Discussion Ⅱ： Effects Of Cistanche Deserticola Phenylethanol Glycoside On Perimenopausal Models in Rats And Mice

3. Study on the effect of Cistanche phenylethanoid glycoside on perimenopausal syndrome

3.1 Research on the functional indications and pharmacological effects of Cistanche

Cistanche, commonly known as Da Yun, is a precious Chinese herbal medicine that grows in Xinjiang, China. It has anti-fatigue, anti-radiation, anti-aging, tonifying kidneys and strengthening yang, improving human immunity, enhancing memory, laxative, and preventing Alzheimer's disease. It is known as People call it "desert ginseng". "Shen Nong's Materia Medica" points out that "Cistanche is responsible for the five labors and seven injuries, nourishes the middle, nourishes the five internal organs, strengthens yin and replenishes essence, and produces many children. It can not only warm the kidney yang, but also nourish the essence and blood [39]" and is often used to treat men. Impotence, female infertility, cold pain in waist and knees, blood dryness and constipation.

Modern research shows that[40][41], Cistanche has androgenic and gonadotropin-like effects, can regulate the endocrine gland axis, and can improve mouse fertility. According to literature reports [42], Cistanche can enhance the luteinizing function of the hypothalamus-pituitary-ovary, improve the pituitary gland's response to luteinizing hormone-releasing hormone and the ovary's response to luteinizing hormone. It also has strong, anti-aging, and enhanced immune functions in mice with yang deficiency. Clinical findings [43] show that Cistanche has the effect of treating menopause.

Yang Hongxin et al. [44] found that Cistanche decoction can significantly increase the weight and number of spontaneous activities in mice with yang deficiency, and can also significantly extend swimming time and reduce LAC and BUN levels after exercise, indicating that Cistanche decoction has anti-fatigue effects. Li Li [45-47] and others found that Cistanche has the effects of antioxidants, promoting material metabolism, improving learning and memory, and enhancing sexual function.

HOW LONG DOES IT TAKE FOR CISTANCHE TO WORK?

3.1 Experimental studies and pharmacological activities of phenylethanoid glycosides from Cistanche

The chemical composition of Cistanche is complex, mainly including phenylethanoid glycosides, iridoid glycosides, lignan glycosides, monosaccharides, disaccharides, polysaccharides, amino acids, polypeptides, proteins, triterpenes, sterols, polyols, etc. Among them, phenylethanoid glycosides have the highest content in the original medicinal materials and are one of the main active ingredients of Cistanche . Phenylethanol glycosides have antibacterial, anti-inflammatory, antiviral, anti-tumor, antioxidant, immune regulation, memory enhancement, kidney tonifying, and protective properties. Liver and cardiotonic effects [48].

Research has found [46] that Cistanche phenylethanol glycoside has a nootropic effect on rats and mice by increasing the SOD content and reducing the MDA content and acetylcholinesterase activity in the brain tissue of rats and mice.

The compound verbascoside contained in Cistanche has androgen-like effects, hepatoprotective effects, myocardial protective effects, brain protective effects, neuroprotective effects, antioxidant effects, anti-radiation effects, anti-aging effects, memory improvement effects, blood vessel relaxation effects, and prostate inhibition. Research on proliferative effect and cholesterol-lowering effect [49]. Phenylethanol glycoside can improve the memory ability of rats with vascular dementia caused by ischemia-reperfusion injury, improve the learning and memory ability of mice with kidney-yang deficiency caused by hydrocortisone, improve the learning and memory acquisition impairment of mice caused by scopolamine, and improve the learning and memory acquisition impairment of mice caused by sodium nitrite. In mice with learning and memory impairment, ethanol-induced regeneration of learning and memory loss in mice, phenylethanol glycosides also show neuroprotective activity [50].

