Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder caused by dopaminergic neuron progressive degeneration. Inhibition of microglial activation may contribute to the treatment and prevention of PD. Plantamajoside (PMS) is a natural compound extracted from plantain seeds. It has a wide range of biological activities, including anti-inflammatory, antioxidative, as well as antitumor effects. However, its possible effects on PD are still unclear. In this study, lipopolysaccharide (LPS) was first injected into the right midbrain substantia nigra (SN) of male C57BL/6 mice to establish the PD mouse model. We found that PMS improved LPS-induced behavioral dysfunction in PD mice. PMS attenuated LPS-induced SN injury in PD mice. PMS could suppress LPS-induced microglial overactivation in PD mice. In addition, MS inhibited LPS-induced activation of the HDAC2/MAPK pathway in PD mice and BV-2 cells. It further revealed that PMS alleviated microglia polarization by inhibiting HDAC2. The limitation of this study was the lack of experiments for investigating the further molecular mechanism and in vivo animal validation, which needs to be further confirmed in the future. Collectively, our data suggested that PMS could serve as a promising drug for PD.

GLP1 receptor agonism ameliorates Parkinson’s disease through modulation of neuronal insulin signalling and glial suppression

“…Exenatide treatment of SNCA neurons led to significant suppression of MAPK pathway kinases JNK and p38. JNK signalling is activated in response to inflammatory stimuli, and has been found to be elevated in postmortem PD brains 65 , whereas pharmacological inhibition of JNK by GLP-1R agonists is protective in animal models of PD 59 , and a number of studies indicate degeneration of nigral dopaminergic neurons is accompanied by an increase in the level of p38 MAPKs 67,68 , while pharmacological inhibition of p38MAPK prevents toxin-induced apoptosis in PD models [69][70][71][72] .…”

The dual face of microglia (M1/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases

“…Further investigation revealed that Plantamajoside exerted its effects in both PD mice and BV-2 cells by suppressing the activation of the histone deacetylase-2 (HDAC2)/MAPK pathway. Notably, Plantamajoside demonstrated its ability to reduce microglia polarization by inhibiting HDAC2 ( Guo et al, 2023 ).…”