Professional Documents
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146]
Abstracts
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(Continued)
06:00–07:00 PM Neurodegeneration puzzle game
08:00 PM onwards Dinner
Day 4: Thursday, 24 August 2017
08:30–09:30 AM Breakfast
09:30–10:30 AM Lecture 1 (Dr. M. Mohamed Essa, Sultan Qaboos University, Sultanate of Oman)
Title: Therapeutic targets for neurodegeneration from natural molecules
10:30–11:30 AM Lecture 2 (Prof. Sarita Aggrawal, SGPGIMS, Lucknow)
Title: Genetics of trinucleotide repeat disorders: Past to present
11:30–12:00 PM Tea/coffee and interaction with IBRO faculty
12:00–01:00 PM Lecture 3 (Dr. Sandhya Koushika, TIFR, Mumbai)
Title: Traffic jams in neurons
01:00–02:30 PM Lunch
02:30–03:30 PM Lecture 4 (Dr. Vaibhav Gaur, Global Medical Affairs, Cipla Ltd., Mumbai)
Title: Career in medical communications: Is it right for you?
03:30–05:30 PM Poster session
05:30–06:00 PM Tea/coffee and interaction with IBRO faculty
06:00–08:00 PM Cultural evening (music and dance programme)
08:00 PM onwards Dinner
Day 5: Friday, 25 August 2017
7:30 AM Departure to Jaipur
9:00 AM–6:00 PM Sightseeing − Jaipur: City Palace; Amer Fort; Jaigarh Fort; Albert Hall; WTP
Day 6: Saturday, 26 August 2017
08:30–09:30 AM Breakfast
09:30–10:30 AM Lecture 1 (Prof. Ranil Desilva, University of Sri Jayewardenepura, Sri Lanka)
Title: Banking the brain and blood: Lifestyle factors, nutrigenomics and nutraceuticals leading to healthy brain aging
10:30–11:30 AM Lecture 2 (Prof. Arvind Kumar, CCMB, Hyderabad)
Title: Deregulation of transcriptionally repressive histone lysine methylation-based epigenetic mechanisms leads to
depression and related psychiatric disorders
11:30–12:00 PM Tea/coffee and interaction with IBRO faculty
12:00–01:00 PM Lecture 3 (Dr. Amit Johrapurkar, Zydus Research Centre, Ahmedabad)
Title: Drug development for obesity and diabetes: Why brain matters
01:00–02:30 PM Lunch
02:30–03:30 PM Prize distribution and valedictory function
03:30–04:30 PM Tea/coffee and interaction with IBRO faculty
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Abstracts
affective disorders. The interesting findings on the role of chronic pain are centered on anatomic alterations, which do
Jumonji-domain-containing demethylases of KDM4 and not necessarily reflect the origin of chronic pain. A potential
KDM7 families in neural, behavioral, and neurogenic biomarker associated with nerve injury and neuroinflammation is
changes gave us not only better insights into the the sigma-1 receptor (S1R). In addition, S1Rs appear to play
etiopathology but also a strategy to treat depression by an active role in pain modulation, both peripherally and
modulating KDMs. centrally. We recently identified a highly selective S1R
antagonist that was transformed into a PET probe candidate
Our lab has also identified a novel KDM7 family member that
and demonstrated high specificity and selectivity for imaging
appears to act on H3K9me2, H3K4me3, and few other H3 and
S1Rs in mice, rats, and monkeys. We have utilized this probe in a
H4 lysine methylations. The level of this novel demethylase was
rat model of nerve injury via PET/MRI. The results have helped
differentially regulated in reward circuitry following CSDS, and
promote the clinical use of the agent in identifying peripheral pain
its overexpression in NAc using intracranial adeno-associated
generators in patients suffering from neuropathic pain.
virus injection could induce depression-like condition in
Furthermore, we have investigated the cold compound and
mice even in the absence of any stress exposure.
similar derivatives as potential pharmacotherapies for
The chromatin immunoprecipitation and next-generation
neuropathic pain in mouse models of nerve injury. These
sequencing approach have led us to identify hundreds of gene
compounds have equipotent or superior analgesic efficacy to
targets of this novel KDM7 family member in Neuro2A cells.
the clinically utilized gabapentin. The compounds have also been
After validation of a few of its targets and further experiments
examined for liabilities in locomotor, rotorod, conditioned place
showed us how this novel demethylase induces alterations in
preference, and in some cases, self-administration assays. The
spine morphology, spine density, and synaptic plasticity, as well
results indicate that the analgesic effects produced by S1Rs
as the characteristics observed in NAc, that is, the critical neural
antagonists are not associated with these potential liabilities.
substrate of the reward circuitry, in depression.
These results confirm the ability of S1Rs to serve as potential
Chronic stress, depression, anxiety, and related mood disorders diagnostic and analgesic agents for neuropathic pain without
as well as cognitive disorders are associated with significant CNS liabilities.
attenuation in adult neurogenesis in the hippocampal DG, the
Funding was provided by NIDA (DA023205), NIGMS
dynamic region of the cognitive circuitry. The proliferation of
(GM104932), US Department of Defense, the Center for
neural stem/progenitor cells gets severely affected, causing
Biomedical Imaging at Stanford University, and the State
attenuation in the turnover of mature healthy neurons in the
of Florida, Executive Office of the Governor’s Office of
hippocampus. Using CSDS model, we have also uncovered the
Tourism, Trade, and Economic Development.
critical role KDM4 family demethylases play in transducing
chronic stress effects on DG neurogenesis, hippocampal S5
remodeling and neural and behavioral plasticity leading to
mood and cognitive disorder phenotype. Thus, the molecular NEUROBEHAVIORAL AND NEUROCHEMICAL ABERRATIONS
IN PARKINSON’S DISEASE AND ITS TREATMENT WITH
insights into the functioning of these two diverse families of
epigenetic regulators have translational implication too, in
addition to their role in etiopathology. THYMOQUINONE
Fakhrul Islam, Mohammed M. Safhi, M. M. Khan1
S4
Department of Pharmacology, Toxicology College of
Pharmacy, Jazan University, Jazan, Saudi Arabia,
SIGMA RECEPTOR LIGANDS: FROM DISCOVERY TO 1
Department of Neurology, University of Tennessee Health
CLINICAL TRANSLATION Science Center, Memphis, TN, USA
Christopher R. McCurdy Address for correspondence: Dr. Fakhrul Islam, Department
of Pharmacology and Toxicology, College of Pharmacy, Jazan
Department of Medicinal Chemistry, College of Pharmacy,
University, Jazan, Saudi Arabia.
University of Florida, Gainesville, Florida, USA
E-mail: drfislam@gmail.com
Address for correspondence: Prof. Christopher R. McCurdy,
Department of Medicinal Chemistry, College of Pharmacy, Parkinson’s disease (PD) is a degenerative disorder of the central
University of Florida, Gainesville 32610, Florida, USA. nervous system that often impairs the sufferer’s motor skills and
speech. The disease is characterized by a progressive
E-mail: cmccurdy@cop.ufl.edu
degeneration of dopaminergic neuron in the SNpc leading to
Peripheral nerve injury, as a consequence of trauma, surgery, dopamine depletion. The primary symptoms of the disease are
inflammation, or other causes, is a major medical problem. This tremor, rigidity, bradykinesia/akinesia, and postural instability.
type of injury is often associated with chronic pain. About 100 Male Wistar rats were divided into four groups. Group-1 was PD,
million people suffer from chronic pain in the United States alone. and 6-hydroxydopamine (6-OHDA) was injected in the striatum.
Diagnosis and treatment are still considered as unmet medical Group-2 was sham, and it was treated in the same way as PD but
needs. Current clinical imaging methods used to evaluate in the place of 6-OHDA, saline was injected in the striatum.
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Abstracts
Group-3 was 6-OHDA (for 3 weeks) followed by thymoquinone antioxidants/nutrients could be able to play a vital role in
(TQ) for 2 weeks, and group 4 was sham treated with TQ for 2 delaying the progression of various NDDs such as PD
weeks. Animals were sacrificed just after 5 weeks. The behavior (Parkinson disease). The benefit of natural antioxidants on
activities were checked a day before sacrificing the animals, cognition, memory, oxidative stress, and inflammation in
which were decreased in the PD group and were protected NDDs including PD-like conditions is discussed here with
significantly with the treatment of TQ. The brains were taken the support of work from our lab. This work was supported
out quickly to dissect the striatum. The increased level of lipid by an internal grant from CAMS, SQU, Oman (IG/AGR/FOOD/
peroxidation and decreased content of glutathione were 17/02) and is highly acknowledged.
protected significantly with the treatment of TQ. The
activities of antioxidant enzymes (glutathione peroxidase, S7
glutathione reductase, superoxide dismutase, and catalase)
were decreased significantly, which were protected NEUROINFLAMMATORY PATHWAYS AND THERAPEUTIC
significantly with the treatment of TQ. The decreased
activities of phospholipase A2, poly-ADP-ribosyl polymerase, STRATEGIES IN DEMENTIA OF ALZHEIMER’S DISEASE
caspase-3, and Na+K+-ATPase were protected significantly with Nirmal Singh
the treatment of TQ. The decreased contents of dopamine, 3,4-
Pharmacology Division, Department of Pharmaceutical
dihydroxyphenyl acetic acid, and dopamine D2 receptors
Sciences & Drug Research, Punjabi University, Patiala,
were also protected significantly with the treatment of TQ.
Punjab, India
The expressions of Cox, inducible nitric oxide synthase
(iNOS), p53, and tyrosine hydroxylase were protected Address for correspondence: Prof. Nirmal Singh,
significantly with the treatment of TQ. The contents of TNF- Pharmacology Division, Department of Pharmaceutical
a and IL-1b and fragmentation of Deoxyribonucleic acid (DNA) Sciences & Drug Research, Punjabi University, Patiala,
in the PD group were also protected significantly with the Punjab, India.
treatment of TQ as compared to the sham group. The TQ has
E-mail: nirmal_puru@rediffmail.com
protected the biomarkers of PD in a 6-OHDA animal model.
