What Are the Benefits of Cistanche Tubulosa Extract?

Cistanche (Cistanches) is a perennial herbaceous parasitic plant in the Orobanchaceae family, known as the “desert ginseng”. Mainly found in China, it is divided into Cistanche deserticola Y. C. Ma, C. tubulosa (Schenk) Wight, C. sinensis G. Beck, and C. salsa (C. A. Mey) G. Beck, and is distributed in Inner Mongolia, Xinjiang, Ningxia, Gansu, Qinghai, and other places [1]. Research (C. sinensis G. Beck) and halophyte C. salsa (C. A. Mey) G. Beck], distributed in Inner Mongolia, Xinjiang, Ningxia, Gansu, Qinghai and other places [1]. Research has proved that Cistanche and its active ingredients have the effects of anti-oxidation, anti-fatigue, anti-aging, anti-tumor, antibacterial, protecting the liver, regulating immunity, improving sexual function, regulating the central nervous system, regulating endocrine, improving memory, preventing Alzheimer's disease, anti-osteoporosis and promoting bone formation [2‒9].

In 19 In 1993, a news article was released at the annual meeting of the International Medical Association in Geneva: China's Alxa League's Chaganhire was ranked among the world's longevity towns. A survey team composed of Chinese A survey team made up of Chinese and foreign experts spent four months investigating Chaganhire and found that there were only 139 people in the village of Chaganhire (Gacha), with four centenarians and a per capita life expectancy of 87.5 years. The incidence of common diseases such as hypertension, stomach disease, kidney disease, and enlarged prostate was extremely low. The expert group found that this is related to the local residents' diet. Two points are that the people here are used to putting Cistanche tubulosa in their lamb stews and drinking home-brewed Cistanche tubulosa wine. Therefore, the anti-aging effect of Cistanche tubulosa has attracted much attention and has become one of the hotspots of research on health foods.

This article mainly reviews the anti-aging effects of Cistanche deserticola, distinguishes the anti-aging mechanism of Cistanche deserticola from the perspective of aging theory, analyzes the relationship between aging theory and Cistanche deserticola and its active ingredients, with a view to providing a reference for the development of Cistanche deserticola health food.

1 Aging aging theory

Human aging is caused by the interaction of multiple genetic and environmental factors. Over time, it manifests as systemic, progressive, degenerative and irreversible changes and functional disorders in the body [10]. Aging can also cause the accumulation of genetic mutations, metabolic abnormalities, and immune system dysfunction [11]. The aging theory is shown in Figure 1.

1. 1. Free radical theory

Unusually active charged molecules or radicals are called free radicals. Common free radicals include superoxide radicals, lipid peroxides, hydrogen peroxide, singlet oxygen and hydroxyl radicals. Free radicals have strong biological activity and can damage DNA, proteins and lipids, causing cell mutations, aging and apoptosis. This indicates that the gradual accumulation of oxidized cells is the basic driving factor of cell aging. In addition , the free radical theory has made great progress in aging research over time [12].

The free radical theory was first proposed by Harman in 1956 [13], which believes that excessive free radicals can cause lipid peroxidation of unsaturated fatty acids on cell membranes through oxidation; attack nucleic acids to cause DNA mutations or replication abnormalities; destroy protein protein polypeptide chains, change protein structure, reduce enzyme activity, etc.; they can damage the integrity of the cell membrane structure, causing serious damage to cell function, and ultimately leading to cell aging and even death, thereby causing damage to the body and leading to aging or death. As research deepens, the free radical theory is placing more and more emphasis on mitochondrial DNA (mtDNA) mutations and the accumulation of mtDNA deletions [14].

1.2 Telomere theory

Telomeres are small DNA-protein complexes at the ends of chromosomes. The special “cap” structure can maintain the integrity of chromosomes and control the cell division cycle. Professor Alexei Olovnikov of the former Soviet Union first proposed the “telomere theory” of aging in 1973, arguing that due to dysfunction of DNA polymerase, cells cannot completely replicate their chromosomes during each division process. Each time DNA is replicated, 40-100 bp of telomere DNA is lost [15]. As the number of cell divisions increases, DNA shortens to a certain limit, making it difficult to maintain the stability of chromosomes. The cell then loses its ability to divide and proliferate and ages until it dies [16]. Telomere length is a biomarker of biological aging and is associated with various aging-related diseases [17]. Studies have found that an increase in telomerase in germ cells and stem cells can lengthen telomeres, thereby delaying aging.

