in HNE-protein adducts and activities of enzymatic and antioxidant systems in schizophrenia. Objectives: Present study focuses on identification of HNE-protein adducts and its related molecular consequences in schizophrenia pathology due to oxidative stress, particularly lipid peroxidation. Material and Methods: Oxyblotting was performed on seven autopsied brain samples each from cortex and hippocampus region of schizophrenia patients and their respective normal healthy controls. Additionally, thiobarbituric acid substances (TBARS), reduced glutathione (GSH) levels and catalase (CAT) activities associated with oxidative stress, were also estimated. Results: Obtained results indicates substantially higher levels of oxidative stress in schizophrenia patients than healthy control group represented by elevated expression of HNE-protein adducts. Interestingly, hippocampus region of schizophrenia brain shows increased HNE protein adducts compared to cortex. An increase in catalase activity (4.8876 ± 1.7123) whereas decrease in antioxidant GSH levels (0.213 ± 0.015µmol/ml) have been observed in SZ brain. Elevated TBARS level (0.3801 ± 0.0532ug/ml) were obtained in brain regions SZ patients compared with their controls that reflects an increased lipid peroxidation (LPO). Conclusion: Conclusion: We propose the role of HNE modified proteins possibly associated with the pathology of schizophrenia. Our data revealed increase lipid peroxidation as a consequence of increased TBARS production. Furthermore, altered cellular antioxidants pathways related to GSH and CAT also highlight the involvement of oxidative stress in schizophrenia pathology.


2017 ◽  
Vol 2 (2) ◽  
pp. 147
Author(s):  
Triswanto Sentat ◽  
Susiyanto Pangestu

Kersen leaf (Muntingia calabura L.) contains tannins, flavonoids and polyphenol compounds allegedly have analgesic effect. The objective was to determine the analgesic effect of ethanol extract of kersen leaves and to determine the most effective analgesic dose. This study was an experimental research. Leaves were extracted with ethanol 70% and the analgesic effect test was divided into 5 groups: negative control treatment (distilled water), positive control (mefenamic acid 2.6mg/kg), kersen leaf ethanol extract first dose (100mg/kg), second dose (200mg/kg) and tthird dose (400mg/kg). Giving treatments by oral, after 30 minutes, the mices were given a pain inductor with 0.5% acetic acid by intra peritonial administration. Analgesic power was calculated by counting the number of writhing in mice for 1 hour. The results showed that the ethanol extract of cherry leaf has analgesic effect. From the calculation of the first dose analgesic power (42.9%), second dose (59.4%) and the third dose 69.9%. Statistical test results kruskal wallis value of p=0.011 (p<0.05) showed a significant difference between all analgesic treatment groups. The conclusion of this study is all of the ethanol extract had analgesic effects on male white mice, whereas a dose of 400mg/kg is the most effective analgesic dose.


Author(s):  
Santosh Fattepur ◽  
Kiran Chanabasappa Nilugal ◽  
Ranya Rajendran ◽  
Fadli Asmani ◽  
Eddy Yusuf

Objective: Hyperlipidemia is one of the risk factors that contribute to the prevalence of coronary heart diseases and antihyperlipidemic agents, such as statin, was used to treat hyperlipidemia as a current therapy. Boesenbergia pandurata has not been exploited for antihyperlipidemic effect. Hence, this study aims to screen for the antihyperlipidemic activity of methanolic extracts of B. pandurata rhizomes (BPR extracts) in hypercholesterolemia-induced Sprague-Dawley rats.Methods: BPR extracts were prepared using the maceration method with 1500 ml of 80% methanol at room temperature for about 7 days. A toxicity study was carried out based on OECD guidelines. Hypercholesterolemia was induced by 6% lard oil, 2% of cheese, and egg yolks. Two different doses of BPR extracts, 200 and 400 mg/kg, were used to screen for antihyperlipidemic effect. Histopathological study was carried out in the liver. The results were evaluated for the statistically significant difference by using the one-way ANOVA followed by post hoc Dunnett test.Results: No mortality was witnessed even till 2 g/kg. Only 400 mg/kg of BPR extracts statistically reduced in total cholesterol (p<0.05), low-density lipoprotein-cholesterol (p<0.05) and an increase in high-density lipoprotein-cholesterol (p<0.05) when compared to the positive control. BPR extracts (400 mg/kg) showed less enlargement of lipid droplets as compared to positive control.Conclusion: BPR extracts can be a promising medicinal plant for treating hyperlipidemia in underdeveloped countries.


2021 ◽  
Vol 13 (Aquaculture) ◽  
pp. 52-63
Author(s):  
Minh Phu Tran ◽  
Thi Kim Duyen Huynh ◽  
Le Anh Dao Nguyen ◽  
Thi Nhu Ha Nguyen ◽  
Quoc Thinh Nguyen ◽  
...  

The aim of this study is to evaluate the effects of Psidium guajava leaves extract on the quality of cobia (Rachycentron canadum) fillets during in ice storage. A group of cobia fillets was soaked in Psidium guajava extract solutions at concentration of 0.03% (w/v) for 30 minutes while the other group soaked in cold ice water, considered as control treatment. The experimental fillets were packed and stored in ice for 15 days. Sampling were done on the 1st, 5th, 10th and 15th day. Analyzed parameters included temperature, total viable counts (TVC), sensory property, pH, moisture, water holding capacity (WHC), texture, total volatile base nitrogen (TVB–N), peroxide value (PV), Thiobarbituric acid reactive substances (TBARs), and fillet color. The results indicated that cobia fillets treated with guava extract solutions 0.03% showed significantly higher sensory property, lower PV and TBARs compared to the control treatment during ice storage. Based on the sensory property and total viable counts, cobia fillets can be used up to 10 days in both treatments remaining high quality of the cobia fillet.


2013 ◽  
Vol 11 (1) ◽  
pp. 54 ◽  
Author(s):  
. Widanarni ◽  
Puguh Widagdo ◽  
Dinamella Wahjuningrum

<p>The use of antibiotics for controlling of luminous vibriosis caused by <em>Vibrio harveyi</em> is restricted now, because it induces antibiotic-resistant bacteria and leave residue in shrimp’s body. An alternative solution that can be done to treat the disease is by using applications of probiotic, prebiotic, and synbiotic. The aim of this research was to examine the effect of probiotic, prebiotic, and synbiotic on the survival rate and growth of Pacific white shrimp against <em>V. harveyi</em> infection. Feed as a treatment was supplemented with probiotic 1%, prebiotic 2%, and probiotic 1%+prebiotic 2% (synbiotic). Shrimps feed without supplementation of probiotic and prebiotic was used as a control treatment. The shrimps were maintainedin the aquarium (60×30×35 cm<sup>3</sup>) with a density of 40 shrimps/40 L and an average weight of 0.4±0.1 g. After 30 days of feeding treatment, the shrimp was challenged by immersion method with <em>V. harveyi</em> solution containing 10<sup>6</sup> CFU/mL. The results showed that before challenge, synbiotic feed treated shrimp has a growth rate (5.89%), feed conversionrate (1.21), and a high survival rate (80%). After challenge, survival rate (83.33%) of shrimp fed diet supplemented with synbiotic was higher than prebiotic (51.67%) and positive control (31.67%).</p> <p>Keywords: probiotic, prebiotic, synbiotic, <em>Vibrio harveyi</em>,Pacific white shrimp</p>


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