4. Selection of perimenopausal syndrome models and perimenopausal depression models

In order to more effectively and in-depth study the pathogenesis of the disease and screen effective drugs, it is crucial to establish a truly effective and feasible animal model. The choice of animal model depends on the clinical manifestations of the disease being simulated. The animal model should be able to better simulate the clinical manifestations of the disease and have a reasonable theoretical basis [51]. The most commonly used animals in model production are rats and mice, because they are close to human physiological conditions and are cheap and easy to obtain. Rats and mice are ideal animals for studying menopausal osteoporosis. Animal models of perimenopausal syndrome commonly used in experiments include: ovarian removal, natural menopause, ovaries damaged by X-ray irradiation, ovaries damaged by alcohol, etc. Animal models of natural menopause are close to clinical practice, but the modeling cycle is long and the cost is high. X-ray irradiation destroys ovary animal models. Due to limitations in laboratory equipment and conditions, the irradiation time and intensity are difficult to control. Common clinical menopausal symptoms such as heat, sweating, depression, forgetfulness, palpitations and insomnia are difficult to manifest in alcohol-damaged ovarian animal models [52].

The modeling method used in this experiment was to remove the ovaries to replicate the perimenopausal model of completely castrated mice. 90% of female estrogen is secreted by the ovaries. Removal of the ovaries can artificially cause a sudden decrease in estrogen, simulating perimenopausal syndrome. This model is relatively classic and has the characteristics of short modeling time, obvious changes in pathobiological indicators, and easy production. The model has a high success rate, is stable and reliable, is cheaper and easier to obtain than old mice, and is widely used by scientific researchers. However, there are differences between the complete ovarian removal model and human perimenopause: the ovarian function of perimenopausal women only declines but is not completely lost. It not only synthesizes estrogen, but also synthesizes other hormones and plays a role in immunity, while the ovariectomy model These features are completely removed. Therefore, the rat experiment in this subject adopts complete removal of one side and 80% removal of the other side of the ovary. This model retains part of the ovary, and the ovarian function has not been completely lost. It is closer to the physiological characteristics of human menopausal syndrome, and the model has a high success rate.

The animal model of perimenopausal syndrome combined with disease and syndrome has the characteristics of using castrated animals, focusing on a certain symptom, and combining it with specific symptoms, and is suitable for screening specific drugs to treat certain symptoms. Therefore, on the basis of the perimenopausal model, the currently recognized mature long-term unpredictable stress method was used to create a perimenopausal depression model [53]. Effectively imitates the clinical manifestations of emotional disorders and depression caused by ovarian function decline in women during perimenopause.

5. The significance of detection indicators

5.1 The significance of serum sex hormone levels and serum osteocalcin levels

The significance of the detection of serum estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH): in patients with menopausal syndrome, ovarian function declines, sex hormone secretion decreases, and gonadotropins increase. . Serum E2 and T levels were lower than those of asymptomatic menopause, while FSH and LH were significantly higher than those of asymptomatic menopause. The measurement of serum E2, T, FSH and LH levels in perimenopausal model animals can be used as visual indicators to identify perimenopausal diseases and reflect the therapeutic effect of drugs on this disease. Studies have proven that ovarian function decline is the connotation of kidney deficiency syndrome, and changes in E2, T, FSH, and LH are an expression of kidney deficiency syndrome [54]. The detection significance of gonadotropin-releasing hormone (GnRH): Gonadotropin-releasing hormone is a decapeptide hormone synthesized by hypothalamic neuroendocrine cells. As an important mediator, GnRH stimulates the synthesis and secretion of gonadotropins in the anterior pituitary gland, thereby maintaining normal gonadotropin-releasing hormone. Reproductive system function plays an important role in regulating reproductive endocrine functions. In addition to being related to negative feedback regulation, GnRH is also closely related to the regulation of a variety of neurotransmitters and neural signals. Serum GnRH levels are significantly increased in patients with perimenopausal syndrome.