1. 3. Immune theory

The body's immune system is divided into an innate immune system and a specific immune system. The innate immune system, which exists in all animals and plants as a rapid anti-infective response, has been studied more. Natural killer cells (NK) are innate defenses against infected host cells [18 ]. With increasing age, neutrophils and macrophages show a marked decline in various functions [19‒20]. Specific immunity mainly includes cellular immunity and humoral immunity, and the body is made resistant to infection through artificial vaccination. According to immunological theory, there is a parallel relationship between aging and the state of immune cells. In other words that in the process of anti-aging, the immune function of the body shows gradual changes, including the body's ability to respond to infections and the ability to maintain long-lasting immune memory. The initial cause of immunosenescence is the atrophy of the thymus due to aging, which causes a series of physiological changes in the immune system [21]. At the same time, the decline in immune function will accelerate the aging process, making the elderly prone to immune deficiency diseases, such as cancer infection, and atherosclerosis of important organs such as the brain, heart, and kidneys. Therefore can increase the level of immune cells, clear inflammatory factors, provide a good living environment for normal healthy cells, reduce the occurrence of diseases, and achieve the purpose of delaying aging. As people's attention to immune cells increases year by year, immunology is also mentioned more and more.

1. 4 The brain center theory

The brain center theory holds that within the central nervous system there is a neural mechanism that controls aging – the aging clock. The monoamine substances govern its operation. Among these, norepinephrine (NE) can prolong life, while 5-hydroxytryptamine (C10H12N2O, 5-HT) promotes aging. In the there is a monoamine oxidase (MAO) enzyme in the nervous system. MAO isozymes are divided into two forms: A and B [22]. It is generally believed that B is positively correlated with aging [23].

1. 5 Other theories

Stem cell transplantation involves artificially infusing stem cells into the body, allowing new cells to replace aging cells and function, while also improving the stem cells' renewal and differentiation abilities [24]. Caloric restriction is also a special means of delaying aging. Studies have found that C. elegans that have undergone dietary restriction can improve immunity and increase lifespan, while overfeeding nematodes can inhibit innate immunity and thus accelerate aging [25].

2. Cistanche extract bioactive ingredients anti-aging effect

Cistanche extract contains a variety of bioactive ingredients, mainly including phenylethanoid glycosides, cyclic enol ether terpenes and their glycosides, lignin and its glycosides, polysaccharides, proteins, amino acids, betaine, etc. [26]. There are also a small number of other compounds, such as monoterpenes, steroids or their glycosides, fatty acids and some trace elements [27].

2.1 Polysaccharides

Studies have shown that Cistanche deserticola polysaccharide extract has anti-aging properties [28-30], mainly through antioxidant, improving learning and memory, enhancing immune function and telomerase activity, etc., to play an anti-aging role, see Table 1.

Ma Hui et al. [39] demonstrated that polysaccharides can improve the learning and memory abilities of aging mice, and the mechanism may be related to the upregulation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) expression in the hippocampal region of the brain. Wu Yan et al. [38] found that Cistanche deserticola polysaccharides can affect the secretion of brain-derived neurotrophic factor (BDNF) through the cAMP/protein kinase A (PKA)/CREB signaling pathway, and by affecting synaptic plasticity, increase dopamine, glutamate, and norepinephrine neurotrophic factor (brain-derived neurotrophic factor, BDNF) secretion, and by affecting synaptic plasticity, it improves the learning and memory abilities of aging mice by increasing the release of dopamine, glutamate, and norepinephrine.

Xu Hui et al. [35] found that Cistanche polysaccharides can significantly reduce the content of malondialdehyde (MDA) and phospholipasea2 (PLA2) activity, increase the activity of Ga2+-ATPase and the fluidity of liver mitochondrial membranes,  improving mitochondrial energy metabolism, and increasing the activity of respiratory chain complexes I+III and II+III, indicating that Cistanche polysaccharides can delay aging in rats by increasing the antioxidant capacity of liver mitochondria and improving mitochondrial energy metabolism in aging rats [36]. Wu Bo et al. [32] found that Cistanche polysaccharides can enhance the resistance of aging mice to lipid peroxidation, increase the activity of superoxide dismutase (SOD) in the serum and liver, and reduce the content of lipid peroxides, indicating that Cistanche polysaccharides can prevent lipid peroxidation damage in subacute mice.