Dementia is a chronic condition characterized by a
S6 progressive cognitive impairment that leads to functional
disability. In 2015, it was estimated that approximately 47
million people worldwide were affected by dementia, and this
THERAPEUTIC TARGETS FOR NEURODEGENERATION number is expected to increase, reaching 131.5 million by
FROM NATURAL MOLECULES 2050. Alzheimer’s disease (AD) accounts for approximately
Musthafa Mohamed Essa, Samir Al-Adawi 60–80% of all dementia cases. AD is a multifaceted
neurodegenerative disorder, with aging, as well as genetic
Department of Food Science and Nutrition, CAMS, Sultan
and environmental factors contributing to its occurrence and
Qaboos University, Oman
advancement. AD has affected more than 37 million people
Address for correspondence: Dr. Musthafa Mohamed Essa, worldwide, and the economic burden in the US alone is
Department of Food Science and Nutrition, CAMS, Sultan estimated to be around $100 billion. Given this evidence,
Qaboos University, Oman. it is clear that dementia represents one of the greatest global
public health challenges. The characteristic histopatho
E-mail: drmdessa@gmail.com
logical hallmarks of AD include extracellular amyloid
Oxidative damage and neuroinflammation are the two main plaques and intracellular neurofibrillary tangles composed
offenders that play an important role in the pathogenesis of of amyloid peptides (Ab) and hyperphosphorylated protein
neurodegenerative diseases (NDDs) including Parkinson’s “tau,” respectively. The generation of Ab requires sequential
disease (PD). Studies showed that naturally occurring cleavage of amyloid precursor protein (APP) by b- and
antioxidants found in fruits, vegetables, herbs, and nuts, could -secretase, respectively. An optional initial cleavage of
potentially delay neurodegeneration, and improve cognition APP by a-secretase precludes subsequent Ab formation. It
and memory. Changes in the behavior, biochemical indices, has become evident that AD is also associated with chronic
and protein expression patterns of oxidative/inflammatory inflammation and dysregulated lipid homeostasis within
markers occurred during NDDs. The current preventive the diseased brain. Studies have revealed that AD patients
measures are very expensive and not long lasting. Therefore, display excessive neuronal loss/dystrophy and a prominent
the need to find intervention strategies using natural antioxidants inflammatory response in their brain. The inflammatory
is of supreme importance. A diet rich in natural antioxidants processes include proliferation and activation of microglia
might influence the risk of brain function and health. The and astrocytes, increased expression of cytokines/
exact mechanism of action behind the benefits of natural chemokines, and activation of the complement system. It
antioxidants is due to the action of these phytonutrients on has been demonstrated that reactive astrocytes surround
diverse signaling pathways associated with the oxidation of both Ab plaques and tau tangles. In this condition, glial
macromolecules and inflammation. These bioactive natural cells lose some of their homeostatic functions and acquire
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a proinflammatory phenotype amplifying neuronal damage. cells. HIV-1 and its proteins are linked to cause motor and
Therefore, molecules that are able to restore their cognitive deficits in HIV/AIDS patients, which are collectively
physiological functions and control the neuroinflammatory termed as HIV-associated neurocognitive deficits (HAND). Up
process offer new therapeutic opportunities for this to 50% of HIV/AIDS patients experience mild cognitive motor
devastating disease. Due to multifactorial etiology, the disorders or HAND, which is primarily due to virus-induced
drug therapy of AD is very complex and poses a big neuronal damage. One of the major challenges of studies with
challenge to the physicians. Currently used drugs alleviate neuroAIDS is the lack of animal models apart from scarcity
the symptoms of AD but do not treat the underlying causes of of brain autopsy samples at various stages of HIV-1
dementia. Hence, a worldwide quest is under way to find new neuropathogenesis. At National Brain Research Centre
treatments to stop, slow, or even prevent AD. Besides the (NBRC), we have established an in-vitro model system of
classic targets of the oldest therapies, represented by human fetal brain-derived neural stem/precursor cells that
cholinergic and glutamatergic systems, new therapeutic can investigate effects of HIV and its proteins on human
approaches targeting b-amyloid (Ab) plaques, tau tangles, neural stem cells, differentiating neural stem cells as well as
and reactive gliosis (neuroinflammation) are emerging. These primary cultures of astrocytes and neurons. Using this unique
targets present multiple opportunities to create disease- primary cell culture resource in the country, we have made
modifying therapies for AD. Perhaps some modulators of several novel research findings. HIV-1 transactivator of
the aforementioned targets have shown promising results in transcription (Tat) protein perturbs the proliferative
animal studies and are currently in clinical trials. and differentiation ability of human neural stem cells by
altering genes important for stemness and neurogenesis.
S8
More recently, we have made significant discoveries in glia-
HUMAN NEURAL STEM CELLS AS MODEL SYSTEMS mediated neuronal damage and demonstrated the role of
purinergic receptors in astrocytes-mediated neuronal
TO UNDERSTAND NEURODEGENERATION damage. The role of stem cell fate determinant such as
Pankaj Seth TRIM32 has also been demonstrated by HIV-1 Tat-
mediated alterations of stemness of neural progenitor cells.
NeuroAIDS Laboratory, Molecular & Cellular Neuroscience,
Our observations have immense clinical importance for
National Brain Research Centre, Manesar, Haryana, India
AIDS patients suffering HIV-1-associated neurocognitive
Address for correspondence: Prof. Pankaj Seth, Neuro disorders.
AIDS Laboratory, Molecular & Cellular Neuroscience,
The research work has been supported by research grants to
National Brain Research Centre, Manesar − 122 051,
PS by the Department of Biotechnology, and core funds of
Haryana, India.
National Brain Research Centre, Manesar, India.
E-mail: pseth@nbrc.ac.in
S9
The human central nervous system (CNS) is susceptible to
bacterial and viral infections. Although rare, CNS infections
have devastating consequences leading to high mortality and NOVEL STRATEGIES FOR NEUROPROTECTION
morbidity. Apart from several neuropathogens, human R. V. Omkumar
immunodeficiency virus (HIV-1) is known to traffic into the
Molecular Neurobiology Division, Rajiv Gandhi Centre for
human brain and cause damage to the neural cells. The presence
Biotechnology, Thiruvananthapuram, Kerala, India
of HIV-1 in HIV/Acquired immune deficiency syndrome
(AIDS) patients prompted basic and clinical neuroscientists Address for correspondence: Dr. R. V. Omkumar,
to study the mechanisms as to how HIV enters the brain and the Molecular Neurobiology Division, Rajiv Gandhi Centre for
subsequent damage it may cause to the brain tissue. It has been Biotechnology, Thiruvananthapuram, Kerala, India.
reported that the virus traffics into the brain by Trojan horse
E-mail: omkumar@rgcb.res.in
mechanism via circulating monocytes, as they assist the virus in
circumventing the protection at the blood–brain barrier level. Neurons are terminally differentiated cells that cannot
Once in the brain, HIV-1 infects and resides in the glial cells, divide. Therefore, the loss of neurons in adulthood causes
particularly the microglia and astrocytes. HIV-1 lodges itself in irreparable damage to the brain. One of the prominent
three major regions of the brain namely frontal cortex, biochemical mechanisms that cause neuronal death in
hippocampus, and basal ganglia. Although infection of the response to various external stressors is excitotoxicity.
neurons by HIV-1 is rare, HIV-1 and its proteins cause Overload of Ca2+ inside the cell due to excessive
significant neuronal death, most of which is through the activation of Ca2+ channels is the primary cause of
infection of neighboring glial cells. Post-mortem studies in excitotoxicity. An approach that has been tried toward
pediatric samples have revealed that HIV-1 also exists in protecting neurons from excitotoxicity is to inhibit
the human neural stem/precursor cells, which necessitated the activity of Ca2+ channels using blockers so that
the investigations into cellular and molecular pathways Ca2+ influx into cytosol is reduced. The major Ca2+
involved in HIV-1-mediated effects on neural stem/precursor channel responsible for excitotoxicity is the NMDA-type
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Abstracts
glutamate receptor (NMDAR). Although several blockers Neuroscience, Faculty of Medical Sciences, University of Sri
of NMDARs were developed, their success in bringing Jayewardenepura (USJP), Sri Lanka.
about neuroprotection at the clinical level has so far been
E-mail: ranil@sjp.ac.lk
limited. This calls for a review of the current strategy and
development of alternative approaches. Studying environmental, cultural, lifestyle, and genetic
factors, such as gene-diet interaction (nutrigenomics)
NMDAR has several subtypes arising from different leading to healthy brain aging and longevity, is crucial for
combinations of subunits. These subtypes differ among identifying differential responses in clinical settings, as well
themselves in their pharmacological and electrophysiological as neurobiologic biomarkers that may be associated with
properties and also in their spatiotemporal distribution. It is neurological diseases. The human brain bank and
necessary that these subtypes be targeted selectively for Deoxyribonucleic acid (DNA) repository established in Sri
effective drug therapy. Most of the currently used drugs lack Lanka is one of the largest biobanks in the Indian
subtype specificity. Greater emphasis on development of subcontinent that could facilitate as a cornerstone in
subtype-specific drugs is a potential new strategy for better translational neuroscience.
success in neuroprotection by NMDAR antagonists.
Primarily, we examined the possible protective role of Sri Lankan
The lack of sufficient number of drugs, particularly those diet on healthy brain aging, and it was studied utilizing the
targeting NMDAR subtypes, could have been a consequence following: the established Human Brain Tissue (n = 76) and
of the difficulties faced by the drug discovery process. DNA/Gene Bank of patients and controls with stroke, as well as
Screening for drugs critically depends on the assay used neurodegenerative and neuromuscular disease, from one of the
for NMDAR activity. Drug screening against NMDAR uses largest biobanks in the South Asian region (over 2500).
electrophysiology or calcium imaging as activity assays. Anatomicopathological studies were performed in cerebral
These methods are real time in nature and, hence, are arteries of 447 adult and 34 fetal postmortem brains and gene
technically demanding as well as expensive. We have expression studies in six cerebral arteries. Age-related
developed a novel endpoint assay for calcium channels cytoskeletal pathologies were studied in 76 aging and diseased
that is simple to use and is less expensive with the human brains using histopathological/immunohistochemical
potential to aid high throughput screening efforts. In a techniques for tau and b-amyloid biomarkers, and vascular
limited screening for NMDAR inhibitors using this assay, genetic variants such as apolipoprotein E, angiotensin-
we have identified several small molecules with NMDAR converting enzyme, methylene tetrahydrofolate reductase
inhibitory potency. We have also identified a plant (MTHFR C677T), and factor V Leiden (FVL G1691A).
extract that inhibits a subtype of NMDAR. The extract
also showed neuroprotective activity against excitotoxicity We performed the first-ever comparison between Sri Lanka
in primary cortical neurons in culture and in vivo. (Colombo, n = 50) and India (Bangalore, n = 42) on age-
related cytoskeletal pathologies in aging autopsy brains,
We have also analyzed biochemical changes in the brain thus indicating the true extent of dementia burden in this
during excitotoxicity toward identifying downstream part of the world. Furthermore, an in-vitro hypoxic model
steps that could be drug targets. Many of the biochemical using human brain epithelial cells was studied with treatment
changes induced by excitotoxicity were prevented upon of Ceylon green tea extract before inducing hypoxia.
neuroprotective treatment by the NMDAR inhibitory plant
The author will discuss the prevention of cumulative risk and
extract that we identified. The facilitation provided by the
formulate interventions in preventative neuroprotective
new calcium channel assay methodology, the realization of
measures through natural products, nutrigenomics, and
the importance of subtype targeting, and the identification of
lifestyle factors for optimization of better brain health.
new downstream steps as druggable targets are new
Furthermore, ongoing research by the author based on natural
approaches toward developing strategies for neuroprotection.
products would lay a stepping-stone for developing
S10 neuroprotective nutraceuticals based on unique regional
natural products.
