INTRODUCTION:

Alzheimer’s disease (AD) is a critical neurodegenerative illness indicated by memory loss and diminished performance, language, andvisuospatialskills¹. Dementia is a mental disorder characterized by loss of intellectual ability sufficiently severe as to interfere with one's occupational or social activities². Dementia is of several types and it invariably involves memory impairment. Alzheimer's disease is the most common cause of dementia and this is associated with loss of neurons in distinct brain areas. Currently, AD affects nearly 5% of people, 65-year old and over 30% of those 85-year old, affecting more than 27 million people in the developed world³.

AD is distinguished by atrophy of cerebral cortex and selective neuronal damage in the hippocampal brain tissues. Oxidative damage and the formation of free radicals may occur for several reasons such as exposure to chemicals, metals, irradiation and toxins causing lipid peroxidation, which in turn affects the activities of protective enzymatic antioxidants that are greatly sensitive indicators of increased oxidation reactions⁴. When lipids are attacked by free radicals, the lipid peroxidation chain reaction proceeds⁵, this lipid degradation reaction leads to broken chemical bonds, cross-linkages, and conformational changes of many biomolecular compounds. The pathological telltale signs of AD are known to be the deposition of extracellular Aβ plaques, the formation of intracellular neurofibrillary tangles (NFTs) (highly phosphorylated tau proteins), and the selective loss of synapses and neuron, which lead to neural death in the hippocampal and cerebral cortical regions⁶.

Aluminium compound is a well-known neurotoxin, and it has a great affinity to bio-membrane and the ability to promote formation and aggregation of insoluble Aβ⁷. Various neurodegenerative diseases such as AD and Parkinsonism disease are strongly linked to Al. Aluminium may exert its neurotoxicity via free radical production and peroxidation damage to lipids and proteins⁸. Chronic aluminum exposure has a great affinity to biomembrane and the ability to promote formation and aggregation of insoluble Aβ plaques and (NFTs) in Alzheimer brain. It has been proved that Al exposure is associated with impairment of mitochondrial functions, in vivo and in vitro, as well as the antioxidant defense system⁹. Al decreases the antioxidant enzyme status¹⁰. It can also cause a disturbance in the enzyme activity involved in acetylcholine metabolism and leads to cognitive dysfunction¹¹. The malfunction and death of neurons cannot be stopped with the treatment available now¹². Available drugs on the market now include inhibitors of acetylcholinesterase such as tacrine, donepezil, rivastigmine, and galantamine.

The use of traditional medicine is widespread and plants represent a large source of natural antioxidants that might serve as leads for the development of novel drugs. Usually, medicinal plants with antioxidant activities have been used in the treatment of several human diseases, cancer, cardiovascular and neurodegenerative diseases such as AD.

Natural antioxidants, which alleviate the oxidative stress or induce the cellular antioxidant would most probably treat and/or protect against Al poisoning. Murraya koenigii, commonly known as curry leaf or kari patta in Indian dialects, belonging to Family Rutaceae is highly regarded as a rejuvenating herb and is reputed to increase intelligence and memory. Numerous active constituents of MK are found to be potent antioxidants in different animal models¹³. It possesses numerous pharmacological effects such as anti-inflammatory¹⁴, anticancer¹⁵, memory improvement¹⁶ and antiobesity activities¹⁶. Recently MK has been reported as a powerful neuroprotectant against different neurodegenerative disorders¹⁷. Based on this background, the present study was carried out to investigate the possible neuroprotective efficacy of MK against Alcl₃-induced neurotoxicity in terms of oxidative stress, behavioural, biochemical and histological aspects of the cerebral cortex, striatum, hypothalamus and hippocampus of rat brain region.

MATERIALS AND METHODS:

Plant material:

The fresh leaves of Murraya koenigii were collected from the outskirts of Maisamaguda situated in the state of Telangana (India). The plant material was identified and authenticated by Dr K. Madhavachetty, H.O.D, Department of Botany, Osmania University, Telangana, India.

