Background Parkinson’s disease (PD) is primarily caused by the loss of dopaminergic neurons (DNs). Reports suggest that the extract of Morinda officinalis has the potential to improve neurologic behavior. However, whether M. officinalis polysaccharide (MOP) possesses potential therapeutic value in neurology still requires exploration. Objective The MPP+-induced SH-SY5Y cell and MPTP-induced DN loss in C57BL/6 mice were utilized as PD experimental models. The viability, death, apoptosis, and morphology of SH-SY5Y cells were evaluated through CCK-8, LDH release test, Calcein-AM/PI staining, flow cytometry, scanning electron microscopy, and various kits. The concentrations of α-synuclein (α-syn), NOD-like receptor protein 3 (NLRP3), inflammatory indicators, pyroptosis, and DN-connected proteins in cells and mouse brain tissues were assessed by immunofluorescence, ELISA, and Western blot. To evaluate the motor ability, DN loss, and glial cell activation in mice, behavioral tests, pathologic staining, TUNEL staining, immunofluorescence, and Western blot were utilized. Results MOP significantly increased cell viability, SOD, and GSH content, as well as reduced both apoptosis and cell death, and decreased levels of ROS and MDA content in SH-SY5Y cells. Furthermore, MOP notably lowered the quantity of α-syn, NLRP3, pro-inflammatory cytokines, and pyroptosis-associated proteins (ASC, Caspase1) in the substantia nigra of SH-SY5Y cells and PD mice. Simultaneously, levels of TH registered a marked increase. MOP also mitigated motor dysfunction in PD mice, led to a rise in the count of DN, while reducing its apoptosis, and lowered the expression of IBA1 and GFAP in glial cells. Conclusion MOP can mitigate neuronal pyroptosis by inhibiting NLRP3 inflammasome activation, thereby safeguarding DN and enhancing PD neurologic function. Graphical abstract Through restraining NLRP3 inflammasome activation and reducing Caspase1 expression, Morinda officinalis polysaccharide can alleviate neuronal death caused by pyroptosis and improve Parkinson's disease motor dysfunction. Highlights <OrderedList> <ListItem> <ItemNumber>1.</ItemNumber> <ItemContent> Morinda officinalis polysaccharide (MOP) can alleviate oxidative stress and inflammatory injury in mice with Parkinson's disease (PD). </ItemContent> </ListItem> <ListItem> <ItemNumber>2.</ItemNumber> <ItemContent> MOP can restrain PD mice motor dysfunction. </ItemContent> </ListItem> <ListItem> <ItemNumber>3.</ItemNumber> <ItemContent> MOP can reduce dopaminergic neurons loss. </ItemContent> </ListItem> <ListItem> <ItemNumber>4.</ItemNumber> <ItemContent> MOP can restrain NLRP3 inflammasome activation and pyroptosis in PD. </ItemContent> </ListItem> </OrderedList>

Morinda officinalis polysaccharide exerts anti-Parkinson’s disease effect via inhibiting NLRP3 inflammasome and improving pyroptosis of dopaminergic neurons

期刊论文
发表日期：

2025年5月6日

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Yanhong Dong,
Fengshuang Wang,
Mingji Jin

摘要

Background

Parkinson’s disease (PD) is primarily caused by the loss of dopaminergic neurons (DNs). Reports suggest that the extract of Morinda officinalis has the potential to improve neurologic behavior. However, whether M. officinalis polysaccharide (MOP) possesses potential therapeutic value in neurology still requires exploration.

Objective

The MPP⁺-induced SH-SY5Y cell and MPTP-induced DN loss in C57BL/6 mice were utilized as PD experimental models. The viability, death, apoptosis, and morphology of SH-SY5Y cells were evaluated through CCK-8, LDH release test, Calcein-AM/PI staining, flow cytometry, scanning electron microscopy, and various kits. The concentrations of α-synuclein (α-syn), NOD-like receptor protein 3 (NLRP3), inflammatory indicators, pyroptosis, and DN-connected proteins in cells and mouse brain tissues were assessed by immunofluorescence, ELISA, and Western blot. To evaluate the motor ability, DN loss, and glial cell activation in mice, behavioral tests, pathologic staining, TUNEL staining, immunofluorescence, and Western blot were utilized.

Results

MOP significantly increased cell viability, SOD, and GSH content, as well as reduced both apoptosis and cell death, and decreased levels of ROS and MDA content in SH-SY5Y cells. Furthermore, MOP notably lowered the quantity of α-syn, NLRP3, pro-inflammatory cytokines, and pyroptosis-associated proteins (ASC, Caspase1) in the substantia nigra of SH-SY5Y cells and PD mice. Simultaneously, levels of TH registered a marked increase. MOP also mitigated motor dysfunction in PD mice, led to a rise in the count of DN, while reducing its apoptosis, and lowered the expression of IBA1 and GFAP in glial cells.

Conclusion

MOP can mitigate neuronal pyroptosis by inhibiting NLRP3 inflammasome activation, thereby safeguarding DN and enhancing PD neurologic function.

Graphical abstract

Through restraining NLRP3 inflammasome activation and reducing Caspase1 expression, Morinda officinalis polysaccharide can alleviate neuronal death caused by pyroptosis and improve Parkinson's disease motor dysfunction.

Highlights

Morinda officinalis polysaccharide (MOP) can alleviate oxidative stress and inflammatory injury in mice with Parkinson's disease (PD).

MOP can restrain PD mice motor dysfunction.

MOP can reduce dopaminergic neurons loss.

MOP can restrain NLRP3 inflammasome activation and pyroptosis in PD.