Research Progress Of Clinical Application And Therapeutic Mechanism Of Herba Cistanche
Mar 11, 2022
Contact: Audrey Hu Whatsapp/hp: 0086 13880143964 Email: audrey.hu@wecistanche.com
CHEN Shi-ya, QIN WeiYANG, Sha-sha, & et al.
ABSTRACT
Herba Cistanche has become one of the study hotspots in tonic Chinese herbs， received widespread attention at home and abroad in recent 30 years. This paper is a review of the clinical application and therapeutic mechanism of Herba Cistanche referred to relevant materials in recent years， as a reference for related research of Herba Cistanche.
KEYWORDS: Herba Cistanche; Clinical application; Therapeutic mechanism
Herba Cistanche (Herba Cistanche) is also known as Zongrong, Goblin, Dayun, Cunyun, Mazu, Machi, Black Sling, etc. It is known as the "desert ginseng"; it was born in the desert at an altitude of 225 to 1150m, mainly distributed in the desert my country's Inner Mongolia, Shaanxi, Ningxia, Gansu, Qinghai, Xinjiang, and other places [1]. In the Flora of China, there are 5 species of Cistanche in my country and 1 suspected species [2]. However, some scholars now believe that there are 6 species and 1 variety in my country, namely, Cistanche, Cistanche tube flower, Cistanche, Lanzhou Cistanche and Cistanche, and 1 variety of Cistanche white flower [3]. In the 2010 edition of the Chinese Pharmacopoeia, the authentic medicinal materials are Cistanche deserticola and Cistanche tubulosa. Its nature is sweet, salty, and warm; it returns to the kidney and the large intestine meridian; it nourishes the kidney and yang, nourishes the essence and blood, moisturizes the intestines, and relaxes bowel movements; it is often used to treat infertility, impotence, dry intestines, constipation, and sore waist and knees. [1].
The chemical components and trace elements of Cistanche have been isolated at home and abroad so far. There are nearly 100 kinds of chemical components and trace elements, mainly including phenethyl alcohol glycosides, iridoids, and their glycosides, lignans and their glycosides, oligosaccharide lipids, and other types such as Betaine, galactitol, polysaccharides, etc. [4]. At present, the research on these chemical components mainly focuses on the total phenethyl alcohol glycosides, echinacoside, and verbascosides in the phenethyl alcohol glycosides. The research on other components and the corresponding pharmacological activities are less reported.
This article summarizes the clinical application and therapeutic mechanism of Cistanche in recent years and provides a reference for related research on Cistanche.
Cistanche tubulosa prevents kidney disease, click here to get the sample
1. Effect on the reproductive system
Cistanche has the effects of nourishing the kidney and yang, strengthening the liver and kidney, nourishing the essence and blood, and strengthening the bones and muscles. It is one of the commonly used tonic drugs in prescriptions for nourishing the kidney and yang. Traditional Chinese medicine believes that "the kidney is the foundation of the innate", and the lack of essence and qi in the kidney will definitely affect the human reproductive function. The relationship between kidney yang and reproduction is very close, and the syndrome of kidney yang deficiency often manifests as decreased libido, impotence, premature ejaculation, and infertility.
1. 1Clinical application
Cistanche is often used clinically to treat impotence, dysmenorrhea, and infertility caused by kidney-yang deficiency and failure. Liu Rong and others have used Cistanche as the main medicine in the treatment of luteal insufficiency infertility, secondary amenorrhea, kidney-yang deficiency menopausal syndrome, yang deficiency, and blood-cold dysmenorrhea, postpartum dysmenorrhea, and have achieved good results. Clinical efficacy [5]. Six elderly patients with low sex hormone levels between 68 and 83 years of age continued to take Cistanche decoction for two weeks, and their serum testosterone levels increased by an average of 24.7% [6].
1.2. Experimental research and mechanism of action
Cistanche phenylethanoid glycosides can improve the pathological changes of uterus, ovaries, thymus, and spleen in perimenopausal model rats; it can increase the level of sex hormones, such as serum estradiol (E2) and testosterone (T); increase the content of related sex hormone receptors, The androgen receptor (AR) in the hypothalamus and the estrogen receptor (ER) in the hypothalamus, pituitary gland, and uterus [7]. phenylethanoid glycosides can increase the protein expression levels of the key enzymes CYP11A1 and CYP17A1 in the testosterone synthesis pathway of male rats, thereby increasing the levels of testosterone and progesterone in the rat serum; at the same time, the levels of testosterone and progesterone in the liver The expression of the metabolic enzyme CYP3A4 is also affected; this may be related to the body's positive and negative feedback regulation of hormones [8].