Sun Yun et al. [40] made mice inhale ozone for 4 consecutive weeks to establish a lung aging model, and tested the hypoxia tolerance of Cistanche polysaccharides. The results showed that Cistanche polysaccharides can prolong the hypoxia tolerance of aging mice, increase SOD activity, reduce MDA content, and delay the degeneration of ultrastructures such as pulmonary cell mitochondria and lamellar bodies mitochondria, lamellar bodies and other ultrastructural degeneration, significantly delaying the physiological degradation and cellular morphological degeneration of the experimental mouse lung; at the same time, Cistanche polysaccharides can reduce NO concentration and inhibit apoptosis of lung tissue cells, thereby improving the degenerative changes of lung tissue cells in aging mice [33]. In addition, Sun Yun et al. [34] used D-galactose model mice to observe the antioxidant effect of Cistanche polysaccharides on the lungs of aging mice, and found that the glutathione peroxidase (GSH-Px) activity in the lungs and plasma was increased peroxidase (glutathione peroxidase, GSH-Px) activity in the lungs and plasma was increased, indicating that Cistanche polysaccharides have a certain antioxidant capacity in lung tissue and can delay lung aging.

Zhang Hong et al. [37] established a D-galactose subacute aging mouse model to detect the MDA content, telomerase activity, interleukin-2 (IL-2) content, lymphocyte proliferation capacity, and phagocytic function of peritoneal macrophages in mice gavaged with Cistanche polysaccharides. The results showed that Cistanche polysaccharides can antagonize free radical damage, enhance telomerase activity in heart and brain tissues and the immune capacity of aging mice, and delay D-galactose-induced aging. swallowing function. The results showed that Cistanche polysaccharides can antagonize free radical damage, enhance the telomerase activity of heart and brain tissues and the immune capacity of aging mice, and delay the aging rate of D-galactose-induced aging mice, which demonstrates from multiple aspects that Cistanche polysaccharides have the effect of delaying aging.

In addition Cistanche polysaccharides also have an anti-fatigue effect [29]; can significantly improve the survival rate of SAM-P8 mice and improve the intestinal flora disorder of SAM-P8 mice [30]; and can be used as an antioxidant to inhibit lipid oxidation modification and protect cells from damage by oxidative molecules in the skin of aging rats [41].

2.2 Total glycosides

Research shows that Cistanche deserticola total glucosides mainly exert anti-aging effects through functions such as anti-oxidation, reducing brain damage and regulating the body's immune system, as shown in Table 2.

Zhang Jing et al. [42‒43] found that Cistanche deserticola total glucosides can improve the survival rate of normal pyramidal cells in the CA1 region of the hippocampus in SAM-P8 mice. It is speculated that Cistanche deserticola total glucosides can activate glutamate receptors, promote the expression of related proteins, improve synaptic plasticity, and improve the learning and cognitive impairment of SAM-P8 mice, thereby delaying aging. Cistanche deserticola can cause the cells in the CA1 region of the hippocampus of Alzheimer's disease (AD) model rats to be neatly arranged and have a normal shape. Meanwhile, rats that have been gavage fed with Cistanche polysaccharides The nuclei of neurons in rats that were gavaged with Cistanche polysaccharides were round and regular, with obvious nucleoli and intact nuclear membranes and mitochondrial structures, indicating that Cistanche total glucosides alleviated the pathological changes and ultrastructural damage of damaged nerve cells [47].

Wu Bo et al. [44] found that Cistanche tubulosa total glucosides can not only increase the activity of SOD in the serum, brain and liver of subacute aging mice, but also reduce the content of lipid peroxides, indicating that Cistanche tubulosa total glucosides can regulate the balance of the body's antioxidant function from the perspective of free radical theory, antagonize free radical damage and play an antioxidant role, so as to achieve the purpose of delaying aging.