Extraction procedure:

The Curry leaves were collected & washed thoroughly in normal tap water and were shade dried till they were dry and crispy and crushed into a coarse dust with mortar and pestle. Maceration is the process of soaking plant materials (coarse or powdered) in a stoppered container with a solvent and allowed to stand at room temperature for a period of minimum 3 days with frequent agitation.500ml of water was taken in a beaker & 50gm crushed leaves powder of Murraya koenigii was added to it, made airtight & kept for 72hrs, with frequent agitation. Then the mixture was filtered & the solvent obtained was evaporated by a direct evaporation method, leaving a small yield of aqueous extract of Murraya koenigii (about 5 gm).

Animals and treatment:

Wistar albino rats (150-250g) were procured from Teena labs, Plot no 41, SV cooperative industrial estate, Bachupally (V), Quthbullapur and maintained in Malla Reddy College of Pharmacy and were maintained at standard conditions with food and water ad libitum. The experimental protocols were endorsed by the Institutional Animal Ethical Committee (Reg. No. 160/1999/ CPCSEA).

Experimental design:

After 1 week acclimatization period, thirty-six rats were randomized and divided into six groups of each containing six animals. Group I animals received saline and were considered as control. Group II rats were administered with AlCl₃ (40mg/kg b.w, oral) for 5 weeks. Group III rats were treated with standard Vitamin E (100mg/kg b.w, p.o) and AlCl₃ (40mg/kg b.w, oral) for 35 days. Group IV received AlCl₃ as group II and MK extract (100mg/kg b.w, p.o). Group V rats received AlCl₃ as group II and MK extract (200mg/kg b.w, p.o). Group VI animals received AlCl₃ as group II and MK extract (400mg/kg b.w, p.o). The dose of aqueous extract of Murraya koenigii engaged in this experiment was chosen according to previous studies that have been subjected to nutritional and safety evaluation.

The rats were given respective treatment for 35 days; on the 35^th day rats were sacrificed to estimate anti-oxidant and anticholinesterase parameters.

Behavioural studies:

One week training was performed in rats in order to prepare them for behavioural study. During the training period, only food and water were administered to rats. The fully trained rats were chosen for the study.

Morris Water Maze Test:

The acquisition and retention of memory were evaluated using the Morris Water Maze. The Morris water maze consists of a large circular pool (150cm in diameter, 45 cm in height, filled to a depth of 30cm with water at 28 ± 1°C) divided into four equal quadrants. The water temperature was maintained at 26±2°C¹⁸. A circular platform was placed in one quadrant of the pool, 1cm above the water level for the acquisition phase and the same platform was placed 1cm below the water level for the retention phase. Each animal was subjected to four consecutive trails with a gap of 5min. The animal was then allowed 120s to locate the platform. Next, the animal was allowed to stay on the platform 20s.

Passive avoidance Test:

The apparatus consist of a box (27cm x 27cm x 27cm) having three walls of wood and one wall of Plexiglas, featuring a grid floor (made up of 3mm stainless steel rods set 8mm apart), with a wooden platform (10cm x7cm x 1.7cm) in the center of the grid floor Electric shock (20 V, A.C.) was delivered to the grid floor. Each rat was placed on the wooden platform set in the centre of the grid floor. When the rat stepped –down placing all its paw on the grid floor, shocks will be delivered for 15 sec and the step-down latency (SDL) was recorded. The second session was carried out 90min after the first test. During the second test, animals will be removed from the shock free zone, if they did not step down for a period of 60 seconds. Retention was tested after 24hrs in a similar manner.

Rota rod Test:

The effect of aluminium chloride, as well as vitamin E on muscle performance was assessed using Rota Rod test. All the rats were given two initial trails of 300s, approximately 10min apart, to maintain posture on the Rota rod. After the initial training trails, a baseline trail of 120s was conducted. The time each animal remains on the Rota rod was recorded. The animals that did not fall off the Rota rod were given a maximum score of 120s.

