Ｒesearch Progress Of Clinical Application And Therapeutic Mechanism Of Herba Cistanche Ⅱ

3 Effects on the nervous system

3.1 Anti-Alzheimer's disease effect

  Alzheimer's disease (AD), also known as Alzheimer's disease, is a degenerative disease of the central nervous system with progressive cognitive function and memory impairment as its main clinical manifestations. Its main pathological features are: neuronal loss; extraneuronal β-amyloid in the cerebral cortex and hippocampus

Senile plaques are formed by peptide deposition; neurofibrillary tangles are formed by abnormal aggregation of tau protein in brain neurons [16].

40-85% GLYCOSIDE CISTANCHE FOR SELL

3.1.1 Clinical application:

Li Nan et al. randomly divided patients with mild AD into three groups: the Cistanche group, the donepezil group and the blank control group. They evaluated the changes in the patient's cognitive abilities before and after 48 weeks of treatment and analyzed the changes in the patients' hippocampal volume; the test results showed that the Cistanche preparations can improve The cognitive ability of patients with mild AD slows down the atrophy of hippocampus [17]. Clinical studies have shown that the brain function of AD patients after Cistanche treatment

The level of t-tau in spinal fluid was effectively cleared with the decrease of TNF-α and IL-1β, suggesting that Cistanche preparations may affect the aggregation of tau protein by inhibiting the expression of TNF-α and IL-1β in cerebrospinal fluid [16] .

3. 1. 2 Experimental research and mechanism of action: 

Cistanche total glycosides can reduce the activity of acetylcholinesterase and Ca2+ content in the hippocampus of the AD rat model replicated with Aβ25-35, maintaining the content of acetylcholine in the brain at normal levels and Improve their learning and memory abilities [18]. Cimicifuga glycosides can inhibit the generation of reactive oxygen species, or regulate the Bcl-2, cytochrome C and caspase-3 apoptosis pathways to resist the damage of SH-SY5Y cells induced by amyloid Aβ25-35 [19]. The above studies have shown that the active ingredients of Cistanche-related preparations can penetrate the blood-brain barrier, maintain normal levels of acetylcholine, and participate in the pathological process of AD. The mechanism may be related to its anti-oxidation, maintaining a high-energy state of mitochondrial membrane potential, thereby inhibiting nerve cell apoptosis. However, the relevant molecular mechanism of action has not been elucidated and needs further research.

3.2 Anti-Parkinson's disease effect

PD (Parkinson's disease, PD) is a neurodegenerative disease characterized by resting tremor, muscle stiffness, bradykinesia, gait disorder and postural instability as its main clinical manifestations, and is the second most common neurodegenerative disease after AD. Its main pathological characteristics are the progressive degeneration and necrosis of dopaminergic neurons in the substantia nigra of the midbrain, and the presence of eosinophilic inclusion bodies, or Lewy bodies, in the cytoplasm of the remaining neurons [20].

3. 2. 1 Clinical application: Currently, traditional Chinese medicine compounds with Cistanche as the main drug combined with basic western medicines such as Madopa have achieved certain clinical effects in the treatment of PD patients. Li Junyan et al. conducted a study on the efficacy of Bushen Huoxue Yin combined with Western medicine in the treatment of primary PD. They found that Bushen Huoxue Yin combined with Western medicine is better than Western medicine alone in improving the motor function and daily living ability of PD patients. It can also reduce the side effects of Western medicine and reduce the symptoms of PD. The occurrence of complications improves the patient's quality of daily life [21]. Zheng Chaoqun's study on kidney-tonifying compound combined with Madopa in the treatment of PD patients also found similar findings [22]

.

