Cistanche in The Treatment Of Parkinson's Disease Ⅱ

4 Research on the modern pharmacological mechanism of Cistanche deserticola

Through in-depth research on network pharmacology, data mining, drug ingredients, and prescriptions of famous traditional Chinese medicine practitioners, it was found that the mechanism of action of Cistanche deserticola in preventing and treating Parkinson's disease is related to antioxidant stress, regulating neuroinflammation, regulating autophagy, inhibiting nerve cell apoptosis, It is related to regulating immunity, protecting mitochondria, regulating protein activity, regulating intestinal flora, etc. [23-24]. Xu Zhaohui et al.[25] used network pharmacology technology and molecular docking research to find that there are seven main active ingredients in Cistanche deserticola for treating Parkinson's disease, including phenylethyl alcohol (verbascoside, echinacoside), quercetin, and arachidonic acid. Acid, beta-sitosterol, salicylic acid, eugenol, paclitaxel, paclitaxel, etc. The following article summarizes the pharmacological effects of Cistanche deserticola and its mechanism of action in treating Parkinson's disease by reading a large number of clinical and experimental research literature.

4.1 Antioxidative stress mechanism

Free radicals are active free radicals. Under normal physiological conditions, metabolism in the body will promote the continuous generation of free radicals. Antioxidant enzymes can remove excess free radicals promptly to ensure that free radicals are in a dynamic equilibrium state. [26]. However, when the body is in an abnormal state, free radicals are excessively generated, and antioxidant enzymes are unable to remove excess free radicals. Free radicals accumulate in the body in large quantities. The balance between the oxidation mechanism and antioxidants in the body is imbalanced, causing the body's cells to and tissues be damaged, thereby causing a series of diseases [27]. Research shows that too many oxygen free radicals can cause the loss of dopaminergic neurons in the substantia nigra in the brain, resulting in hyper acetylcholine. The relative imbalance between dopamine and acetylcholine in the brain causes increased muscle tone, which is a major cause of PD. factors [28]. echinacoside, the monomer with the highest content among phenylethanol glycosides in Cistanche deserticola, can significantly increase the protein content and antioxidant properties in rat brains and regulates the substantia nigra-striatum by inhibiting the active component of acetylcholine (AChE).

It can improve the clinical symptoms of PD and provide new ideas for the prevention and treatment of PD [29]. Li M et al. [30] used zebrafish to prepare an animal experimental model of 6-hydroxydopamine (6-OHDA)-induced neuronal damage. They administered Cistanche deserticola verbascoside (VB) 150 mg/ml via intraperitoneal injection and found that VB could reverse hypoxic nerve damage. It inhibits the depolarization of cell mitochondria and increases the survival rate of dopamine neurons. LIU C et al.

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[31] proposed that Cistanche deserticola quercetin can increase the expression of dopamine transporter and tyrosine hydroxylase (TH) in the mouse brain, and can effectively reduce the production of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) triggers oxidative stress, thereby alleviating MPTP-induced DA neuron loss. Zhang Y J et al.

[32] found that echinacea, the active ingredient of Cistanche deserticola, can increase the content of glutamic acid (GLU), thereby improving the activity of PC-12 nerve cells and superoxide dismutase (SOD), reducing the intracellular calcium ion concentration, and ultimately achieving antioxidant purposes. HONG et al. [33] showed through animal experiments that verbascoside (VB) activates Nrf2 and upregulates the expression of oxygen stress-inducible HO-1 (which is a key factor in oxidative stress damage response) through the ERK and PI3K/Akt pathways. Antioxidative stress effect. Li N et al. [34] used verbascoside (VB) for intragastric administration and found that it could protect 6-hydroxydopamine by inhibiting the Nrf2/ARE signaling pathway, upregulating antioxidant enzymes, reducing the level of reactive oxygen species in brain cells, and reducing oxidative stress. (6-OHDA)-induced dopaminergic neuron damage and VB can also directly penetrate the blood-brain barrier to treat Parkinson's disease. Khaled Radad et al. [35] confirmed that Cistanche deserticola verbascoside can protect 6-hydroxydopamine (6 -OHDA)-induced damage to dopaminergic neurons and alleviate symptoms of Parkinson's disease.