Locomotor Activity:

The spontaneous locomotor activity of each rat was recorded individually for 10min using actophotometer. The locomotor activity can be easily measured using an actophotometer which operates on photoelectric cells which are connected in circuit with a counter. When the beam of light falling on the photocell is cut off by the animal, a count was recorded. The counts were recorded after each animal was placed inside the actophotometer chamber one by one. The initial & final body weight of the animals of each group were measured and recorded.

Biochemical Parameters:

Assessment of oxidative stress markers:

The animals were anaesthetized and sacrificed by CO₂ euthanasia chamber; the brain was transferred to ice cold phosphate buffered saline quickly. It was blotted to free of blood, tissue fluids, weighed and chopped with a surgical scalpel into fine slices. The minced pieces were homogenized with ten volumes of phosphate buffer (0.1mol/L, pH 7.4) using homogenizer and were centrifuged at10,000 r/min for 20 min and the resultant supernatant was collected and stored at 4°C.

The clear supernatant was used for the determination of lipid peroxidation [LPO (nmol MDA/mg wet tissue)], superoxide dismutase [SOD (Unit/mg wet tissue)], catalase [CAT (µ mol H₂O₂decomposed/mg wet tissue)], reduced glutathione [GSH (nmol GSH/mg wet tissue)].

Estimation of tissue AChE:

AChE belongs to cholinesterase family. The enzyme activity was assessed according to the procedure of Ellman et al. Acetylthiocholine was hydrolysed by AChE to acetic acid and thiocholine. The catalytic activity was measured by following the increase of yellow anion, 5-thio-2-nitrobenzoate, produced from thiocholine when it reacted with DTNB at 410 nm. In brief, an aliquot of the cerebrum and cerebellum homogenate (0.02 mL) was added to tubes containing 3 mL of phosphate buffer (100 mmol/L, pH 8.0), 0.02 mL of acetylthiocholine solution (75 nmol/L) and 0.1 mL of DTNB.

Histopathological studies [haematoxylin and eosin (H&E) staining]:

Samples (entire brains: cerebrum and cerebellum) from each group were selected, transversely cut and fixed in 10% buffered formaldehyde solution, then conserved in paraffin. Four-micrometer tissue sections were realized and dried at an adequate temperature to get paraffin removed from the glass slides. The next step was to rehydrate sections then stain them with haematoxylin and eosin as nuclear and cytoplasmic stains. The sections were analysed using Leica^®DM5000B microscope and photographed with Leica EC3 digital camera.

RESULTS:

Statistical analysis:

The outcomes are expressed as the mean±SEM. Statistical evaluation was carried out by using one-way analysis of variance (ANOVA) followed by Bonferroni multiple comparison test. P<0.05 was considered to be significant.

Table 1: Preliminary Phytochemical Investigation:

S. No

Phytoconstituents

Murraya koenigii

Alkaloids

Mayer`s Test

Dragendrof`s Test

Wagner`s Test

Flavonoids

Shinoda Test

Alkaline Reagent

FeCl3

Phenolic compounds

Lead Acetate Test

FeCl3 Test

Gelatin Test

Tannins

Lead Acetate Test

FeCl3 Test

Glycosides

Borntrager`s Test

Keller-killiani Test

Amino Acid

Millons Test

Ninhydrin Test

Protein

Biuret Test

Millons Test

Carbohydrates

Molisch`s Test

Fehling Test (reducing sugar)

Oil and fat

Saponins

Frothing Test

Table 2: Estimation Effect of aqueous extract of leaves of Murraya Koenigii on body weights of control and rats treated with Alcl3 after 35 days of treatment:

Group

Intial weight

(gm)

Final weight

(gm)

Change in body weight

(gm)

Control

74.75

77.5

2.75

AlCl₃treated(40mg/kg,b.w,p.o)

190

152

VitaminE+AlCl₃ (100mg/kg+40mg/kg, b.w p.o)

