DOSE-DEPENDENT EFFECT OF WITHANIA SOMNIFERA ON THE CHOLINERGIC SYSTEM IN SCOPOLAMINE-INDUCED ALZHEIMER’S DISEASE IN RATS
HTML Full TextDOSE-DEPENDENT EFFECT OF WITHANIA SOMNIFERA ON THE CHOLINERGIC SYSTEM IN SCOPOLAMINE-INDUCED ALZHEIMER’S DISEASE IN RATS
G. Visweswari * 1, 2, Rita Christopher 1 and W. Rajendra 2
Department of Neurochemistry 1, National Institute of Mental Health and Neuro Sciences, Bangalore - 560029, Karnataka, India.
Department of Zoology 2, Sri Venkateswara University, Tirupati - 517502, Andhra Pradesh, India.
ABSTRACT: The present study was aimed to determine whether the methanol and aqueous extracts from the medicinal plant, Withania somnifera (root), could inhibit acetylcholinesterase (AChE) in scopolamine-induced Alzheimer’s rats. The rats were randomly divided into different groups of 5 each: normal control rats treated with saline; Scopolamine (2mg/Kg b.w. i.p.) – induced Alzheimer’s rats treated with saline; Scopolamine-induced Alzheimer’s rats post-treated with methanol extract of three different concentrations (100, 200 and 300mg/Kg b.w. oral); Scopolamine-induced Alzheimer’s rat post-treated with aqueous extract of three different concentrations (100, 200 and 300mg/Kg b.w. oral); and scopolamine-induced Alzheimer’s rat post-treated with donepezil, a reference control (5mg/Kg b.w. oral) for 10 successive days. Increased AChE activity and decreased Acetylcholine content were recorded in different brain regions in scopolamine-induced Alzheimer’s rats. Post-treatment with W. somnifera extracts caused recovery of the levels of AChE and acetylcholine (ACh) in a dose-dependent manner. These findings suggest that W. somnifera causes perceptible changes in the cholinergic system as one of the facets of its anti-alzheimeric activity.
Keywords: |
Alzheimer’s disease, Withania somnifera, Scopolamine, Donepezil, Cholinergic system, Different brain regions
INTRODUCTION: Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms is biochemically characterized by a significant decrease in acetylcholine (ACh) and increase in the AChE activity, a member of the α/β hydrolase protein superfamily, hydrolyzes Acetylcholine (ACh) into acetate and choline at the central and peripheral cholinergic synapses 1.
AChE, (EC 3.1.1.7) is found in cholinergic synapses in the brain as well as in autonomic ganglia, the neuromuscular junction, and the target tissues of the parasympathetic system 2. This enzyme plays a major role in acetylcholine-mediated neurotransmission 3. Loss of ACh activity in the brain correlates with the severity of AD 4.
The burden of Alzheimer’s disease is continually rising globally and especially in the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy is still very limited. AChE is one of the most studied enzyme/protein in the field of Alzheimer’s disease. Although the primary cause of AD is unclear, brain ACh deficiency, oxidative stress, and neuroinflammation may be considered the principal pathogenic factors 4, 5.
Alzheimer’s disease is commonly treated by Acetylcholinesterase inhibitor (AChEI) drug therapy. Treatment of AD patients with cholinesterase inhibitors causes symptomatic benefit and seems to delay disease progression for 6-12 months 6. Because of the varying side effects of Alzheimer’s drugs, interest in the exploitation of medicinal plants as an alternative to AChEIs has greatly increased in recent years.
AChE inhibitor drugs have been designed to inhibit the breakdown of ACh in the brain and thus to increase cholinergic neurotransmitter activity in AD patients. Several types of research have been conducted to evaluate the AChE inhibitory activity of various plant species, for instance, Tabernaemontana divaricata, Fumaria sp., Vaccinium angustifolium, Corydalis spp., Lavandula pedunculata, Mentha suaveolens, and Hypericum undulatem 7, 8. Nevertheless, until now no plant species has scored full marks for its potential to replace the AChEI AD drugs.
Scopolamine, a muscarinic antagonist that induces central cholinergic blockade, produces a reversible and well-described impairment in both (i) maintaining attention; and (ii) processing of information and the acquisition of new knowledge in rodents 9 and humans 10.
The cognitive deterioration observed in scopolamine-induced rats resembles the memory disturbances seen in AD. Hence, the scopolamine-induced rat has been used as an experimental model for Alzheimer's disease 11, 12.