The significance of the detection of serum osteocalcin (BGP): Serum BGP is a non-collagen protein in bone tissue, a type of polypeptide substance produced by osteoblasts, and a new biochemical marker for studying bone metabolism. The matrix of bone is synthesized under the influence of sex hormone protein synthesis. The main effect of estrogen on bone metabolism is to inhibit the number and activity of osteoclasts and is an anti-resorptive agent. Patients with perimenopausal syndrome have significantly lower serum BGP levels and develop osteoporosis.

5.2 The significance of detection of plasma neuropeptides and brain tissue neurotransmitters:

β-Endorphin (β-EP): The occurrence of hot flashes in postmenopausal women is not only related to the degradation disorder of 5-HT, but also related to β-endorphin (β-EP). Abnormal activity of β-EP will cause It affects the heat dissipation center in the preoptic area, causing the expansion of peripheral blood vessels, causing symptoms such as heat and sweating in perimenopausal women; at the same time, β-EP also affects the metabolism of various central neurotransmitters, thereby affecting mood and actions. .

Detection of 5-hydroxytryptamine (5-HT) and dopamine (DA) in the brain: Among the pathogenesis of depression, the more generally accepted view is the 5-HT low hypothesis. Levels of the monoamine neurotransmitters 5-HT and DA are decreased in the cerebrospinal fluid of patients with depression. The initiating factor of this disease is the dysfunction of the hypothalamic-pituitary-gonadal axis (HPO) caused by the decline of ovarian function, which in turn affects the imbalance of monoamine neurotransmitters in the hypothalamus [55] and leads to the symptoms of perimenopausal depression. 5.3 The significance of detecting estrogen and androgen receptor levels in body tissues

Estrogen receptor (ER): Estrogen needs to bind to the estrogen receptor (ER) on the target organ to produce biological effects. The effect depends on the level of estrogen and the ER content of the target cell [56], hypothalamus ER is distributed in tissues such as , pituitary gland, and uterus. As women enter perimenopause, estrogen levels decrease, and the ER content in target tissues and organs also decreases [57]. Androgen Receptor (AR): Testosterone (T) is the most active androgen in the female body and combines with the androgen receptor (AR) to produce effects. AR is widely distributed in the central nervous system, such as the hypothalamus; the ovarian source of testosterone About 25%. With the gradual loss of ovarian function after menopause, T secretion from the ovary decreases. Reduced T levels will affect bone structure and is one of the signs of female osteoporosis. E2 can induce AR and reduce estrogen, which also affects The production of biological effects of androgens [8].

5.4 The significance of behavioral testing in rats and mice

Open-Field measurement: Observe the horizontal-vertical movement integral of rat perimenopausal model animals to reflect the rat's curiosity about the new environment. Dark avoidance method: observe the improvement of learning and memory functions of perimenopausal model animals and perimenopausal combined depression model animals. Autonomous activities: The degree of curiosity of perimenopausal model mice and perimenopausal depression model mice towards novel environments. Forced swimming and tail suspension experiments: The degree of despair of perimenopausal depression model mice towards adverse environments is reflected by measuring the immobility time within a certain period of time. 5.5 The significance of observing pathological tissue changes in relevant organs of rats and mice:

Thymus, spleen, uterine index and pathological observation of thymus, spleen, uterus and pituitary gland: In patients with perimenopausal syndrome, ovarian function declines, reproductive organs begin to atrophy, and pituitary gland function degenerates. The pituitary gland is the link between the central and peripheral endocrine systems and is the HPO Changes in the number of two types of cells in the anterior pituitary, an important component of the pituitary axis, can directly affect the secretion of two types of gonadotropins in the anterior pituitary [58]. Causes disorders of sex hormone secretion in the hypothalamus-pituitary-ovarian axis. Lesions can involve the thymus, spleen, and various other organs, resulting in low immunity. Lesions can involve degeneration of brain function and memory loss. The HPO axis regulates the entire reproductive activity process of the body, including sexual differentiation, sexual maturation, reproduction and other sexual physiological activities, and plays an important regulatory role in growth, development and reproduction. The disorder of HPO axis function during perimenopause not only affects the function of the corresponding hormone effector organs, but also directly or indirectly causes an imbalance in the autonomic nervous system, causing a series of complex pathological changes throughout the body, leading to the occurrence of perimenopausal syndrome [59 ].