206

197

Aq. Extr.M.koenigii+AlCl₃ (100mg/kg+40mg/kg,b.w, p.o)

147

128

Aq.Extr.M.koenigii+AlCl₃ (200mg/kg+40mg/kg,b.w, p.o)

172

157

Aq.Extr.M.koenigii+AlCl₃ (400mg/kg+40mg/kg,b.w, p.o)

193

187

Table 3: Effect of aqueous extract of leaves of Murraya Koenigii on absolute whole brain weights of control and rats treated with Alcl3 after 35 days of treatment:

Group	Brain Weight (gm)
Control	2.01
AlCl₃treated(40mg/kg,b.w,p.o)	5.04^{^}
VitaminE+AlCl₃ (100mg/kg+40mg/kg, b.w ,p.o)	1.90^#
Aq.Extr.M.koenigii + AlCl₃ (100mg/kg + 40mg/kg, b.w, p.o)	4.10*
Aq.Extr.M.koenigii+AlCl₃ (200mg/kg+40mg/kg, b.w, p.o)	3.33**
Aq.Extr.M.koenigii+AlCl₃ (400mg/kg+ 40mg/kg, b.w, p.o)	1.80 ***

Table 4: Effect of Behavioral Parameters of aqueous extract of leaves of Murraya koenigii in Aluminium chloride induced toxicity in rats by Passive avoidance:

S.No	Group	Step Down Latency(seconds)
1	Control	87.8 ± 6.28
2	AlCl3treated(40mg/kg,b.w,p.o)	138±2.68^
3	VitaminE+AlCl3 (100mg/kg+40mg/kg, b.w,p.o)	69±1.87#
4	Aq.Extr.M.koenigii+AlCl3 (100mg/kg + 40mg/kg, b.w, p.o)	120.10±1.33*
5	Aq.Extr.M.koenigii+ AlCl3 (200mg/kg+40mg/kg, b.w, p.o)	97±1.88**
6	Aq.Extr.M.koenigii +AlCl3 (400mg/kg+ 40mg/kg, b.w, p.o)	90.25±1.03***

Table 5: Effect of Behavioral Parameters of aqueous extract of leaves of Murraya koenigii in Aluminium chloride induced toxicity in rats by Rota Rod:

S. No	Groups	Muscular Strength (Seconds)
1	Control	80.1 ± 1.22
2	AlCl₃treated(40mg/kg,b.w,p.o)	40.55±1.75^
3	VitaminE+AlCl₃ (100mg/kg+40mg/kg, b.w, p.o)	70.05±7.20^#
4	Aq.Extr.M.koenigii+AlCl₃ (100mg/kg + 40mg/kg, b.w, p.o)	25.88±1.02*
5	Aq.Extr.M.koenigii+AlCl₃ (200mg/kg+40mg/kg, b.w ,p.o)	24.46±0.31**
6	Aq.Extr.M.koenigii+AlCl₃ (400mg/kg+ 40mg/kg, b.w ,p.o)	49.05±1.31***

Table 6 Effect of Behavioral Parameters of aqueous extract of leaves of Murraya koenigii in Aluminium chloride induced toxicity in rats by Morris’s Water Maze:

S. No	Groups	Quadrant 1 (Latency)	Quadrant 2 (Latency)	Quadrant 3 (Latency)	Quadrant 4 (Latency)
1	Control	18.00± 2.10	25.55± 4.21	22.40±2.11	25.60± 12
2	AlCl₃treated (40mg/kg,b.w,p.o)	37.15±0.98^	43.25 ± 5.50 ^	36.75±4.54^	15.25 ± 1.83 ^
3	VitaminE+AlCl₃ 100mg/kg+40mg/kg, b.w, p.o)	13 ± 1.28 ^#	10.25 ± 1.85 ^#	17.75±0.48^#	07 ± 1.84 ^#
4	Aq.Extr.M.koenigii+AlCl₃ (100mg/kg+40mg/kg,b.w,p.o)	31.35±2.17*	15.00 ± 1.15*	16.57±3.80*	16 ± 0.99*
5	Aq.Extr.M.koenigii+AlCl₃ (200mg/kg+40mg/kg, b.w, p.o)	19.66±4.01*	10.97±2.04**	14.85±2.3**	09.25±0.91**
6	Aq.Extr.M.koenigii+AlCl₃ (400mg/kg+40mg/kg, b.w, p.o )	13.25±0.6**	08.32±1.6***	08.40±0.3***	6.25±1.11***

