Parkinson's disease (PD) is a common neurodegenerative disorder that causes motor dysfunction (slow limb movements, postural instability, rigidity, localized instability, etc.) and non-motor symptoms (cognitive deficits, depression, dementia, psychosis, etc.), and imposes serious burden on PD patients and their families [1]. One neuropathological feature of PD is the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta, which is responsible for most of the disease-related motor dysfunctions [2]. Another common and important feature of PD pathology is the accumulation of insoluble cytoplasmic α-synuclein (α-Syn) and the formation of Lewy bodies and Lewy neurites in neurons [3]. Mitochondrial dysfunction, neuroinflammation, oxidative stress, and apoptosis have all been implicated as possible risk factors associated with the onset and progression of PD, but the predominant primary etiologic factor is currently unknown [[4], [5], [6], [7]]. Besides, no treatments that can cure PD currently, and the specific factors and mechanisms of PD still need to be further explored.

Apoptosis, also known as programmed cell death, has a very important influence on the development of the body, the maintenance of homeostasis, and the development of various diseases [8]. As one of the main pathways for neuronal cell degeneration or loss, apoptosis mainly includes cell shrinkage, cytoplasmic condensation, and nuclear chromatin condensation [9]. The mitochondrial pathway is an intrinsic pathway of apoptosis and plays an indispensable role in apoptosis, which has been found to be activated in PD models in vitro and in vivo. Growing evidence suggests that mitochondrial dysfunction and oxidative stress have a crucial influence on the pathogenesis of PD. Thus, mitochondria become the pivot point of neurodegenerative diseases and play a crucial role in the pathogenesis of neurodegenerative diseases [10,11]. In addition, several important findings connect oxidative stress with the pathogenesis of PD. The oxidative stress theory believes that the excessive intracellular oxidative stress caused by dopamine oxidative metabolites and insufficient cellular antioxidant capacity are the main causes of spontaneous degeneration of PD substantia nigra dopaminergic neurons [12,13]. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is not only a key factor in cellular oxidative stress but also a central regulator of maintaining intracellular redox homeostasis, which has been found as a core transcription factor to resist the anti-oxidative response of exogenous stimuli and toxicants [14,15]. By interacting with an antioxidant response element (ARE), Nrf2 regulates various antioxidant proteins to alleviate cellular damage caused by reactive oxygen species (ROS). The central nervous system has a high oxygen consumption and is extremely sensitive to oxidative stress [[16], [17], [18]]. Therefore, the research on Nrf2/HO-1 signal transduction pathway has received more and more attention in the central nervous system.

Natural products play a vital role in the discovery of new chemical entities and novel lead compounds. Aureusidin is a kind of natural flavonoid compound, which exists in many plants of Cyperaceae, such as Heliocharis dulcis (Burm. f.) Trin. Since inflammation is recognized as an early symptom of Parkinson's disease, targeting inflammatory pathways may be more effective in preventing disease progression than reversing existing pathology [19]. Studies have shown that Aureusidin has significant anti-inflammatory and antioxidant activities, making it an ideal candidate for novel inflammation inhibitors [20,21]. Our previous study showed that activating Nrf2/HO-1 signaling and preventing the mitochondria-dependent apoptotic pathway can protectively against 6-OHDA-induced neurotoxicity in PD, and the underlying molecular mechanisms of Aureusidin against PD are still not fully understood [22]. In this study, we aimed to investigate the potential therapeutic effect of Aureusidin in SH-SY5Y cells and C. elegans induced by 6-OHDA, and explored the potential mechanisms.