الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 101 |  |  |
| | | from | 101 | | |
Abstract
Parkinson’s disease (PD) is a progressive incurable neurodegenerative disorder affecting 1% – 2% of people over the age of sixty. It is presented mainly as a combination of motor symptoms such as bradykinesia, rigidity, and tremor. PD also has a variable presentation, including the occurrence of non-motor symptoms such as cognitive impairments and sleep disruption. Clinically, the diagnosis is made by recognizing these key features and ruling out other causes of parkinsonism.
Rotenone is a commonly utilized neurotoxin in different animal models to generate PD-relevant pathology and behavioral phenotypes. It triggers mitochondrial electron transport chain disruptions and nigral ROS accumulation, which precede a buildup of α-synuclein deposits, and other pro-apoptotic and cytotoxic factors, eventually leading to the loss of DNs.
Alchemilla vulgaris L (Lady’s mantle or Lion’s foot) is an herbaceous plant widely distributed throughout Europe and Asia. Although the chemical composition and biological properties of the Lady’s mantle revealed its medicinal potential, data on the plant interactions in living systems is scarce and numerous investigations should be performed to provide evidence of in vivo biological effects.
The current study aimed at investigating the potential neuroprotective effect of Alchemilla vulgaris extract on the brains of rotenone-induced PD mice through histopathological, histochemical, immunohistochemical, and biochemical studies.
Thus, to achieve this aim rotenone was given subcutaneously every other day alone or after the oral administration of Alchemilla vulgaris extract day-to-day for fourteen days. Locomotor activity was estimated under the open field test conditions. MDA content, TAC, and 8-OHdG levels were assessed in brain homogenate samples while the histopathological changes, iron deposition, and TH expression levels were assessed in the brain paraffin slides.
The results of the present study could be summarized as the following:
I. locomotor activity:
Locomotor activity significantly decreased in the protective group (89.50 ± 25.93) and rotenone group (43.88 ± 14.45) at p < 0.001 compared to the normal control group (144.8 ± 27.95) and vehicle group (120.8 ± 18.48). A significant increase in the locomotor activity of the protective group was noticed at p < 0.001 compared to the rotenone group’s locomotor activity.
II. Biochemical parameters:
A significant increase in the MDA content was noticed in both the protective group (135.9 ± 2.44) and rotenone group (177.0 ± 10.4) at p < 0.001 compared to the normal control group (68.58 ± 9.01) and vehicle group (72.47 ± 7.51). The protective group’s MDA content significantly decreased in comparison with the rotenone group’s MDA content at p < 0.001.
Summary, Conclusion & Recommendations
50
A significant reduction of TAC in both the rotenone group (0.60 ± 0.09) and protective group (0.85 ± 0.23) was observed at p < 0.001 in comparison with the normal control group (1.19 ± 0.17) and vehicle group (1.16 ± 0.14). TAC significantly increased in the protective group at p < 0.001 compared to the rotenone group.
8-OHdG levels insignificantly increased in both the rotenone group (1.8033 ± 0.1144) and protective group (1.7662 ± 0.1148) at p = 0.709 compared to the normal control group (1.7241 ± 0.2058) and vehicle group (1.7286 ± 0.1607). An insignificant reduction of 8-OHdG levels was noticed in the protective group in comparison with the rotenone group at p = 0.709.
III. Histopathological findings: The rotenone group coronal sections revealed severe neurodegenerative changes with numerous apoptotic neurons, neuropil vacuolation, and vasodilation compared to the normal histology observed through the SNpc of the normal control group and vehicle group. Fewer degenerative changes with, neuropil vacuolation, vasodilation, and some normal neurons were observed in the protective group coronal sections compared to the rotenone group coronal sections.
IV. Histochemical findings:
Coronal sections of the rotenone group revealed strong iron deposition compared to the mild deposition observed in both the normal control group and vehicle group. Moderate iron deposition was seen in the coronal sections of the protective group.
V. Immunohistochemical findings and image analysis results:
Rotenone group immunostained sections revealed a significant decrease in TH staining intensity to be mild (10.52 ± 7.14) in the cell bodies of DNs. Moderate TH staining intensity in the cell bodies and processes of protective group DNs (27.48 ± 12.23) was seen compared to the strong intensity observed in both the normal control group (59.30 ± 10.03) and vehicle group (55.11 ± 9.79) DNs at p < 0.001.
6.2. Conclusion
Results of the present study indicated the beneficial effect of Alchemilla vulgaris extract on nigral damage and dopaminergic neurons (DNs) loss evoked by rotenone injections. This neuroprotective effect of Alchemilla vulgaris extract involved the reduction of oxidative stress via reducing MDA levels and restoring TAC. Reduced oxidative stress in turn was reflected on the enhanced TH staining intensity in the substantia nigra pars compacta (SNpc) and enhanced locomotor activity under open field test conditions. Therefore, Alchemilla vulgaris extract could be further developed as a potent neuroprotective candidate for PD.
6.3. Recommendations
This study recommends the worth of Alchemilla vulgaris extract use as an adjuvant drug in clinical trials.