Research On The Pharmacological Mechanism Of Traditional Chinese Medicine Cistanche in The Treatment Of Parkinson's Disease

Abstract： Parkinson's disease (PD) is a kind of neurodegenerative disorder belonging to the extrapyramidal system. It has a great impact on People's Daily life. The pathological features are the loss of dopamine neurons in the dense area of substantia nigra and the appearance of eosinophilic inclusion bodies in the cytoplasm of neurons. Cistanche tubulosa, a commonly used Chinese medicine in the treatment of Parkinson's disease, has the effects of tonifying kidney Yang, invigorating blood, and moistening the bowel. The pharmacological effect of Cistanche is very extensive. According to the relevant literature, it is found that Cistanche can treat Parkinson's disease with multiple targets and multiple approaches, and can effectively delay the progression of the disease. It contains a variety of effective ingredients, mainly including verminin, echinoside, quercetin, arachidonic acid, β -glutamol, dessalicylic acid, eugenol, paclitaxel, etc., which plays the role of anti-oxidative stress, regulation of neuroinflammation, regulation of autophagy, inhibition of apoptosis of nerve cells and regulation of intestinal flora, and has significant therapeutic effect on Parkinson's disease. This article summarized the pharmacological mechanism of the active components of Cistanche in treating Parkinson's disease and provided a reference for the future research direction of Cistanche in treating Parkinson's disease. 

Keywords: Parkinson's disease; Cistanche tubulosa; pharmacological mechanism; research progress

Parkinson's disease (PD) is a neurodegenerative disease characterized by resting tremors, bradykinesia, muscle rigidity, and postural balance disorders [1]. The pathological mechanism of PD is related to the loss of dopamine (DA) neurons in the substantia nigra-striatum, abnormal aggregation of α-synuclein, oxidative stress disorder, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. It is related to various factors such as irritation disorder, neuro excitotoxicity, uncontrolled autophagy, kinase signaling pathways, neurotrophic factor deficiency, and nerve cell apoptosis [2-4]. Because the pathogenesis of the disease is very complex, the prevention and treatment of PD are faced with great difficulties. Its clinical manifestations can be divided into two types: one is dyskinesia type, including slow movement, resting tremor, general muscle rigidity, and postural balance disorder. The second type is the non-motor disorder type, including constipation, hyposmia, increased bladder residual urine volume, mental depression, sleep, and arousal disorders, orthostatic hypotension, hyperhidrosis, etc. [5] Eduardo Tolosa[6] proposed that most PD patients are older than 60 years old, and the incidence rate increases with age. There are approximately 6 million people worldwide suffering from PD, which has increased by 2.5 times compared with 2000. The disease has a hidden onset, an increasing incidence rate year by year, and a low cure rate. It can lead to a decline in PD patients' daily living abilities, affect their work and social participation, and even endanger their lives.

1 Traditional Chinese Medicine's understanding of Parkinson's disease

PD belongs to the category of "tremor syndrome" in traditional Chinese medicine, also known as "tremor", "tremor", "tremor syndrome", "tremor", etc. [7]. Zhang Zihe stated in "Confucianism Shiqinzheng": "Xinsma Sou, who is fifty-nine years old, owes taxes in the autumn and has an official staff of sixty. He has been frightened and has been suffering from wind and convulsions for three years. He has been seriously ill and has suffered severe disease in his limbs." The tremor falls and cannot hold things. When eating, the patient has to be fed, the mouth and eyes are open, the lips and tongue are chewed, and the posture is trembling, like a puppet with strings." This is an early record describing the tremor syndrome [8]. "Su Wen Zhi Zhen Yao Da Lun" says: "All winds, dizziness, spasms, and ankylosis all belong to the liver." Among them, "arrhythmia" and "ankylosis" refer to limb tremors, unsteady walking, and muscle rigidity, which are all related to the main symptoms of PD. Similar. Wang Kentang of the Ming Dynasty said in "The Criterion of Syndrome and Treatment Zhenxiao": "This disease is rare in the prime of life, but occurs after middle age, especially in the elderly [9]". Dou Cai recorded in "Bian Que Xinshu Cure Tremors": "If the hands and feet are trembling and unable to hold objects, it means true yang deficiency [10]", indicating that yang deficiency is closely related to tremor syndrome. The main pathogenesis of tremor syndrome is old age and physical weakness, depletion of marrow sea, loss of kidney essence, insufficient Qi, blood, and essence, resulting in loss of nourishment of tendons and arteries, and internal disturbance of deficiency and wind. This disease disease is located in the tendons and meridians involves the brain and is closely related to the liver, kidneys, and spleen.

