Ramasamy K

References (11)

Title : Genetic polymorphisms of microsomal epoxide hydrolase and UDP-glucuronosyltransferase (UGT) and its effects on plasma carbamazepine levels and metabolic ratio in persons with epilepsy of South India: A cross-sectional genetic association study - Venkatraman_2023_Indian.J.Pharmacol_55_149
Author(s) : Venkatraman S , Ramasamy K , Nair PP
Ref : Indian J Pharmacol , 55 :149 , 2023
Abstract : OBJECTIVES: Carbamazepine (CBZ), an anti-seizure drug, is widely prescribed for the management of focal seizures. At a given therapeutic dose, CBZ exhibits marked interindividual variation in the plasma CBZ levels. The aim wasto study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on plasma carbamazepine (CBZ) levels in persons with epilepsy (PWE) from South India. METHODS: 115 PWE belong to South India origin who are on carbamazepine monotherapy were recruited. Genotyping of the two variants weredone using RT-PCR method. PWE who had seizure freedom for one year and their last dose which was not changed for one year duration were included and their plasma levels of CBZ and its active metabolite CBZ 10,11 epoxide were analysed by reverse phase HPLC. RESULTS: In EPHX1 c. 337 (T>C) polymorphism, the PWE carrying CC had lower plasma CBZ levels when compared to CT genotype (2.45 microg/ml vs 3.15 microg/ml. In UGT2B7*2, PWE carrying homozygous mutant TT had higher levels when compared with CT (3.09 microg/ml vs 2.74 microg/ml) genotype but found no statistical significance. Mutant genotype of EPHX1 (CC) had higher metabolic ratio compared to TT genotype (1.33 vs 1.17) but not found to be statistically significant. Mutant genotype of UGT2B7*2 (TT) was found to be having lower metabolic ratio when compared with CC genotype (1.18 vs 1.35; p value =0.08). CONCLUSION: PWE carrying EPHX1 c.337 T>C (rs1051740) and UGT2B7*2 (rs7439366) genetic polymorphisms did not affect the plasma CBZ levels and metabolic ratio of PWE of South Indian origin. However, this finding should be confirmed in a larger sample size which may help in optimization and personalized CBZ therapy in South Indians.
ESTHER : Venkatraman_2023_Indian.J.Pharmacol_55_149
PubMedSearch : Venkatraman_2023_Indian.J.Pharmacol_55_149
PubMedID: 37555408

Title : Mahanimbine Improved Aging-Related Memory Deficits in Mice through Enhanced Cholinergic Transmission and Suppressed Oxidative Stress, Amyloid Levels, and Neuroinflammation - Mani_2021_Brain.Sci_12_12
Author(s) : Mani V , Mohd Azahan NS , Ramasamy K , Lim SM , Abdul Majeed AB
Ref : Brain Sci , 12 :12 , 2021
Abstract : Murraya koenigii leaves contain mahanimbine, a carbazole alkaloid, reported with improving cholinergic neuronal transmission and reducing neuroinflammation in the CNS. The current research investigated the effects of mahanimbine on age-related memory deficits, oxidative stress, cholinergic dysfunction, amyloid formation, and neuroinflammation in aged mice (16 months old). Mahanimbine was administered (1 and 2 mg/kg, p.o.) daily to groups of aged mice for 30 days. The Morris water maze (MWM) task was performed to study spatial learning (escape latency (EL) and swimming distance (SD)) and memory (probe test). The levels of malondialdehyde (MDA), glutathione (GSH), acetylcholine (ACh), acetylcholinesterase (AChE), beta-amyloid (Abeta(1-40) and Abeta(1-42)), beta-secretase (BACE-1), as well as neuroinflammation markers (total cyclooxygenase (COX) and COX-2 expression), were measured from the isolated brain. Mahanimbine reduced the EL time and SD in the MWM test. From the probe trial, the mahanimbine-treated group spent more time in the targeted quadrant related to the age-matched control, which indicated the enhancement of memory retention. From the biochemical tests, the treatment decreased MDA, AChE, Abeta(1-40), and Abeta(1-42), BACE-1, total COX activity, and COX-2 expression. It also raised the brain GSH and ACh levels in aged mice compared to age-matched control. These results have supported the reversal of memory dysfunctions by mahanimbine in aged mice and hypothesized that it could be a potential target to treat age-related neurodegenerative disease.
ESTHER : Mani_2021_Brain.Sci_12_12
PubMedSearch : Mani_2021_Brain.Sci_12_12
PubMedID: 35053756

