2. Academic Validation
  3. Total flavonoids isolated from Fructus Mume (Prunus mume Sieb. et Zucc.) mitigate Parkinson's disease progression by promoting neuronal mitophagy via activation of the CaMKKβ/AMPK signaling pathway

Total flavonoids isolated from Fructus Mume (Prunus mume Sieb. et Zucc.) mitigate Parkinson's disease progression by promoting neuronal mitophagy via activation of the CaMKKβ/AMPK signaling pathway

  • J Ethnopharmacol. 2026 Apr 24:361:121244. doi: 10.1016/j.jep.2026.121244.
Chunling Wang 1,  Xiaotao Feng 2,  Wentao Zhang 1,  Lizhen Huang 1,  Xiangdong Lu 3,  Mengjie Sun 3,  Mengyuan Gao 3,  Xiaodong Wen 4
Affiliations

Affiliations

  • 1 College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.
  • 2 Scientific Experimental Center, Guangxi University of Chinese Medicine, Nanning, 530000, China.
  • 3 Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530000, China.
  • 4 Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530000, China. Electronic address: [email protected].
PMID: 41564984 DOI: 10.1016/j.jep.2026.121244
Abstract

Ethnopharmacological relevance: Fructus Mume (FM) is derived from the nearly ripe fruit of Prunus mume Sieb. et Zucc., and widely used as a traditional medicine in Asian countries. FM has the effect of calming Liver to stop endogenous Wind, and has been used for thousands of years in the treatment of Parkinson's disease (PD), as recorded in ancient formulas such as Wumei Pills. However, the specific mechanism by which it treats PD remains larger unclear.

Purpose: The aim of this study was to investigate the effects and mechanisms by which the active ingredients of FM (Fructus Mume Flavonoids, FMF) mitigate the progression of PD.

Methods: We isolated FMF from FM and explored its chemical composition and active compound content. In vivo and in vitro PD models were employed to investigate the alleviative effects of FMF on PD and its underlying mechanisms.

Results: We identified 193 compounds and quantified 154 flavonoid compounds in the FMF. Six compounds were present at concentrations exceeding 100 μg/g, namely Isorhamnetin (1287.0639 μg/g), Narcissin (764.9639 μg/g), Nicotiflorin (613.8568 μg/g), Quercetin (435.5215 μg/g), Nepitrin (295.4833 μg/g), and Kaempferol (241.9767 μg/g). Moreover, FMF alleviated behavioral deficits in PD rats. FMF also inhibited the loss of neurons and the formation of α-synuclein aggregates, and promoted the expression of Tyrosine Hydroxylase in the substantia nigra pars compacta in PD rats. In vivo and in vitro PD models demonstrated that Autophagy inhibition significantly abolished the neuroprotective effects of FMF. Mechanically, FMF could enhance Mitophagy to attenuate the mitochondrial dysfunction by activating the CA2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK) signaling pathway.

Conclusion: FMF promotes neuronal Mitophagy to exert the neuroprotective effects by activating the CaMKKβ/AMPK signaling pathway. These findings provide a theoretical foundation for the application of FM in the treatment of PD and promote the clinical application of FM.

Keywords

CaMKKβ/AMPK signaling pathway; Fructus mume flavonoids; Mitophagy; Neuroprotective; Parkinson's disease.

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