Abstract Parkinson's disease (PD) is a progressive nervous system disorder characterized by dysfunction or degeneration of dopaminergic neur
Abstract Parkinson's disease (PD) is a progressive nervous system disorder characterized by dysfunction or degeneration of dopaminergic neurons in the substantia nigra leading to motor symptoms. Parkinson's disease is more common in the elderly and severely reduces quality of life. There has been no cure for PD, the therapy is mainly based on symptomatic treatment. Because of the strong relationship between oxidative stress and PD, antioxidant compounds have been considered a novel therapy for PD treatment. However, long-term treatment with a compound may cause potential risks and adverse effects. Consequently, screening natural compounds with therapeutic properties has elicited significant interest, thereby contributing to the expansion of the pharmacological source for disease treatment. Sim (Rhodomyrtus tomentosa) is one kind of shrub, that belongs to the Myrtaceae family and has been used for a long time in traditional medicine of many Asian countries. All parts of sim can be used as medicine such as berried sim for treatment of diarrhea, and dysentery; leaves for wound healing, and roots for stomach cure. Previous studies suggested that sim fruit is rich in fiber, minerals, antioxidants, and anti-neurotoxic compounds. Utilizing antioxidant compounds from natural plants for PD therapy recently attracted attention. Because of its advantages, sim fruit has been supposed to be a potential candidate for drug screening. No scientific evidence has been reported proving sim fruit's PD treatment capacity. This study thus aimed to evaluate the potential of the sim fruit water extract (SFWE) for PD treatment using the dUCH knockdown Drosophila melanogaster model which owns hallmark PD symptoms such as dopaminergic neuron degeneration and locomotor dysfunction. Our results showed that SFWE has a strong antioxidant capacity with an IC50 value of 55.55 ± 2.012 µg/mL. As expected, when treated with SFWE at 1.25 mg/mL, ROS induced by knockdown of dUCH specifically at dopaminergic neurons (DA) were reduced. Notably, the degeneration of DA neurons on the PD fly model was ameliorated by sim fruit extract. Consequently, the movement-defected symptoms were also rescued when the PD fly model was fed with sim fruit extract. Interestingly, SFWE caused no significant difference in fruit flies' development and lifespan, suggesting it’s safe to use. Taken together, our results strongly demonstrated that sim fruit, with its high antioxidant content, induced the decline of oxidative stress, and relieved symptoms, which is considered a potential candidate for PD treatment.