BANKING THE BRAIN AND BLOOD: LIFESTYLE S11
FACTORS, NUTRIGENOMICS, AND NUTRACEUTICALS
LEADING TO HEALTHY BRAIN AGING TRAFFIC JAMS IN NEURONS
K. Ranil D. De Silva Sandhya Koushika
Interdisciplinary Center for Innovation in Biotechnology & Department of Biological Sciences, Tata Institute of
Neuroscience, Faculty of Medical Sciences, University of Sri Fundamental Research (TIFR), Mumbai, Maharashtra, India
Jayewardenepura (USJP), Sri Lanka
Address for correspondence: Dr. Sandhya Koushika,
Address for correspondence: Prof. K. Ranil D. De Silva, Department of Biological Sciences, Tata Institute of
Interdisciplinary Center for Innovation in Biotechnology & Fundamental Research (TIFR), Mumbai, Maharashtra, India.
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lithium-like effects in a range of pre-clinical models including Department of Pharmacy, University of San Carlos and
reduced function of a specific Gq-coupled 5-HT receptor School of Healthcare Professions, Philippines
(5-HT2A) in molecular and behavioural assays. The latter
Address for correspondence: John Carlo Combista,
observation is of interest because the 5-HT2A receptor is
Department of Pharmacy, University of San Carlos and
linked to impulsivity control. Indeed, our experiments show
School of Healthcare Professions, 6000, Philippines.
that ebselen decreases impulsivity in different behavioural
models, likely through a 5-HT2A receptor mechanism. E-mail: combistajohncarlo@gmail.com
These findings have provided a rationale for the repurposing
The orchid, Vanda tessellata was chosen by the researchers
of ebselen for disorders such as bipolar depression, which
because of the presence of the constituents such as alkaloids,
feature high impulsivity, and its rapid progression to proof-
flavanoids, and glycosides in the family Orchidaceae hat might
of-concept studies in healthy volunteers, which are ongoing.
give an inhibition activity of the carbonic anhydrase enzyme.
S14 This study aimed to determine the in vitro inhibition of carbonic
anhydrase of V. tessellata flower extract. With the use of
CAREER IN MEDICAL COMMUNICATIONS: IS IT RIGHT modified colorimetric Maren T.H. (1960) method, the time in
FOR YOU? seconds for each test solution to change its color after the rate of
Vaibhav Gaur CO2 hydration was recorded. Two solvents were used for the
extraction: the semipolar, 95% ethanol and the nonpolar,
Global Medical Affairs (Respiratory), Cipla Ltd., Mumbai, dichloromethane solvents. The percent inhibition activity of
Maharashtra, India carbonic anhydrase of the different concentrations of ethanol-
Address for correspondence: Dr. Vaibhav Gaur, Global based extract (1, 25, and 50%) and dichloromethane-based
Medical Affairs (Respiratory), Cipla Ltd., Mumbai, extract (1 and 10%) test solutions were determined. Results
Maharashtra, India. showed that the ethanol-based extracts of V. tessellata in
different concentrations have an inhibitory effect, whereas
E-mail: vaibhav2india@gmail.com the dichloromethane-based extracts of V. tessellata showed
Be it academics or industry, no one can deny the importance and noinhibitory effect in all. For ethanol-based extracts, the
significance of communicating the data or the information that is concentration with the highest activity was 50% followed
generated. Especially, from a pharmaceutical company by 25%, which changed its color from red to yellow with an
standpoint, development of a drug takes years before it average time of 13.11 and 11.57 s, respectively. However, 1%
reaches the hands of a patient. It goes through different concentration with an average time of 7.56 s did not exhibit
phases from molecule synthesis, preclinical phases, to clinical an effect. The researchers recommend utilizing different
phases, which generate huge amount of information about the blood types to observe different reactions to the inhibition of
product. Furthermore, even after the approval, companies would carbonic anhydrase. The enzymes to be added to the test
keep on generating more data in the form of postmarketing solutions must be quantified. The positive control, freshly
studies, surveys, and studies for other indications. Medical prepared, should not be limited to only one concentration,
Communications (med comms) has emerged as a very and the test solutions should have concentrations greater
important department in the pharmaceutical industry to than 50%. Phenol red indicator and pH of the buffer must be
generate written, audiovisual, oral, or online materials dealing checked and monitored from time to time to ensure their
with medicine and healthcare. Although the conduct of sensitivities. Other indicators were used especially when
pharmaceutical development has always been heavily working with colored extracts or test solutions. Finally, the
regulated, regulations on the communications have also specific active constituent of V. tessellata that is responsible
started evolving since the last decade. The session will for the inhibitory effect of carbonic anhydrase enzyme is
provide an overview of medical writing and where it fits in isolated.
the spectrum of a pharmaceutical company, guidelines for P2
publications, good publication practices, and career
possibilities for the researchers and students in med comms.
GENOTYPE–PHENOTYPE CHARACTERIZATION OF
PARTICIPANTS ABSTRACT
P1
SPINOCEREBELLAR ATAXIAS (SCAS) IN SRI LANKA
Lakmal Gonawala, Nalaka Wijekoon, Vindika
IN VITRO DETERMINATION OF CARBONIC ANHYDRASE Suriyakumara, Darshna Sirisena1, Ranjani Gamage2,
Harsha Gunasekara3, Sunethra Senanayake2,
INHIBITION OF THE FLOWERS OF VANDA ORCHID, 4 5
Mohammed Faruq , Ashwin Dalal , Harry W. M.
VANDA TESSELLATA ROXB. (1795) BY MODIFIED Steinbusch6, Ranil De Silva
COLORIMETRIC MAREN T.H. (1960) METHOD Interdisciplinary Center for Innovation in Biotechnology
John Carlo Combista, Dorothy Mae Perez, Jimbert A. & Neuroscience, University of Sri Jayewardenepura,
1
Tan Teaching Hospital, Kurunegala, 2National Hospital of
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Abstracts
Sri Lanka, Colombo, 3Sri Jayewardenepura General Address for correspondence: M. Bade, Department of
Hospital, Colombo, Sri Lanka, 4Institute of Genomics and Physiology, Kathmandu University School of Medical
Integrative Biology, New Delhi, Delhi, 5Centre for DNA Sciences, Dhulikhel, Nepal.
Fingerprinting & Diagnostics, Hyderabad, Telangana, India,
6 E-mail: manibade@gmail.com
European Graduate School of Neuroscience, Department
of Translational Neuroscience, The Netherlands Reaction time is the minimum time needed to respond to a
stimulus. It is a non-invasive procedure for determining
Address for correspondence: Lakmal Gonawala, Inter-
sensorimotor coordination. The objective of the study was
disciplinary Center for Innovation in Biotechnology
to find out whether the reaction time was faster for auditory
& Neuroscience, University of Sri Jayewardenepura,
or visual stimuli in males and females. The study was
Sri Lanka.
conducted on 120 young right-handed healthy participants
E-mail: lak.gonawala@gmail.com (60 males and 60 females) of age 10–14 years with normal
hearing and sighted vision after obtaining approval from the
Personalized therapies for spinocerebellar ataxias (SCAs) is
Ethical and Institutional Review Committee. Auditory and
challenging given the diverse genetic causes of SCA and
Visual reaction time was recorded using Direct RT software
variability in clinical features, even in a defined genetic cause,
program. Participants performed both visual and auditory
which can vary among ethnic populations. To perform genetic
reaction tests. The mean auditory and visual reaction time
analysis of Sri Lankan clinically diagnosed SCA patients
was calculated by excluding the first and last values after the
and to evaluate genotype–phenotype correlation, SCA patients
data was obtained. There was a significant variation of
(n = 68) aged 18–73 years [male − 34 (50%) and female − 34
auditory and visual reaction time in both males and
(50%)] [familial inheritance n = 38 (56%); paternal − 22 and
females. Auditory reaction time was faster than visual
maternal − 16] were studied. Sociodemographic factors,
reaction time in both males and females. Visual and
clinical data (scale for the assessment and rating of ataxia
auditory reaction time was shorter in males compared to
(SARA), unified Huntington disease rating scale − Unified
females.
Huntington Disease Rating Scale (UHDRS) functional scale,
extrapyramidal symptoms (EPS), ophthalmological signs, P4
oculomotor deficits, etc.), and family history were recorded.
Connected Acyclic Graph (CAG) repeat analysis was performed
for SCA1, SCA2, SCA3, and SCA12. SCA subtypes were SYNAPTIC PLASTICITY AND MEMORY DEFICITS IN RAT
SCA1 (n = 29, mean AO = 35.8 ± 10 years), SCA2 (n = 10, MODEL OF ACUTE KIDNEY INJURY
mean AO = 33.8 ± 13 years), and SCA3 (n = 11, mean
Maryam Arab Firouzjaei, Mostafashid Moosavi
AO = 39 ± 9 years). Genetic etiologies of n = 20 were to be
elucidated for other subtypes with clinical heterogeneity. Zanjan University of Medical Science, Iran
Mean CAG repeat length of normal/abnormal alleles of
Address for correspondence: Maryam Arab Firouzjaei,
SCA1 was 28.3 ± 2/54.6 ± 6, for SCA2 was 22 ± 1/42.3 ± 5,
Zanjan University of Medical Science, Iran.
and for SCA3 was 26 ± 2/58.6 ± 10. UHDRS functional
scale mean score was as SCA3 > SCA2 > SCA1; SCA1 E-mail: mfirouzjaei@sums.ac.ir
versus SCA2–P > 0.03 and SCA1 versus SCA3–P > 0.009;
Recent evidence suggests that renal ischemia/reperfusion may
SARA mean score was as SCA1 > SCA2 > SCA3; SCA1
have impairment effects on brain function. Therefore, this study
versus SCA3–P > 0.003 and SCA2 versus SCA3–P > 0.03.
aims to investigate the effects of bilateral or unilateral renal
Oculomotor, nystagmus (P > 0.04), slow saccades (P > 0.01),
ischemia reperfusion on learning memory and hippocampal
and dysphagia (P > 0.03) were significant in SCA1; SCA1
synaptic plasticity. The model groups were established by
functional ability correlates with EPS − myoclonus P > 0.007
bilateral or unilateral renal ischemia for 60 and 120 min,
and rigidity P > 0.03. Resultant interpatient variability in
respectively and 24 h of reperfusion. A shuttle box apparatus
genotypes to clinical phenotypes from a genetically admixture
was used for passive avoidance learning and memory
population of South Asian origin warrants similar studies with a
assessment. Moreover, the animals were evaluated for
large sample size that would be a unique resource toward future
synaptic plasticity by field potential recording. The results of
personalized medicine.
this study demonstrated that the 60 min bilateral or 120 min
P3 unilateral renal ischemia along with 24 h of reperfusion resulted
in impaired long-term potentiation and memory performance.