Table 7: Effect of Behavioral Parameters of aqueous extract of leaves of Murraya koenigii in Aluminium chloride induced toxicity in rats by Actophotometer:

S. No	Groups	Locomotor Function (10 min)
1	Control	103.4±7.227
2	AlCl3treated (40mg/kg, b.w, p.o)	68.1±1.51 ^
3	VitaminE+AlCl3 (100mg/kg+40mg/kg, b.w, p.o)	77.08±1.0 #
4	Aq.Extr.M.koenigii+AlCl3 (100mg/kg+40mg/kg, b.w, p.o)	59.08 ±2.9*
5	Aq.Extr.M.koenigii+AlCl3 (200mg/kg+40mg/kg, b.w, p.o)	58.75±0. 70 **
6	Aq.Extr.M.koenigii+ AlCl3 (400mg/kg+ 40mg/kg,b.w, p.o)	61.88±1.08***

Table 8: Effect of aqueous extract of leaves of Murraya koenigii on Antioxidant parameters in Aluminium chloride induced toxicity in rats:

S. No	Groups	GSH (µmol/g)	MDA (mM^-1cm^-1)	Catalase (K/min)	GR (µ/ml)	GP_X (nm/gm)
1	Control	26.60±0.811	165.18 ± 1.4	19.5 ±1.0	22.00 ± 1.0	35.00 ± 1.0
2	AlCl₃treated (40mg/kg, b.w, p.o)	16.17 ± 0.47 ^	448 ± 1.01^	16.15 ± 0.44 ^	19.11 ± 0.88 ^	24.11 ±0.78^
3	VitaminE+AlCl₃ (100mg/kg+40mg/kg, b.w, p.o)	34.8 ± 0.6 ^#	165.68 ± 0.1^#	19.21 ± 2.0 ^#	20.34 ± 4.0 ^#	32.8 ± 0.47 ^#
4	Aq.Extr.M.koenigii+AlCl₃ (100mg/kg + 40mg/kg, b.w ,p.o)	31.6 ± 1.56*	150.8 ± 1.88*	14.4 ± 0.5 *	19.1 ± 0.75*	23.88 ±0.34*
5	Aq.Extr.M.koenigii+AlCl₃ (200mg/kg+40mg/kg,b.w ,p.o)	28.13± 0.19**	146.2 ± 0.18 **	21.09 ±0.33**	18.22 ± 1.0 **	20.1 ±0.14**
6	Aq.Extr.M.koenigii+AlCl₃ (400mg/kg+40mg/kg,b.w ,p.o)	33.41±0.9***	139.34±1.22***	24.48±0.99***	20.00±0.11***	31.8±0.35***

Effect of treatment on brain histopathological changes:

In ×40 magnification, the Alcl₃-treated group showed severe damage of the neurons along with hippocampal edema, pyknotic cells. The groups treated with Vitamin E and Aq.Extr. M.koenigii protected neurons and showed mild hippocampal edema as compared to the diseased group.

Figure 1: (A) Image of the brain section of a control rat showing a normal histological structure of the hippocampus. (B) Image of the brain section of an Alzheimer's disease-induced rat's plaques formation. (C)AD group treated with vitamin E (D) AD group treated with Aq.Extr. M.koenigii (100mg/kg, b.w)(E)AD group treated with Aq.Extr. M.koenigii (200mg/kg, b.w). (F) AD group treated with Aq.Extr. M.koenigii (400mg/kg, b.w).