Zhang et al. [45] found that Cistanche deserticola total glucosides can reverse the immune deficiency of aged SAM-P8 mice, significantly increasing the proportion of blood Sca-1 positive cells, naive T cells, and NK cells. Zhang Tao et al. [46] showed that Cistanche total glucosides can improve the lymphocyte transformation capacity, peripheral blood IL-2 content, NK cell activity, and peritoneal macrophage phagocytic function of D-galactose-induced aging mice, indicating that Cistanche total glucosides can enhance the immune function of mice to delay their aging, supporting the anti-aging immune theory.

2. 3 Phenylethanoid glycosides

Phenylethanoid glycosides are the main active ingredients in Cistanche extract, and have a significant anti-aging effect. Xuan Guo Dong et al. [48] found that phenylethanoid glycosides extracted from Cistanche deserticola can improve the learning and memory abilities of mice and significantly increase the spleen index of mice after being continuously gavaged for 4 weeks. This indicates that phenylethanoid glycosides may delay aging by regulating the immune function of the body. In addition , studies have found that Cistanche benzoides phenylethanoid glycosides have an anti-fatigue effect, can increase the swimming time of mice, increase the level of tissue glycogen, and improve blood biochemical levels [49]. They can also effectively prevent osteoporosis caused by estrogen deficiency [50]. These effects all indicate that phenylethanoid glycosides have an anti-aging effect, as shown in Table 3.

Currently , 70 phenylethanoid glycosides have been isolated from Cistanche deserticola[26‒27], including echinacoside, verbascoside, isoverbascoside, cistanoside A, tubuloside B, haloxycistane D, etc. . Among them, the Chinese Pharmacopoeia uses echinacoside and mulberrofuranoside as reference substances for the quality control of Cistanche deserticola. It is stipulated that the total content of the two substances in Cistanche deserticola (dried product) should not be less than 0.30%, and that in Cistanche tubulosa (dried product) it should not be less than 1.5%. Many studies have proved that echinacoside and acteoside have certain anti-aging effects. CHEN et al. [51] found that echinacoside is an effective anti-aging ingredient in Cistanche deserticola, which can prolong the lifespan of Caenorhabditis elegans through the reactive oxygen species signaling pathway, dietary restriction signaling pathway and insulin/insulin-like growth growth factor signal pathway to prolong the lifespan of Caenorhabditis elegans. At the same time, it was found that echinacoside can induce the secretion of growth hormone by rat pituitary cells, and in the future, it can be considered for development into a non-peptide analog of growth hormone (endogenous hormone) releasing peptide [52].

At the same time , PENG et al. [53] found that echinacoside can activate peroxisome proliferator-activated receptor (PPAR-γ) signaling, exerting antioxidant, anti-inflammatory, anti-apoptotic and anti-activated microglial cells, alleviates cognitive impairment caused by sevoflurane anesthesia; in addition, echinacoside can also reduce blood glucose and blood lipid levels in db/db mice, delay the deterioration of cardiac function in mice, improve myocardial tissue in db/db mice, and significantly reduce the oxidative stress level of cardiomyocytes. In addition , echinacoside can also inhibit lipid accumulation by inhibiting PPAR-α/M-CPT-1 signal transduction [54].

Zhang Hongquan et al. [55] examined the anti-aging effect of acteoside on D-galactose-induced aging mice and found that acteoside can reduce the MDA content in the heart, liver and brain of aging mice, increase telomerase activity, enhance lymphocyte proliferation response and peritoneal macrophage phagocytic function, indicating that mulberrofuran glycosides can delay aging by protecting against free radical damage, enhancing telomerase activity and regulating immune function.

PE NG, etc. [57] found that mulberrofuran glycosides can reverse some cognitive impairments and improve spatial learning in mice induced by D-galactose and AlCl3 in combination. The mechanism may be related to the prevention of neuronal apoptosis caused by oxidative stress, or to the increase in nerve growth factor (NGF) and TrkA expression in the hippocampus [58], which proves that acteoside is an effective treatment for mild neurodegenerative diseases, for example, as an early treatment for Alzheimer's disease.

2. 4 Cistanche Tubulosa extract

There are many types of Cistanche, and the extraction processes and parameters vary, so the anti-aging effects and mechanisms of different Cistanche extracts differ greatly. However, in general, Cistanche extract mainly delays aging through antioxidant effects, alleviates memory impairment, and improves the body's immune function, as shown in Table 4.

