Research Progress On The Effect Of Cistanche Cistanche On The Nervous System

For more information:ali.ma@wecistanche.com

Meng Shengxi, Huo Qingping

Department of Traditional Chinese Medicine, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China

Abstract: Cistanche contains many chemical components such as phenylethanoid total glycosides and iridoid glycosides. Its active components can inhibit neuronal cell apoptosis, reduce ischemic brain damage, and treat Alzheimer’s disease, Parkinson’s disease, and vascular disease. Dementia, improve learning and memory function, etc. Its effect on the nervous system has attracted more and more attention from scholars at home and abroad. This article reviews the effects of the effective components of Cistanche in the nervous system.

Keywords: Cistanche; active ingredients; nervous system; review

DOI: 10.3969/j.issn.1005-5304.2016.10.031

Chinese Library Classification Number: R285.5 Document Identification Code: A Article Number: 1005-5304(2016)10-0123-04

Cistanche, also known as Dayun, Goblin, and Golden Bamboo, is known as the "desert ginseng". It is the dry fleshy stem with scaly leaves of Cistanche deserticola Y. C. Ma. The main types are Cistanche, Cistanche tubulosa and salt. Raw cistanche, etc., have multiple functions such as protecting the nervous system, improving immunity, anti-tumor, and moistening the intestines, and are very safe [1]. Scholars at home and abroad have discovered that the effective ingredients of Cistanche are playing an increasingly important role in the prevention and treatment of neurological diseases. The relevant research is summarized as follows.

Cistanche can protect nerves

1 Main chemical composition

At present, nearly one hundred chemical components and trace elements have been isolated and identified from Cistanche, such as phenethanol glycosides, iridoid glycosides, lignan glycosides, monosaccharides, disaccharides, polysaccharides, amino acids, polypeptides, proteins, and Terpenes, sterols, and polyols, etc. Among them, the content of phenethyl alcohol glycosides (PhGs) is the highest, and it is one of the main active components of the Cistanche genus, and it is also the key component for the identification and content determination of Cistanche in the Chinese Pharmacopoeia [2].

1.1 Phenylethanol glycosides

PhGs are a class of compounds containing hydroxyl, methoxy substituted phenethyl and hydroxy, methoxy substituted cinnamoyl, mainly composed of caffeic acid, phenethyl alcohol aglycone, and glycosyl. Among them, echinacoside (ECH) and ergosteroside are the main components, and ECH is the first phenethanol glycoside compound recorded in the literature [3].

1.2 Iridoids and their glycosides

Iridoid glycosides are one of the main components of Cistanche genus plants and have a variety of biological activities [2]. Iridoids are a type of monoterpene widely distributed in the plant kingdom. Its structure has cyclopentapyrans and mostly exists in the form of glycosides. Such compounds can be divided into iridoid glycosides, secoiridoids, non-glycosides iridoids, polymeric iridoids, and the like.

1.3 Other

At present, lignans and lignan glycosides have been isolated from plants of the genus Cistanche; in addition, there are also monoterpene glycosides, phenol glycosides, alkaloids, sugar alcohols, sterols, sugars, amino acids, and trace inorganic elements in Cistanche [4 ].

Click to  cistanche deserticola ma to improve memory

2 Effects on the nervous system

2.1 Inhibit nerve cell apoptosis

Apoptosis is very important for the development of the nervous system. It is closely related to the pathogenesis of cerebrovascular disease and some neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). It is the neuron in these diseases. The common mechanism of death. In the process of neuronal apoptosis, oxidative stress and the decrease of mitochondrial membrane potential are particularly critical.

PhGs have anti-oxidant effects, can resist DNA damage caused by oxidative stress, effectively remove superoxide anions and hydroxyl free radicals, and ECH can resist reactive oxygen free radical damage [5], and inhibit the generation of reactive oxygen free radicals in the cell. The activity of caspase-3 of cystine increases and maintains the high-energy state of the mitochondrial membrane potential, thereby inhibiting tumor necrosis factor alpha from inducing neuroblastoma cell apoptosis [6]; ECH passes Reduce the generation of reactive oxygen species (ROS) in PC12 cells to inhibit 6-hydroxydopamine-induced mitochondrial dysfunction and inflammation [7]; ECH improves the scavenging ability of oxygen free radicals, reduces lipid peroxidation damage in brain tissue, and reduces brain deficiency Apoptotic cells caused by blood. Tubuloside B is a phenethyl alcohol glycoside compound isolated from Cistanche Tubulosa. Tubuloside B pretreatment can maintain the mitochondrial membrane potential in a normal state, reduce the activity of caspase-3, the toxic effect of hydrogen peroxide (H2O2), and inhibit neuronal apoptosis [8].