In the present study, we determined the AChE inhibitory effect of Withania somnifera (W. somnifera), a native medicinal plant which is popularly used for curing various ailments. The root extract of W. somnifera has been shown to have health promoting effects such as anti-stress, anti-arthritic, anti-inflammatory, analgesic, anti-pyretic, anti-oxidant, and immunomodulatory properties 13-15. Besides these properties, it also has anti-aging, aphrodisiac, thermoregulatory, anti-peroxidative 16, anti-inflammatory 17, antitumor 18, antioxidant, hemopoietic and rejuvenating properties 19. The root of W. somnifera contains several alkaloids, withanolides, and a few flavonoids and reducing sugars 20.
More than 20 active constituents have been reported to date, including withaferin A, sitoindosides VII–X, withanosides I–VII, choline, and beta-sitosterol 21. Since, the estimation of Acetylcholinesterase activity provides valuable information on cholinergic neurotransmission, an attempt was made in the present study to investigate the neuropharmacological action and anti-alzheimeric properties of different concen-trations of two different extracts of the medicinal plant W. somnifera, in scopolamine-induced AD concerning cholinergic neurotransmission.
In view of its broad spectrum of reported therapeutic properties, but with only limited scientific reports on the effective activity of this plant in different regions in albino rat, Cerebral cortex (CC), Cerebellum (CB), Hippocampus (HC), Hypothalamus (HT) and Pons, impairment of which leads to AD, we aimed to determine whether or not the extract from W. somnifera root could inhibit AChE activity in different brain regions of Scopolamine-induced AD rats. The results obtained from our study might facilitate the inhibited AChE activity in different regions of scopolamine-induced AD rat brain.
MATERIALS AND METHODS:
Collection of Plant Material: Withania somnifera Linn. (W. somnifera) (common name: Ashwagandha) is an Indian medicinal plant that grows as an evergreen shrub in dry parts of India (Ayurveda). W. somnifera is also one of the members of GRAS (Generally regarded as safe) category of plants that can be used for therapeutic purposes 22. Roots of W. somnifera was purchased from an Ayurvedic products distributor (Indian Drugs and Stores, Bangalore) and authenticated by a botanist, Department of Botany, S.V. University, Tirupati, Andhra Pradesh. A voucher specimen was deposited in the herbarium of the Department of Botany, S.V. University, Tirupati (Voucher No. 2437).
Extract Preparation: The dried roots were ground into a coarse powder using a pulverizer. Powdered plant material was soaked in methanol for 24 hr at room temperature, and the solvent was filtered with Whatman filter paper (125 mm). This was repeated 3-4 times until the extract gave no coloration. The extract was distilled and concentrated under reduced pressure in the Buchi Rotavapor R-114 yielding a gum-like residue. The same was repeated with distilled water. Finally, the crude extracts of methanol and water (aqueous) were collected, weighed, and stored in the refrigerator at 4 ºC for further use to treat the animals.
Experimental animals: Adult male Wistar rats, 4 months of age, with weights between 300-350g were maintained in polypropylene cages (5 in each cage at 26 ºC; 12 h light: dark cycle). The animals were fed standard pellet diet and water ad libitum. The animal study was performed by the guidelines provided by the Institutional Animal Ethics Committee of the National Institute of Mental Health and Neuro Sciences.
The rats were divided into the following groups and treated for 10 successive days:
Group I: Controls treated with normal saline (oral)
Group II: Scopolamine dissolved in normal saline (2mg/Kg b.w., i.p.)
Group III: Scopolamine (2mg/Kg b.w., i.p.) + methanol extract (100mg/Kg b.w., oral)
Group IV: Scopolamine (2mg/Kg b.w., i.p.) + methanol extract (200mg/Kg b.w., oral)
Group V: Scopolamine (2mg/Kg b.w., i.p.) + methanol extract (300mg/Kg b.w., oral)
Group VI: Scopolamine (2mg/Kg b.w., i.p.) + Aqueous extract (100mg/Kg b.w., oral)
Group VII: Scopolamine (2mg/Kg b.w., i.p.) + Aqueous extract (200mg/Kg b.w., oral)
Group VIII: Scopolamine (2mg/Kg b.w., i.p.) + Aqueous extract (300mg/Kg b.w., oral)
Group IX: Scopolamine (2mg/Kg b.w., i.p.) + Donepezil hydrochloride (5mg/Kg b.w., oral)
The animals from each group were decapitated after 10 days treatment, the brains quickly removed and washed in ice-cold saline. Different regions such as Cerebral Cortex (CC), Cerebellum (CB), Hippocampus (HC), Hypothalamus (HT) and Pons from the brain were quickly dissected out on an ice-cold petri-dish and stored at -80 ºC till used for ACh and AChE assays.