Particularly, the field potential recording demonstrated that
COMPARATIVE STUDY OF SIMPLE VISUAL AND bilateral and unilateral renal ischemia led to extreme
AUDITORY REACTION TIME IN HEALTHY PARTICIPANTS inhibition in long-term potentiation compared to the control
and sham groups; this inhibition was accompanied by a
M. Bade, N. Banjara
significant increase of the normalized Polypropylene random
Department of Physiology, Kathmandu University School of copolymer (PPR) (PPR after HFS/PPR and before Hardware
Medical Sciences, Dhulikhel, Nepal functionality scan (HFS)) as an index for release probability.
116 International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017
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Abstracts
The behavioral results verified the electrophysiological deficit was scored at 24 h after the MCAO, and the results did
assessment data, in which the renal ischemia groups showed not show a significant difference between MCAO + V and
significant increase in step-through latency during passive MCAO + FTY720 groups. However, the neurological
avoidance task in comparison with the sham and control deficit scores of both ischemic groups were statistically higher
groups. Our data suggest that renal ischemia/reperfusion than the control and sham groups. MCAO caused infarct damage
induces injurious distant effects on the hippocampus in the rat’s brain tissue. The administration of FTY720
associated with synaptic plasticity and memory deficits. significantly reduced the size of the lesion, improved
Studies on other techniques are ongoing, such as western the memory impairment of MCAO rats, and increased the
blotting for evaluating the expression of caspase 3 and a STL time. In addition, the field potential recording
stereologic study for the assessment of the hippocampus demonstrated a marked reduction in induction of long-term
structure. potentiation of MCAO animals. However, administration of
FTY720 recovers the magnitude of the LTP without
P5
any effects on presynaptic plasticity and neurotransmitter
release probability. The results of this study demonstrated that
FTY720 AMELIORATES MEMORY PERFORMANCE AND MCAO in rats impairs the retention of passive avoidance tasks,
SYNAPTIC PLASTICITY DEFICITS IN A RAT MODEL OF and multiple injection of FTY720 improved the memory
performance after MCAO by LTP induction via postsynaptic
BRAIN ISCHEMIA mechanisms. In addition, a single injection was not sufficient to
M. Nazari, S. Keshavarz, A. Rafati, M. R. Namavar, M. rescue at least the neurological score 24 h after ischemia. Thus,
Haghani administration of FTY720 may be a promising therapy for
recovery of memory and synaptic plasticity impairment after
School of Advanced Medical Sciences and Technologies, Iran
MCAO.
Address for correspondence: M. Nazari, School of Advanced
Medical Sciences and Technologies, 7197673567, Iran. P6
E-mail: nazari_290@yahoo.com
Ischemic stroke occurs when an artery in the brain is blocked. The INVESTIGATING THE LOCUS COERULEUS NEUROPATHIC
middle cerebral artery is most often occluded by atherosclerotic PAIN-INDUCED SYNAPTIC PLASTICITY AND THE ROLE
or thrombotic processes. The brain ischemia elicits numerous
OF THIS NUCLEUS IN ATTENTION DEFICIT DISORDER
pathogenic cascades that develop over time and space, causing
injury to the neurons. In the hippocampal CA1 pyramidal cells, Parisa Moazen, Saeed Semnanian
hypoxia induces major change in the electrophysiological Shiraz University, Iran
responses. It has been suggested that middle cerebral artery
occlusion (MCAO) impairs the long-term potentiation (LTP) Address for correspondence: Parisa Moazen, Shiraz
induction in Schaffer collateral-CA1 synapses. Fingolimod University, Iran.
(FTY720) is a known sphingosine-1-phosphate receptor
E-mail: moazen.parisa@gmail.com
agonist. Several studies have shown the therapeutic efficacy
of FTY720 in neurodegenerative disorders. However, the Pain is a multidimensional experience with sensitive −
neuroprotective mechanisms in brain ischemia have not been discriminative and motivational − affective dimensions.
adequately studied. Therefore, this study aimed to investigate the Persistent pain, including chronic pain syndromes, is a
effects of FTY720 on the impairment of learning and memory common condition associated with a wide spectrum
and hippocampal synaptic plasticity induced by MCAO in of disorders including cancer, inflammation, and
ischemic brain injury. Twenty-eight male rats were randomly neuropathic pain. Neuropathic pain (NP) is caused by a
divided into four groups of control (n = 7), sham (n = 8), primary lesion or dysfunction of the nervous tissue and
ischemic-reperfusion + vehicle (I/R + V; n = 7), and I/ results in prolonged hyperalgesia, allodynia, and
R + FTY720 (n = 6). After 1 h of the occlusion of artery, the spontaneous pain. NP results from a process of
filament was gently withdrawn to allow reperfusion for the next 7 peripheral and central sensitization that generates an
days. The animals first received a dose of FTY720 (0.5 mg/kg) or enhanced transmission of nociceptive input to the brain,
its vehicle (intra-peritoneal) 24 h before surgery in I/R + FTY720 which may impair the endogenous supra-spinal pain
and I/R + V groups, respectively. The administration of FTY720 control system. On the other hand, chronic pain induces
or its vehicle continued every other day. Neurologic assessment cognitive disorder, including attention deficit disorder
was performed 24 h after the surgery. The passive avoidance test (ADD). In chronic pain, action potentials fire at a higher
and field potential recording were used for evaluation of learning, rate in nociceptors, which carry pain information to several
memory, and synaptic plasticity. The field potential recording brain areas that are common between pain and cognition.
was performed 7 days (reperfusion period) after the initial Cognitive and behavioral disorders might be the result of
procedure. The brain infarct volume was measured by functional impairment of neural substrates that affect pain,
triphenyltetrazolium hydrochloride staining. The neurologic emotion, reward, motivation, and cognitive processing.
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017 117
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Abstracts
One of the most important substrates that might impinge on Results The patients were predominantly females (nearly
these different circuits is noradrenergic nucleus locus 60%) with age ranging from 5 to 70 years. School-aged
coeruleus (LC). LC provides the bulk of norepinephrine children constituted 35% of the patients. The three
found in the Central nervous system (CNS). ADD could be common manifestations were seizures (95%), headache
the result of a functional impairment in noradrenergic and/or vomiting (40%). Computed Tomography (CT)
circuits associated with LC and prefrontal cortex, where scan demonstrated a single parenchymal ring or nodular
cognitive and sensorial pain processes overlap. The LC is a enhancing lesion in 84% of the cases with perilesional
central component of the descending inhibitory system oedema in nearly 85% of the cases. A large majority of
and plays a crucial role in cognitive processes such as the patients were treated only with the anti-convulsant
attention. Moreover, the LC may be involved in cognitive drugs for 9 months. Follow-up with repeat CT after 9
disorders caused by pain. On the other hand, it is possible months showed a complete resolution of NCC in most of
that neuroplasticity in LC that is caused by persistent pain the cases without the need for cysticidal treatment.
may contribute to create or develop these disorders. In
Conclusion NCC should be considered first in the
addition, electrophysiological studies indicate that changes
differential diagnosis of new-onset seizure among the
in the LC activity can be caused by chronic pain situations,
patients of developing countries, where taeniasis is
such as neuropathic pain. The onset of behavioral changes
endemic. Most of the patients with neurocysticercosis do
caused by neuropathic pain coincided with irruption
not need anti-cysticercal therapy.
of noradrenergic dysfunction, evident as an increase in
LC bursting activity, tyrosine hydroxylase expression, P8
noradrenaline transporter amount, and sensitivity of a2-
adrenoceptors in the LC. Therefore, we hypothesized THE EFFECT OF ACUTE EXERCISE ON WORKING
that chronic pain induces ADD that is associated with
neuroplasticity of the LC. To assess this hypothesis, we
MEMORY PERFORMANCE
will perform an attention behavioral test for comparing S. K. Deo, P. Bhattrai, K. Agrawal
attention between neuropathic rats and the same rats in Department of Physiology, Birat Medical College, Morang,
which their LC is pharmacologically lesioned. In addition, Nepal
electrophysiological studies shall be performed for
evaluating synaptic plasticity in the LC after the Address for correspondence: Dr. P. Bhattrai, Department of
induction of neuropathy. Physiology, Birat Medical College, Morang, Nepal.
P7 E-mail: devdsantosh@gmail.com
The purpose of this study was to compare the influence of
NEUROCYSTICERCOSIS: CLINICO-RADIOLOGICAL acute, moderate-intensity aerobic exercise on the speed and
PROFILE AND OUTCOME AT BPKM CANCER HOSPITAL accuracy of working memory tasks. Participants (N = 30; 20
males and 10 females; age: M = 22.3; range = 21–28 years)
Quamrul Haque Ansari, Laxmi Narayan Singh
completed a dual n-back working memory task before the
B.P. Koirala Memorial Cancer Hospital, Bharatpur, Chitwan, start, immediately after and 5 min after an intervention of
Nepal exercise. Findings revealed a significant beneficial influence
(t = 2.55, P 0.05) of moderate exercise on the accuracy of
Address for correspondence: Dr. Quamrul Haque Ansari,
working memory after a rest of 5 min after exercise. In
B.P. Koirala Memorial Cancer Hospital, Bharatpur, Chitwan
contrary, no significant relation between the speed of
44200, Nepal.
working memory performance and exercise was found.
E-mail: kamrulhak@yahoo.com This work indicates that acute aerobic exercise is effective
in improving working memory function and may be
Introduction Neurocysticercosis (NCC) is one of the beneficial for healthy adults whose cognitive performance
most common causes of seizures and epilepsy in the is relatively low.
developing world. There is insufficient information
about NCC in Nepal. This study was, therefore, P9
conducted to evaluate the clinical, neuro-radiographic
and therapeutic aspects of NCC at B.P. Koirala ACTIVATION OF THE COMPLEMENT CASCADE AND THE
Memorial (BPKM) Cancer Hospital.
