Parkinson's disease (PD), a widely prevalent and slowly advancing neurodegenerative disorder, impacts over 1 % of individuals across the globe (Grotewold and Albin, 2024). Mitochondrial dysfunction serves as core contributors to disease progression in PD (Hattori and Sato, 2024). Ameliorating mitochondrial dysfunction in neurons may represent a novel therapeutic strategy for PD. Mitophagy, the selective autophagic degradation of impaired or surplus mitochondria, is essential for maintaining mitochondrial health and cellular function (Lu et al., 2023). Accumulating evidence suggests that impaired mitophagy may trigger mitochondrial dysfunction (Li et al., 2025; Sriwastawa and Kumar, 2024). Contrarily, activation of mitophagy can alleviate mitochondrial dysfunction. Recent studies demonstrated that promoting mitophagy would mitigate the progression of PD by alleviating mitochondrial dysfunction (Malpartida et al., 2021; Williamson et al., 2023).

Although the term PD does not appear in ancient Chinese medical literature, the “Tremor syndrome” described in ancient China shares many clinical similarities with modern PD (Chen, P. et al., 2022). Traditional Chinese Medicine (TCM) operates on the principles of “holistic concepts and treatment based on pattern differentiation” and believes that “Tremor syndrome” is often related to “Liver Wind Stirring Internally”. Therefore, in treating “Tremor syndrome”, TCM usually adopts the principle of “Liver-Calming and Wind-Extinguishing”. Fructus Mume (FM) is derived from the nearly ripe fruit of the Rosaceae plant, Prunus mume Sieb. et Zucc., which is processed by fumigating at low temperature (40 °C) until the fruit darkens. According to the Shennong's Herbal Classic of Materia Medica (Shen Nong Ben Cao Jing), FM possesses the therapeutic properties of “calming the liver and extinguishing wind” (Lee et al., 2012). Notably, the Ming Dynasty pharmacological classic Commentary on the Classic of Materia Medica (Shennong's Herbal Classic of Materia Medica) contains descriptions of the use of FM in the treatment of “Tremor syndrome”. Additionally, classical prescriptions such as Wumei Pills, documented in the Treatise on Febrile Diseases by Zhang Zhongjing in the Han Dynasty, incorporate FM as a core component specifically for the treatment of tremor-related disorders (Zheng et al., 2013). The renowned Qing Dynasty physician Ke Qin recorded the use of Wumei Pills to treat tremor-related disorders in his work Typhoid Treatise: A Compilation for Recovery (Shang Han Lai Su Ji). Moreover, the Qing Dynasty physician Chen Xiuyuan noted in A Simplified Annotation of the Treatise on Febrile Diseases that the therapeutic principles of Wumei Pills correspond to the pathogenesis of tremor syndromes, supporting its application for such disorders. In modern clinical practice, several empirical prescriptions containing FM, such as Pabing I Formula (Zhao et al., 2013), Pabing II Formula (Wen et al., 2013) and Pabing III Formula (Zheng and Luo, 2006), are also widely used as core herbal combinations for managing PD. Despite its long history of clinical use, the precise mechanisms by which FM exerts therapeutic benefits in PD remain insufficiently understood. Elucidating its underlying pharmacological mechanisms is therefore essential for facilitating the rational development of FM-based therapies and promoting advances in PD treatment.

Noticeably, Wang et al. identified 89 compounds in FM by using plant metabolomics, and these compounds predominantly divided into flavonoids, organic acids, triterpenes and amino acids (Wang, S. et al., 2022). Flavonoids are among the most abundant bioactive constituents of FM, contributing substantially to its diverse pharmacological activities (Park et al., 2024; Zhu et al., 2022). Accumulating evidence showed that flavonoids could attenuate the progression of PD by regulating oxidative stress, neuroinflammation, gut microbiota and protein aggregation (Acar et al., 2023; Varshney and Siddique, 2024). Moreover, dietary flavonoids may mitigate the progression of neurodegenerative diseases through their antioxidant properties (Goyal et al., 2022). Notably, our previous study found that Fructus Mume flavonoids (FMF) could alleviate mitochondrial dysfunction by activating mitophagy to attenuate the development of PD in rats (Wang, C.L. et al., 2022; Wen et al., 2020). However, the mechanisms by which FMF promote mitophagy remain large unknown and need to be further investigated. Here, we regard FMF as the mainly active constituents of FM in this study. Additionally, we investigated the therapeutic efficacy of FMF in PD and explored its potential underlying mechanisms.

This study aimed to explore whether FMF could ameliorate mitochondrial dysfunction though promoting mitophagy, thereby alleviating the progression of PD, and explore the underlying mechanisms. Our findings would provide a theoretical basis for the use of FM in the treatment of PD and promote the clinical application of FM.