Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

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Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
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It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Original article / research
Year : 2009 | Month : August | Volume : 3 | Issue : 4 | Page : 1657 - 1662

Effect Of Aqueous Fruit Extract Of Emblica Officinalis On Haloperidol Induced Catalepsy In Albino Mice

SUDHAKAR PEMMINATI*, V NAIR**,DORABABU.P**, GOPALAKRISHNA HN***, PAI MRSM ****.

*Lecturer,**PG Sudent, ***Assc.Prof., ****Professor & Head, Department of Pharmacology, Kasturba Medical College, MANGALORE-575 001, Karnataka, INDIA.

Correspondence Address :
Sudhakar Pemminati (Ph.D),Lecturer,
Dept. of Pharmacology,Kasturba Medical College,
MANGALORE – 575 001 Ph No.:0824 -2423452 Ext. 5568.
E-mail:pemmineti@yahoo.com

Abstract

Neuroleptic drugs used in the treatment of schizophrenia and other affective disorders are known to produce extrapyramidal side effects. Catalepsy was induced by these drugs in animals and these have been used as models for the extrapyramidal side effects associated with antipsychotic agents in human beings. In the present study, we have attempted to evaluate the protective effect of the aqueous extract of the fruits of Emblica officinalis (EO) on haloperidol (1.0mg/kg intraperitoneal administration) induced catalepsy in mice by employing the standard bar test. Mice were allocated to seven groups, each group containing six animals. The effects of the test drug EO (0.8, 2.0 and 4.0mg/kg doses) and the standard drugs scopolamine (1.0mg/kg) and ondansetron (0.5 and 1.0mg/kg doses) were assessed after single and repeated dose administration for seven days, 30 minutes prior to the haloperidol. Mice were sacrificed on the seventh day and super oxide dismutase (SOD) activity in the brain tissue was estimated by using the Beauchamp and Fridovich method. A significant (P<0.001) reduction in the cataleptic scores was observed in all the test drug treated groups as compared to the control, with maximum reduction in the dose 4.0mg/kg group. Similarly, the maximum reduction in SOD activity (P<0.01) was observed in the dose 4.0mg/kg group. Our study suggests that EO has significantly reduced oxidative stress and the cataleptic score induced by haloperidol. It could be used to prevent drug- induced extrapyramidal side effects.

Keywords

Emblica officinalis, haloperidol , catalepsy

Introduction
Neuroleptics that are commonly used in the treatment of schizophrenia and other affective disorders (1) are often associated with distressing extrapyramidal side effects [2,3]. The phenomenon of cataleptic immobility induced in rodents by typical neuroleptics (eg.haloperidol) is a robust behavioural model to study the nigrostriatal function and its modulation by cholinergic, 5-hydroxytryptamine (5-HT, serotonergic), nitrergic and other neurotransmitter systems [4,5]. Haloperidol induced catalepsy (HIC) occurs due to the blockage of dopamine (D2) receptors and reduced dopaminergic transmission (6). Enhanced stimulation of the intrinsic central cholinergic system has also been implicated in haloperidol induced catalepsy, as it has been reported to be enhanced and antagonised by cholinergic agonists and the blocker, atropine respectively (7). Evidence also suggests that the central serotonergic system modulates nigrostriatal dopaminergic transmission and 5-HT3 antagonists are reported to alleviate neuroleptic- induced catalepsy (4). Hence, scopolamine (a known anticholinergic agent) and ondansetron (a known 5-HT3 antagonist) have been used as standard drugs in this study to compare the anticataleptic effect of the test compound, EO.

Emblica officinalis Gaertn. (Phyllanthus emblica L.) belongs to the family Euphorbiaceae, popularly known as Amla, which is a common household remedy that finds its use in the Indian indigenous system of medicine against several ailments. Its fruits have been reported to possess expectorant, purgative, spasmolytic, antibacterial, hypoglycaemic (8), hepatoprotective (9) and hypolipidaemic (10) activities. The aqueous extract of the fruits of EO has been reported to have a cytoprotective activity against radiation and heavy metal induced toxicities (11) . It also antagonizes serotonin and acetylcholine induced contractions of oestrogenised rat uterus (12). These anticholinergic and antiserotonergic properties are important to treat neuroleptic induced catalepsy. EO fruits mainly contain tannins and vitamin C like substances in abundance and their chemical constituents include gallic acid, ellagic acid, emblicanin A and B, punigluconin and some 10-12 flavanoids (13). The aqueous extract of the EO fruits contain 30.0% tannins and 10.0% Gallic acid (estimation and purity of active principle was done by the Quality Control Laboratory, M/s. Natural Remedies, Bangalore, lab reference no.0505211, dt.31-05-2005). Recent studies on antioxiadant property of EO fruits in rat brain; by increasing super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) in rat brain; frontal cortex and striatum, concomitant with reduction in lipid peroxidation (LPO) (14).