NLRP3 INFLAMMASOME BY HSOD1G93A PROTEIN
Materials and Methods One hundred patients with
Vandana Deora, Luke McAlary1,2, Justin Yerbury1,2,
neurocysticercosis were studied prospectively for 12
Richard Gordon, Trent M. Woodruff
months in the BPKM Cancer Hospital, a secondary-
level referral hospital in central Nepal. The diagnosis of School of Biomedical Sciences, University of Queensland,
NCC was based primarily on the neuro-imaging Computed Brisbane, 1School of Biological Sciences, Faculty of Science,
Tomography (CT)scan findings. University of Wollongong, Wollongong, New South Wales,
118 International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017
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Abstracts
2
Illawarra Health and Medical Institute, University of Address for correspondence: Achal Mishra, Faculty of
Wollongong, Wollongong, New South Wales, Australia Pharmaceutical Sciences, Shri Shankaracharya Technical
Campus, Durg, Bhilai, Chhattisgarh, India.
Address for correspondence: Vandana Deora, School of
Biomedical Sciences, University of Queensland, Brisbane, E-mail: achal.mishra03@gmail.com
Australia.
A two- and three-dimensional quantitative structure-activity
E-mail: v.deora@uq.edu.au relationship (QSAR) using MLR, PCR, PLS and k-nearest
neighbor molecular field analysis methods was performed on
Motor neuron disease (MND) is an incurable neurodegenerative
a series of isatin derivatives as carboxylesterase (CE) inhibitors.
disorder characterized by a progressive loss of motor
This study was performed with 49 compounds (data set) using
neurons in the motor cortex, brain stem, and spinal cord. It
sphere exclusion (SE) algorithm for the division of the data set
leads to atrophy and weakness of bulbar, limb, and respiratory
into training and test set. SE algorithm allows constructing
muscles. There is increasing evidence that activation of the
training sets covering all descriptor space areas occupied by
innate immune system leading to chronic neuroinflammation
representative points, between 3.0 and 5.5 dissimilarity levels,
can drive the progression of MND. Two key components
which comprise test set size 4–10. Medical Loss Ratio (MLR),
of the innate immune system that have recently been
Partial least Square (PLS), Polymerase Chain Reaction (PCR)
proposed to play an important role in MND pathology
and k-nearest neighbor method (kNN-MFA) methodologies
and progression are the NLRP3 inflammasome and the
with stepwise (SW), simulated annealing (SA) and genetic
complement system. The NLRP3 inflammasome is an
algorithm (GA) were used for building the QSAR models. Four
intracellular protein complex that mediates the generation of
predictive models were generated with SW-kNN MFA
mature IL-1b via caspase-1 activation and has been recently
(pred_r2 = 0.7552–0.9376), three predictive models were
implicated in Alzheimer’s disease pathology by responding to
generated with SA-kNN MFA (pred_r2 = 0.7019–0.9367)
beta-amyloid fibrils. The complement system is a cascade of
and two predictive models were generated with GA-kNN
secreted molecules that react to pathogens and protein
MFA (pred_r2 = 0.8226–0.8497). Most significant model
aggregates, which also has documented roles in MND.
generated by stepwise kNNMFA showed internal predictivity
The current study aimed to determine if the NLRP3
as 82.11% (q2 = 0.8211) and external predictivity as 93.76%
inflammasome and the complement system are activated in
(q2 = 0.9376). In this model, hydrophobic and steric interactions
response to a MND-relevant protein, SOD1G93A. Microglial
dominate the CE inhibitory activity. Hydrophobic field
cultures were treated with mutant SOD1G93A protein,
descriptor (H_977) with positive range indicates that positive
and inflammasome activation determined by western blotting
hydrophobic potential is favourable for increase in activity and,
and ELISA. We found that soluble and aggregated mutant
hence, more hydrophobic substituent group is preferred in that
SOD1 protein triggers IL-1b secretion from LPS-primed
region. Steric field descriptor (S_619) with negative range
microglia, as well as generating the cleaved form of caspase-
indicates that negative steric potential is favourable for
1. These results indicate that activation of the inflammasome
increase in activity and, hence, less bulky substituent group is
pathway, leading to increased expression of caspase-1, IL-1b,
preferred in that region. The kNN-MFA contour plots provided
and NLRP3 can occur in response to a MND mutant protein.
further understanding of the relationship between structural
In addition, we found that SOD1G93A protein aggregates
features of substituted isatin derivatives and their activities,
also activated the complement cascade, generating the
which should be applicable to design newer potential CE
terminal complement component C5a from lepirudin plasma.
inhibitors.
Taken together, these findings suggest that NLRP3
inflammasome activation and C5a signaling could be P11
potential downstream pathological mechanisms triggered by
neurotoxic proteins seen in MND. Inhibiting these innate
immune pathways may thus be a means to slow propagative FORMULATION DEVELOPMENT AND EVALUATION OF
neuroinflammatory cell death in MND and ameliorate disease GASTRORETENTIVE MUCOADHESIVE MICROSPHERES OF
progression. METFORMIN HYDROCHLORIDE
Alka Lohani, Anurag Verma
ABSTRACTS OF NATIONAL PARTICIPANTS School of Pharmaceutical Science, IFTM University,
P10 Moradabad, Uttar Pradesh, India
Address for correspondence: Dr. Alka Lohani, School of
QSAR ANALYSIS OF ISATIN (INDOLE-2,3-DIONE) AS Pharmaceutical Science, IFTM University, Moradabad, Uttar
SELECTIVE INHIBITOR OF CARBOXYLESTERASES Pradesh, India.
Achal Mishra, Sarvesh Paliwal E-mail: alkalohani06@gmail.com
Faculty of Pharmaceutical Sciences, Shri Shankaracharya The aim of this work is to formulate the mucoadhesive
Technical Campus, Durg, Bhilai, Chhattisgarh, India microparticulate system for oral delivery of metformin
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017 119
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Abstracts
hydrochloride by using different mucoadhesive polymers of biochemical and histopathological studies was also
[carbopol 934P, hydroxyl propyl methyl cellulose performed. The extent of oxidative stress was measured
(HPMC) E15 and HPMC E60] alone or in combination. by estimating the levels of brain glutathione (GSH)
Microspheres were prepared by emulsification solvent and thiobarbituric acid reactive species (TBARS). Brain
evaporation method using span-80 as an emulsifying acetylcholinesterase (AChE) activity was estimated
agent. Prepared microspheres were evaluated for shape, to assess cholinergic activity. The brain level of
size, percentage yield, entrapment efficiency, in-vitro myeloperoxidase (MPO) was measured as a marker of
mucoadhesion, in-vitro drug release and stability. The inflammation. STZ (i.c.v.) and aging result in marked
microspheres obtained were spherical and free flowing. decline in MWM performance of the animals, reflecting
Percentage drug entrapment efficiency of microspheres impairment of learning and memory. STZ-treated mice and
was in the range of 68.2 ± 1.28 to 85.8 ± 2.22%. The result aged mice exhibited a marked enhancement of AChE activity,
of the mucoadhesion study shows that all the formulations as well as TBARS and MPO levels, along with a fall in GSH
exhibit good mucoadhesion for more than 10 h. The drug level. Furthermore, the stained micrographs of STZ-
release study shows that microspheres containing treated mice and aged mice indicate pathological changes,
polymers in combination show sustained release for severe neutrophilic infiltration and amyloid deposition. A
more than 12 h. By fitting the data into various kinetic combination of tacrolimus and forskolin significantly
models, it was calculated that the drug release followed attenuated STZ-induced and age-related memory deficits,
zero-order release, as the correlation coefficient (r2) as well as biochemical and histopathological alterations.
value was high for zero order and the value of release The findings demonstrate that the combination of
exponent (n) >1 indicated super case-II transport. On the CaN inhibitor and PKA activator has significantly
basis of the results of evaluation tests, microspheres alleviated memory dysfunction, biochemical alteration,
containing combination of carbopol 934P and HPMC and histopathological changes. It is concluded that the
E60 in the ratio of 1:1 and 6:4 (F10, F11), respectively combination of CaN and PKA can be explored as a
were concluded to be the best formulations. The potential therapeutic target for dementia.
stability data of optimized formulation indicated no
P13
significant difference in percent entrapment efficiency,
mucoadhesion and in-vitro drug release from the TO DISCOVER NOVEL AND SELECTIVE JNK3
optimized formulations before and after storage. The
results of this study showed that mucoadhesive INHIBITORS AS ANTI-ALZHEIMER’S AGENTS
microspheres could be a viable approach to improve the Ashima Nagpal, Sarvesh Paliwal
bioavailability of metformin hydrochloride.
Banasthali University, Banasthali, Rajasthan, India
P12
Address for correspondence: Ashima Nagpal, Banasthali
University, Banasthali − 304 022, Rajasthan, India.
COMBINED POTENTIAL OF CALCINEURIN INHIBITOR AND
E-mail: ashima_nagpal@yahoo.com
PKA ACTIVATOR IN THE IMPROVEMENT OF MEMORY
C-Jun-N-terminal kinase (JNK) inhibitors that have been
LOSS AND NEUROPATHOLOGICAL CHANGES IN MOUSE developed and brought under clinical trials so far were
MODEL OF DEMENTIA more or less found to be inefficient or unsafe due to a
Amit Kumar, Nirmal Singh number of reasons. The major and the most common
problem encountered with JNK inhibitors is the lack of
Department of Pharmaceutical Sciences and Drug Research,
specificity and selectivity, which is required for their
Punjabi University Patiala, Punjab, India
therapeutic use against a single target. Due to poor
Address for correspondence: Dr. Amit Kumar, Department selectivity or specificity or both, JNK inhibitors inhibit the
of Pharmaceutical Sciences and Drug Research, Punjabi complete JNK activity instead of any single activity. As JNKs
University Patiala, Punjab − 147 002, India. regulate a number of cellular functions, inhibiting complete
JNK activity will certainly affect multiple processes, some of
E-mail: amit2050@yahoo.co.in
which are not linked to patho-physiology of disease. This
The study was designed to investigate the outcome of the could probably generate undesired side effects, which indeed
combination of calcineurin (CaN) inhibitor (tacrolimus) and will be more pronounced in case of chronic conditions. This is
protein kinase A (PKA) activator (Forskolin) in mouse the reason why no JNK inhibitor developed so far has been
models of experimental dementia. Streptozotocin [STZ, used against a particular disease or condition. With an aim to
3 mg/kg, injected intracerebroventricularly (i.c.v.)] was overcome the aforementioned drawbacks of the previously
used to induce memory deficits in NIH mice, and developed JNK inhibitors, an attempt will be made to design
aged mice separately taken served as a natural model of novel JNK3 inhibitors with better specificity, selectivity
dementia. Morris water maze (MWM) test was employed as well as efficacy through the application of a battery of
to evaluate learning and memory of the animals. A battery in-silico and in-vitro tools.