4.2 Regulate neuroinflammation

In Parkinson's disease, abnormally folded α-synuclein mediates neuroinflammatory responses, activates microglia, and prompts them to secrete a large number of inflammatory factors, such as prostaglandins (PG), interferons (IFN), and interleukin-1 ( IL-1β), etc., induce the damage of DA neuronal cells in the substantia nigra-striatum [36-38]. Xie Qian [39] cultured microglia in vitro and used detection technologies such as qRT-PC and Western blot to observe the expression of Cistanche deserticola-related inflammatory factors and its impact on the SIRT1/NF-κB signaling pathway, and came to two conclusions: First, Cistanche deserticola total glycosides can inhibit lipopolysaccharide-induced microglial activation and the expression of related inflammatory factors (interleukin-1β, cyclooxygenase-2). Its total glycosides from Cistanche deserticola can improve lipopolysaccharide (LPS)-induced microglial inflammatory response, reduce neuronal cell apoptosis, and prevent PD by activating the sirtuin 1 (SIRT1)/nuclear factor kappa B (F-κB) signaling pathway. progress. Zhang Yanhong et al. [40] replicated a PD mouse model by intraperitoneally injecting MPTP and found that Cistanche deserticola

After echinacoside intervention, the pro-inflammatory factor endogenous chemokine (CX3CL1) was down-regulated in mice, resulting in a decrease in the expression of microglia (MC) marker OX-42, achieving the effect of protecting neurons. Chen Qing [41] prepared MPTP subacute Parkinson's mouse model and observed that Cistanche deserticola echinacoside has a protective effect on neurons in subacute Parkinson's mice, and echinacoside can reduce tyrosine hydrogenase in neurons. number, reduce the production of the reactive astrocyte marker GFAP, inhibit the release of pro-inflammatory factors such as IBA1 and TNF-a in the substantia nigra-striatal area of the midbrain, thereby exerting an anti-neuroinflammation effect and ultimately delaying the progression of PD.. Liang Y et al. [42] induced a mouse Parkinson's model through MPTP and showed that Cistanche deserticola echinacoside can reduce the activation rate of microglia (MC), reduce the release of inflammatory mediators and nerve cell damage by activating the ERK signaling pathway. Zhang C et al. [43] explored the protective mechanism of Cistanche deserticola quercetin on neuroinflammation. They used Nrf2/NLRP3 as the signaling pathway and stimulated BV2 cells with CuCl2 to establish an inflammation model. It showed that Cistanche deserticola quercetin can exert anti-inflammatory and anti-inflammatory effects through the Nrf2/NLRP3 pathway. The antioxidant effect promotes the reduction of the number of microglia and the gradual decline of cell activity, thus exerting an anti-PD effect. Qin Rong et al.[44] found through animal experiments that quercetin can increase the permeability of the blood-brain barrier in rats and reduce serum interleukin-6 and tumor necrosis factor. They concluded that quercetin can regulate neuroinflammation through The blood-brain barrier plays a role.

4.3 Regulation of autophagy

Autophagy refers to phagocytosis of proteins or organelles in one's cytoplasm, wrapping these proteins or organelles into vesicles, and then fusing them with lysosomes to form autophagy lysosomes, which decompose the materials in them to satisfy the needs of the cell. meet its own metabolic needs and update some organelles [45]. Parkinson's disease is caused by the abnormal accumulation of a large number of α-Synuclein in the central nervous system, forming aggregates. The autophagy system is therefore activated to remove mutations, damage, and misfolded proteins. This is the degradation of abnormal proteins in the body.