From our laboratory, we have reported the anticataleptic activity of NR-ANX-C (a polyherbal product) on haloperidol induced catalepsy in mice (15). Emblica officinalis is one of the components of NR-ANX-C. The evidence of the anticholinergic, antiserotonergic and antioxidant properties of EO prompted us to evaluate for its anti-cataleptic activity.

Material and Methods

Animals
Adult male albino mice (weighing 25-30gm), bred in the central animal house of Kasturba Medical College, Mangalore, were used for the study. The animals were housed under standard 12hr: 12hr light/dark cycles and were provided with food and water ad libitum. The animals were acclimatized to laboratory conditions before testing. Each animal was used once. Experiments were performed between 10.00 and 16.00hrs. The experimental protocol was approved by the Institutional Animal Ethics Committee and the study was conducted according to the Indian National Science Academy Guidelines for the use and care of experimental animals.

Drugs and Dosage
The test drug: the aqueous extract of the fruits of Emblica officinalis (dry powder supplied by Natural Remedies Pvt. Ltd., Bangalore). The fresh fruits of EO were collected locally after proper identification, they were air dried, powdered and extracted with double distilled water. The extract thus obtained was vacuum evaporated in order to make it into powder form to be redissolved in double distilled water. It is a brown to very dark brown coloured powder with a characteristic odour and taste and was stored in air tight containers which are protected from light. Phytochemical analysis was done for total tannins by a spectrophotometer and Gallic acid was tested for by HPLC.

The standard drugs, scopolamine (German Remedies Ltd., Mumbai) and ondansetron ( Cipla Ltd.,Mumbai ) were suspended/ dissolved in 1% gum acacia solution while haloperidol (RPG Life Sciences Ltd.,Mumbai) was dissolved in distilled water. The treatments received by each group (each group consists of six animals, n=6) are shown in Table1 and 2. The group was received 1% gum acacia (10ml/kg) served as control. 1% gum acacia, scopolamine (1.0mg/kg), ondansetron (0.5 and 1.0mg/kg) and EO (0.8, 2.0 and 4.0mg/kg) were given orally, whereas haloperidol was given intraperitoneally.

Experimental design
Haloperidol Induced Catalepsy (HIC):Catalepsy was induced with haloperidol (1.0mg/kg i.p.) and was assessed at 30 minute intervals until 120 minutes and at the end of 240 minutes by means of a standard bar test [16,17]. Haloperidol (1mg/kg i.p.) was chosen so that it could elicit and thus enable the detection of either attenuation or potentiation of the phenomenon (6). Catalepsy was assessed in terms of the time for which the mouse maintained an imposed position with both front limbs extended and resting on a 4 cms high wooden bar (1.0cm diameter). The end point of catalepsy was considered to occur when both front paws were removed from the bar or if the animal moved its head in an exploratory manner. A cut-off time of 1100 seconds was applied. Between determinations, the animals were returned to their individual home cages. All observations were made between 10.00 and 16.00 hrs in a quiet room at 23-25º C.

Scoring method
If the animal maintained the imposed posture for at least 20 seconds, it was considered to be cataleptic and was given one point. For every additional 20 seconds for which the cataleptic posture was maintained, one extra point would be given. The animals were tested twice at 30 minute time intervals and only the greater duration of immobility was considered (16).

In the acute study, EO, scopolamine and ondansetron were administered only once 30 min prior to the haloperidol administration. In the chronic study, these drugs were administered once daily, 30 min prior to the haloperidol administration for seven days. Catalepsy was determined 30 min after haloperidol administration on the first and on the seventh day of treatment. The animals were then sacrificed by cervical dislocation and the SOD activity of the whole brain tissue was estimated by using the Beauchamp and Fridovich method (18).

Assay of SOD
The assay of SOD was carried out, based on the SOD mediated inhibition of the reduction of nitroblue tetrazolium to blue formation by super oxide anions, as described by Beauchamp and Fridovich. The total protein present in the homogenate was estimated following the method described by Lowry et al.(19). The units of SOD activity determined, were expressed in terms of milligrams of total protein (TP).The brains isolated from the individual groups of mice were homogenized (20% w/v) in 10 mM phosphate buffer pH 7.8. The homogenate was subjected to centrifugation. 0.1 ml aliquot of the homogenate (1:10 dilution) was used for the assay.

Statistical analysis
For each group, mean± SEM was calculated and the data was analyzed >by one way ANOVA, followed by Dunnet’s Multiple Comparison test. P values <0.05 was considered to be statistically significant.