Drugs and Chemicals: Scopolamine hydro-bromide (Scopolamine), Donepezil hydrochloride (Donepezil), Acetylthiocholine iodide, 5, 5'-Dithio-bis (2-Nitrobenzoic acid) (DTNB) and Hydroxylamine hydrochloride were obtained from Sigma Chemicals. All other chemicals used were analytical reagent grade.
Acetylcholinesterase (AChE) Assay: Acetylcholi-nesterase activity was estimated by Ellmann’s method modified by Srikumar et al., 2004 with small modifications 23. The tissues were weighed and homogenized in 0.1M Phosphate buffer (pH 8). The aliquot of the homogenate was added to a microwell containing 0.1M phosphate buffer and 0.01M DTNB. The contents are mixed thoroughly and measured the initial reading at 412 nm. The 0.075M substrate, i.e., acetylthiocholine was added, and change in absorbance was recorded in microplate reader for a period of 10 min at intervals of 2min. Change in absorbance per minute was thus determined.
Acetylcholine (ACh) Estimation: Acetylcholine in different regions of the brain was estimated using Hydroxylamine method by Hestrin and modified by Stepankova et al., 24 with small modifications. The reaction mixture was prepared and mixed with the aqueous hydroxylamine hydrochloride and 3.5M aqueous KOH (1:1 v/v). The resulting mixture was mixed 2 min. To convert ACh totally to acetohydroxamic acid. Then the pH value was changed again by adding Conc. HCl/H20 (1:2 v/v). The reddish brown color formed after adding 0.37M ferric nitrate was read at 540nm in a microplate reader. The ACh content was calculated concerning the standard values.
Statistical Analyses: All data presented are means, standard errors and ANOVAs were calculated using SPSS statistical software.
RESULTS: From the present data it was observed that scopolamine-treated rats showed significant increase in AChE activity in all the brain regions Cerebral cortex (CC), Cerebellum (CB), Hippocampus (HC), and Pons except in Hypothalamus (HT) where it showed non-significant increase in AChE activity when compared to normal saline-treated controls. In contrast to this, the rats treated with methanol extract (ME) of W. somnifera 100mg, 200mg and 300mg/Kg b.w. showed decrease in AChE activity in all the brain regions in a dose-dependent manner. 200mg/Kg of ME showed significant decrease in Hippocampus (HC) whereas 300mg/Kg showed significant decrease in all the brain regions when compare to scopolamine-treated rats Table 1; Fig 1. The rats treated with an aqueous extract (AE) of W. somnifera also showed the decrease in AChE activity in a dose-dependent manner Table 2; Fig 2. But unlike ME, 100 and 200mg/Kg of AE showed significant anti AChE activity in CB and HC regions. Rats treated with 300mg/Kg of AE showed a highly significant decrease in AChE activity in all the brain regions except in HT, where it was insignificant. The rats treated with reference standard Donepezil Hydrochloride (DH) showed decreased AChE activity in all the regions when compare to scopolamine-treated rats but it was highly significant in CC and CB regions only.
TABLE 1: EFFECT OF DIFFERENT CONCENTRATIONS OF METHANOL EXTRACT OF W. SOMNIFERA ROOT POWDER ON ACHE ACTIVITY IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of substrate hydrolyzed/mg tissue/min)
S. no. | Name of the tissue | Normal Control | Scopolamine | Scopolamine + Methanol Extract | Scopolamine+
Donepezil |
||
100mg/Kg | 200mg/Kg | 300mg/Kg | |||||
1 | CC | 0.393±0.01 | 0.669 Ϯ Ϯ±0.018 | 0.613± 0.02 | 0.518*±0.038 | 0.388**±0.019 | 0.368**± 0.005 |
2 | CB | 0.379±0.019 | 0.684 Ϯ Ϯ±0.013 | 0.622±0.007 | 0.589±0.009 | 0.368**±0.004 | 0.443**±0.033 |
3 | HC | 0.537±0.062 | 1.783 Ϯ Ϯ±0.299 | 0.814±0.109 | 0.604*±0.128 | 0.463**±0.052 | 0.854± 0.255 |
4 | HT | 0.601±0.149 | 1.575 Ϯ Ϯ±0.507 | 0.978±0.188 | 0.796*±0.246 | 0.472*±0.064 | 0.842± 0.475 |
5 | Pons | 0.475±0.048 | 1.786 Ϯ Ϯ±0.154 | 0.729±0.049 | 0.641*±0.054 | 0.492**±0.055 | 0.985± 0.088 |
All values are Mean ±SEM; n=5; Ϯ P≤0.05, ϮϮ P≤0.005 as compared with Control; *P ≤0.05, **P≤0.005 as compared with Scopolamine. (CC-cerebral cortex; CB-cerebellum; HC-Hippocampus; HT-Hypothalamus)
GRAPH 1: GRAPHICAL REPRESENTATION OF DIFFERENT CONCENTRATIONS OF METHANOL EXTRACT OF W. SOMNIFERA ROOT POWDER ON ACHE ACTIVITY IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of substrate hydrolyzed/mg tissue/min.)