6 Effects of Cistanche phenylethanol glycosides on rat and mouse perimenopausal models and mouse perimenopausal depression models 

6.1 Effects of Cistanche phenylethanol glycosides on mouse perimenopausal models

Through the mouse autonomous activity test, it can be judged whether the mice have changes in behavioral characteristics such as decreased exercise ability, social interaction ability, exploratory behavior, and deficiencies in aggression. Horizontal movement reflects the animal's mobility, and standing movement reflects the animal's curiosity about the novel environment. Dark avoidance test latency and number of electric shocks can measure the animal's learning and memory ability. Serum E2, T levels and LH, FSH levels can detect whether sex hormones are disordered. The degree of tissue changes in the pituitary gland and uterus can reflect whether the function of the hypothalamus-pituitary-ovary axis is normal, and the changes in the immune tissue of the thymus and spleen can reflect whether the immune function of perimenopausal mice is normal.

The results of this experiment showed that the serum E2 and T levels of model animals were significantly reduced, the LH and FSH levels were significantly increased, the number of active activities and standing times of mice were significantly decreased, the dark avoidance latency was significantly shortened, and the number of electric shocks was significantly increased. , indicating that the mouse perimenopausal model was successfully replicated. Cistanche phenylethanol glycoside can significantly increase the number of active activities and standing times of mice, significantly extend the dark avoidance latency, significantly reduce the number of electric shocks, significantly increase the E2 and T levels of model mice, and significantly reduce LH, FSH levels can significantly improve lesions of the pituitary gland, uterus, thymus, and spleen. It shows that Cistanche phenylethanol glycoside enhances the exercise ability, curiosity about new environment and learning and memory ability of perimenopausal mice, has the effect of adjusting disordered sex hormone levels, improving sex hormone disorders in perimenopausal mice, and improving the hypothalamus-pituitary gland- Ovarian axis function and improved immunity in perimenopausal mice. 6.2 Effect of Cistanche phenylethanol glycoside on rat perimenopausal model

The number of horizontal activities and the number of vertical activities in the rat's open-field activity experiment can reflect the animal's activity and curiosity about the new environment.

In perimenopausal women, ovarian function declines and estrogen levels decrease, especially estradiol (E2) and testosterone (T). The negative feedback effect on the hypothalamus-pituitary gland weakens, causing luteinizing hormone-releasing hormone, The levels of follicle-stimulating hormone-releasing hormone increase, and FSH and LH also increase. GnRH is synthesized by the hypothalamus and its main function is to control the release of FSH and LH, playing an important role in hormone regulation. During perimenopause, estrogen secretion decreases, negative feedback regulation decreases, and GnRH content increases. Osteocalcin, also known as bone γ-carboxyglutamic acid-containing protein (BGP), is an active polypeptide secreted by osteoblasts and a biochemical marker for studying bone metabolism. The bone matrix is synthesized under the influence of sex hormone proteins; the main effect of estrogen on bone metabolism is to inhibit the number and activity of osteoclasts, and is an anti-absorptive agent. Low estrogen levels weaken bone tissue synthesis, increase bone resorption, and result in low osteocalcin levels, leading to osteoporosis. β-Endorphin (β-EP) is a highly active endogenous opioid peptide synthesized and secreted by the arcuate nucleus of the hypothalamus and the middle lobe of the pituitary gland. It inhibits the hypothalamic-pituitary system and reproductive hormones, and can inhibit GnRH and Secretion of LH; when ovarian function decreases and gradually declines, E2 levels decrease, reducing the negative feedback regulation of the hypothalamus and pituitary gland, and the release and activity of hypothalamic β-EP are affected, which is the main cause of perimenopausal hot flashes. reason.

