• Users Online: 187
  • Print this page
  • Email this page


 
 
Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 68  |  Issue : 4  |  Page : 269-273

Saraswatarishta reverses neuronal injury in brain tissues of scopolamine-induced rat model


1 Department of Anatomy, Sree Balaji Medical College, Chrompet, Chennai, Tamil Nadu, India
2 Department of Anatomy, Chettinad Academy of Research and Education, Kanchipuram, Tamil Nadu, India

Date of Submission26-Apr-2019
Date of Acceptance10-Jan-2020
Date of Web Publication28-Feb-2020

Correspondence Address:
Dr. S Jayakumari
Department of Anatomy, Sree Balaji Medical College and Hospital, Bharath Institute of Higher Education and Research, Chromepet, Chennai - 600 044, Tamil Nadu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JASI.JASI_45_19

Rights and Permissions
  Abstract 


Introduction: Neuroinflammation has been implicated in the pathogenesis or the progression of the variety of acute and chronic neurological and neurodegenerative disorders, including Alzheimer's disease. The Saraswatarishta is an Ayurvedic medicine utilized in many health conditions such as anti-aging, to improve memory, immunity, and quality of semen and sperms to treat epilepsy and cosmetic use for skins. It is a liquid Ayurvedic medicine. Saraswatarishta contains 5%–10% of self-produced alcohol in it, which serves as a vehicle to deliver water- and alcohol-soluble active herbal components to the body. It is also called Sarasvatarishtam. The aim of this study was to find the possible neuroprotective role of Saraswatarishtam as a preventive Ayurveda and Siddha drug to hamper cholinergic dysfunctions and histopathological changes in scopolamine-treated rat model. Material and Methods: The compound Saraswatarishtam was obtained from standard Ayurvedic vendor at Chennai. Group 1 – normal control animals received normal saline for 8 continuous days. Group 2 – positive control treated with scopolamine (0.4 mg/kg). Group 3 – received 200 mg/kg of piracetam for 8 continuous days. Group 4 and Group 5 served as a test and received 200 mg/kg and 400 mg/kg of Saraswatarishtam, respectively, for 8 continuous days. On the 8th day, after 90 min of drug administration, Group 2, Group 3, Group 4 and Group 5, were treated with 0.4 mg/kg of scopolamine. Brain tissues were dissected out and analyzed for histopathological changes after sacrifice with high dose of halothane. Results: Administration of scopolamine produced marked focal gliosis with mononuclear infiltration. The hippocampal region showed neuronal degeneration with sclerosis. Piracetam treated group showed pyknotic nucleus in neurons of the cerebral cortex and mild edema. Low dose (200 mg/kg) treatment with Saraswatarishtam followed by scopolamine administration showed moderate histopathological changes such as mild infiltration of monocytes but normal neuronal architecture. High dose (400 mg/kg) treatment with Saraswatarishtam followed by scopolamine administration shows abnormal morphology of cerebrum, cerebellum, basal nuclei, and hippocampus. Discussion and Conclusion: The results of the present study suggested that Saraswatarishtam exhibits neuroprotective properties against scopolamine-induced neuronal damage.

Keywords: Albino mice, ayurvedic, neuroinflammation, neuroprotective, saraswatarishta


How to cite this article:
Prabhu J, Jayakumari S, Prabhu K, Kumar JA, Subramanian M, Kavimani. Saraswatarishta reverses neuronal injury in brain tissues of scopolamine-induced rat model. J Anat Soc India 2019;68:269-73

How to cite this URL:
Prabhu J, Jayakumari S, Prabhu K, Kumar JA, Subramanian M, Kavimani. Saraswatarishta reverses neuronal injury in brain tissues of scopolamine-induced rat model. J Anat Soc India [serial online] 2019 [cited 2020 Jul 13];68:269-73. Available from: http://www.jasi.org.in/text.asp?2019/68/4/269/279739




  Introduction Top


Neuroinflammation is an inflammatory response characterized by gliosis in the central nervous system due to triggering of the immune system. There are various medicines to treat neuronal inflammation such as nonsteroidal anti-inflammatory drugs (NSAIDS), opioid antagonists, selective cyclooxygenase inhibitor, N-methyl-D-aspartate receptor antagonists, and occasionally antibiotics.[1],[2] However, those allopathic drugs are efficient to relive analgesia and inflammation, but they create unwanted adverse effects. For example, NSAIDS causes gastric irritation, pain abdomen, nausea, cramping, ringing in ears, confusion[3] diminish the motility of the sperm.[4] While the opioid antagonist induces adverse effects such as loss of appetite, dizziness, and nervousness. To avoid these adverse effects, the researchers tried to explore the neuroprotective role of certain drugs in the Indian system of medicine, one such preparation found in the ancient Indian treatment is Saraswatarishta.