The deficiency of kidney-yang is closely related to the hypofunction or dysfunction of the hypothalamic-pituitary-target gland axis system [9]. The effect of Cistanche on nourishing the kidney and strengthening yang is derived from one of its active ingredients, phenethyl alcohol glycosides, which acts on the reproductive system mainly through two ways: One is to enhance the function of the hypothalamus-pituitary-adrenal axis and promote related transmitters in the body And hormone release, improve libido; the second is to play a role through anti-fatigue and improve body function [10]
2. Effects on the digestive system
2. 1. Clinical application
The effect of Cistanche on the digestive system is mainly manifested clinically as a laxative effect. Constipation is manifested by a decrease in the frequency of bowel movements, dry and hard stools, and/or difficulty in defecation. Cistanche has the functions of nourishing the intestines, nourishing blood, diuresis, and laxative, and is commonly used clinically to treat various types of constipation
Clinical trials have shown that single-flavored Cistanche has a good clinical effect in the treatment of constipation caused by hemodialysis; Wang Lingfen and others divided the patients into a Cistanche group and a dialysis group. The patients in the Cistanche group were decocted with 30g of Cistanche to 100mL with dialysis. After 3 months of treatment, it was discovered that the single-flavored Cistanche decoction can effectively improve bowel movements, its effect is long-lasting, and no adverse reactions such as abdominal pain and diarrhea were found [11].
2. 2 Experimental research and related mechanisms
The crude extract of Cistanche has a laxative effect, which can cause the contraction of guinea pig ileum and rat gastric fundus muscle strips, and this effect can be inhibited by atropine [12]. The total extract of Cistanche can shorten the defecation time of the first stool in rats with a yang deficiency constipation model, increase the amount of stool, enhance the contraction function of the colon, and increase the content of serum motilin and vasoactive intestinal peptide [13]. Another study found that echinacoside, as one of the main bioactive components of Cistanche, can significantly promote the proliferation and survival of intestinal epithelial cells MODE-K cells. This effect may be through the promotion of transforming growth factor (TGF) -β1 The expression to achieve [14].
At present, the effect of Cistanche on the digestive system is clinically limited to its laxative function. The laxative active ingredients may be total oligosaccharides and galactitol [15]. The mechanism may be related to its mimetic cholinergic activity or the correction of gastrointestinal hormone levels, thereby increasing the contractility of the digestive tract. It is speculated that Cistanche is more suitable for Qi-deficiency constipation and Yang-deficiency constipation. The repairing effect of echinacoside, another component of Cistanche, on intestinal epithelial cells is currently only seen in experimental studies, and it is expected to be applied in clinical practice to develop new drugs in the future.
3. Effect on the nervous system
3. 1 Anti-Alzheimer's disease effect
Alzheimer's disease (Alzheimer's disease, AD), also known as senile dementia, is a kind of progressive cognitive function and memory impairment as the main clinical manifestations of Degenerative diseases of the central nervous system. Its main pathological characteristics are: neuron loss; senile plaques formed by β-amyloid peptide deposition outside cerebral cortex and hippocampal neurons; neurofibrillary tangles formed by abnormal accumulation of tau protein in brain neurons (16)
3. 1. 1 Clinical application:
Li Nan et al. randomly divided patients with mild AD into the Cistanche group, donepezil group, and blank control group. Before and after 48 weeks of treatment, they evaluated the changes in cognitive ability of the patients and analyzed the changes in hippocampal volume; the test results showed that Cistanche preparations can improve The cognitive ability of patients with mild AD slows down hippocampal atrophy [17]. Clinical studies have shown that the level of t-tau in the cerebrospinal fluid of AD patients after treatment with Cistanche is effectively eliminated with the decrease of TNF-α and IL-1β, suggesting that Cistanche preparations may inhibit the expression of TNF-α and IL-1β in the cerebrospinal fluid It affects the aggregation of tau protein [16]
3.1.2 Experimental study and mechanism of action:
Cistanche glycosides can reduce the activity of acetylcholinesterase and the content of Ca 2 + in the hippocampus of AD rat model replicated with Aβ25-35, and maintain the content of acetylcholine in the brain at a normal level And improve their learning and memory ability [18]. Lacteroside can inhibit the production of reactive oxygen species, or regulate the apoptosis pathways of Bcl-2, cytochrome C, and caspase-3 to resist the amyloid Aβ25-35-induced damage to SH-SY5Y cells [19].
The above studies show that the active ingredients of Cistanche-related preparations can penetrate the blood-brain barrier, maintain the normal level 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, and inhibiting neuronal cell apoptosis. However, the relevant molecular mechanism of action has not yet been clarified, and further research is needed
3.2 Anti-Parkinson's disease PD
(Parkinson's disease, PD) is the main clinical manifestation of resting tremor, muscle stiffness, bradykinesia, gait disturbance, and postural instability, second only to AD. Degenerative diseases. Its main pathological features are the progressive degeneration and necrosis of dopaminergic neurons in the substantia nigra of the midbrain, and the presence of eosinophilic inclusion bodies in the cytoplasm of residual neurons, namely Lewy bodies [20]
3. 2. 1 Clinical application:
At present, the traditional Chinese medicine compound with Cistanche as the main medicine combined with basic western medicine such as Madopar for the treatment of PD patients has achieved certain clinical effects. Li Junyan and others studied the efficacy of Bushen Huoxue Decoction combined with western medicine in the treatment of primary PD and found that Bushen Huoxue Decoction combined with Western medicine is better than Western medicine alone in improving the motor function and daily life ability of PD patients, and can reduce the side effects of Western medicine and reduce The occurrence of complications improves the quality of daily life of patients [21]. Zheng Chaoqun's research on the treatment of PD patients with kidney-tonifying compounds combined with Madopar has similar findings [22].