Title : Virgin Coconut Oil-Induced Neuroprotection in Lipopolysaccharide-Challenged Rats is Mediated, in Part, Through Cholinergic, Anti-Oxidative and Anti-Inflammatory Pathways - Rahim_2020_J.Diet.Suppl__1
Author(s) : Rahim NS , Lim SM , Mani V , Hazalin N , Majeed ABA , Ramasamy K
Ref : J Diet Suppl , :1 , 2020
Abstract : Neuroinflammation is associated with neuronal cell death and could lead to chronic neurodegeneration. This study investigated the neuroprotective potential of virgin coconut oil (VCO) against lipopolysaccharide (LPS)-induced cytotoxicity of neuroblastoma SK-N-SH cells. The findings were validated using Wistar rats, which were fed with 1-10 g/kg VCO for 31 days, exposed to LPS (0.25 mg/kg) and subjected to the Morris Water Maze Test. Brain homogenate was subjected to biochemical analyses and gene expression studies. alpha-Tocopherol (alpha-T; 150 mg/kg) served as the positive control. VCO (100 microg/mL) significantly (p < 0.01) improved SK-N-SH viability (+57%) and inhibited reactive oxygen species (-31%) in the presence of LPS. VCO (especially 10 g/kg) also significantly (p < 0.05) enhanced spatial memory of LPS-challenged rats. Brain homogenate of VCO-fed rats was presented with increased acetylcholine (+33%) and reduced acetylcholinesterase (-43%). The upregulated antioxidants may have reduced neuroinflammation [malondialdehyde (-51%), nitric oxide (-49%), Cox-2 (-64%) and iNos (-63%)] through upregulation of IL-10 (+30%) and downregulation of IL-1beta (-65%) and Interferon-gamma (-25%). There was also reduced expression of Bace-1 (-77%). VCO-induced neuroprotection, which was comparable to alpha-T, could be mediated, in part, through inflammatory, cholinergic and amyloidogenic pathways.
ESTHER : Rahim_2020_J.Diet.Suppl__1
PubMedSearch : Rahim_2020_J.Diet.Suppl__1
PubMedID: 33962540

Title : HPTLC based approach for bioassay-guided evaluation of antidiabetic and neuroprotective effects of eight essential oils of the Lamiaceae family plants - Romero_2019_J.Pharm.Biomed.Anal_178_112909
Author(s) : Romero Rocamora C , Ramasamy K , Meng Lim S , Majeed ABA , Agatonovic-Kustrin S
Ref : J Pharm Biomed Anal , 178 :112909 , 2019
Abstract : A high-performance thin-layer chromatography (HPTLC) method combined with effect-directed-analysis (EDA) was developed to screen the antioxidant, neuroprotective and antidiabetic effects in essential oils derived from lavender flower, lemon myrtle, oregano, peppermint, sage, and rosemary leaves (Lamiaceae family). HPTLC hyphenated with microchemical (DPPH*, p-anisaldehyde, and ferric chloride) derivatizations, was used to evaluate antioxidant activity, presence of phytosterols and terpenoids, and polyphenolic content, while the combination with biochemical (alpha-amylase and acetylcholine esterase (AChE) enzymatic) derivatizations was used to asses alpha-amylase and AChE inhibitory activities. The superior antioxidant activity of oregano leaf extract is attributed to the presence of high levels of aromatic compounds, like polyphenolic acids. The strongest alpha-amylase inhibition was observed in lemon myrtle and rosemary plus extracts due to the presence of monoterpenes. Rosemary and sage extracts exhibit the highest AChE inhibition activity, with 1muL essential oils being more potent than the recommended daily dose of donepezil. This superior neuroprotection was attributed to the presences of di- and triterpenes that displayed strong AChE inhibition and antioxidant potential in DPPH* free radical assay. Antioxidant activity was related to phenolic content (R=0.49), while alpha-amylase inhibitory activity was positively related to antioxidant activity (R=0.20) and terpenoid/sterol content (R=0.31). AChE inhibitory activity was correlated (R=0.80) to the combined effect of phenolics and terpenoids. Thus, the superior AChE inhibitory and neuroprotection potential of rosemary and sage essential oils could be attributed to joint effects of main phenolic and terpene constituents. The hyphenated HPTLC method provided rapid bioanalytical profiling of highly complex essential oil samples.
ESTHER : Romero_2019_J.Pharm.Biomed.Anal_178_112909
PubMedSearch : Romero_2019_J.Pharm.Biomed.Anal_178_112909
PubMedID: 31618702