Various naturally available elements have been anticipated as a potential treatment for reduction or slow down the process of different types of acute and chronic neurological and neurodegenerative disorders, including Alzheimer's disease.[5],[6] In the formulation of Ayurvedic medicines, many herbal and herbo-mineral elements are commonly used to treat various conditions these formulations are based on the concept that they provide synergistic therapeutic outcomes and aids in reducing the adverse effects of major drugs[7] (Bhattacharya SK 1994). One such multi-ingredient plant-based herbo-mineral formulation is “Saraswatarishta” which comprises 18 plants.[8] Some of which include Ashwagandha, Brahmi, and Shatavari which are Medhya rasayanas. Medhya rasayanas are used to improve memory and cognitive deficits.[9] Saraswatarishtais claimed to be helpful for the management of acute anxiety, fatigue, insomnia, partial loss of memory, low grasping power, and slurred speech, etc.,[8] In view of the central nervous system effects of Saraswatarishta described in Ayurveda, it was of interest to study whether it has a protective effect on neurons of the central nervous system.


  Material and Methods Top


Preparation of saraswatarishta

Saraswatarishtam

The compound Saraswatarishtam was obtained from standard Ayurvedic vendor at Chennai. Integrands of this formulation are illustrated in [Table 1].
Table 1: List of ingredients used in the preparation of Saraswatarishta

Click here to view


Animals

Healthy adult Swiss Albino mice of both sexes weighing 25–30 g were selected as exterminate animals. Standard laboratory procedures were maintained for animals. The laboratory temperature was kept at 22°C ± 3°C, and the humidity was maintained at 45%–55%. 12 h dark/light cycles were maintained.

All the animal experiments were conducted according to the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). Experimental protocol was approved by Institution of Animal Ethical Committee of KMCH governed by CPCSEA, Government of India. Proposal number: 685/po/02/a/DPCSE.[10]

Group 1 – normal control animals they received normal saline for 8 continuous days. Group 2 – negative control treated with scopolamine (0.4 mg/kg). Group 3 – received 200 mg/kg of piracetam for 8 continuous days. Group 4 and Group 5 served as test and received 200 mg/kg and 400 mg/kg of Saraswatarishtam, respectively, for 8 continuous days. Saraswatarishtam was dissolved in water and administered by oral feeding with a feeding needle. On the 8th day, after 90 min of test drug administration, Group 2, Group 3, Group 4 and Group 5 were treated with 0.4 mg/kg of scopolamine.

Histopathology

Brain tissue was dissected out after sacrifice with a high dose of halothane. Tissues were fixed in 10% buffered formalin, dehydrated with alcohol, cleared with xylene, impregnated with paraffin, embedded in paraffin wax, and sectioned with microtome to obtain 4–5 μm thick paraffin sections, Dewaxed sections were stained with hematoxylin and eosin and observed under microscope for scopolamine-induced changes and neuroprotective efficiency of Saraswatarishtam.


  Results Top


Group 1 animals showed normal histoarchitecture of the cerebral cortex and cerebellar cortex [Figure 1]a, no changes were seen in the molecular and Purkinje cell layer of the cerebral cortex [Figure 1]b. Brain sections of scopolamine treated rats (Group 2) showed focal gliosis with marked monocyte infiltration suggestive of inflammation in the cerebral cortex, and the neurons exhibited pyknotic nucleus suggestive of chromatolysis [Figure 2]a and [Figure 2]b. Brain sections of Group 3 animals showed tissue edema in the cerebral cortex [Figure 3]b in addition to the Pyknotic nucleus [Figure 3]a.
Figure 1: (a) The cerebrum of group showing normal histological features. H and E, ×10. (b) Photomicrographs of the cerebellum of Group 2 showing a normal cerebellum with Purkinje cells. H and E, ×40

Click here to view
Figure 2: (a) Photomicrographs of the cerebrum of Group 2 showing focal gliosis with mononuclear infiltration (arrow). H and E, ×10. (b) Photomicrographs of the cerebrum of Group 2 showing pyknotic nucleus (arrow). H and E, ×40

Click here to view
Figure 3: (a) Photomicrographs of the cerebrum of Group 3 showing the brain parenchyma with Swollen neurons (arrow). H and E, ×10. (b) Photomicrographs of the cerebrum of Group 3 showing neurons with pyknotic nucleus (arrow) and edema. H and E, ×40