TABLE 2: EFFECT OF DIFFERENT CONCENTRATIONS OF AQUEOUS EXTRACT OF W. SOMNIFERA ROOT POWDER ON ACHE ACTIVITY IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of substrate hydrolyzed/mg tissue/min)
S. no. | Name of the tissue | Normal Control | Scopolamine | Scopolamine + Aqueous Extract | Scopolamine+
Donepezil |
||
100mg/Kg | 200mg/Kg | 300mg/Kg | |||||
1 | CC | 0.393±0.01 | 0.669 Ϯ ±0.018 | 0.607±0.029 | 0.590±0.013 | 0.446**±0.012 | 0.268**± 0.005 |
2 | CB | 0.379±0.019 | 0.684 Ϯ Ϯ±0.013 | 0.514**±0.031 | 0.485**±0.023 | 0.419**±0.0133 | 0.443**±0.033 |
3 | HC | 0.537±0.062 | 1.783 Ϯ Ϯ± 0.299 | 0.745±0.161 | 0.632±0.157 | 0.502**±0.048 | 0.854± 0.255 |
4 | HT | 0.601± 0.149 | 1.575 Ϯ Ϯ± 0.507 | 0.989±0.324 | 0.784*±0.127 | 0.544**±0.062 | 0.842±0.475 |
5 | Pons | 0.475±0.048 | 1.786 Ϯ Ϯ± 0.154 | 1.5730.262 | 1.1470.300 | 0.573**±0.262 | 0.985± 0.088 |
All values are Mean ±SEM; n=5; Ϯ P≤0.05, ϮϮ P≤0.005 as compared with Control; *P ≤0.05, **P≤0.005 as compared with Scopolamine. (CC-cerebral cortex; CB-cerebellum; HC-Hippocampus; HT-Hypothalamus)
GRAPH 2: GRAPHICAL REPRESENTATION OF DIFFERENT CONCENTRATIONS OF AQUEOUS EXTRACT OF W. SOMNIFERA ROOT POWDER ON ACHE ACTIVITY IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of substrate hydrolyzed/mg tissue/min.)
Acetylcholine (ACh) content in scopolamine-treated rats was decreased significantly in all the brain regions (Table 3, 4; Fig. 3, 4) as AChE activity showed an increase with scopolamine-treatment. In contrast to this, the rats treated with ME and AE with 100mg, 200mg, and 300mg/Kg BW showed the recovery in ACh content in all the brain regions in a dose-dependent manner.
All the three doses mentioned above showed an increase in all the regions, while rats treated with 300mg/Kg b.w. ME and AE showed a significant increase in ACh content in all the regions.
At the same time, 200mg/kg BW of ME showed a significant decrease in AChE and increased in ACh in HC, and 200mg/Kg BW of AE showed a significant decrease in AChE and increase in ACh in CB and HT regions. The effect of 300mg/Kg was highly significant in all the five brain regions were 100 and 200mg/Kg showing a significant effect in limited regions. The significant response with 300mg/Kg of ME and AE in scopolamine-treated rats suggests that this dose maintains the homeostasis of the cholinergic system in all the cerebral structures discussed above.