The biological effects of estrogen require binding to the estrogen receptor (ER) on the target organ. The strength of its effect depends on the level of estrogen and the ER content of the target cells [60]. It is found in the hypothalamus, pituitary gland, uterus and other tissues. ER distribution. T is the most active androgen in women. It combines with the androgen receptor (AR) to produce effects. AR is widely distributed in the central nervous system. When women enter perimenopause, the levels of estrogen and androgens decrease, and ER, AR content is also reduced, resulting in reduced biological effects, leading to perimenopausal syndrome. The results of this experiment show that the horizontal and vertical activities of perimenopausal model rats were significantly weakened within the specified time. The serum E2, T, and BGP levels, plasma β-EP content, hypothalamus, and The ER levels of the pituitary gland and uterus and the AR levels of the hypothalamus were significantly reduced, and the serum levels of LH, FSH, and GnRH were significantly increased. Cistanche phenylethanol glycoside can significantly enhance the horizontal and vertical activities of perimenopausal model rats, significantly increase the serum E2, T, BGP levels, plasma β-EP content, hypothalamus, pituitary gland, and uterus of perimenopausal model rats. ER levels and AR levels in the hypothalamus, significantly reduced serum LH, FSH, and GnRH levels in perimenopausal model rats, and significantly improved lesions in the uterus, ovary, thymus, and spleen of rats. It shows that Cistanche phenylethanol glycoside can enhance the activity and curiosity of perimenopausal rats in new environments; improve sex hormone disorders caused by low levels of estrogen and androgen; and enhance the synthesis of bone tissue by increasing the levels of estrogen and androgen and their receptors. , thereby preventing perimenopausal osteoporosis. Increase the levels of estrogen and its receptors, restore the negative feedback regulation of the hypothalamus and pituitary gland, promote the increased release and activity of hypothalamic β-EP, thereby preventing the occurrence of perimenopausal hot flashes. Restore the functions of the uterus and ovaries by improving their lesions. Improve the immunity of rats by improving the lesions of thymus and spleen. 6.3 Effect of Cistanche phenylethanol glycoside on mouse perimenopausal depression model

Through the mouse autonomous activity test, it can be judged whether the mice have changes in behavioral characteristics such as decreased exercise ability, social interaction ability, exploratory behavior, and deficiencies in aggression. Horizontal movement reflects the animal's mobility, and standing movement reflects the animal's curiosity about the novel environment. Dark avoidance test latency and number of electric shocks can measure the animal's learning and memory ability. The tests of immobility time in a certain period of time in the tail suspension test and the forced swimming test can reflect the despair of perimenopausal depressed mice towards adverse environments. Serum E2 and T levels and LH and FSH levels can detect whether sex hormones are disordered. Changes in 5-HT and DA levels in the brain can cause depression. 5-HT levels are related to patients' mood, loss of appetite, insomnia, and endocrine dysfunction. , closely related to reduced sports activities. The results of this experiment show that perimenopausal depression model mice have a significant decrease in the number of spontaneous activities, a shortened dark avoidance latency, a significant increase in the number of electric shocks, a significant increase in tail suspension immobility time and forced swimming immobility time, and serum E2, T The levels of LH and FSH were significantly reduced, the levels of LH and FSH were significantly increased, and the 5-HT and DA contents of brain tissue homogenates were significantly reduced, indicating that the mouse perimenopausal depression model was successfully replicated. Cistanche phenylethanol glycoside can significantly increase the number of spontaneous activities of perimenopausal depressed mice, significantly extend the dark avoidance latency, and significantly reduce the number of electric shocks, tail suspension immobility time and forced swimming immobility time. Cistanche phenylethanol glycoside can significantly increase the E2 and T levels in the serum of perimenopausal depressed mice, significantly reduce the LH and FSH levels, and significantly increase the 5-HT and DA contents of brain tissue homogenates. Improve lesions of the uterus, thymus, and spleen. It shows that Cistanche phenylethanol glycoside can enhance the exercise ability, exploration ability, curiosity about new environments, and weaken the despair of adverse environments in perimenopausal depressed mice, and can enhance the memory of perimenopausal depressed mice. Adjusting the disordered hormone levels to restore them to normal improves uterine lesions, increases 5-HT and DA levels in brain homogenates, fights the occurrence of depression, and improves the immunity of perimenopausal depressed mice by improving thymus and spleen lesions.