2.2 Reduce ischemic brain injury

Cerebral ischemia-reperfusion injury is a complex cascade reaction with increased release of excitatory amino acids (EAA), intracellular calcium instability, energy disorders, immune-inflammatory response, free radical production, and large amounts of nitric oxide (NO) release and activation of apoptotic genes are related to multiple links.

Cistanche glycosides (GCs) can reduce the content of aspartic acid in the brain tissue of rats after cerebral ischemia and reperfusion, regulate the content of EAA in the cerebral cortex, and protect against ischemic brain injury [9]. ECH can reduce the elevation of monoamine neurotransmitters in the extracellular fluid of the striatum caused by cerebral ischemia, and improve the damage of cerebral ischemic tissue [10]; ECH can also reduce the striatum during cerebral ischemia. The EAA neurotransmitters in the extracellular fluid can reduce the infarct range after cerebral ischemia and protect the brain tissue from ischemic damage [11]; ECH can also effectively reduce the generation of free radicals and increase the total protein content of brain tissue. Total antioxidant capacity, reduce acetylcholinesterase activity and serum interleukin-2 content, protect brain neurons [12]; ECH can also improve nerve damage and cell synthesis caused by free radical damage after cerebral ischemia Enzyme synthesis disorder caused by decreased function increases cholinesterase (AChE) activity, improves acetylcholine (ACh) metabolism, increases ACh content, reduces choline content, and restores cholinergic neurotransmitter levels [13]. The cimicifuga in the phenylethanoid total glycosides of Cistanche can improve cell survival, reduce cell apoptosis and the production of reactive oxygen species, inhibit the decrease of mitochondrial membrane potential, the release of cytochrome c, and the clearance of caspase-3, thereby preventing SH-SY5Y cytotoxicity caused by amyloid (Aβ) 25-35 plays a protective role [14].

2.3 Effect on Alzheimer's disease

AD is a central nervous system degenerative disease with progressive cognitive impairment and memory impairment as the main clinical manifestations. The main pathologies include cholinergic system damage, Aβ deposition, abnormal phosphorylation of microtubule-associated proteins, neurofibrillary tangles, oxidative stress, and calcium homeostasis imbalance.

Roche et al. [15] made an AD model by subcutaneously injecting aluminum chloride into mice and found that GCs can increase the activity of superoxide dismutase (SOD) in brain tissue, reduce the content of malondialdehyde (MDA) and increase the brain weight coefficient. Thereby improving the learning and memory impairment caused by AlCl3. GCs capsules can significantly improve patients' cognitive ability and self-care ability, slow down the progression of dementia, and thereby treat AD [16]. Cistanche tubulosa extract containing a large amount of echinacoside and citrichosides can improve the cognitive dysfunction induced by Aβ1-42 by blocking amyloid deposition, reversing the function of cholinergic and hippocampal dopamine neurons [17 ].

2.4 The role of Parkinson's disease

PD is a neurodegenerative disease common in middle-aged and elderly people. Its pathology is characterized by brain striatal-melanosome degeneration, characteristic eosinophilic inclusions in the cytoplasm, and the resulting striatal dopamine (DA) The content is reduced.

The extract of meat from puree can inhibit 1-methyl-4-phenyl-pyridinium (MPP+)-mediated SH-SY5Y cell damage by regulating DNA damage-inducing gene 153 [18]. Phenylethanoid total glycosides can significantly improve the behavioral characteristics of the PD model of C57BL/6 mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and increase DA in the striatum The content and the expression of tyrosine hydroxylase in the substantia nigra can effectively inhibit MPP+

The resulting decline in the viability of cerebellar granule cells and the activation of caspase-3 and 8 [19]. Zhao et al. [20] found that ECH reduces the increase in biliverdin reductase B caused by oxidative stress through anti-oxidation, and protects DA neurons from oxidative stress damage; ECH can also inhibit the PD caused by MPTP. The reduction of dopaminergic neurons, DA, and their transporters in the rat substantia nigra increases the expression levels of glial cell-derived nutrient factors and brain-derived neurotrophic factors mRNA and protein, reduces cell apoptosis, and reduces Bax/Bcl- 2 The ratio of mRNA to protein [21]. In the rat model of PD caused by 6-hydroxy DA, ECH can increase the content of DA, dihydroxyphenylacetic acid, and homovanillic acid in the extracellular fluid of the striatum, and protect the DA neurons of PD [22]. ECH can also inhibit the reduction of monoamine neurotransmitters in the extracellular fluid of the striatum and hippocampus of PD rats, and treat PD [23].