Title : Enhanced memory in Wistar rats by virgin coconut oil is associated with increased antioxidative, cholinergic activities and reduced oxidative stress - Rahim_2017_Pharm.Biol_55_825
Author(s) : Rahim NS , Lim SM , Mani V , Abdul Majeed AB , Ramasamy K
Ref : Pharm Biol , 55 :825 , 2017
Abstract : CONTEXT: Virgin coconut oil (VCO) has been reported to possess antioxidative, anti-inflammatory and anti-stress properties. OBJECTIVE: Capitalizing on these therapeutic effects, this study investigated for the first time the potential of VCO on memory improvement in vivo. MATERIALS AND
METHODS: Thirty male Wistar rats (7-8 weeks old) were randomly assigned to five groups (n = six per group). Treatment groups were administered with 1, 5 and 10 g/kg VCO for 31 days by oral gavages. The cognitive function of treated-rats were assessed using the Morris Water Maze Test. Brains were removed, homogenized and subjected to biochemical analyses of acetylcholine (ACh) and acetylcholinesterase (AChE), antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GRx)], lipid peroxidase [malondialdehyde (MDA)] as well as nitric oxide (NO). alpha-Tocopherol (alphaT; 150 mg/kg) was also included for comparison purposes.
RESULTS: VCO-fed Wistar rats exhibited significant (p < 0.05) improvement of cognitive functions [reduced escape latency (>/= 1.8 s), reduced escape distance (>/= 0.3 m) and increased total time spent on platform (>/= 1 s)]. The findings were accompanied by elevation of ACh (15%), SOD (8%), CAT (>/= 54%), GSH (>/= 20%) and GPx (>/= 12%) and reduction of AChE (>/=17%), MDA (> 33%) and NO (>/= 34%). Overall, memory improvement by VCO was comparable to alphaT. DISCUSSION AND CONCLUSION: VCO has the potential to be used as a memory enhancer, the effect of which was mediated, at least in part, through enhanced cholinergic activity, increased antioxidants level and reduced oxidative stress.
ESTHER : Rahim_2017_Pharm.Biol_55_825
PubMedSearch : Rahim_2017_Pharm.Biol_55_825
PubMedID: 28118770