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International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017 121
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Abstracts
Department of Pharmacology, Bombay College of Pharmacy, diseases. Due to lack of efficacy and adverse effects of
Kalina, Mumbai, Maharashtra, India NMDAR antagonists, search for herbal remedies that may
act as therapeutic agents is an active area of research to
Address for correspondence: Dimple Jhonsa, Department of
combat these diseases. Withania somnifera (WS) is being
Pharmacology, Bombay College of Pharmacy, Kalina,
used for centuries as a nerve tonic and nootropic agent. This
Mumbai − 400 098, Maharashtra, India.
in-silico study was designed to evaluate the neuroprotective
E-mail: dimple.jhonsa@gmail.com efficacy of W. somnifera phytochemicals by allosteric
inhibition of the GluN2B-containing NMDARs. We
Parkinson’s disease is a chronic, progressive neuro-
predict blood–brain barrier penetration, mutagenicity, drug-
degenerative disorder, whose exact cause as well as its cure
likeness and human intestinal absorption properties of 40 WS
is unknown. Exposure to paraquat is employed to induce
phytochemicals. Furthermore, molecular docking was
oxidative stress neurotoxicity and sporadic Parkinson’s
performed to know whether these phytochemicals inhibit
disease. In this study, the therapeutic antioxidant properties
the GluN2B-containing NMDARs or not. The results
of betanin against paraquat-induced oxidative damage and
suggest that withanolide A − a phytosteroid − can inhibit
neurotoxicity in Drosophila melanogaster were examined.
GluN2B-containing NMDARs through allosteric mode
Adult flies were exposed to paraquat for 12 h and then
similar to the well-known selective antagonist ifenprodil.
treated with betanin. Mortality, locomotor behavior by
Therefore, withanolide-A could be developed as a potent
negative geotaxis assay, and oxidative stress by determining
neurotherapeutic drug to counter NMDARs mediated
total Reactive Oxygen Species (ROS), glutathione, and
excitotoxicity and to treat multi-neurodegenerative diseases.
activities of superoxide dismutase and catalase were
evaluated. Significant locomotor disability was observed P19
among adult flies on exposure to paraquat solution for 12 h.
More than 45% of flies fed on betanin survived as compared to
100% mortality observed in paraquat-treated flies at 24 h. In
MODULATION OF CYCLOOXYGENASE, NITRIC OXIDE
addition, the locomotor activity of paraquat-exposed flies was AND VGSC CONTRIBUTES TO THE ANALGESIC EFFECT
enhanced by 80–85% when treated with betanin for 24 h. OF BERGAPTEN
Betanin ameliorated intracellular ROS levels, superoxide
Gurjit Singh, Anudeep Kaur, Palwinder Singh1, Rajbir
dismutase, and catalase as compared to the levels increased
Bhatti
by paraquat. They also reduced acetylcholinesterase activity,
which was increased by paraquat. The levels of reduced Departments of Pharmaceutical Sciences and 1Chemistry,
glutathione, which were diminished by paraquat, were also Guru Nanak Dev University, Amritsar, Punjab, India
enhanced by betanin. This study demonstrated that feeding flies
Address for correspondence: Dr. Rajbir Bhatti, Department
with betanin after exposure to paraquat showed antioxidant and
of Pharmaceutical Sciences, Guru Nanak Dev University,
neural protective effects leading to the recovery of locomotor
Amritsar, Punjab, India.
behavior and extension of life span. The project confirmed the
utility of Drosophila melanogaster as a model in screening E-mail: gurjitfauji@gmail.com
putative therapeutic molecules prior to their use in mammalian
Bergapten (5-methoxypsoralen), a naturally occurring
models.
furanocoumarin, has been documented to have an interesting
P18 biological profile in several preliminary studies. The current
investigation is aimed at exploring the analgesic and anti-
VIRTUAL SCREENING OF WITHANIA SOMNIFERA TO inflammatory activities of bergapten. Swiss albino mice
were used. Analgesic and anti-inflammatory activities of
SEARCH A POTENT NEUROPROTECTANT BY INHIBITING bergapten (10 mg/kg) were determined in formalin, and
GLUN2B-CONTAINING NMDA RECEPTORS acetic acid induced hyperalgesia and anti-inflammatory
Gaurav Kumar, Ranjana Patnaik activities were investigated using carrageenan-induced paw
oedema. Modulation of Cyclooxygenase (COX), inducible
School of Biomedical Engineering, Indian Institute of
nitric oxide synthase (iNOS) and voltage-gated Na+ channels
Technology (Banaras Hindu University), Varanasi, Uttar
(VGSC) were studied by pre-treatment with substance P,L-
Pradesh, India
arginine and veratrine, respectively. The serum cytokine
Address for correspondence: Gaurav Kumar, School of (TNFa and IL-6) levels were determined using ELISA kits.
Biomedical Engineering, Indian Institute of Technology Bergapten treatment was found to reduce the number of
(Banaras Hindu University), Varanasi − 221 005, Uttar flinchings in formalin-induced hyperalgesia and significantly
Pradesh, India. reduce the number of writhings induced by acetic acid. In
addition, paw inflammation induced by carrageenan was
E-mail: gaurav.rs.bme14@iitbhu.ac.in
significantly reduced. Pre-treatment with substance P,L-
N-methyl-d-aspartate receptors (NMDARs) mediated excito- arginine and veratrine was found to reverse the analgesic
toxicity has been implicated in multi-neurodegenerative effect of bergapten. Furthermore, increased bergapten
122 International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017
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Abstracts
treatment was found to significantly inhibit inflammatory Address for correspondence: Kriti Sharma, Banasthali
cytokines TNFa and IL-6. It is concluded that bergapten University, Rajasthan, India.
has significant analgesic and anti-inflammatory effects in
E-mail: kriti252325@gmail.com
mice, and the plausible modulation of COX, iNOS and Na+
channel pathway may be contributing to the analgesic effect Clitoria ternatea is a medicinal herb traditionally called as
of bergapten. Furthermore, bergapten inhibits the release of Shankh Pushpi, an Ayurvedic medicine used to promote
inflammatory cytokines TNFa and IL-6. health. It shows promise in animal models for its memory-
enhancing effects and has a wide spectrum of neurological
P20
benefits (memory enhancing, anti-depression, anxiolytic and
NMITLI118RT+: A NEUROPROTECTIVE LEAD IN
anti-pyretic). Benefits have been seen with its ethanolic
component; therefore, multiple bioactive compounds (in
EXPERIMENTAL STROKE regards to brain boosting) are likely. We examined the
Hafsa Ahmad, Sheeba Saji Samuel1, Rakesh Shukla1, Anil effectiveness of ethanolic extracts of leaves of C. ternatea at
Kumar Dwivedi 50 mg/kg and 100 mg/kg doses orally in rats in attenuating
electroshock-induced amnesia. Extract at 100 mg/kg dose
Divisions of Pharmaceutics and 1Pharmacology, CSIR-
produced significant memory retention, and the leaves were
Central Drug Research Institute, Lucknow, Uttar Pradesh,
found to be more effective. To delineate the possible mechanism
India
through which C. ternatea elicits the anti-amnesic effects, we
Address for correspondence: Dr. Hafsa Ahmad, Division of studied its influence on central cholinergic activity by estimating
Pharmaceutics, CSIR-Central Drug Research Institute, the acetylcholine content of the medulla and cerebellum. Our
Lucknow, Uttar Pradesh, India. results suggest that C. ternatea extract increases rat brain
acetylcholine content and acetylcholinesterase activity in
E-mail: ahmadhafsa.cog@gmail.com
comparison to cerebro-protective drug, Pyritinol.
Withania somnifera Dunal commonly known as
P22
Ashwagandha, is an Indian medicinal plant endowed with
numerous beneficial pharmacological properties and has A POSSIBLE LINK BETWEEN SPATIAL MEMORY TASK
long been used in the traditional systems of medicine.
CSIR, India has developed several chemotypes of
PERFORMANCES WITH SLEEP QUALITY AT EXTREME
this plant such as NMITLI-101, NMITLI-118 and ALTITUDE
NMITLI-128. NMITLI118RT+ represents a standardized Koustav Roy, Garima Chauhan, Punita Kumari, Meetu
concentrated ethanolic extract of a new chemotype of W. Wadhwa, Sanjeev Kumar, Koushik Ray, Usha Panjwani,
somnifera roots characterized by a uniform composition Krishna Kishore
with respect to its secondary metabolites − withanolides.
Applied Physiology Division, Defence Institute of Physiology
Real-time stability studies on this lead were completed, and
and Allied Sciences (DIPAS), Defence Research and
different delivery systems of NMITLI118RT+ were
Development Organization (DRDO), Timarpur, Delhi, India
prepared to improve its bio-pharmaceutical properties and
evaluated for their neuro-protective effects in experimental Address for correspondence: Koustav Roy, Applied
stroke using the middle cerebral artery occlusion (MCAO) Physiology Division, Defence Institute of Physiology and
model in rats. It was observed that vesicle-based and Allied Sciences (DIPAS), Defence Research and Development
complex-based formulations containing NMITLI118RT+ Organization (DRDO), Lucknow Road, Timarpur − 110 054,
were physically stable and demonstrated better protection Delhi, India.
over the parent drug in the post-treatment groups. The
E-mail: koustavroy001@gmail.com
formulations could augment the beneficial effects of this
lead in brain function restoration in ischemia reperfusion Fragmented sleep is one of the common features of high altitude
injury and present a promising approach in the management exposure. Hypobaric hypoxia (HH) affects non-rapid eye
of stroke. movement sleep (NREM) followed by alteration in rapid eye
movement sleep. Although the reason for altered sleep remains
P21
unknown, NREM plays a major role in spatial memory
consolidation and retrieval, which is hampered after HH
INFLUENCE OF ETHANOLIC LEAF EXTRACT OF CLITORIA exposure. However, the role of poor quality of sleep on
behavioural performance during HH exposure still needs to
TERNATEA LINN (NERVINE TONIC) ON MEMORY be understood. Therefore, this study is designed to evaluate the
ENHANCEMENT AND CENTRAL CHOLINERGIC ACTIVITY role of NREM2 sleep during HH-induced cognitive decline. We
IN RATS trained our rat in Morris water maze (MWM), and rats were
exposed at 25,000 feet altitude continuously for 7 days.