Cistanche can significantly improve the behavioral performance of MPTP-induced C57 mice, increase the content of DA in the striatum, the number of dopaminergic neurons in the substantia nigra, and the alpha-synuclein protein in the substantia nigra Level [24]; It can also counteract the damage of DA neuron SH-SY5Y cells caused by rotenone, reduce the release of cellular lactate dehydrogenase, inhibit the degradation of PD-related protein Parkin and the formation of α-synuclein protein dimers [25]. Verbascoside is a kind of phenethanol glycoside compound separated and purified from the sycamore of the tube flower. It can increase the survival rate of SH-SY5Y cells induced by MPP+, reduce the rate of apoptosis and the level of reactive oxygen species in the cell, and restore mitochondria The high-energy state of membrane potential, inhibits the activity of caspase-3, and up-regulates the expression of Bcl-2 [26]. 2.5 Effect on vascular dementia

Vascular dementia (VaD) refers to a group of clinical syndromes characterized by cognitive decline caused by a series of cerebrovascular factors that cause damage to the brain tissue. VaD is currently the only preventable dementia, and early treatment may reverse it.

Yang et al. [27] conducted clinical observations on the efficacy of oral GCs in 37 patients with VaD and found that GCs can significantly improve the cognitive function and self-care ability of VaD patients, and reduce the degree of dementia. Phenylethanol glycosides can protect the hippocampal neurons of VaD by inhibiting the phosphorylation of tubulin P-tau and up-regulating the expression of brain failure response regulatory protein-2 [28]. ECH improves the activity of choline acetyltransferase (ChAT) and AChE in the cortex and hippocampus of VaD rats, improves the metabolism of ACh, and improves the enzyme synthesis obstacles caused by the decline of cell synthesis function caused by free radical damage after cerebral ischemia. , Improve enzyme activity, increase ChAT and AChE activity. ECH can improve the learning and memory ability of VaD rats, and its mechanism may be related to reducing oxygen free radicals in the cortex and hippocampus and improving the metabolic rate of cholinergic neurotransmitters [29].

2.6 Improve learning and memory function

GCs can promote memory and improve memory damage caused by chemical drugs. For example, GCs can regulate the memory-related transmitter system, increase the activity of its transmitter synthase, and improve the learning and memory function of normal mice [30]. ECH can increase the activity of SOD in the cortex and hippocampus of AD rats, reduce the content of MDA, reduce the production of NO and nitric oxide synthase (NOS), enhance the ability to scavenge free radicals, and protect the rat brain by intra-hippocampal injection of Aβ25-35 Induced oxidative damage. ECH can resist the effects of D-galactose-induced amyloid deposits in the hippocampus of rats, promote the scavenging of oxygen free radicals, reduce cell deformation and loss caused by oxygen free radical damage, and improve learning and memory ability [31].

Cistanche polysaccharides can promote the formation of synapses, increase synapses, increase synaptic plasticity, and improve learning and memory disorders by increasing the expression levels of synaptic plasticity-related proteins. Choi et al. [33] found that Cistanche extract can increase the level of nerve growth factor in rat glioma C6 cells, promote the axon growth of rat pheochromocytoma PC12 cells, and stimulate mouse cortex and hippocampus. The secretion of NGF promotes the differentiation of hippocampal neurons, axon growth and synapse formation, thereby significantly improving learning and memory capabilities.

2.7 Other

PhGs can significantly increase the SOD activity in the brain tissue of D-galactose-induced aging model mice, improve learning and memory capabilities, body immunity, and enhance antioxidant capacity [34]. PhGs can also reduce the water content of brain tissue, down-regulate the expression of water channel 4 genes and proteins in the brain tissue of rats with plateau brain edema, and improve the pathological changes of brain edema in rats with plateau brain edema [35].

Cistanche can improve memory

3 Outlook

The clinical application value of the national second-level protected plant Cistanche deserticola is very high. In recent years, the research on its chemical composition and pharmacological effects has been progressing and in-depth. Modern medical and pharmaceutical research has shown that it has many new functions and activities in the nervous system, and has a wide range of pharmacological effects. The effective components of Cistanche are not only clear in structure, simple in composition, and clear in physical and chemical properties, but also have the characteristics of multi-target, multi-pathway, and multi-level action. Therefore, they will have more important roles and advantages in the nervous system, and the development of its preparations will also have Greater potential and better prospects.

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