Title : Lactobacilli-fermented cow's milk attenuated lipopolysaccharide-induced neuroinflammation and memory impairment in vitro and in vivo - Musa_2017_J.Dairy.Res_84_488
Author(s) : Musa NH , Mani V , Lim SM , Vidyadaran S , Abdul Majeed AB , Ramasamy K
Ref : J Dairy Res , 84 :488 , 2017
Abstract : Nutritional interventions are now recommended as strategies to delay Alzheimer's disease (AD) progression. The present study evaluated the neuroprotective effect (anti-inflammation) of lactic acid bacteria (either Lactobacillus fermentum LAB9 or L. casei LABPC) fermented cow's milk (CM) against lipopolysaccharide (LPS)-activated microglial BV2 cells in vitro. The ability of CM-LAB in attenuating memory deficit in LPS-induced mice was also investigated. ICR mice were orally administered with CM-LAB for 28 d before induction of neuroinflammation by LPS. Learning and memory behaviour were assessed using the Morris Water Maze Test. Brain tissues were homogenised for measurement of acetylcholinesterase (AChE), antioxidative, lipid peroxidation (malondialdehyde (MDA)) and nitrosative stress (NO) parameters. Serum was collected for cytokine analysis. CM-LAB9 and CM-LABPC significantly (P < 0.05) decreased NO level but did not affect CD40 expression in vitro. CM-LAB attenuated LPS-induced memory deficit in mice. This was accompanied by significant (P < 0.05) increment of antioxidants (SOD, GSH, GPx) and reduction of MDA, AChE and also pro-inflammatory cytokines. Unfermented cow's milk (UCM) yielded greater cytokine lowering effect than CM-LAB. The present findings suggest that attenuation of LPS-induced neuroinflamation and memory deficit by CM-LAB could be mediated via anti-inflammation through inhibition of AChE and antioxidative activities.
ESTHER : Musa_2017_J.Dairy.Res_84_488
PubMedSearch : Musa_2017_J.Dairy.Res_84_488
PubMedID: 29154736

Title : Ciproxifan improves cholinergic transmission, attenuates neuroinflammation and oxidative stress but does not reduce amyloid level in transgenic mice - Mani_2017_Life.Sci_180_23
Author(s) : Mani V , Jaafar SM , Azahan NSM , Ramasamy K , Lim SM , Ming LC , Majeed ABA
Ref : Life Sciences , 180 :23 , 2017
Abstract : AIM: The present study is aimed to investigate the ability of ciproxifan, a histamine H3 receptor antagonist to inhibit beta-amyloid (Abeta)-induced neurotoxicity in SK-N-SH cells and APP transgenic mouse model. MATERIALS AND
METHODS: In vitro studies was designed to evaluate the neuroprotective effects of ciproxifan in Abeta25-35 - induced SK-N-SH cells. For the in vivo study, ciproxifan (1 and 3mg/kg, i.p.) was administrated to transgenic mice for 15days and behaviour was assessed using the radial arm maze (RAM). Brain tissues were collected to measure Abeta levels (Abeta1-40 and Abeta1-42), acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO), antioxidant activities, cyclooxygenases (COX) and cytokines (IL-1alpha, IL-1beta and IL-6), while plasma was collected to measure TGF-1beta.
RESULTS: The in vitro studies demonstrated neuroprotective effect of ciproxifan by increasing cell viability and inhibiting reactive oxygen species (ROS) in Abeta25-35-induced SK-N-SH cells. Ciproxifan significantly improved the behavioural parameters in RAM. Ciproxifan however, did not alter the Abeta levels in APP transgenic mice. Ciproxifan increased ACh and showed anti-oxidant properties by reducing NO and LPO levels as well as enhancing antioxidant levels. The neuroinflammatory analysis showed that ciproxifan reduced both COX-1 and COX-2 activities, decreased the level of pro-inflammatory cytokines IL-1alpha, IL-1beta and IL-6 and increased the level of anti-inflammatory cytokine TGF-1beta. CONCLUSION: This present study provides scientific evidence of the use of ciproxifan via antioxidant and cholinergic pathways in the management of AD.
ESTHER : Mani_2017_Life.Sci_180_23
PubMedSearch : Mani_2017_Life.Sci_180_23
PubMedID: 28501482

