Research Progress On The Prevention And Treatment Of Alzheimer's Disease And Parkinson's Disease By Dihuang Yinzi*
Oct 23, 2024
Abstract: Neurodegenerative diseases are a class of diseases characterized by the loss of specific types of neurons and progressive disease progression. The main representatives include Alzheimer's disease (AD) and Parkinson's disease. PD) etc. Due to the intractable symptoms and irreversible condition of this type of disease, it brings great physical and psychological burden to patients and seriously disturbs their normal life. In terms of treatment, there is currently no specific clinical treatment for AD, and the first-line treatment drugs for PD also have great limitations. The theory of traditional Chinese medicine believes that the kidney governs bones, generates marrow, and connects to the brain. In clinical syndrome classification, premature aging, fatigue, forgetfulness, and limb tremors caused by kidney deficiency and marrow loss are considered to be the main pathogenesis of this type of disease. Dihuang Yinzi comes from "Shengji Zonglu" and is recorded in ancient books as a good prescription for nourishing kidney yin and replenishing kidney yang. Clinical data shows that this prescription has a significant effect on neurodegenerative diseases caused by kidney essence deficiency. With. Modern research results show that its mechanism of action involves inhibiting inflammatory responses, regulating mitophagy, reversing hypothalamic-pituitary-adrenal axis abnormalities and neuroprotection, and the main active ingredients in this prescription include loganin, echinaceaside, Schizandrol A and so on. This article aims to discuss the TCM etiology and pathogenesis of AD and PD, sort out the clinical efficacy, mechanism of action, and active ingredients of Rehmannia glutinosa in treating these two diseases in recent years, and summarize and analyze the role of Rehmannia glutinosa in neurodegenerative diseases. The current research status provides direction and reference for subsequent in-depth clinical and mechanism research on this compound.
NEW TRADITIONAL HERB CISTANCHE FOR TREAT AD AND PD
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Keywords: Rehmannia glutinosa, Alzheimer's disease, Parkinson's disease, kidney essence deficiency, pharmacological mechanism, active ingredients
Alzheimer's disease (AD), which is characterized by cognitive impairment, and Parkinson's disease (PD), which is characterized by limb tremor, are the neurodegenerative diseases with the highest incidence rate [1]. The majority of patients with these diseases are elderly people [2]. The national prevalence rate is about 1.7%, which is increasing year by year. The cure rate is low and the symptoms are difficult to treat. This not only brings an economic burden to the social medical system, but also brings great trouble to the normal life of patients. At present, there is no specific treatment for AD in clinical practice. The commonly used acetylcholinesterase inhibitor drugs have great limitations in practical application due to their poor efficacy and associated side effects [3].
At present, the first-line treatment drugs for PD are still monoamine oxidase inhibitors, exogenous dopamine supplements or dopamine receptor agonists. A large amount of clinical experience has shown that their side effects are obvious, and there are serious problems such as dyskinesia and "switching effect" [4]. TCM theory has a unique understanding of the etiology and pathogenesis of the above two neurodegenerative diseases and clinical syndrome treatment, and TCM compound prescriptions for the intervention of such diseases also show unique clinical advantages.
NEW TRADITIONAL HERB CISTANCHE FOR TREAT AD AND PD
This article aims to explore the TCM etiology and pathogenesis of neurodegenerative diseases represented by AD and PD, and review the clinical efficacy, mechanism of action and effective ingredients of Rehmannia Decoction on the above two diseases.
By systematically combing the research status of Rehmannia Decoction in neurodegenerative diseases, it is hoped to provide direction and reference for the subsequent in-depth clinical and mechanism research of the compound.
2 Research progress on the prevention and treatment of AD with Rehmannia glutinosa yinzi
AD is the neurodegenerative disease with the highest incidence rate. Currently, there are approximately 47 million patients worldwide, and it is expected that the number of patients will reach 131 million in 2050 [7]. The clinical manifestations of the disease include memory impairment, language dysfunction, limited cognitive ability, and weakened executive ability.
2.1 Clinical efficacy research
Rehmannia glutinosa is widely used clinically to treat AD memory decline, spatial cognitive impairment and other accompanying symptoms, and clinical experimental data show significant effects. In terms of cognitive impairment: Zhang Na et al[8]
, Jia Qian et al. [9] divided the collected outpatient and inpatient patients into two groups: traditional Chinese medicine treatment group and Western medicine treatment group for clinical observation, and compared and analyzed the Mini-Mental State Examination Scale and Montreal Cognitive Assessment of the two groups of patients. The changes in scores of the scale and the activities of daily living scale have identified that Dihuang Yinzi can significantly improve the cognitive function of AD patients; Yao Aina et al. [10] demonstrated through clinical observation of 48 AD patients that Dihuang Yinzi combined with acupuncture Baihui The acupoint treatment effect is obvious and the long-term effect is ideal. In terms of the accompanying symptoms of AD: Zuo Qinjing [11] collected 56 patients with AD complicated by depression, divided them into the Dihuang Yinzi group and the sertraline group, and conducted treatment and Hamilton Depression Scale scores. The final results were
It was finally proposed that Dihuang Yinzi can treat AD patients with depression, and the efficacy is better than that of traserin. The data from the above clinical trials show that Dihuang Yinzi can not only treat AD, but also has a good effect on its accompanying depression, and the long-term effect of Dihuang Yinzi treatment is better.