Kriti Sharma, Renu Bist, Ekta Singh Chauhan
Phosphorylated delta sleep-inducing peptide was given as an
Banasthali University, Rajasthan, India intervention at a dose of 10 mg/kg/day for enhancement of deep
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International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017 125
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Abstracts
of P. aculeata are effective in scavenging free radicals and have Address for correspondence: Pooja Mishra, Banasthali
the potential to be a powerful antioxidant. Thus, the results University, Tonk, Jaipur − 304 022, Rajasthan, India.
obtained in this study indicate that root extract of P. aculeata
E-mail: pujamshr89@gmail.com
could be considered as a potential source of natural antioxidant,
which could be used as an effective source against bacterial A number of potential approaches have been proposed for the
diseases. treatment of various Central nervous system (CNS) disorders.
Histone deacetylases (HDACs) are enzymes that catalyze the
P28 deacetylation of lysine remnants located at the N-terminus of
several protein substrates, such as nucleosomal histones. Histone
NEUROPROTECTIVE EFFECT OF NORDIHYDROGUAIARETIC acetylation is an important decisive gene expression. Histone
ACID (NDGA) IN AN IN-VITRO MODEL OF acetyltransferases and HDACs are the two types of enzymes that
PARKINSON’S DISEASE are primarily amenable for the catalysis of particular lysine
residues of histones. Inhibition of HDACs and their different
Pallavi Rane1, Deepaneeta Sarmah1, Shashikala Bhute1,
isoforms are broadly reported against brain disorders, such as
Kiran Kalia1, Pallab Bhattacharya1,2
Alzheimer disorder, Huntington disease, depression, shocking
1
Department of Pharmacology and Toxicology, National brain injury, post-traumatic stress disorder, anxiety, and
Institute of Pharmaceutical Education and Research (NIPER), dependence. The HDAC inhibitors consist of three defined
Ahmedabad, Gandhinagar, Gujarat, India, 2Boston Children’s structural parts of ideal pharmacophore, that is, (a)
Hospital, Harvard Medical School, Boston, MA, USA recognition cap group, (b) hydrophobic linker, and (c) the
zinc-binding group. HDACi can be classified into many
Address for correspondence: Pallavi Rane, Department of
structural classes including hydroxamates, cyclic peptides,
Pharmacology and Toxicology, National Institute of
aliphatic acids, and benzamides. Hydroxamic acid constitutes
Pharmaceutical Education and Research (NIPER),
an important class of HDACi with nanomolar activity as
Ahmedabad, Gandhinagar − 382 355, Gujarat, India.
reported both in the literature and in patent disclosures. In
E-mail: ranepallavi47@gmail.com addition, in-vivo efficacy studies have demonstrated that the
hydroxamate class has enormous therapeutic potential. We
Parkinson’s disease (PD) is associated with motor dysfunction,
have synthesized some new compounds of this class
and its clinical symptoms are tremors, bradykinesia, muscle
considering suberoylanilide hydroxamic acid (vorinostat) as a
rigidity, postural instability, and akinesia. The neuro-
lead compound. Various heterocyclic motifs were incorporated
pathological hallmarks of PD are characterized by progressive
in the chosen scaffold to obtain molecules with improved
and profound loss of dopaminergic neurons in the substantia
therapeutic profile in terms of specificity and potency.
nigra pars compacta. There is also a depletion of postsynaptic
Incorporation of spacers such as heteroatoms N and O may
dopamine within the striatum along with the presence of
provide additional sites of interaction, thus giving the
protein alpha-synuclein in Lewy bodies and Lewy neurites.
desired selectivity with increased potency. The structures of
Nordihydroguaiaretic acid (NDGA) is a polyphenolic
the newly synthesized compounds were established using
compound that has shown to inhibit aS filament assembly by
nuclear magnetic resonance, ultraviolet and infrared
forming soluble, noncytotoxic, oligomeric complexes with the
spectroscopy, mass spectrometry, and elemental analysis.
aS protein. Therefore, we hypothesized that NDGA may have
The purity of the compounds were checked with the help of
neuroprotective effect in rotenone-induced animal model of PD.
Thin layer chromatography (TLC). Microwave-mediated
First, we performed an in-silico test of NDGA with aS protein
synthesis of the compounds were performed to develop
molecule and further cell viability assays, antioxidant assays, and
new synthetic techniques to synthesize the designed
immunocytochemistry in in-vitro model of PD. NDGA exhibited
compounds, which otherwise is a very tedious, time-
good docking score and also showed a promising outcome in in-
consuming process. The newly synthesized compounds were
vitro studies. This hints toward the probable neuroprotective role
evaluated by neurite outgrowth assay, neurite activity, and
of NDGA in in-vitro model of PD. On the basis of our
inhibition of Human Ether related gene (hERG) and
preliminary data in in-vitro model, inhibition of aS can be
Cytochrome (CYP) activities. On the basis of in-vitro data,
further tested in vivo.
in-vivo activity was performed.
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P30
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Abstracts
Pharmacology Research Laboratory, University Institute of Address for correspondence: Richa Arya, Department of
Pharmaceutical Sciences, UGC − Centre of Advanced Study, Pharmacy, Banasthali University, Newai, Rajasthan, India.
Panjab University, Chandigarh, India
E-mail: Richapharma2011@gmail.com
Address for correspondence: Priyanka Saroj, Pharma-
Alzheimer’s is observed as a fatal disease with complex
cology Research Laboratory, University Institute of
neuropathology. b-site amyloid precursor protein cleaving
Pharmaceutical Sciences, UGC − Centre of Advanced
enzyme 1 (BACE-1) is a promising molecular target for the
Study, Panjab University, Chandigarh − 160 014,
development of drugs against Alzheimer’s. Hydantoins have
India.
emerged as potent BACE-1 inhibitors. Therefore, with an aim
E-mail: priyanka1960@gmail.com to elucidate the important features responsible for
their activity, Quantitative Structure activity relationship
Huntington’s disease (HD) is a autosomal, fatal, and
(QSAR) studies using stepwise multiple linear regressions,
progressive neurodegenerative disorder for which
partial least square, and neural network were performed.
clinically available drugs offer only symptomatic relief.
The multiple linear regression (MLR) and partial least
Decreased activity of Cyclic adenosine monophosphate
squares (PLS) models showed good correlation values of
(cAMP) responsive element-binding protein (CREB) is
0.80 and 0.75, respectively. The model revealed the
thought to contribute to the death of striatal medium
importance of the following descriptors: inertia moment 2
spiny neurons in HD. Therefore, therapies that increase
length (subs 2), total dipole moment, dipole moment Y
levels of activated CREB and Brain-derived neurotrophic
component (whole molecule), dipole moment 2 component
factor (BDNF) may be effective in fighting neuro-
(subs 2), and molecular refractivity (whole molecule).
degeneration in HD. Phosphodiesterase-4 (PDE4) has
Thorough study of the reported descriptors revealed that
been implicated in various neurological diseases. This
the replacement of the groups at substituent 2 with dipole
study has been structured to investigate the role of
moment enhancing groups would impose significant positive
roflumilast, a selective PDE4 inhibitor in quinolinic
effect on the overall biological activity. In addition to MLR
acid (QA)-induced HD symptoms in rats. Rats were
and PLS, neural network was also constructed for similar
administered QA (200 nmol/2 ml saline) intrastriatal
descriptors to evaluate the mode of dependencies of
bilaterally on 0 day. Roflumilast (0.5 mg/kg, 1 mg/kg,
biological activity on obtained descriptors. Using the
and 1.5 mg/kg, po) each were administered for 21 days
aforementioned descriptor-based information in future,
once a day. Motor performance was assessed using, open-
important BACE-1 inhibitors can be developed that exhibit
field, rotarod test, grip strength test, and narrow beam
improved pharmacological characteristics.
walk test on a weekly basis. On day 22, animals were
sacrificed and rat striatum was isolated for biochemical P32
(lipid peroxidation (LPO), Glutathione (GSH), and
nitrite), neuroinflammation (TNF-a, IL-6, and IL-1b),
and neurochemical analyses. Alterations in mito- NEUROPROTECTIVE ROLE OF CHLOROGENIC ACID IN
chondrial complex enzymes (I, II, and IV) in the rat MPTP-INDUCED PARKINSON’S MICE MODEL
brain were also examined. Treatment with roflumilast
Saumitra Sen Singh, Sachchida Nand Rai, Hareram Birla,
reduced brain striatum oxidative and nitrosative
Walia Zahra, Surya Pratap Singh
(nitrite/nitrate) stress, inflammation, and mitochondrial
dysfunctions. These results indicate that PDE4 inhibitor Department of Biochemistry, Institute of Science, BHU,
has attenuated QA-induced behavioral and biochemical Varanasi, Uttar Pradesh, India
alterations in experimental Huntington’s disease.
Address for correspondence: Saumitra Sen Singh,
Roflumilast was effective in increasing significantly
Department of Biochemistry, Institute of Science, BHU,
the level of BDNF in the striatal spiny neurons,
Varanasi, Uttar Pradesh, India.
which might account for the beneficial effect
observed in this model. Therefore, roflumilast can be E-mail: suryasinghbhu16@gmail.com
developed as a potential pharmacotherapeutic adjunct
Parkinson’s disease (PD) is the second most common
for HD.
neurodegenerative disorder after Alzheimer’s disease. It is
P31 characterised by a slow and progressive degeneration of
dopaminergic neurons in the substantia nigra. Although
dopaminergic neurons in other regions are also affected, they
2D QUANTITATIVE STRUCTURAL ACTIVITY RELATION are affected to a lesser extent. The pathology of PD has not yet
OF HYDANTOINS been fully investigated, although a number of factors
contributing to the selective degeneration of substantia nigra,
Richa Arya, Sarvesh Paliwal, S. P. Gupta
including mitochondrial dysfunction, proteasomal impairment,
Department of Pharmacy, Banasthali University, Newai, oxidative stress, excitotoxicity and inflammation, have been
Rajasthan, India extensively studied. Chlorogenic acid (CGA) is a natural
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017 127
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Abstracts
polyphenolic compound found in various medicinal plants. Its model was obtained along with selective descriptors such as
anti-inflammatory and antioxidant activity has been extensively inertia moment 2, Vectorized Austin model package (VAMP)
studied. In our study, we have evaluated the antioxidative and polarization YY, VAMP dipole Y component, VAMP dipole Z
anti-inflammatory activity of CGA using 1-methyl-4-phenyl- component, and Kier chiV6 path and having excellent statistical
1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of PD. values such as S = 0.38, F = 48.41, r = 0.95, r2 = 0.91, and
MPTP administration caused motor impairment and significant r2cv = 0.86. Furthermore, external set of molecules was used
reduction in endogenous antioxidants such as superoxide to confirm the soundness of the model. The findings of the
dismutase and catalase. MPTP challenge-induced lipid present QSAR analysis will be useful for the design of more
peroxidation was evidenced by increased malondialdehyde potent Rho kinase inhibitors as active neurological agents.