DISCUSSION:

The outcome from the present research indicate that Al exposure has changed the B.W and relative weights of the whole brain and cerebrum, which reveal a possible detrimental effect of Al on the body and brain weight as compared to the control. These results concur with the previous research data. It has been reported that sub-acute Al exposure of rats generated a loss of about 27.8 g in animals B.W¹⁹. It is also noticed that there is a significant reduction of about 50.44% gain in weight in Al-treated rats. The loss of brain weight after sub-acute Al treatment could be a result of the spongiosis of the neuropil resulting in the retarded development of the animals²⁰. This agrees with our results about histology of studied organs. In the present study, we have investigated the behavioural and the potential neuropathological effect of acute/sub-chronic experimental exposition of rats to Al chloride, and concluded that the tested animals presented neurological disorders including learning impairments and memory deficits as well as the neuronal loss when compared to controls.

To delineate the mechanism by which M.koneigii exerts its neuroprotective activity, M.koneigii was administered during 35 days consecutively 1 h prior Alcl₃ (40 mg/kg i.p.) injection. The MWM test was used as a behavioural task. M.koneigii reduced the time to the invisible platform during acquisition and the latency time to the non-existing platform during retention phase. M.koneigii also significantly increased the time spent in the target quadrant during this retention phase. Our results with the Morris water maze suggest that M.koneigii improves spatial long-term memory. The results of MWM confirmed that pretreatment with M.koneigii counteracted Alcl₃induced learning and memory deficit thus is neuroprotective.

Al exposure is known to produce neurotransmission disruption and cholinotoxicity²¹, and acetylcholine is usually related to short-term memory. Our finding demonstrated that Al causes disturbances in cholinergic neurotransmission, and M.koneigii extract co-administrated with Al revealed a better effect on learning in animals since passive avoidance in this group were improved in comparison with intoxicated animals. These results concur with previously reported data indicating that a co-administration of some plant preparation like Vitis vinifera extract with Al showed a recovery from amnestic troubles²².

AChE is usually located in membranes (erythrocytes) of vertebrates and non-vertebrates. The enzyme controls ionic current in excitable membranes and plays an essential role in nerve conduction process at the neuromuscular junction and motor function²³.Al altered the muscular-locomotion activities by decreasing the levels of acetylcholine, which can explain our result about behavior (crossing task values) since high levels of Al not only interfered with the memory but also attenuated the motor functions and led to decreased motor activities and grip strength⁴¹. However, giving M.koneigii antioxidant extract could restore altered motor function and acquisition-memory process (closed to normal) by modulating AChE activity. Although AChE enzyme always receives a big attention in the study of Al neurotoxicity, the elevated acetylcholine levels are known to improve learning and memory and AChE plays an essential role in cognitive functions by two mechanisms including elevating acetylcholine levels and promoting the cholinergic neurogenesis²⁴.

Also, it has been observed that Al influences the metabolism of acetyl-CoA which leads to a possible reduction in the formation of acetylcholine and hence the substrate for AChE enzyme²⁵.

M.koneigii extract administered in parallel with Al improved modestly the decreased enzyme activity in brain regions. The positive response of cholinergic neurons in term of system reactivation has been explained by two hypotheses: antioxidant plant extract/flavonoids administration changed the configuration of AChE. Since it was reported that the manifestation of oxidative stress generation in the brain was a response to sub-chronic exposure to Al, we undertook the present study based on measuring LPO levels and quantitating endogenous antioxidants (CAT, GR, GSH, GPx). Now, it is well documented that Al-induced oxidative stress in neurons involves an imbalance between the generation of ROS and antioxidants²⁶. Lipid oxidation products are one of the main consequences associated with oxidative stress and brain is considered to be the most sensitive target to be damaged due to the high level of lipid content and tissue oxygen consumption²⁷. The significantly increased cerebrum and cerebellum levels of MDA found in our study reflect the efficiency of Al inactivation of lipid production process. These results corroborated the previous findings that Al exposure enhanced iron dependant LPO in rat brain²⁸. GSH is an important intracellular non-enzymatic antioxidant, and it is considered the most important scavenger of free radicals and cofactor of many detoxifying enzymes against oxidative stress like GPx, GR and others. It is able to regenerate the most important antioxidants, vitamins C and E, back to their active forms²⁹. In our case, we noted decreased GSH levels in cerebrum and cerebellum of intoxicated rats compared to those found in controls. Antioxidant enzymes are the first cellular molecules required for defence against ROS generation. Thus, in the present work, increased oxidative stress and brain injury were evident by decreased GPx, GR activities and CAT level in cerebrum and cerebellum.