Title : Effects of the Total Alkaloidal Extract of Murraya koenigii Leaf on Oxidative Stress and Cholinergic Transmission in Aged Mice - Mani_2013_Phytother.Res_27_46
Author(s) : Mani V , Ramasamy K , Ahmad A , Wahab SN , Jaafar SM , Kek TL , Salleh MZ , Majeed AB
Ref : Phytother Res , 27 :46 , 2013
Abstract : Alzheimer's disease (AD) is characterized by signs of major oxidative stress and the loss of cholinergic cells. The present study was designed to investigate the role of the total alkaloidal extract from Murraya koenigii (MKA) leaves on age related oxidative stress and the cholinergic pathway in aged mice. Ascorbic acid (100 mg/kg, p.o.) was used as a standard drug. The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p.o.). Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p.o.). Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain. In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process. The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer's disease. Copyright (c) 2012 John Wiley & Sons, Ltd.
ESTHER : Mani_2013_Phytother.Res_27_46
PubMedSearch : Mani_2013_Phytother.Res_27_46
PubMedID: 22447662

Title : Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain - Ahmad_2013_Food.Chem.Toxicol_65C_120
Author(s) : Ahmad A , Ramasamy K , Jaafar SM , Majeed AB , Mani V
Ref : Food & Chemical Toxicology , 65C :120 , 2013
Abstract : The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1beta and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation.
ESTHER : Ahmad_2013_Food.Chem.Toxicol_65C_120
PubMedSearch : Ahmad_2013_Food.Chem.Toxicol_65C_120
PubMedID: 24373829

Title : Protective effects of total alkaloidal extract from Murraya koenigii leaves on experimentally induced dementia - Mani_2012_Food.Chem.Toxicol_50_1036
Author(s) : Mani V , Ramasamy K , Ahmad A , Parle M , Shah SA , Majeed AB
Ref : Food & Chemical Toxicology , 50 :1036 , 2012
Abstract : Dementia is a syndrome of gradual onset and continuous decline of higher cognitive functioning. It is a common disorder in older persons and has become more prevalent today. The fresh leaves of Murraya koenigii are often added to various dishes in Asian countries due to the delicious taste and flavor that they impart. These leaves have also been proven to have health benefits. In the present study, the effect of total alkaloidal extract from M. koenigii leaves (MKA) on cognitive functions and brain cholinesterase activity in mice were determined. In vitro beta-secretase 1 (BACE1) inhibitory activity was also evaluated. The total alkaloidal extract was administered orally in three doses (10, 20 and 30 mg/kg) for 15 days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine-, and ageing-induced amnesia served as the interoceptive behavioral models. MKA (20 and 30 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. Furthermore, the same doses of MKA reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, the brain cholinesterase activity was also reduced significantly by total alkaloidal extract of M. koenigii leaves. The IC50 value of MKA against BACE1 was 1.7 mug/mL. In conclusion, this study indicates MKA to be a useful remedy in the management of Alzheimer's disease and dementia.
ESTHER : Mani_2012_Food.Chem.Toxicol_50_1036
PubMedSearch : Mani_2012_Food.Chem.Toxicol_50_1036
PubMedID: 22142688

Title : Reversal of memory deficits by Coriandrum sativum leaves in mice - Mani_2011_J.Sci.Food.Agric_91_186
Author(s) : Mani V , Parle M , Ramasamy K , Abdul Majeed AB
Ref : J Sci Food Agric , 91 :186 , 2011
Abstract : BACKGROUND: Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models. RESULTS: CSL (5, 10 and 15% w/w of diet) produced a dose-dependent improvement in memory scores of young as well as aged mice. CSL also reversed successfully the memory deficits induced by scopolamine (0.4 mg kg(-1), i.p.) and diazepam (1 mg kg(-1), i.p.). Interestingly, brain cholinesterase activity and serum total cholesterol levels were considerably reduced by CSL administration in daily diets concomitantly for 45 days. CONCLUSION: CSL may be a useful remedy in the management of Alzheimer's disease on account of its multifarious effects such as, memory-improving property, cholesterol-lowering property and anticholinesterase activity.
ESTHER : Mani_2011_J.Sci.Food.Agric_91_186
PubMedSearch : Mani_2011_J.Sci.Food.Agric_91_186
PubMedID: 20848667