following disturbance of antioxidant defence. Apart from
P34
oxidative stress, MPTP also activated pro-inflammmatory
molecules and enhanced inflammatory mediators such as
tumor necrosis factor a, nuclear factor-B (NF-B) and IMPROVEMENT IN COGNITIVE FUNCTION BY SMALL
inducible nitric oxide synthase. The immunofluorescence HETEROCYCLIC MOIETY
analysis revealed a significant increase in the number of
Shashikala Bhute, Pallab Bhattacharya
activated astrocytes accompanied by loss of dopamine
neurons in the substantia nigra pars compacta area upon NIPER, Ahmedabad, Gujarat, India
MPTP injection. CGA treatment improved motor
Address for correspondence: Dr. Shashikala Bhute, NIPER,
impairments, restored antioxidant enzymes, suppressed the
Ahmedabad, Gujarat, India.
production of pro-inflammatory molecules, modulated the
astrocytes and microglia activation and blocked the activation E-mail: shashikala.rbhute@gmail.com
of NF-B. Results of our study suggest that CGA has promising
Mild cognitive impairment may eventually develop into
neuroprotective effect against degenerative changes in PD,
Alzheimer’s and other types of dementia. Alzheimer’s disease
and the protective effects are mediated through its antioxidant
(AD) is a chronic neurodegenerative disorder that manifests
and anti-inflammatory properties. Thus, this work reveals
into disturbances of cognitive functions such as amnesia.
the potential of CGA as a promising drug candidate for PD
This study is designed to investigate the antiamnesic effect of
treatment.
a small heterocyclic lead compound on behavioral and
P33 neurochemical changes in animal model of cognitive
impairment and AD. All compounds were designed taking
QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIP into account Lipinski’s rule of five. We first performed an in-
silico testing of the lead compound. The parameters that
ANALYSIS OF SELECTIVE RHO KINASE INHIBITORS AS were analyzed for determining in-silico competence were
NEUROREGENERATOR AGENTS: APPLICATION OF docking score, 3D pKa predictions, and density function
MULTIVARIATE STATISTICAL APPROACH theory studies. The test compound selected exhibited an in-
vitro anticholinesterase activity in Ellman’s assay. Preclinical
Seema Kesar, Pooja Mishra, Sarvesh Paliwal
testing is under progress. We plan to perform an acute toxicity
Department of Pharmacy, Banasthali Vidyapith, Banasthali, testing of the lead compound to find out the optimal dose to be
Rajasthan, India administered. Furthermore, the improvement in cognitive
functions will be tested against scopolamine-induced rodent
Address for correspondence: Seema Kesar, Department
model of amnesia and quinolinic acid induced rodent model
of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan,
of AD. The molecule will also be tested against multiple
India.
targets sharing cross-talk in AD. We hypothesize that the lead
E-mail: kesar.seema15@gmail.com heterocyclic moiety will show promising therapeutic effects in
the animal model of cognitive impairment and AD.
Rho kinases (ROCK), the first Rho effectors to be accounted, are
serine/threonine kinases that are important in elementary P35
processes of cell migration, proliferation, and survival. The
Rho-ROCK pathway is involved in many aspects of neuronal PHARMACOLOGICAL STUDIES ON NEUROPROTECTIVE
functions including neurite outgrowth and retraction and
becomes an attractive target for the development of drugs for EFFECT OF NECROSTATIN-1 AND ITS INTERACTION
treating neurological disorders; ROCK inhibitors, therefore, WITH -3 FATTY ACID IN MPTP-INDUCED
have potential for preventing neurodegeneration and PARKINSON’S DISEASE
stimulating neuroregeneration process. Quantitative Structure
Shipra Kartik, Rishi Pal, Prafulla Chandra Tiwari,
activity relationship (QSAR) studies were performed on a
Mayank Jain
series of urea-based derivatives from aniline and benzylamine
analogs by using multiple linear regression, partial least Department of Pharmacology & Therapeutics, King George’s
square, and feed-forward neural network methods; good Medical University, Lucknow, Uttar Pradesh, India
128 International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017
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Abstracts
Address for correspondence: Shipra Kartik, Department of elimination limit the advancement of the use of curcumin in
Pharmacology & Therapeutics, King George’s Medical clinical settings. Therefore, the objective of the study was to
University, Lucknow − 226 003, Uttar Pradesh, India. prepare curcumin-loaded solid lipid nanoparticles to improve its
therapeutic efficacy as neuroprotective agent. Curcumin-loaded
E-mail: kartikshipra@gmail.com
solid lipid nanoparticles were prepared by double emulsion
Parkinson’s disease (PD), a neurodegenerative disorder, solvent method. Various formulation variables such as
is characterized by inflamed dopaminergic neurons. homogenization speed, drug-polymer ratio, and volume of
Programmed cell death is a mechanism of cell demise in PD, aqueous phase were optimized. Optimized formulation
which includes apoptosis, autophagy, or programmed necrosis exhibited high drug load (85.67 ± 6.24%), small particle
(necroptosis), which are types of cell death. The role of RIP size (150.45 ± 7.84 nm), good physical stability indicated by
kinase inhibitor and -3 fatty acid is not known in PD. Therefore, zeta potential (−27.34 ± 5.41 mV), and prolonged drug release
this study is designed to explore the neuroprotective role behavior for 10 h. In-vitro biocompatibility and neuroprotective
of Receptor-interacting protein kinase (RIP) kinase inhibitor effect of curcumin and curcumin-loaded nanoparticles
and their interactions with -3 fatty acid. PD was induced in mice were evaluated on SH-SY5Y human neuroblastoma
by administration of 1-methyl-4-1,2,3,6-tetrahydropyridine cells. The cellular uptake studies confirmed that higher
(MPTP) (20 mg/kg), intraperitoneally. Simultaneously, RIP amount of intracellular localization of curcumin nanoparticles
kinase inhibitor (NEC-1) and -3 fatty acid were administered was responsible for improved neuroprotective activity of
for consecutive 1 week. The animals were observed for the formulation in peroxide-induced cellular damage.
elevated plus maze and open field test for behavioral analysis
P37
and oxidative stress markers in brain. Necrostatin-1 (Nec-1)
inhibits RIPK1-mediated necroptotic pathway. We observed
that MPTP-induced changes in behavioral and locomotor EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE,
activities were significantly reversed by NEC-1 as well as by CANNABINOID TYPE 1 RECEPTOR, AND SOMATOSTATIN
-3 fatty acid alone and in combination of both. Histopathological
and biochemical studies for oxidative markers also substantiate IN THE SPINAL CORD OF MORPHINE-TOLERANT RATS
these neuroprotective results. The synergistic effect or the Shivani Gupta, Mayank Gautam, Pranav Prasoon,
interaction between Nec-1 and -3 fatty acid may have better Subrata Basu Ray
neuroprotective effects on MPTP-induced PD. The signal
Department of Anatomy, All India Institute of Medical
transduction pathways involved in PD pathogenesis may
Sciences, New Delhi, Delhi, India
be mediated trough RIP kinase and antioxidant defence
system in the brain. Further studies are needed to confirm Address for correspondence: Shivani Gupta, Department of
and understand neuroprotective role of RIP kinase inhibitors Anatomy, All India Institute of Medical Sciences, New Delhi
and necroptosis of dopaminergic neuron, which may provide − 110 029, Delhi, India.
new pharmacotherapeutics for PD patients.
E-mail: raysb48@gmail.com
P36
Opioids such as morphine are the most effective drugs for
the treatment of cancer pain, but chronic administration
IMPROVED NEUROPROTECTIVE POTENTIAL OF produces tolerance, which limits its use. However, the
mechanism underlying the development of tolerance is
CURCUMIN VIA DESIGNING SOLID LIPID still unknown. It is hypothesized that pain signals are
NANOPARTICLES modulated by many neurotransmitters such as nitric
Manu Sharma, Siddhika Pareek oxide, endocannabinoids, and somatostatin at the level
of the spinal cord. In turn, these may be adversely
Department of Pharmacy, Banasthali University, Banasthali,
affected by repeated administration of morphine. Hence,
Rajasthan, India
the aim was to determine the expression of these
Address for correspondence: Dr. Manu Sharma, neurotransmitters in morphine-tolerant rats. Adult male
Department of Pharmacy, Banasthali University, Sprague Dawley rats (N = 66) were implanted with
Banasthali − 304 022, Rajasthan, India. intrathecal catheters under isoflurane anesthesia. These
were treated with either physiological saline or morphine
E-mail: sharmamanu10@gmail.com
(10 mg twice daily) through these catheters for 9 days.
Neurodegenerative disorders such Alzheimer’s and Parkinson’s Antinociception was tested by the hot-plate apparatus. At
diseases are difficult to treat with current therapies due to the end of this period, rats were sacrificed and perfused
complex pathogenesis of disease. Curcumin, plant polyphenol, with 4% paraformaldehyde solution. The lower
targets molecular pathways including Nuclear factor erythroid -2 lumbar segments (L4–L5) of the spinal cord were
(Nfr-2) and Nuclear factor kappa-light-chain (NFKB) involved processed for immunohistochemical localization of
in the modulation of inflammation and oxidative stress. inducible nitric oxide sythase (iNOS), cannabinoid type
However, its poor solubility, rapid first-pass metabolism, and 1 (CB1) receptor, and somatostatin. Repeated intrathecal
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017 129
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Abstracts
P39
HARNESSING NEUROPROTECTION AND REGENERATION
IN TRAUMATIC BRAIN INJURY: A TRANSLATIONAL
NEUROCHEMICAL EXPLORATION IN RODENTS TO COMPUTED NEUROBIOLOGY PLATFORM WITH
REVEAL PATHOBIOLOGY OF EPILEPSY AND COMORBID PRECLINICAL–CLINICAL SUBSTANTIATION
DEPRESSION Vikas Pareek, V. P. Subramanyam Rallabandi, Prasun
Tanveer Singh, Rajesh Kumar Goel Roy
Department of Pharmaceutical Sciences and Drug Research, National Neuro-Imaging Facility, National Brain Research
Punjabi University, Patiala, Punjab, India Centre, Manesar, Gurgaon, Haryana, India
Address for correspondence: Dr. Tanveer Singh, Department Address for correspondence: Vikas Pareek, National
of Pharmaceutical Sciences and Drug Research, Punjabi Neuro-Imaging Facility, National Brain Research Centre,
University, Patiala, Punjab − 147 002, India. Manesar, Gurgaon − 122 050, Haryana, India.
130 International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017
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Abstracts
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 4 ¦ October-December 2017 131