The effect of l-3,4-dihydroxyphenylalanine (=DOPA) on akinesia in parkinsonism¹

This study aimed to verify whether the combined use of Da Dingfengzhu and Western medicine in treating Parkinson's disease (PD) can lead to therapeutic efficacy and symptom alleviation, thereby achieving a complementary and synergistic effect.

In this study, 158 patients were initially enrolled, with 116 eligible patients randomly divided into a control and an observation group. The control group received levodopa/benserazide and pramipexole, while the observation group received Da Dingfengzhu combined with levodopa/benserazide and pramipexole for 12 weeks. Baseline patient characteristics, adverse reactions, and blood samples were collected at baseline and 12 weeks post-treatment. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess symptom severity at baseline, four weeks into treatment, and 12 weeks post-treatment.

Adverse reactions during treatment were similar in both groups, suggesting that the combined therapy in the observation group did not increase adverse effects. Both groups showed improvements in UPDRS scores, with the observation group displaying more significant symptom alleviation at 4 and 12 weeks. Moreover, the observation group exhibited more pronounced increases in serum neurotrophic factor-3 and dopamine levels and greater reductions in oxidative stress and inflammatory response markers.

In conclusion, the combination of Da Dingfengzhu with levodopa/benserazide and pramipexole for treating PD shows significant clinical potential and is worthy of broader application.

Motor awareness is the acknowledgment of (i) one's motor state while executing a movement or remaining still and (ii) one's motor abilities. The integrated contribution of different networks involving the parietal cortex, medial and lateral frontal regions, and subcortical structures gives rise to motor awareness. The damage to these structures or their disconnection results in a number of motor awareness disorders, such as the well-known Anosognosia for hemiplegia and apraxia, and the Anarchic Hand Syndrome. The deficit of motor awareness may also be present in other disorders such as Parkinson's and Huntington's diseases, Tics, and Tourette's Syndrome.

Chrysoeriol is a plant flavone extracted from the roots and leaves of the genus Phyllanthus. Although many biological properties of chrysoeriol have been reported, such as its antioxidant and anti-inflammatory activities, the effects of chrysoeriol on the cellular models of Parkinson's disease (PD) have not yet been elucidated. In the present study, we aimed to investigate whether chrysoeriol prevents neurotoxicity induced by 1-methyl-4-phenylpyridinium iodide (MPP⁺) in SH-SY5Y cells, a typical in vitro PD model. The cell viability was measured by MTT assay. The morphological changes of apoptotic cell nuclei were observed by Hoechst 33,342 staining. The expression of Bax, Bcl-2 and Caspase-3 were detected by western blot analysis. The mitochondria location in the cells was observed by Mitotracker staining. Mitochondrial membrane potential was evaluated by the JC-10 assay. Treatment with MPP⁺ significantly caused a decrease in the viability of cells and an increase in apoptosis, as evidenced by the upregulation of apoptotic cells, caspase-3 activity and antiapoptotic ratio. These effects were all reversed by pretreatment with chrysoeriol in SH-SY5Y cells. Moreover, pretreatment with chrysoeriol markedly mitigated the MPP⁺-caused increases in the levels of the prosurvial signaling proteins, phosphorylated Akt and phosphorylated mTOR. The presence of a specific PI3K inhibitor, wortmannin, particularly abolished the chrysoeriol-induced activation of Akt phosphorylation and prevented the chrysoeriol-induced survival effect. These results indicate that the neuroprotective effect of chrysoeriol against MPP⁺ treatment requires the activation of PI3K/Akt pathway. Ultimately, chrysoeriol could be a promising therapeutic agent for the further experiment on the treatment of PD.

Deficit of striatal dopamine was first discovered in postmortem brain of patients with Parkinson's disease in 1960. This observation was the starting point for dopamine replacement therapy, and successful introduction of high dose l-dopa therapy in the 1969 revolutionized the treatment of Parkinson's disease. Since then, constant attempts have been made to enhance the efficacy of l-dopa and reduce motor complications by providing more continuous dopamine stimulation.

This chapter traces the hallmarks of medical treatments for Parkinson's disease throughout centuries including the first description of antiparkinsonian effects of anticholinergics, the birth of apomorphine in the 1900s, then discovery of l-dopa in the 1960s, and development of dopamine agonists since the 1970s.