M.koneigii administration to Al-treated rats was found to significantly re-equilibrate antioxidant parameters back to normal values. This positive effect of M.koneigii on oxidative stress defence is probably due to its secondary metabolites composition including Carbazole alkaloids koenigine and mahanimbine, polyphenols and flavonoids.

The examination of H&E stained sections revealed that Al can cause marked histopathological abnormalities in brain tissues (cerebrum and cerebellum). These results are correlated to those claimed by many authors³⁰ all reported the same modifications induced by Al on cerebral cortex histoarchitecture. Therefore, these alterations are associated with learning-memory impairments.

The co-administration of Al and M.koneigii showed better improvement in cerebrum and cerebellum histology than that of the intoxicant group. In conclusion, the results of the present study indicate that M.koneigii extract is a potential formulation which can be used for the treatment of Al neurotoxicity. It shows more efficient recovery from the toxicant-induced oxidative damage, histopathological changes and AChE activity inhibition.

CONCLUSION:

In the present study, we tried to investigate the protective and therapeutic effect of Murraya koenigii on Alzheimer’s disease. The aqueous extract of Murraya koenigii was found to be having the maximum antioxidant activity which may be due to the presence of high amount of carbazole alkaloids, koenigine, mahanimbine and flavonoids. All the behavioural parameters were found to be significantly different in the AlCl₃ treated group as compared to control. As when the rats were pretreated with aqueous extract of Murraya koenigii leaves a dose dependent protection of the activities was observed. The latency period in passive avoidance and Morris's water maze has decreased dose-dependently. The locomotory activity and muscle strength were increased dose-dependently. These results indicate that aqueous extract of Murraya koenigii leaves is capable to steady down the above parameters as well as repair the misfolding of the proteins caused by AlCl₃. Reduction in anti-oxidants like catalase, reduced glutathione and increased levels of malondialdehyde were observed in AlCl₃ induced rats significantly when compared to normal control rats. Oral administration of aqueous extract of Murraya koenigii at doses 100, 200, 400 mg/kg body weight showed an increase in catalase, and reduced glutathione and decreased levels of malondialdehyde significantly in a dose-dependent manner when compared to AlCl₃ induced rats. In the present study, results suggest that treatment with aqueous extract of Murraya koenigii exerted neuroprotective action against AlCl₃ induced behavioural and oxidative parameters.

ACKNOWLEDGEMENTS:

The authors are thankful to the management of Malla Reddy College of Pharmacy, for providing the chemicals and required facilities to carry out the research work. We are thankful to Dr.K.Madhava Chetty, H.O.D, Dept. of Botany, Osmania University, Hyderabad for authentication of the plant.

AUTHORS CONTRIBUTION:

All the authors have contributed to some or all parts of the study.

ABBREVIATION:

AD= Alzheimer’s disease,

Al=aluminium,

AChE=acetylcholinesterase,

CAT=catalase,

GSH=reduced glutathione,

SOD=superoxide dismutase,

MK= Murraya koenigii,

SDL= step down latency

CONFLICTS OF INTEREST:

None.

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Received on 10.12.2018 Modified on 19.01.2019

Research J. Pharm. and Tech. 2019; 12(4):1927-1934.

DOI: 10.5958/0974-360X.2019.00323.8