7 Theoretical discussion on this experimental treatment of perimenopausal diseases

The results of this experiment show that soy isoflavone vitamin E soft capsules and Gengnianan capsules can significantly increase the thymus, spleen, uterine index and serum E2 and T levels of perimenopausal model animals, and reduce FSH and LH levels, significantly improving The serum BGP levels, ER in the hypothalamus, pituitary gland, uterus, and AR content in the hypothalamus of perimenopausal model rats indicate that soy isoflavone soft capsules mainly directly supplement estrogen in the body and increase the total estrogen and androgen receptor content in related tissues. Restoring the balance of various hormones in the body to achieve the purpose of treating perimenopausal syndrome, it can also increase the content of monoamine neurotransmitters in the brain homogenates of perimenopausal depression model mice. Therefore, whether it is restoring the body's hormone balance, improving general symptoms of perimenopause, or treating perimenopausal depression, the positive control drug has a good effect. The role of soy isoflavones is mainly reflected in supplementing the body's estrogen and regulating hormones in the body. Balance and improve the function of the hypothalamus-pituitary-ovary axis. The function of Gengnian'an Capsule is mainly reflected in improving the function of the hypothalamus-pituitary-gonad axis, and can also regulate the body's immunity and improve osteoporosis.

Kidney deficiency is the root cause of perimenopausal syndrome. The kidney is the origin of human life and is called the "innate foundation" and "the foundation of yin and yang of the five internal organs." Women who have experienced the middle-aged and postpartum period after pregnancy have During this transitional period between old age, which is perimenopause, more attention should be paid to the kidneys, which are the foundation of yin and yang in the five internal organs. The kidney is the foundation of congenital life, storing essence and qi. The rise and fall of essence and qi in the kidney governs growth and development and the maturation and decline of reproductive functions. "Tiangui arrives on the 27th, the Ren pulse is weak on the seventh and seventh day, the Taichong pulse is weak, and Tiangui is exhausted." Abundance of kidney qi is a prerequisite for Tiangui. The essence of the kidneys has two aspects: kidney yin and kidney yang. When kidney qi is strong, kidney yin and kidney yang must be in harmony. They are interdependent, restrictive, and mutually reinforcing each other to maintain the dynamic balance of yin and yang. The onset of perimenopausal syndrome lasts for a long time, and symptoms of yin and yang deficiency often occur. Therefore, according to the principle of mutual roots of yin and yang, "seeking yang from yin and seeking yin from yang", it has certain guiding significance for the clinical application of kidney-tonifying and yang-boosting traditional Chinese medicine in the treatment of perimenopausal syndrome. Warming and nourishing kidney yang, replenishing essence and blood, and consolidating and protecting kidney qi are its important treatment principles. Studies have shown that ovarian function decline is the essence of kidney deficiency syndrome in women. The imbalance of yin and yang in the kidney is closely related to the disorder of sex hormone secretion in the reproductive endocrine system and the disorder of autonomic nervous system. Changes in E2, FSH, LH, 5-HT, and NA are related to kidney deficiency and kidney deficiency. An expression of Yin and Yang imbalance [15-16].

