Protective effect and mechanism of glycosides of cistanches on Parkinson's disease mouse via the Nrf2/HO-1 pathway
10.19405/j.cnki.issn1000–1492.2026.09.012
- VernacularTitle:肉苁蓉总苷通过Nrf2/HO-1通路对帕金森病小鼠的保护作用及其机制
- Author:
Zhipeng XU
1
;
Xingyu WANG
1
;
Shuqing YAO
1
;
Jiayi ZHANG
2
;
Chaoran XU
3
;
Fengyan LIU
1
;
Dongsheng HUO
1
Author Information
1. School of Basic Medicine and Forensic Medicine，
2. School of Medical Technology and Anesthesiology， Baotou Medical College， Baotou 014040
3. School of Clinical Medicine， The Third Hospital of Baotou Iron and Steel Group， Baotou 014017
- Publication Type:Journal Article
- Keywords:
Parkinson’s disease;
glycosides of cistanches;
oxidative stress;
Nrf2/HO-1 pathway;
dopaminergic neuron;
reactive oxygen species
- From:
Acta Universitatis Medicinalis Anhui
2026;61(9):1603-1610
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the neuroprotective effect of glycosides of cistanches （GCs） in 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）-induced Parkinson’s disease （PD） model mice and its potential mechanism. MethodsForty mice were randomly divided into control group， PD group， GCs group and levodopa （L-DOPA） group， with 10 mice in each group. The control group received intraperitoneal injection of normal saline， while the other groups were intraperitoneally injected with MPTP （30 mg/kg） once daily for 5 consecutive days. After model establishment， the control group and PD group were intragastrically administered normal saline， and the GCs group and L-DOPA group received intragastric administration once daily for 28 consecutive days， at doses of 100 mg/kg and 50 mg/kg， respectively. The open field test and rotarod test were used to evaluate motor function. Immunohistochemistry was performed to detect the number of tyrosine hydroxylase （TH）-positive neurons in the substantia nigra of the midbrain. Transmission electron microscopy was adopted to observe the ultrastructure of mitochondria in the substantia nigra. Biochemical assays were used to determine the levels of glutathione （GSH）， malondialdehyde （MDA）， total superoxide dismutase （T-SOD） and reactive oxygen species （ROS） in substantia nigra tissues. Western blot was applied to detect the protein expression of TH， nuclear factor erythroid 2-related factor 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap-1） and heme oxygenase-1 （HO-1） in substantia nigra tissues. ResultsCompared with the control group， mice in the PD group exhibited markedly impaired motor function， significantly decreased T-SOD activity， obvious reductions in the number of TH-positive neurons and GSH content， as well as elevated MDA and ROS levels in the substantia nigra （P<0.01）. Compared with the PD group， mice in the GCs group showed improved motor function， increased T-SOD activity， higher number of TH-positive neurons and elevated GSH content， accompanied by decreased MDA and ROS levels （P<0.05）. In the control group， mitochondria in the substantia nigra displayed normal morphology without obvious blurred membrane structures or vacuolar degeneration. The PD group presented mitochondrial swelling， disordered cristae and vacuolar changes， whereas these mitochondrial pathological alterations were alleviated in the GCs group. Compared with the control group， the protein levels of TH， Nrf2 and HO-1 were significantly downregulated， while Keap-1 protein expression was markedly upregulated in the PD group （P<0.01）. Compared with the PD group， the GCs group showed significant upregulation of TH， Nrf2 and HO-1 protein levels and a notable reduction in Keap-1 protein level （P<0.05）. ConclusionGCs ameliorate motor dysfunction and attenuate dopaminergic neuronal and mitochondrial damage in MPTP-induced PD model mice. These effects may be associated with modulation of Nrf2/HO-1 pathway-related protein expression， enhancement of antioxidant capacity， and alleviation of oxidative stress.