Results

Acute study (Table/Fig 1)
In the acute phase of the study, at the end of 30 min, there was no significant decrease in the cataleptic scores with both the standard drugs and the test drug. However, from 60 min onwards after haloperidol administration, scopolamine (1.0 mg/kg) and ondansetron (0.5 and 1.0 mg/kg) lowered cataleptic scores significantly (P<0.001) than the vehicle treated groups in mice. On the other hand, at 2.0 mg/kg and 4.0mg/kg doses, EO showed significantly (P<0.001) lowered cataleptic scores than the vehicle-treated group in a dose and time dependent manner. At doses 2.0 and 4.0mg/kg, EO was more protective against haloperidol induced catalepsy than standard drugs.

Chronic study (Table/Fig 2)
In the chronic phase of the study, administration of the standard drugs and all doses of the test drug 30 min after the last haloperidol dose on the seventh day, gave cataleptic scores similar (except ondansetran 1.0mg/kg and EO 4.0 mg/kg) to that of the vehicle-treated group. However, 60 min after haloperidol administration, scopolamine (1.0 mg/kg), ondansetron (0.5 and 1.0 mg/kg), and EO (0.8, 2.0 and 4.0 mg/kg) showed significantly (P<0.001) lower cataleptic scores than the vehicle-treated group in a dose and time dependent manner.

SOD activity
The SOD activity (Table/Fig 3) in brain tissue was also found to be elevated from the normal values (5.51) in the vehicle treated group (9.45). Maximum reduction in SOD values was seen in EO at 4.0mg/kg (6.27) (P<0.01) than the standard drug scopolamine 6.58 (P<0.01) and moderate reduction was seen at EO 0.8mg/kg (P<0.05) as compared to normal SOD values. The SOD activity in the brain of the mice treated with haloperidol and the test drugs are shown in Table 3. The SOD activity in the brain was found to be elevated in the haloperidol treated group and the observed increase was about 80% above the normal values.

Discussion

Typical neuroleptic agents like chlorpromazine, haloperidol and reserpine induce a cataleptic state in rodents and these are being used as modesl to test the extrapyramidal side effects involved with it. Neuroleptic induced catalepsy has been linked to a blockade of postsynaptic striatal dopamine D1 and D2 receptors (20). Despite this evidence, several other neurotransmitters such as acetylcholine, serotonin, angiotensin, adenosine, or opioids have also been implicated (21). In addition to implications of various neurotransmitters in catalepsy, many preclinical and clinical studies have proposed reactive oxygen species in haloperidol induced toxicity (22). Evidence indicates that drugs which potentiate or attenuate neuroleptic catalepsy in rodents might aggravate or reduce the extrapyramidal signs respectively, in human beings (23).
In the present study, EO was found to effectively reduce the HIC and it is comparable to that produced by the standard drugs, scopolamine and ondansetron. The protective effect of EO against HIC was consistent with our earlier report on the anticataleptic effects of a polyherbal product NR-ANX-C (15), in which EO is one of the components. EO has been found to significantly decrease the SOD levels in rat brain; this suggested that it shows significant antioxidant properties in rat brain. Earlier neuropharmacological studies with EO in rodents have suggested that it has anticholinergic and sedative properties [7,24]. Recent investigations have shown that the tannoid principles of EO comprising emblicanin A and B, punigluconin and pedunculagin, have significant perse antioxidant effects in rat brain frontal cortex and striatum (25). The super oxide dismutase enzyme (SOD) is a major factor in oxygen toxicity and the SOD enzyme constitutes an essential defence against it. In the presence of a free radical quenching agent, the induction of the antioxidant enzyme is minimised. It is well established that the administration of haloperidol leads to an increase in the oxidative stress in the brain tissue. The increase in SOD observed in the present study supports the above concept. This study reveals that the EO treated groups significantly reduce (P<0.001) both oxidative stress and the catalepsy score induced by haloperidol.
EO fruits are a rich source of vitamin C which was held responsible for its major biological actions including antioxidant properties. However, more recent investigations have indicated that vitamin C alone was not responsible for its antioxidant potential (26). The anticataleptic effects of EO might be due to both its anticholinergic and antioxidant properties. Based on our results, we suggest the EO can be used as an alternative/adjuvant drug in preventing and treating the extrapyramidal side effects of antipsychotic agents in clinical practice. It was shown that the in addition to vitamin C, other polyphenols like tannins and gallic acid may contribute to its effectiveness to reduce oxidative stress and catalepsy. Further studies may help to elucidate the possible mechanisms of action of Emblica officinalis.

Key Message

Neuroleptics (antipsychotic drugs) are usually associated with extrapyramidal side effects. The mice were treated by standard drugs like scopolamine or centrally acting anticholinergics; but these have many side effects like dryness of mouth, blurred vision etc. Emblica officinalis is a commonly available fruit in India. It was the best alternative to treat the extrapyramidal side effects induced by neuroleptics.

Acknowledgement

M/s. Natural Remedies Pvt. Ltd., Bangalore. Provided the test drug Emblica officinalis

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