Traditional Chinese medicine that nourishes kidney yang can adjust HPO axis function and delay ovarian aging; it has a regulating effect on neuro-endocrine-immunity, improves immune function, prevents osteoporosis, regulates the central and autonomic nervous systems, delays aging, and has few side effects. For example: Morinda officinalis has an estrogen-like effect. Its ethanol extract has an estrogen-like effect. It enhances the luteinizing function of HPO by increasing the pituitary response to luteinizing hormone-releasing hormone and the ovarian response to luteinizing hormone [61 ], can control the body weight of ovariectomized mice, increase uterine weight, increase estrogen levels in the body, thicken endometrial columnar epithelial cells, and reduce the degree of uterine atrophy [62]. Clams can significantly improve HPO axis function in mice and increase the weight of the uterus and ovaries of young female mice. And it can significantly reduce the level of follicle-stimulating hormone in the blood of mice and significantly increase the level of estradiol in the blood. Gecko ethanol extract can effectively inhibit the apoptosis of rat ovarian granulosa cells, reduce the atresia of rat ovarian follicles, and thus delay the aging of rat ovaries [63]. Ligustrum lucidum has a bidirectional regulatory effect, which can adjust the functions of each link of the HPO axis and significantly increase endogenous estrogen levels [64]. It can be seen that kidney-tonifying drugs treat perimenopausal syndrome by acting on the hypothalamic-pituitary-ovarian axis to regulate hormone levels or directly exert hormone-like effects to regulate ovarian function [65].

Cistanche is sweet and salty in taste, warm in nature, nourishes kidney yang, replenishes essence and blood, and moisturizes the intestines. Li Shizhen said: "This thing is tonic but not steep, so it is calm." "The kidney yang is replenished and the essence and blood are replenished, and the kidney qi will be consolidated." The functions of Cistanche are consistent with those of traditional Chinese medicine. Therefore, this study believes that Cistanche phenylethanol glycoside can provide new treatment ideas for perimenopausal syndrome, a disease caused by imbalance of body function due to insufficient kidney qi. And further consolidate the theory of "anti-governance and adjustment of balance". "Treat women's diseases by men", expand the scope of medication for gynecological diseases, and further deepen the traditional Chinese medicine theory of "seeking yang from yin, seeking cause from yang" and "mutual roots of yin and yang".

Deficiency of kidney yang will lead to low immune function and disorder. By nourishing the kidney, Cistanche can play an immunoregulatory role from the early stage of immune cell generation, promote the secretion of erythropoietin in the renal interstitium and the secretion of glucocorticoids in the adrenal cortex, thereby enhancing bone marrow hematopoiesis. Function, significantly increase the output rate of mouse granulocyte progenitor cells, maintain the balance and stability of the ratio of red and white cell lines under stress [66], thereby enhancing the body's immunity. Cistanche phenylethanoid glycoside is the main active ingredient of Cistanche. It has hormone-like effects and has various biological activities such as kidney tonifying, liver protection, antioxidant and so on [18]. Therefore, selecting phenylethanoid glycosides from Cistanche for targeted research can greatly improve the efficiency and convenience of perimenopausal syndrome treatment, and its quality standards are easy to control, which is conducive to innovative research and industrial development of drugs.

Phenylethanol glycoside can significantly increase the levels of serum E2, T, and plasma β-EP in model animals, and reduce the levels of LH, FSH, and GnRH. Since all or most of the ovaries of the model animals have been removed, it is reflected that Cistanche phenylethanol glycoside can regulate the upstream organs of the hypothalamic-pituitary-gonadal axis, thereby stimulating the production of estrogen, achieving an overall balance of hormones, and improving the symptoms of perimenopausal syndrome. symptom. Cistanche phenylethanol glycoside can significantly increase AR in the hypothalamus, ER content in the hypothalamus, pituitary gland, and uterus, adjust the levels of estrogen receptors, and enhance the biological effects of estrogen and androgens. It can significantly increase the number of activities and horizontal-vertical integrals of model animals, extend the dark avoidance latency, reduce the number of electric shocks, shorten the time of tail suspension and forced swimming immobility, improve spirit and mobility, enhance learning and memory abilities, and reduce the degree of despair. Enhance the body's immune function. It can significantly increase serum BGP levels in model animals and prevent perimenopausal osteoporosis. Estrogens combine with estrogen receptors in various tissues and organs to enhance the biological effects of estrogen, repair the endometrium, and nourish hypothalamic nerve cells, thereby regulating the hypothalamic-pituitary-gonadal axis, and ultimately achieving the purpose of treatment.