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Therapeutic Propensity of Selected Spice Actives Against Experimentally Induced Neuropathy.

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Relation http://ir.cftri.com/11761/
 
Title Therapeutic Propensity of Selected Spice Actives
Against Experimentally Induced Neuropathy.
 
Creator Sathya, N. Prasad
 
Subject 10 Plants
04 Diabetes Mellitus
 
Description Neuropathy is defined as a collection of disorders that occurs due to the
damage to the nerves. Although more commonly referred to the damage to the
peripheral nervous tissue, neuropathy can be damage and associated
dysfunction in either the central or peripheral nervous system. Current
understanding of the pathology encompasses oxidative stress, inflammatory
reactions, mitochondrial dysfunction and apoptosis in the nervous tissue. Over
production of reactive oxygen species (ROS) and reactive nitrogen species
(RNS), a decreased antioxidant defense system or both results in oxidative
stress and have been implicated in neuropathy.
Effective management of neuropathic symptoms by the various drugs
available is limited due to their side effects. Hence, in general there is a need for
alternative medicine for management of neuropathy especially in diabetes,
chemotherapy induced or toxin induced neuropathy. In the recent past, various
herbal actives including spices and phytoconstituents are being extensively
employed as complementary therapeutic agents in the management of
neuropathy. Humans have been consuming various spices since time
immemorial either as a component of various food preparations or medicinal
formulations. Hence, in this proposal, the neuroprotective efficacy of selected
spice actives were investigated employing Drosophila system, cell model
(human neuroblastoma cell line) and the efficacy were further validated in two
models of neuropathy (neurotoxin and diabetic model). To induce neurotoxicity
and neuropathy, a well-known neurotoxin, acrylamide (ACR) was employed in
fly/ rat model, while streptozotocin (STZ) was used to induce diabetic neuropathy
(DN) among rats.
Evidence obtained in the Drosophila model for the first time demonstrated
the utility value of the system in understanding the neurotoxicity of ACR.
Development of locomotor phenotype and induction of oxidative stress in this
system was consistent with those reported in higher animals with ACR
intoxication. Mitochondrial oxidative stress coupled with altered cholinergic
function (acetyl cholinesterase (AChE) activity) and depleted dopamine (DA)
levels among flies with ACR exposure corroborate with biochemical
Abstract
perturbations demonstrated in the brain/ peripheral nerves of rodent models.
Spice active (eugenol, EU; isoeugenol, IE; curcumin, CU; geraniol, GE)
enrichment markedly abrogated the ACR induced lethality, locomotor
dysfunction, oxidative stress (head and body) with concomitant increase in GSH
levels. EU enhanced the depleted DA levels in head region, and IE and EU
restored the cholinergic function (AChE activity in head/ body regions). Flies
maintained on medium enriched with GE and CU exhibited robust decrease in
the levels of ROS and hydroperoxides, suggesting their propensity to attenuate
oxidative damage which in part may be related to enhanced levels of GSH and
activities of antioxidant enzymes. Further, similar protective effect was also
discernible in the mitochondrial enzymatic and neurotoxicity markers (restoration
of AChE activity and DA levels).
In view of the increased exposure of humans to ACR through
consumption of various thermally processed foods, it is highly imperative to
explore newer therapeutic strategies to abrogate ACR-induced neurotoxicity/
neuropathy. Accordingly, the neuroprotective efficacy of spice actives was
validated in vivo. Data obtained in the ACR- rat model clearly demonstrates the
beneficial effects of spice actives/ phytoconstituents in alleviating neuropathyassociated
locomotor dysfunctions and oxidative stress -mediated impairments
in sciatic nerve (SN) and brain regions.
Having demonstrated the efficacy of selected spice actives in the ACRmodel,
their potential to modulate various biochemical/neurochemical markers
was investigated in cell models and experimentally induced DN model. Data
obtained in the DN rat model demonstrated that GE (a monoterpene) markedly
attenuates behavioral responses, oxidative stress and mitochondrial
dysfunctions. The protective effect of GE was highly comparable to that of CU.
Interestingly, EU supplements exhibited significant curative potential in an
intervention model of DN. Collectively these findings suggest the possible
therapeutic usage of these actives as adjuvants in the management of diabetic
and other forms of neuropathy in humans.
 
Contributor Dr., Muralidhara
 
Date 2014
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Language en
 
Identifier http://ir.cftri.com/11761/1/Sathyaprasad.pdf
Sathya, N. Prasad (2014) Therapeutic Propensity of Selected Spice Actives Against Experimentally Induced Neuropathy. Doctoral thesis, University of Mysore.