Neuroprotective properties of Centella asiatica (L.) urban on chronic unpredictable mild stress induced male wistar rats
Stress could have a major impact on the physiology and psychology of an individual. Stress can be viewed from the perspective of duration as acute and chronic. The chronic stress has a major role in the aetiopathogenesis of several neuropsychiatric conditions primarily depression. The characteris...
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| Format: | Thesis |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/97649/1/FPSK%28p%29%202021%2020%20-%20IR.1.pdf |
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| Summary: | Stress could have a major impact on the physiology and psychology of an individual.
Stress can be viewed from the perspective of duration as acute and chronic. The
chronic stress has a major role in the aetiopathogenesis of several neuropsychiatric
conditions primarily depression. The characteristic hyper-responsiveness of
glucocorticoids in these situations have an influence on the ultrastructural and
biochemical functions of the neurons of the hippocampus and prefrontal cortex. The
presently available medications for the management of depression have multiple
limitations. They generally have long latency for positive results, are not universally
suitable and have multiple adverse effects. These factors encourage the need for
innovative pharmaceuticals which could override these deficiencies. The most
promising source for such novel molecules are the herbs used in traditional medicines.
Centella asiatica (CA) has historically prominent use in traditional medicine for its
putative neuroprotective and neuro-regenerative properties. Extracts of CA were
assessed in chronic stress induced rats and the results analysed. Healthy male Wistar
rats of age between 8 – 10 weeks were procured and maintained under laboratory
conditions. The rats were held in six groups. One group was a control. Chronic
unpredictable mild stress was administered to the rest of the groups. The mild stress
was delivered by restrainers, forced swimming in cold water, an overnight food and
water deprivation, placement on wet bedding, placement in cage tilt, tail pinching,
overcrowding the cages and changing the cage mates. These unpredictable stress
were randomly delivered over 64 days. One of the group subjected to these stresses
was retained as model group. The rest of the groups were administered with crude
extracts of CA at the doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, while one group
received fluoxetine (Flx) 10 mg/kg body weight. The aforementioned medications
were administered daily for 64 days, 30 minutes before the commencement of
experiment. Following the sixty-four days of experiment, behavioural test including Forced Swim Test (FST), Open Field Test (OFT), Elevated Plus Maze Test (EPM)
And T-Maze Test were performed. At the completion of these behavioural test, the
rats were euthanised and the brain tissue were collected and blood samples obtained.
The neural tissue were analysed using Nissl’s stain and transmission electron
microscope (TEM). The neural tissues were also quantitatively assessed for
malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and
acetylcholinesterase (AChE). Polymerase chain reaction (PCR) was done to identify
the genes for mSOD and mCAT. The blood samples were assessed for quantitative
estimation of cortisol levels. The rats which received CA extract were compared with
the stress model group of rats. The rats receiving CA showed less impact on behaviour,
while the Nissl’s staining revealed a higher number and density of viable neurons of
hippocampus. The rats which received CA extract at dosages of 400 and 800 mg/kg
had significantly less ultrastructural alterations in the mitochondria, nucleus, synapse
and myelin sheath. In the same rat groups, MDA (oxidative stress protein) was
significantly lesser and the levels of SOD and CAT (antioxidant) were higher. The
levels of cortisol and AChE were significantly lesser than in the stress model group.
The efficacy of CA was similar to Flx. In conclusion CA effectively prevents the
changes in behaviour, neuronal ultrastructure, levels of AChE and oxidative stress
biomarkers due to chronic stress in the brain and mitigates cortisol release. CA could
prove an useful agent for use in the long term prevention of neurologic and behavioural
changes in stress. |
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