Strong Binding of Phytochemicals to the Catalytic Domain of Tyrosine Hydroxylase as a Trojan Horse Decreases Dopamine in Dopaminergic Cells: Pharmaceutical Considerations in Schizophrenia and Parkinson’s Disease

Abstract

Background: Imbalances in dopamine levels result in neurological and psychological disorders such as elevated dopamine in Parkinson’s disease. Objective: Despite a considerable number of advertisements claiming Aloe-vera’s effectiveness in PD treatment, it has hidden long-term disadvantages for healthy people and PD patients. Methods: In the present investigation, the impacts of Aloe-vera on dopaminergic cells were evaluated. Results: The results indicated that the focal adhesion kinase (FAK) enhancement was in line with the Bax/Bcl2 ratio decrement, reactive oxygen specious (ROS) production, and nonsignificant alteration in the sub-G1phase of the cell cycle. It led to glial cell-derived neurotrophic factor (GDNF) upregulation but did not significantly change the BDNF level involved in depression and motor impairment recovery. These events apparently resulted in the enhancement in dopaminergic cell viability and neurite length and attenuated PI+ cells. However, it also induced neuronal nitric oxide synthase (nNOS) overexpression and nitric oxide (NO) and lactate dehydrogenase (LDH) production. Notably, docking results of the catalytic domain in tyrosine hydroxylase (TH) with the Aloe-vera constituents showed strong binding of most Aloe-vera constituents with the catalytic domain of TH, even stronger than L-tyrosine as an original substrate. Following the docking results, Aloe-vera downregulated TH protein and attenuated dopamine. Conclusion: It can be hypothesized that Aloe-vera improves PD symptoms through enhancement in antiapoptotic markers and neurotrophic factors, while it suppresses TH and dopamine in the form of a Trojan horse, later resulting in the future deterioration of the disease symptoms. The results provide cues to pharmaceutical companies to use the active components of Aloe-vera as putative agents in neurological and psychiatric disorders and diseases to decrease dopamine in patients with enhanced dopamine levels.