Full
Outline
To demonstrate that neferine (Nef) alleviates Parkinson’s disease (PD) by inhibiting microglial pyroptosis mediated through the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/Caspase-1 pathway.
BV2 microglial cells were divided into: control group, lipopolysaccharides (LPS)-adenosine triphosphate (ATP) group, and LPS-ATP+Nef group. Pyroptosis was induced by 1 μg/mL LPS + 5 mmol/L ATP, with 2 mmol/L Nef pretreatment. Eighteen 10-12-week-old male C57BL/6 mice (22~25 g) were randomly assigned to: control (n=6), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (n=6), and MPTP+Nef (n=6) groups. Detection methods included: flow cytometry for pyroptosis, Cell Counting Kit-8 (CCK-8) for viability, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) for ROS, commercial kits for malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), ELISA/Western blot for interleukin-1β (IL-1β)/IL-18, immunofluorescence/immunohistochemistry for NLRP3/Caspase-1, tyrosine hydroxylase (TH) immunohistochemistry, hematoxylin-eosin staining for neuropathology, and modified neurological severity score (mNSS).
Versus control, LPS-ATP group showed decreased viability (P=0.002), increased pyroptosis (P<0.001), elevated ROS (P<0.001)/MDA (P<0.001)/IL-1β (P<0.001)/IL-18 (P<0.001), upregulated NLRP3 (P<0.001)/Caspase-1 (P<0.001), and reduced GSH (P<0.001)/SOD (P<0.001). Nef treatment reversed these effects (all P<0.05). According to the results of murine studies, compared with the control group, the MPTP group had increased mNSS (P<0.001)/tissue ROS (P<0.001), downregulated TH (P<0.001), upregulated NLRP3 (P<0.001)/Caspase-1 (P<0.001). Nef treatment significantly attenuated the MPTP-induced deleterious effects (P<0.05). Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology; MPTP group showed neuronal swelling, interstitial edema, and nuclear atrophy; MPTP+Nef group demonstrated ameliorated neuronal damage.
Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis, ameliorating PD neuroinflammation and pathology.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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