TABLE 3: EFFECT OF DIFFERENT CONCENTRATIONS OF METHANOL EXTRACT OF W. SOMNIFERA ROOT ON ACH CONTENT IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of Acetylcholine/mg tissue)
S. no. | Name of the tissue | Normal Control | Scopolamine | Scopolamine + Methanol Extract | Scopolamine+
Donepezil |
||
100mg/Kg | 200mg/Kg | 300mg/Kg | |||||
1 | CC | 0.539
±0.044 |
0.252 Ϯ Ϯ
±0.027 |
0.351
± 0.056 |
0.442
± 0.023 |
0.506*
± 0.048 |
0.480*
± 0.030 |
2 | CB | 0.393
±0.047 |
0.180 Ϯ Ϯ
±0.011 |
0.237
± 0.028 |
0.271
± 0.026 |
0.362*
± 0.016 |
0.369*
±0.033 |
3 | HC | 0.478
± 0.014 |
0.194 Ϯ Ϯ
± 0.021 |
0.204
± 0.027 |
0.418*
± 0.033 |
0.486**
± 0.064 |
0.399*
± 0.017 |
4 | HT | 0.447
± 0.051 |
0.169 Ϯ
± 0.010 |
0.265
± 0.027 |
0.314
± 0.054 |
0.474*
± 0.060 |
0.300
± 0.050 |
5 | Pons | 0.475
± 0.019 |
0.203 Ϯ Ϯ
± 0.044 |
0.295
± 0.030 |
0.330
± 0.043 |
0.445*
± 0.055 |
0.407
± 0.025 |
All values are Mean ±SEM; n=5; Ϯ P≤0.05 ϮϮ P≤0.005 as compared with Control; *P ≤0.05, **P≤0.005 as compared with Scopolamine. (CC-cerebral cortex; CB-cerebellum; HC-Hippocampus; HT-Hypothalamus)
GRAPH 3: GRAPHICAL REPRESENTATION OF DIFFERENT CONCENTRATIONS OF METHANOL EXTRACT OF W. SOMNIFERA ROOT POWDER ON ACH CONTENT IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of Acetylcholine/mg tissue)
TABLE 4: EFFECT OF DIFFERENT CONCENTRATIONS OF AQUEOUS EXTRACT OF W. SOMNIFERA ROOT ON ACH CONTENT IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of acetylcholine/mg tissue)
S.
no. |
Name of the tissue | Normal Control | Scopolamine | Scopolamine + Aqueous Extract | Scopolamine+
Donepezil |
||
100mg/Kg | 200mg/Kg | 300mg/Kg | |||||
1 | CC | 0.539±0.044 | 0.252 Ϯ Ϯ±0.027 | 0.351±0.048 | 0.473±0.016 | 0.495*±0.025 | 0.480*±0.030 |
2 | CB | 0.393±0.047 | 0.180 Ϯ Ϯ±0.011 | 0.344±0.044 | 0.369*±0.028 | 0.391**±0.009 | 0.369*±0.033 |
3 | HC | 0.478±0.014 | 0.194 Ϯ Ϯ± 0.021 | 0.312±0.020 | 0.321±0.023 | 0.455**±0.045 | 0.399*± 0.017 |
4 | HT | 0.447±0.051 | 0.169 Ϯ± 0.010 | 0.267±0.324 | 0.446*±0.127 | 0.463*±0.035 | 0.300±0.050 |
5 | Pons | 0.475±0.019 | 0.203 Ϯ Ϯ± 0.044 | 0.231±0.027 | 0.378±0.308 | 0.434*±0.048 | 0.407±0.025 |
All values are Mean ±SEM; n=5; Ϯ P≤0.05 ϮϮ P≤0.005 as compared with Control; *P ≤0.05 **P≤0.005 as compared with Scopolamine. (CC-cerebral cortex; CB-cerebellum; HC-Hippocampus; HT-Hypothalamus
GRAPH 4: GRAPHICAL REPRESENTATION OF DIFFERENT CONCENTRATIONS OF AQUEOUS EXTRACT OF W. SOMNIFERA ROOT POWDER ON ACH CONTENT IN DIFFERENT BRAIN REGIONS OF SCOPOLAMINE-INDUCED AD RAT BRAIN (µmoles of Acetylcholine/mg tissue)
DISCUSSION: Alzheimer’s disease (AD) is a disorder coupled with progressive degeneration of memory and cognitive function. Cholinesterase inhibitors are the recommended drugs for treating patients with mild to severe AD 25, 26. The cholinergic theory assumes that memory impairment in patients with AD occurs from a shortfall of cholinergic activity in the brain. Acetylcholinesterase inhibitors can reinstate the amount of acetylcholine by inhibiting AChE. Over the years, medicinal plants have offered components with decent AChE inhibitory activity 27 and could be a potential source.
