Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis.
J Ethnopharmacol
; 308: 116294, 2023 May 23.
Article
in En
| MEDLINE
| ID: mdl-36804201
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Alzheimer's disease (AD) was considered to be a neurodegenerative disease that caused cognitive impairment. Reactive Oxidative stress (ROS) was considered to be one of a major cause of the onset and progression of AD. Platycodin D (PD), a representative saponin from Platycodon grandiflorum, has conspicuous antioxidant activity. However, whether PD could protect nerve cell against oxidative injury remains unknown. AIM OF STUDY This study investigated the regulatory effects of PD on neurodegeneration caused by ROS. To determine whether PD could play its own antioxidant role in neuronal protection. MATERIALS AND METHODS:
First, PD(2.5, 5 mg/kg) ameliorated the memory impairment induced by AlCl3 (100 mg/kg) combined with D-galactose (D-Gal) (200 mg/kg) in mice, using the radial arm maze (RAM) test, and neuronal apoptosis in the hippocampus was evaluated by hematoxylin and eosin staining (HE). Next, the effects of PD (0.5, 1, and 2 µM) on okadaic-acid (OA) (40 nM) -induced apoptosis and inflammation of HT22 cells were investigated. Mitochondrial ROS production was measured by fluorescence staining. The potential signaling pathways were identified through Gene Ontology enrichment analysis. The role of PD in regulating AMP-activated protein kinase (AMPK) was assessed using siRNA silencing of genes and an ROS inhibitor.RESULTS:
In vivo, PD improved memory in mice, and recovered the morphological changes of brain tissue and nissl bodies. In vitro experiment, PD increased cell viability (p < 0.01; p < 0.05;p < 0.001), decreased apoptosis (p < 0.01), reduced excessive ROS and MDA, rised SOD and CAT content(p < 0.01; p < 0.05). Morover, it can block the inflammatory response caused by ROS. Be important, PD strengthen antioxidant ability by elevating AMPK activation both in vivo and in vitro. Furthermore, molecular docking suggested a good likelihood of PD-AMPK binding.CONCLUSION:
AMPK activity is vital for the neuroprotective effect of PD, suggesting that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saponins
/
Neurodegenerative Diseases
/
Alzheimer Disease
Limits:
Animals
Language:
En
Journal:
J Ethnopharmacol
Year:
2023
Document type:
Article
Affiliation country: