Toxicity study of erythroxylumcuneatum kurz, and its effects on rodent neurobehavioural properties
Therapeutic and new alternative potential compounds of natural product have been widely used in pharmaceutical industry. Interest on alternative efforts to search for new compounds with less or no adverse effects has led to the discovery of new potential plants in the treatment of diseases. Eryth...
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| Format: | Thesis |
| Language: | English |
| Published: |
2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/67823/1/FPSK%28m%29%202015%2063%20IR.pdf http://psasir.upm.edu.my/id/eprint/67823/ |
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| Summary: | Therapeutic and new alternative potential compounds of natural product have
been widely used in pharmaceutical industry. Interest on alternative efforts to
search for new compounds with less or no adverse effects has led to the
discovery of new potential plants in the treatment of diseases. Erythroxylum
cuneatum, also known as „Chinta Mula‟ plant among Malaysians has been
discovered and recently proven to possess antiwithdrawal properties with a
potential to be explored as a source of new drugs for the treatment of addiction.
Erythroxylum cuneatum can be found in primary and secondary forests. Due to
less information on this plant, this elusive plant was investigated advancely to
understand its roles and potential as a new source of pharmacologically in the
pharmaceutical industry. Thus, further scientific exploration was made to
understand the mechanisms of action involving toxicity and neurobehavioral
properties were proposed. Three different extracts were produced from the
leaves of Erythroxylum cuneatum which were aqueous, methanol and alkaloid
extracts and three semi pure compounds were fractionized from the crude
alkaloid extracts by different solvent systems. There is no toxicity profile on this
plant, thus, their toxicity on cell lines, brine shrimp and mice were determined.
In the cytotoxicity and Brine Shrimp Lethality Assay (BSLA) studies, alkaloid
extract was found to be toxic to the cells and brine shrimp compared to the
aqueous extract. Indeed, in the BSLA study, aqueous extract seems to give no
toxic effect to the shrimp at the high dose as compared to the alkaloid extract.
However, for the in-vivo toxicity study, aqueous extract showed almost similar
toxic effect as alkaloid extract. The presence of alkaloid compounds that is
typically associated with the central nervous system (CNS) has directed the
study of behavioral profiles. Locomotor activity in Open-Field Test (OFT),
anxiety study using elevated-plus maze (EPM) and working memory task using
Novel Object Discrimination test (NOD) were performed for the determination
of neurobehavioral profiles. Sixty four male Wistar rats were used in the study and divided into eight groups which were normal group, control group, three
groups of positive drug control and three groups of three different doses of
alkaloid extracts (5, 25 and 50 mg/kg). All doses were chronically administrated
intraperitoneally to the test group for 21 consecutive days and evaluated on
day 21 after the last dose. The findings showed that locomotor activity was not
significantly increased (P>0.05) in all doses of alkaloid extracts. In anxiety
study, two parameters were performed on each rat including time spent in open
arms and open arm entries frequency. All doses did not increase in both
parameters as compared to the standard drug Diazepam. In the Novel Object
Discrimination test, alkaloid treated rats did not show any significant
discrimination between the old and new object (P>0.05) thus, it can be
interpreted as a memory deficit. After the completion of behavioral study, rats
were sacrificed and their kidney and liver were collected to evaluate any
morphological changes. Normal to mild changes were noted in both liver and
kidney of treated rats with 5 and 25 mg/kg of alkaloid extract while the highest
dose (50 mg/kg) did not show any morphological changes. From this data, it is
clear that Erythroxylum cuneatum does not affect behavioral properties. In
conclusion, Erythroxylum cuneatum could be a scientist new hope in the
process of developing new anti withdrawal drugs as Erythroxylum cuneatum
has a low toxic effects and does not produce any behavioural changes. |
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