2 Advantages of traditional Chinese medicine in treating Parkinson's disease

At present, Western drugs against Parkinson's disease mainly include dopamine receptor agonists, monoamine oxidase B inhibitors, cholinergic inhibitors, catechol-O-methylase inhibitors, and amantadines [11]. Western medicine has definite efficacy in treating PD and has a positive therapeutic effect on the motor symptoms of PD. However, serious complications such as "drug efficacy attenuation", "end-of-dose phenomenon" and "dyskinesia" are prone to occur during the treatment process, and the efficacy is limited. Western medicine has a limited effect on the motor symptoms of PD. The efficacy of the non-motor symptoms of PD is not ideal, but the traditional Chinese medicine Cistanche tubulosa can work through multiple targets and multiple components and has relatively good specificity for the non-motor symptoms of Parkinson's disease. As well as the side effects of traditional Chinese medicine on Western medicine, it can It has the effect of treatment and control [12-13]. Therefore, to improve the therapeutic effect of the disease, slow down the progression of the disease, reduce the pain of patients, and improve the quality of life of patients, traditional Chinese medicine plays a great advantage.

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3 Chinese medicine's interpretation of Cistanche tubulosa

According to the 2020 edition of the "Chinese Pharmacopoeia" [14], Cistanche tubulosa is a large herb suitable for growing on sandy soil in arid areas. Its fleshy stems have special dry scaly leaves. Its medicinal properties are "calm and gentle", hence the name "Cistanche tubulosa". Ni Zhumo said in "Compendium of Materia Medica": "Cistanche tubulosa nourishes the vital gate, nourishes the kidneys, and replenishes the essence and blood. It is warm but not hot, slippery but not diarrhea, warm but not dry, and tonic but not harsh, so it has The name of Cistanche tubulosa[15]". The aliases of Cistanche tubulosa include "Dayun", "Dan Dayun", "Connong", "Bishuilong", "Black Siming", etc. The main production areas are in northwest my country, including Gansu, Xinjiang, Inner Mongolia, Shaanxi, and Qinghai. , and other places. It was first recorded in "Shen Nong's Materia Medica" and was listed as a top grade, known as "Desert Ginseng [16]". Cistanche tubulosa has mild medicinal properties and a sweet and salty taste. It enters the meridian of the kidney and large intestine. Cistanche tubulosa has the effect of nourishing the kidneys and replenishing the marrow. Wan Mingzhu [17] proposed in "Su Wen Ni Tiao Lun": "If the kidneys do not produce marrow, the brain will not be full." Moreover, Luan Zhenxian [18] used the Traditional Chinese Medicine Inheritance Computing Platform to study the clinical medication rules of kidney-tonifying method in the treatment of Parkinson's disease. Among them, frequent medication use

There are 20 traditional Chinese medicines with a frequency greater than 120 times, and Cistanche tubulosa has the highest frequency of use, accounting for 63% of the total frequency of use. Cistanche bark replenishes essence and blood. "Medical Records Has Been Compiled: Zhan Zhenli" records: "Most of the time, the qi and blood are too weak to nourish the muscles and bones, so they are shaken and unable to regulate [19]". "Jingyue Quanshu Miscellaneous Syndrome Mo Jiao," says: "Anyone with yin deficiency and low blood who cannot nourish the muscles and veins, resulting in twitching and stiffness, all have this syndrome." This shows that the essence and blood are deficient and the limbs cannot be nourished externally. If the tendons and meridians are weak, the limbs will tremble uncontrollably, the brain meridians cannot be moisturized, and the head will shake and tremble. Cistanche purpura can moisturize the intestines and relieve constipation. Studies have shown that [20] the brain-gut-axis theory is related to Parkinson's disease. It is believed that the brain is related to Parkinson's disease. The intestines are physiologically interdependent, pathologically influence each other, and are connected through meridians. "Lingshu Dynasty Shu" was the first to record that the brain and intestines are interconnected, saying: "Yangming is connected to the Governor Vessel, connected to the brain, and governs its gods. [21]", subsequent research found that Cistanche tubulosa has the effects of nourishing the kidneys, nourishing the brain, and moisturizing the intestines and laxatives [22]. Therefore, this drug plays an important role in the treatment of Parkinson's disease accompanied by constipation.

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