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.
Where did the research take place?
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Nanning, CN · Author affiliation
College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.Location evidence
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Original 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.