Click here to view


In Group 4 animals, the white matter of cerebrum did not show any degenerative changes [Figure 3]a. Group 4 animals were treated with low dose of Saraswatarishtam which showed normal cyto-architecture of the cerebral cortex [Figure 4]a but mild infiltration of monocytes [Figure 4]b. The hippocampus of Group 5 animals showed normal architecture with normal polymorphic, pyramidal, and granular layers [Figure 5]a, the cerebellum of this group showed normal morphology [Figure 5]b.
Figure 4: (a) Photomicrographs of cerebrum of group 4 showing normal white matter ×10 H and E. (b) Photomicrographs of cerebrum of group 4 showing mild infiltration of mononuclear cells ×40 H and E

Click here to view
Figure 5: (a) Photomicrographs of hippocampal region Group 5 showing normal neuro architecture of hippocampus with three distinguish layers (arrow = polymorphic layer, arrowhead = pyramidal layer, star = ganglion layer). H and E, ×10. (b) Photomicrographs of cerebellum of Group 5 showing normal neuronal architecture (arrow = Purkinje cell layer, arrowhead = granular cell layer, star = molecular layer). H and E, ×40

Click here to view



  Discussion Top


The findings of the current study suggest that Saraswatarishtam rescues the neurons from the scopolamine-induced neuroinflammation. Scopolamine, a nonselective muscarinic antagonist, stops cholinergic signaling and induces memory and cognitive impairment.[11] Administration of scopolamine has been extensively and successfully utilized as a model for Alzheimer's disease in rats.[12],[13] Various studies have suggested that oxidative stress might be associated with the pathophysiology of many neurological disorders and brain dysfunction.[14] Therefore, neuronal cell death by oxidative stress and progression of neurodegenerative disorders can be attenuated by the supplementation of antioxidants and free radical scavengers.[15] Administration of scopolamine is associated with increased brain lipid peroxides and reduced brain anti-oxidant levels.[16] Histopathological examination of brain sections of control rats demonstrated the normal morphology of the cerebral cortex and hippocampus. While scopolamine induced at brain sections illustrated severe congestion in the capillaries with perivascular edema in the cortex. In the meantime, the hippocampus revealed encephalomalacia and edema in the tissue matrix with demyelination and neuronal degeneration.[17] Thus, previous studies concluded that scopolamine administration leads to neuronal inflammation, neuronal degeneration, encephalomalacia, cerebral edema, and demyelination. In the present study, the administration of scopolamine induced neuroinflammation in the brain tissue of the rat model.

The piracetam is a standard drug to treat Alzheimer's disease, dementia, memory dysfunction, alcoholism, Raynaud's phenomenon, deep-vein thrombosis, stroke, tardive dyskinesia, dyslexia, convulsions, brain injury, and vertigo. Piracetam helps by enhancing cell membrane permeability and boost oxygen consumption and serves as an enhancer of acetylcholine action through muscarinic cholinergic receptors, and these receptors give an essential contribution in memory and learning.[18],[19] Piracetam can induce neuroplasticity which improves memory and learning process, thereby preventing lesions and ischemic damages. Even it increases microcirculation and will be administered as treatment of cerebral ischemia. However, piracetam administration can cause obesity, insomnia, depression, muscle spasm, hyperactivity, and skin rashes.

Group 3 animals were treated with this drug as a standard or negative control to compare the efficience of Saraswatarishtam. Ayurveda believes in treating complex diseases with a complex combination of natural products, including animals, plants, and minerals.[20] Saraswatharishta is a capable agent in prophylaxis and management of neuropsychiatric and neurodegenerative conditions. Earlier studies stated that Sarawatharishtam has anxiolytic and antidepressant activities, but there is a shortage of data concerning neuroprotective activity. Thus, the current study evaluates its role in neuroprotection.

Histopathological sections of scopolamine-induced animal brain tissue show abnormal cellular morphology with inflammatory changes such as focal gliosis with mononuclear infiltration and hippocampal neuronal degeneration with sclerosis. In piracetam-treated animals, few neurons with the pyknotic nucleus and mild edema of tissue fluid were observed. On the other hand, the animal receiving 200 mg/kg of Saraswatarishtam showed similar structure as piracetam-treated animals except mild gliosis in the cerebral cortex.

The brain sections of Saraswatharishtam treated animals at a dose of 400 mg/kg were similar to control animals. When compared with sections of with piracetam-induced animals, the Saraswatharishtam fairly inverted the scopolamine-induced neurodegeneration, and the reports were almost similar to piracetam treatment. Further, dose regulation and experimental modification are required to substitute Saraswatharishtam as a neuroprotective agent against neuroinflammation.