The main pathway, if autophagy is defective, will lead to the occurrence of PD [46], and microglia may play an important role in the transmission process [47]. WANG W W et al. [48] found that Cistanche deserticola quercetin (30 mg kg-1) inhibited α-protruding nuclear protein aggregation, upregulated MDA, ROS, and SOD activities, and reduced mitochondrial damage through the PINK1/Parkin-mediated mitophagy pathway. exert an anti-PD effect. Feng Yu [49] established a chronic Parkinson's mouse model through MTPT and showed that Cistanche deserticola echinacoside can downregulate α-protrusion by upregulating the expression levels of autophagy-related factors Beclin-1 protein and LC3-11 protein and downregulating P62 protein levels. Reverse nuclear protein to protect dopamine nerves and improve Parkinson's symptoms. Specifically, in the pole climbing experiment, echinacea can shorten the total time of mice to climb the pole, relieve the symptoms of motor retardation in mice, and can also coordinate the movement of mice. Movement balance ability. Zhang Z N et al.[50] observed that Cistanche deserticola echinacoside could decrease the expression of rapamycin target protein (mTOR) kinase in the substantia nigra-striatum of mice, thereby increasing the formation of autophagosomes and degrading abnormally aggregated α -synuclein to improve symptoms in mice.

4.4 Anti-neuronal cell apoptosis

The occurrence of Parkinson's disease is closely related to the apoptosis of dopamine neurons and reduced neurotransmitter release in the substantia nigra pars compacta. The causes mainly include environmental factors (such as pesticides, herbicides, MPTP poisons, etc.), genetic factors, aging, etc.[ 51]. Lin Yao et al. [52] used 1-methyl-4-phenylpyridine (MPP+) to induce SH-SY5Y neuroblast cell line to establish a PD animal model and observed that the cell viability was significantly enhanced and the cell staining changed after the intervention of Cistanche deserticola echinacea. uniformly, reducing the pyknosis and apoptosis rate of PD cell nuclei, and the expression level of anti-apoptosis-related protein B lymphoma-2 gene (Bcl-2) increased, and the pro-apoptotic protein caspase-3 (cleaved caspase-3) was significantly down-regulated. Huang Yunmei[53] established a PD model through rotenone and observed the effect of Cistanche deserticola echinacoside on the ultrastructure of the midbrain of Parkinson's disease model rats. They found that Cistanche deserticola echinacoside could increase the size of neuronal cells in the rat brain area. , the number of mitochondria in the cells increased significantly, and the body ridges were arranged regularly. The above results show that echinacea prevents and treats PD by reducing mitochondrial damage and neuronal apoptosis. Zhong Jianan [54] used a rotenone-induced PD model and confirmed that Cistanche deserticola pinealosin can inhibit the expression of ERS-related apoptosis pathway proteins, bind GRP78 to IRE1α, reduce the autophosphorylation expression activation of IRE1α, thereby reducing the activation of downstream ASK1, JNK phosphorylation, and the Caspase apoptosis pathway, jointly reduce the degree of endoplasmic reticulum stress and reduce the apoptosis of dopamine neurons in PD model rats.

5 Summary and Outlook

In summary, Cistanche deserticola has a significant effect in treating Parkinson's disease. This article summarizes the pharmacological effects of Cistanche deserticola and its mechanism of action in treating Parkinson's disease. It combines the functions of Cistanche deserticola in nourishing the kidneys and marrow, replenishing essence and blood, and entering the large intestine. It has the function of moistening the intestines and laxative, which shows that Cistanche deserticola plays an indispensable role in the treatment of Parkinson's disease. Cistanche deserticola has the advantages of multi-target and multi-component treatment for Parkinson's disease. Cistanche deserticola contains various active ingredients such as verbascoside, echinacoside, quercetin, and arachidonic acid, which regulate neuroinflammation and antioxidant effects. It can stimulate, and regulate cell autophagy, resist nerve cell apoptosis, and regulate intestinal function. In addition, after reviewing the literature, it was found that Cistanche deserticola's use in animal and cell experiments for treating Parkinson's disease deviated from actual clinical observations. This may be related to certain differences in the pathogenesis of the human body. More clinical experiments need to be carried out to further verify traditional Chinese medicine. Effectiveness of Cistanche deserticola in treating Parkinson's disease. Due to the wide variety of active substances in Cistanche deserticola and the complex pathways related to Parkinson's disease, there is still no complete pharmacological model to describe the correlation with Parkinson's disease pathways. Therefore, in subsequent clinical and experimental studies, the pharmacological model of Cistanche deserticola should be used as the basis. Basics, in-depth study of the pathways related to Cistanche deserticola and Parkinson's disease to provide new ideas for the treatment of Parkinson's disease

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