2.2 Research on the mechanism of action
With the progress of research, the more recognized pathogenesis of AD mainly includes central cholinergic damage, β-amyloid protein deposition, microtubule-associated protein-tau protein abnormalities, gene mutations, reduced immunity, etc. Objective: The mechanism of Rehmannia glutinosa in treating AD involves inflammation, mitochondrial protection, production of β-amyloid, and improvement of synaptic structure and function. In terms of inflammation, Rehmannia glutinosa can improve inflammation by regulating the protein kinase R-like endoplasmic reticulum kinase/eukaryotic cell initiation factor 2α pathway and the Toll-like receptor 4/adapter protein myeloid differentiation factor/nuclear transcription factor-κB signaling pathway. The inflammatory microenvironment in the brains of AD mice improves the cognitive dysfunction of AD; in terms of mitochondrial protection, Dihuang Yinzi improves mitochondrial biosynthesis capacity and enhances mitochondrial respiration by activating the CREB/PGC-1α signaling pathway in the brain tissue of AD rats. chain enzyme activity, thereby improving memory ability [12];
In terms of β-amyloid protein generation, Rehmannia glutinosa can reduce the amount of β-amyloid protein deposited in the brain by inhibiting the cleavage process of β-amyloid precursor protein[13]; in terms of synaptic improvement, Rehmannia glutinosa can improve synaptic structure and function by enhancing the glutamate reuptake function of astrocytes[14]. In addition to experimental studies, some scholars have also explored the mechanism of action of Rehmannia glutinosa in improving AD through network pharmacology and cell apoptosis network, and believed that Rehmannia glutinosa can regulate the mitogen-activated protein kinase signaling pathway, Jun amino-terminal kinase/c-Jun amino-terminal kinase signaling pathway, etc. to inhibit the expression of apoptotic proteins[15]; and affect the tumor necrosis factor signaling pathway, neurotrophic signaling pathway, and estrogen signaling pathway to exert therapeutic effects[16].
Through the above evidence, it is found that Rehmannia glutinosa improves abnormal behavior of AD, which may be achieved by regulating certain specific intracellular signaling pathways. These studies on drug intervention mechanisms explain to a certain extent the possible reasons why Rehmannia glutinosa is effective in clinical treatment of AD. Unfortunately, the above studies are too fragmented and unsystematic, and most of them only explore the drug action mechanism of a specific signaling pathway or a certain cell function. In the case of complex drug groups, it may be more helpful to conduct systematic and in-depth mechanism research by combining drug component analysis with omics technology to effectively reveal the drug intervention mechanism.
2.3 Exploration of active ingredients
In order to further clarify the target types of different drug ingredients and better provide theoretical and experimental basis for clinical medication, researchers conducted a series of studies based on the monomer components of Rehmannia glutinosa for the treatment of AD. In the treatment of AD, the main ingredients of Rehmannia glutinosa that play a role are glycosides, sugar substances and lignans. Among them, glycosides are mainly represented by catalpol, polygala saponin, total glycosides of Cistanche deserticola, echinacoside and loganin. A series of studies on the above-mentioned individual compounds have also demonstrated their anti-AD activity: catalpol can improve the structure of cerebral cortical neurons in AD rats under transmission electron microscopy, increase the expression of the M1 subtype of cholinergic muscarinic receptors in the cerebral cortex [17], reduce the content of lactate dehydrogenase in hippocampal neurons, and reduce the rate of cell apoptosis [18]; Polygala tenuifolia saponins can increase the average and maximum lifespan of tau-transgenic AD model fruit flies [19], reduce the inhibition of superoxide dismutase activity in the brain, and enhance the inhibition of malondialdehyde activity [20]; total glycosides of Cistanche deserticola can enhance synaptic plasticity and cognitive function by reducing the content of free radicals and excess peroxides [21]; echinacea glycosides inhibit the occurrence of amyloid by targeting the endoplasmic reticulum stress sensor-endoplasmic reticulum stress protein kinase R-like endoplasmic reticulum kinase [22], and inhibit NOD-like receptor pyrin domain-associated protein 3/caspase-1/interleukin-1β =Protein expression can protect neurons[23]; Loganin can effectively reduce the level of phosphorylated tau[24], thereby improving AD.
The carbohydrate substances in Rehmannia Decoction mainly include Poria cocos polysaccharide and Cornus officinalis polysaccharide. Poria cocos polysaccharide can reduce the activity of superoxide dismutase in the brain, and Cornus officinalis polysaccharide can reduce the expression of phosphorylated tau protein in the hippocampus, and both can improve AD[25]. The lignans in Rehmannia Decoction are mainly Schisandrin A. Schisandrin A can improve the function of hippocampal and cortical neurons in dementia mice by downregulating the expression of advanced glycation end product receptor and downstream p38, and improve endoplasmic reticulum stress to alleviate cognitive dysfunction caused by AD[26-27]; it can also protect nerves through the phosphatidylinositol 3 kinase/protein kinase B pathway in combination with bovine citrinin, thereby inhibiting inflammation and cell apoptosis[28].