  Conclusion Top


The findings of the present study conclude that Saraswatarishtam has a protective role against neuronal inflammation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, et al. Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol 2009;183:2089-96.  Back to cited text no. 1
    
2.
Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J 2008;22:383-90.  Back to cited text no. 2
    
3.
Rostom A, Wells G, Tugwell P, Welch V, Dube C, McGowan J. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2000;(4):CD002296.  Back to cited text no. 3
    
4.
Balaji T, Aruna S, Ramanathan M, Srinivasan M, Menon VP. Suppression of constitutively expressed cyclooxygenase-2 in the epididymis of mice by nimesulide decreases sperm motility. J Basic Clin Physiol Pharmacol 2009;20:357-76.  Back to cited text no. 4
    
5.
Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223-9.  Back to cited text no. 5
    
6.
Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287:3230-7.  Back to cited text no. 6
    
7.
Bhattacharya SK. Behavioural studies on BR-16A (Mentat), a herbal psychotropic formulation. Indian J Exp Biol 1994;32:37-43.  Back to cited text no. 7
    
8.
Shastri RV, Atha Vajikaranaprakaranam., editor. Bhaisajyaratnavali, Vidyotini – Hindivyakhya – Vimarsh-Parishishtasahita. Varanasi: Chaukhamba Sanskrit Bhavan; 2002. p. 796-7.  Back to cited text no. 8
    
9.
Shastri RV Atha Vajikaranaprakaranam., editor. Bhaisajyaratnavali, Vidyotini – Hindivyakhya – Vimarsh-Parishishtasahita. Varanasi: Chaukhamba Sanskrit Bhavan; 2002. p. 775-6.  Back to cited text no. 9
    
10.
Department of Indian Systems of Medicine and Homoeopathy, Ministry of Health and Family Welfare, Government of India. 1st ed. Part I. Department of Indian Systems of Medicine and Homoeopathy, Ministry of Health and Family Welfare, Government of India; New Delhi: 2003. Ayurvedic Formulary of India; p. 119.  Back to cited text no. 10
    
11.
Souza AC, Bruning CA, Acker CI, Neto JS, Nogueira CW. 2-Phenylethynyl-butyltellurium enhances learning and memory impaired by scopolamine in mice. Behav Pharmacol 2013;24:249-54.  Back to cited text no. 11
    
12.
Karimi S, Hejazian SH, Alikhani V, Hosseini M. The effects of tamoxifen on spatial and nonspatial learning and memory impairments induced by scopolamine and the brain tissues oxidative damage in ovariectomized rats. Adv Biomed Res 2015;4:196.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Reza Sadeghnia H, Soukhtanloo M. Effects of the hydro-alcoholic extract of Nigella sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med 2015;21:438-44.  Back to cited text no. 13
    
14.
Reddy VP, Zhu X, Perry G, Smith MA. Oxidative stress in diabetes and Alzheimer's disease. J Alzheimers Dis 2009;16:763-74.  Back to cited text no. 14
    
15.
15. Schroeter H, Williams RJ, Matin R, Iversen L, Rice-Evans CA. Phenolic antioxidants attenuate neuronal cell death following uptake of oxidized low-density lipoprotein. Free Radic Biol Med 2000;29:1222-33.  Back to cited text no. 15
    
16.
Zaki HF, Abd-El-Fattah MA, Amina S, Attia AS, Naringenin protects against scopolamine-induced dementia in rats. Bull Fac Pharm Cairo Univ 2014;52:15-25.  Back to cited text no. 16
    
17.
Zaki HF, Abd-El-Fattah MA, Attia AS. Naringenin protects against scopolamine-induced dementia in rats. Bull Fac Pharm Cairo Univ 2014;52:15-25.  Back to cited text no. 17
    
18.
Leuner K, Kurz C, Guidetti G, Orgogozo JM, Müller WE. Improved mitochondrial function in brain aging and Alzheimer disease - the new mechanism of action of the old metabolic enhancer piracetam. Front Neuro sci 2010;4:44.  Back to cited text no. 18
    
19.
Suliman NA, Mat Taib CN, Mohd Moklas MA, Adenan MI, Hidayat Baharuldin MT, Basir R. Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic. Evid Based Complement Alternat Med 2016;2016:4391375.  Back to cited text no. 19
    
20.
Aneesh TP, Mohamed H, Sekhar S, Manjushree MM, Deepa TV. International market scenario of traditional Indianherbal drugs. Int J Green Pharm 2009;3:184-90.  Back to cited text no. 20
  [Full text]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Material and Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed209    
    Printed1    
    Emailed0    
    PDF Downloaded52    
    Comments [Add]    

Recommend this journal