Some studies reported a very significant increase in AChE activity in scopolamine treated group 28. The reports showed that the increase in AChE due to the scopolamine leads to the amnesia and which is reversed by prunus amygdalus in rats 29. Studies on the brain from patients suffering from AD have shown reduced AChE activity in the hippocampus and cortex 30. Biopsy studies in AD patients reported decreased AChE activity with concurrent loss of cognitive function 30. AChE is known to have many classical functions and morphological role in a growing body. During early development, AChE expression is tightly correlated with neurite outgrowth, in addition to its role in cell survival and growth 31.
In this study, we observed the reversible action of different doses ME and AE against the scopolamine-induced hyperactivity of AChE.
Previous studies have found the anti-cholinesterase activity of methanol, and aqueous extracts from many natural fruits and vegetables in AD brain 32. It has been reported that an aqueous extract of W. somnifera root inhibited AChE in a concentration-dependent manner in-vitro 33.
The studies on the whole brain showed that this aqueous root extract might be useful in improving memory and other cognitive functions associated with the cholinergic system 33. Histological and biochemical studies reported that significant inhibitory effect of W. somnifera leaf juice on AChE in mice brain 34.
It has been already reported that W. somnifera leaf extract and it's component withanone shows downregulation of neuronal cell markers NF-H, MAP2, PSD-95, GAP-43 and glial cell marker, GFAP, and upregulation of DNA damage-γH2AX and oxidative stress-ROS markers in scopolamine-induced cytotoxicity in IM32 neuronal and C6 glioma cells 35. Administration of defined extracts like sitoindosides VII-X and withaferin A i.p. for 7 days reduced the cholinergic neurons in the vertical, diagonal band whereas increased in lateral septum and globus pallidus regions in rat brain 36.
The rats administered with higher doses of aqueous and chloroform extracts along with ibotonic acid, which develops syndrome with pathological features similar to AD, significantly lowered cholinergic deterioration in rat brain 37.
Since flavonoids show AChE inhibitory activity, W. somnifera rich in flavonoids in its root and whole plant shows significant effects on recovery from Scopolamine - induced AD 38, 39.
From these results, it is obvious that ME and AE of W. somnifera extracts have conspicuous effects on recovery from Scopolamine - induced AD. The increase in AChE activity and decrease in ACh content in different regions of the brain seems to augment the anti-Alzheimeric effect of scopolamine-induced AD.
In contrast, the decreased AChE activity and increased ACh levels resulting from post-treatment with ME and AE in all regions of the brain imply their anti-Alzheimeric effect. Quite interestingly, the changes in AChE activity and ACh content occurred in all regions of the brain, whether targeted or non-targeted areas. This indicates that the anti-Alzheimeric effect of W. somnifera extracts proceeds through generalized changes in different brain regions in addition to their specific impact on targeted regions.
Although several synthetic cholinesterase inhibitors such as tacrine, rivastigmine, and donepezil, are being used for management of conditions such as AD, their side effects have become noticeable 40. Some promising results have been achieved by acetylcholinesterase inhibitors, but effective therapeutic intervention in Alzheimer’s disease remains an important goal.
CONCLUSION: In the present study, the changes in AChE activity and ACh content were maximal with 300mg/Kg b.w. of ME and AE. Hence it may be concluded that these extracts with this concentration have anti-alzheimeric activity and cause perceptible changes in the cholinergic system, at least as part of their anti-alzheimeric effect.
Besides cholinergic blockade, scopolamine-induced memory loss, cognitive impairment, and oxidative stress may be associated with Alzheimer’s and W. somnifera may serve as a potential preventive and therapeutic agent for neurodegenerative disorders. Hence further studies are warranted in this area.
ACKNOWLEDGEMENT: The authors acknow-ledge with profound gratitude to the Science and Engineering Research Board (SERB), Govt. of India for providing the funds under “Fast Track Scheme for Young Investigators” (Ref No. SR/FT/LS-199-2009).
CONFLICT OF INTEREST: Nil
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How to cite this article:
Visweswari G, Christopher R and Rajendra W: Dose-dependent effect of Withania somnifera on the cholinergic system in scopolamine-induced alzheimer’s disease in rats. Int J Pharm Sci & Res 2014; 5(10): 4240-48. doi: 10.13040/IJPSR.0975-8232.5(10).4240-48.
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Article Information
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4240-4248
773
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English
IJPSR
G. Visweswari *, R. Christopher and W. Rajendra
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
visweswari.g@gmail.com
20 March 2014
27 May 2014
09 July 2014
10.13040/IJPSR.0975-8232.5(10).4240-48
01 October 2014