Study On The Mechanism Of Cistanche Phenylethanoid Glycosides Against Midbrain Neuron Apoptosis

Mar 07, 2022

Study on the Mechanism of Cistanche Phenylethanol Glycoside Against Midbrain Neuron Apoptosis


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Cistanche Phenylethanol Glycoside Against Midbrain Neuron Apoptosis

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Purpose: The traditional Chinese medicine Cistanche has a wide range of medicinal values. Studies on the anti-apoptosis mechanism of midbrain neurons of various compounds such as phenethyl alcohol glycosides and iridoid glycosides have not been reported yet. The purpose of this study is to explore the anti-apoptotic effects and mechanisms of these compounds.


Methods: Adopt 14-16 day-old fetal rats to conduct joint culture of primary midbrain nerve cells, and use 1-methyl-4-Phenylethanol Glycoside ion (MPP) as the inducer to establish the Midbrain nerve cell, apoptosis model. By MTT, LDH, tyrosine hydroxylase (TH) and Caspase-3 immunohistochemical staining, in situ TUNEL method apoptotic cell detection, Western blot and RT-PCR and other analytical methods, the MPP + induced midbrain nerve cells The apoptosis model and the mechanism of Cistanche Phenylethanoid glycosides against neuronal apoptosis were studied.


Result :

1. Dopaminergic neurons and midbrain cells express tyrosine hydroxylase (TH), and the intensity of TH expressed by dopaminergic neurons is significantly higher than that of non-dopaminergic neurons. Compared with the normal control group and the administration group, the dopaminergic neurons expressing TH in the model group were significantly reduced, and the cell axons were broken, shortened, or disappeared. Image analysis showed that the area and average gray value of TH-positive cells in the model group were lower than those of the normal control group and the drug-treated group, and there was a statistically significant difference (P<0.01).

2. In the normal control group and the medication group, only a few cells expressed Caspase-3, and the cells expressing Caspase-3 were apoptotic or necrotic cells. The cells in the model group that express Caspase-3 are mainly apoptotic dopaminergic neurons, and non-dopaminergic neurons express Caspase-3 weakly.

Analysis by image analyzer shows that the average gray value and total area of Caspase-3 expression in the model group are higher than those in the normal control group and the administration group, and the difference is significant (P<0.01).

3. MPP+ can induce apoptosis of midbrain nerve cells and selectively act on dopaminergic neurons.

4. Caspase-3 participates in the apoptosis of midbrain nerve cells induced by MPP+. PARP is lysed during this process of apoptosis, producing large fragments of 85kDa.

5. The activity of Caspase-3 can be inhibited by its inhibitor Ae-DVD-CHO.

6. Cistanche Phenylethanoid glycosides can inhibit the activity of Caspase-3 to achieve their anti-MPP+-induced apoptosis of midbrain neuronal cells.

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Conclusion: The midbrain nerve cell apoptosis model induced by MPP+ is simple and reliable, and can be used to study the pathogenesis of PD. Caspase-3 plays a key role in the process of midbrain nerve cell apoptosis. Cistanche phenylethanoid glycosides may have a good development prospect in the prevention and treatment of Parkinson’s disease.

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The main pathological manifestation of Parkinson's disease is the degeneration of dopamine neurons in the substantia nigra, which leads to a decrease in the content of central neurotransmitters. At the same time, it is accompanied by abnormalities and balance disorders of various neurotransmitters such as acetylcholine and norepinephrine, causing a series of Parkinson's symptoms. Through mouse experiments, the Cistanche Phenylethanoid glycosides extract in Cistanche Tubulosa can prevent the apoptosis of mouse cerebellar neuronal cells; Echinacoside, one of the active ingredients in cistanche tubulosa can protect dopamine neurons from oxidative emergency damage through its anti-oxidative stress effect, and can also increase the activity of nerve cells and protein levels.

Acteosides have obvious cytoprotective effects on mouse cell apoptosis.

Summary: The active ingredients of Cistanche Tubulosa have a certain significance in the screening of drugs for the treatment of Parkinson's disease.

Cistanche Tubulosa have a certain significance in the screening of drugs for the treatment of Parkinson's disease.


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