3. 2. 2 Active ingredients and related mechanisms: Tian Yun, Lin Shaogang, etc. found in animal experiments and cell experiments that Cistanche can upregulate the expression of Bcl-2 in MES23.5 dopaminergic nerve cells, reduce the expression of Fasl, and increase NGF and GDNF. Endogenous content; It is speculated that Cistanche plays a protective role in nerve cells by regulating the expression of dopaminergic nerve cell apoptosis factors and neurotrophic factors [23]. Another study showed that total phenylethanoid glycosides can significantly improve the behavioral characteristics of the C57BL/6 mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It increases the content of dopamine in the striatum, increases the expression of tyrosine hydroxylase in the substantia nigra, inhibits the decrease in cerebellar granule cell activity caused by MPP +, and inhibits the activation of caspase-3 and caspase-8 [24]. Echinacea can also improve the behavioral performance of MPTP model PD mice and inhibit the activation of caspase-3 and 8 in cerebellar granule cells [25]. Echinacea can slow down the apoptosis of SH-SY5Y cells induced by MPP +, and experiments show that it protects the survival of nerve cells by upregulating the GFRal/AKT pathway [26]. Deng Min et al. used verbascoside

After pretreating SH-SY5Y cells induced by MPP +, it was found that it can significantly increase the expression of Bcl-2 and effectively antagonize the toxic effects of MPP + on mitochondria [27].

In addition, comimiculin-like glycosides among phenylethanoid glycosides can resist nerve damage in MPTP-induced PD model mice, improve their behavioral defects, and increase the number of dopaminergic neurons, dopamine transmitter content, and α-synuclein protein levels [ 28〕. Cimicifuga glycosides can also resist rotenone-induced SH-SY5Y cell damage, reduce the content of lactate dehydrogenase, inhibit the degradation of PD-related proteins and the formation of α-synuclein protein dimers [29].

Current research on the anti-PD effect of Cistanche mainly focuses on its extract Cistanche total glycosides and its monomers. The mechanism may be related to up-regulating the GFRal/AKT pathway, anti-oxidation, inhibiting apoptosis, and protecting nerves; promoting TH expression, increasing tyrosine hydroxylase, inhibiting the release of lactate dehydrogenase, and increasing the synthesis of monoamine transmitters, etc. .

3. 3 Anti-fatigue effect Chronic fatigue syndrome (CFS) is a syndrome characterized by unexplained physical and mental fatigue, accompanied by physical symptoms such as fatigue, headache, low fever, and emotional disorders such as depression. Zheng [30]. Experiments by Li Yongchao and others finally confirmed that phenylethanoid glycosides are the most direct anti-fatigue substances of Cistanche ; and the experiments suggest that Cistanche 's anti-fatigue effect can increase the energy reserves of body tissues, improve the body's tolerance to overexertion, and reduce the effects of excessive exercise. Undesirable metabolites are generated and promptly cleared during exercise in large quantities free

Basic related [31]. Cistanche can increase the level of NOS3 in liver cells and endothelial cells of weight-bearing swimming mice, thereby dilating blood vessels, increasing blood flow, accelerating glycogen synthesis, and maintaining the body's normal physiological level to exert anti-fatigue effects [32].

4 other functions

At present, many studies have shown that Cistanche can also protect the liver [33] and myocardium [34]

, anti-aging [35], immune regulation [36], and promotion of bone formation [37]. There are also individual literature reports that Cistanche also has the effect of relaxing blood vessels [38] and lowering cholesterol [39]. However, there are few studies on it, which are limited to cell and animal experimental studies, and have almost never been applied in clinical applications.

In short, Cistanche is a traditional Chinese herbal medicine with high clinical application value and a wide range of pharmacological effects. Studies have shown that the main pharmacologically active ingredients of Cistanche are phenylethanol glycosides and polysaccharides [40]

. Phenylethanoid glycosides have neuroprotective, antioxidant, antibacterial, antiviral, anti-inflammatory and hepatoprotective effects, while the main function of polysaccharides is to improve the body's immunity [41]. However, the research is not in-depth enough. For example, regarding the neuroprotective effect, how do the active ingredients of Cistanche enter the nervous system? Do they enter directly or in the form of metabolites? Can they directly pass through the blood-brain barrier? This protection

Is the protective effect the effect of a single component or the clustered effect of multiple components? How long does this effect last in the nervous system? The above issues still need to be analyzed from different levels such as the whole body, organs, tissues, cells, proteins, genes, and molecular expression. Dig deeper. The remaining chemical components (such as iridoids and their glycosides, benzyl alcohol glycosides, etc.) and pharmacological mechanisms also need to be further elucidated.

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