ZH ANG et al. [59] used Cistanche deserticola extract (ECD) to treat aging SAM-P8 mice and found that ECD not only significantly reversed age-related immune aging changes, but also significantly prolonged the average lifespan of SAM-P8 mice. ZHANG et al. [60] found that Cistanche deserticola water extract had the effect of improving the memory of aged mice. Analysis by open-field test found that the levels of catalase (CAT) and acetylcholinesterase (AchE) in brain tissue were both increased to some extent, indicating that Cistanche deserticola water extract can reduce oxidative damage to brain tissue to achieve the purpose of alleviating aging. Zhang Yuequan et al. [61] used a decoction of Cistanche deserticola water to gavage senescence accelerated mouse prone 6 (SAM-P6) mice, and found that it can effectively improve the serum bone gla-containing protein (BGP), bone mineral density (BMD), and bone morphogenetic proteins-2 (BMP-2) levels of SAM-P6 male mice, and has a certain therapeutic effect on osteoporosis. e gla-containing protein, BGP), bone mineral density (bone mineral density, BMD), and bone morphogenetic proteins-2 (BMP-2) levels in male SAM-P6 mice, and has a certain therapeutic effect on osteoporosis.

LIN et al. [62] found that Cistanche tubulosa water extract can increase the average lifespan and maximum lifespan of Drosophila, enhance the resistance of Drosophila to oxidative stress, inhibit the memory impairment associated with Drosophila aging, reduce the rate of cognitive decline in aging Drosophila, and determine the mammalian target of rapamycin (mTOR) and Nocth network mechanism targets involved in the regulation of the above pharmacological effects.

Different species Cistanche species also have different effects on improving learning and memory. WANG et al. [63] compared the effects of Cistanche tubulosa and Cistanche deserticola water decoctions on stress-induced depression and memory in mice. used the monoamine system and HPA axis to characterize the relationship between the antidepressant properties and cognitive improvement of a mammalian model. The results showed that Cistanche deserticola water decoction had a significant effect on the HPA axis, indicating a stronger pharmacological effect.

Fan Yanan et al. [64] found that the content of MDA and NO in Cistanche deserticola after soaking in yellow wine was significantly lower than that in unprocessed Cistanche deserticola, while the content of SOD was higher, which reduced mitochondrial DNA loss; at the same time, Cistanche deserticola soaked in yellow wine can increase the spleen and thymus coefficients of aging mice, concluding that it may have anti-aging effects. In addition, Cistanche deserticola also has whitening and anti-aging effects, and can be used in the cosmetics industry [65].

3 Conclusion

Aging Aging is a complex and irreversible molecular process in human life. It is a comprehensive manifestation of the decline and degeneration of physiological functions, including physiological aging, psychological aging, and pathological aging. Regarding the study of pathological aging, the main purpose of delaying aging is to reduce the occurrence of diseases, enhance immunity, and improve the body's antioxidant capacity.

Cistanche is one of the most popular traditional food-drug homologous substances, and is described in many ancient traditional Chinese medicine books as having anti-aging properties. Cistanche and its active ingredients exert anti-aging effects in four main ways: (1) reducing brain damage, preventing Alzheimer's disease, and improving learning and memory; (2) improving the body's antioxidant capacity, reducing free radical damage,  relieve the degree of oxidation of tissues and organs; (3) enhance immunity, improve the phagocytic function of abdominal macrophages and the proliferation capacity of lymphocytes; (4) increase telomerase activity and reduce the loss of DNA sequences during DNA replication.

At present, the anti-aging effects and mechanisms of Cistanche deserticola and its active ingredients have not been fully studied, especially in terms of improving telomerase activity, increasing telomere length, improving the intestinal tract, metabolomics technology, genomics technology, etc. Research still needs to be carried out by scientific research institutions and and its active ingredients have not yet been fully researched in terms of their anti-aging effects and mechanisms. In particular, research on improving telomerase activity, increasing telomere length, improving the intestinal tract, metabolomics technology, genomics technology, etc. requires continuous efforts from scientific research institutions and enterprises. Meanwhile,

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