3. 2. 2 Active ingredients and related mechanisms:
Tian Yun, Lin Shaogang, and others found in animal experiments and cell experiments that Cistanche can up-regulate 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 can protect nerve cells by regulating the expression of dopaminergic nerve cell apoptosis factors and neurotrophic factors [23]
Other studies have shown that total phenethyl alcohol 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). Increase the content of dopamine in the striatum, increase the expression of tyrosine hydroxylase in the substantia nigra, inhibit the decline of cerebellar granule cell viability caused by MPP +, and inhibit the activation of caspase-3 and caspase-8 [24]. Echinacoside 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]. Echinacoside can slow down the apoptosis of SH-SY5Y cells induced by MPP+. Experiments have shown that it plays a role in protecting the survival of nerve cells by up-regulating the GFRal/AKT pathway [26]. Deng Min et al. pretreated SH-SY5Y cells induced by MPP + with verbascoside and found that it can significantly increase the expression of Bcl-2 and effectively antagonize the toxic effects of MPP + on mitochondria [27]. In addition, the cohodosides in the phenethyl alcohol glycosides can resist MPTP-induced nerve damage in PD model mice, improve their behavioral defects, and increase the number of dopaminergic neurons, the content of dopamine transmitters, and the level of α-synuclein protein [ 28]. Cimicifuga glycosides can also resist the damage of SH-SY5Y cells caused by rotenone, reduce the content of lactate dehydrogenase, inhibit the degradation of PD-related proteins and the formation of α-synuclein protein dimers [29]
The current research on the anti-PD effect of Cistanche is mainly focused on its extract, the total glycosides of cistanche, and its monomers. The mechanism may be related to up-regulation of GFRal/AKT pathway, anti-oxidation, inhibition of apoptosis, protection of nerves; promotion of TH expression, an increase of tyrosine hydroxylase, inhibition of release of lactate dehydrogenase, and increased synthesis of monoamine transmitters, etc.
3. 3 Anti-Fatigue Function Chronic Fatigue Syndrome
(Chronic fatigue syndrome, CFS) is a syndrome characterized by unexplained physical and mental fatigue, accompanied by physical symptoms such as fatigue, headache, low-grade fever, and mood disorders such as depression [30]. The experiment of Li Yongchao and others finally confirmed that the phenethyl alcohol glycosides are the most direct anti-fatigue substances of Cistanche; and the experiment suggests that the anti-fatigue effect of Cistanche and its ability to increase the energy reserve of body tissues, improve the body's tolerance to fatigue, and reduce after excessive exercise The production of bad metabolites and timely removal of a large number of free radicals produced during exercise is related to [31]. Cistanche can increase the level of NOS3 in hepatocytes and endothelial cells of load-bearing swimming mice, thereby expanding 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 protect the liver [33], protect the myocardium [34], anti-aging [35], immune regulation [36], and promote bone formation [37]. There are also individual reports in the literature that Cistanche has the effect of relaxing blood vessels [38], reducing cholesterol [39], and so on. However, there is little research on it, only limited to cell and animal experimental research, and it has hardly been applied in clinical practice.
In short, Cistanche is a traditional Chinese herbal medicine with high clinical application value, with a wide range of pharmacological effects. Studies have shown that the main pharmacologically active ingredients of Cistanche are phenethyl alcohol glycosides and polysaccharides [40]. Phenyl ethanol glycosides have neuroprotective, anti-oxidant, antibacterial, antiviral, anti-inflammatory, and hepatoprotective effects. The main role of polysaccharides is to improve the body's immunity [41]. However, the research is not deep enough, such as neuroprotection. How do the effective 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? The protective effect is a single ingredient. Or is it a clustering effect of multiple components? How long does the effect last in the nervous system? The above problems need to be studied in depth from different levels of the whole, organs, tissues, cells, proteins, genes, and molecules. The other chemical components (such as iridoids and their glycosides, benzyl alcohol glycosides, etc.) and their pharmacological action mechanisms need to be further elucidated.
References
[1] Compiled by the National Pharmacopoeia Committee. Chinese Pharmacopoeia 2010 Edition [S]. Beijing: Department of Traditional Chinese Medicine Technology Press, 2010.
[2] Wei Zhenzhen. The effect of Cistanche phenylethanoid glycosides on perimenopausal models of rats and mice [D]. Henan University of Traditional Chinese Medicine, 2014.
