Effects Of Cistanchis Glycosides On The Learning And Memory Of Kidney Yang Deficiency Mice
Mar 06, 2022
Effects of Cistanchis Glycosides on the Learning and Memory of Kidney Yang Deficiency Mice
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With the aging of the population, the search for safe and effective drugs for the prevention and treatment of Alzheimer's disease has become a hot spot in drug research. In recent years, traditional Chinese medicine has made great progress in the treatment of Alzheimer's disease. Cistanche deserticola, a traditional Chinese medicine, was first published in Shennong herbal classic. It has the effects of Tonifying Kidney Yang, benefiting essence and blood, moistening intestines, and defecating. It is now widely used in the treatment of senile dementia, impotence, habitual constipation, and other diseases. Studies have shown that it has the effects of anti-dementia, anti-oxidation, anti-hypoxia, anti-radiation, and enhancing immune function. The main components are phenylethanoid glycosides. The total glycosides of Cistanche deserticola were extracted and refined from the dried fleshy stem of Cistanche deserticola. They contain 90.7% phenylethanoid glycosides, of which the main component is echinacoside 44.3%. In this paper, the effects of total glycosides of Cistanche deserticola on learning and memory impairment in mice with kidney yang deficiency induced by hydrocortisone were studied, so as to provide the basis for its development into a new drug for promoting intelligence and preventing and treating Alzheimer's disease.

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1 Material and Methods
1.1 animals
There are 120 healthy Kunming white mice, weighing 18g ~ 22g, half male and half female, provided by the animal center of China Pharmaceutical University, and the certificate number is 97004.
1.2 drugs and reagents
The total glycosides of Cistanche deserticola and the extract of Cistanche deserticola contain 90.7% of the total phenylethanoid glycosides and 44.3% of echinacoside. The dark brown powder is provided by the chemistry room of the modern research center of traditional Chinese medicine of Peking University with batch number 980601.
Hydrocortisone injection is produced by Yangzhou Pharmaceutical Factory with batch number 980301.
1.3 instruments
Wx-z mouse platform jumping instrument is produced by the Institute of Medicine, Chinese Academy of Medical Sciences.
1.4 method
Mice were randomly divided into normal control group (normal group), model control group (model group), positive control group (positive group), high dose group (high dose group, 400mg kg), medium-dose group (200mg kg), and low dose group (100mg kg), with 20 mice in each group, half male and half female. Intragastric administration, 0.2ml 10g body weight. The normal group and the model group were given the same volume of distilled water once a day for 30 days. From the 11th day of the experiment, except the normal group, each group was given hydrocortisone 1mg by gavage for 8 days.
General observation: during the experiment, the general state and death of mice in each group were observed and recorded every day, and the mortality of mice in each group in the two stages was calculated 8 days after hydrocortisone administration and 10 days after hydrocortisone withdrawal.
From the 19th day of the experiment, the mice were put into the reaction box of the platform jumping instrument to adapt to the environment for 3 minutes, and then immediately connected with 36V AC. after receiving the electric shock, most of the mice jumped onto the platform to escape the electric shock, and the mice jumped off the platform and jumped back to the platform after receiving the electric shock for 5 minutes. After 24 hours of testing, the mice were placed on the platform, and the time when the mice first jumped off the platform (as the incubation period) and the number of errors within 5 minutes were recorded. The test was conducted again on the 30th day of the experiment, and the latency of each animal and the number of errors in 5 minutes were recorded.

2 Results
2.1 effect on improving the general state and mortality of Yang deficiency model mice caused by hydrocortisone. After 8 days of intragastric administration of hydrocortisone, the model group mice showed obvious Yang deficiency symptoms such as less movement, bristling, eating less, drinking less, and shaking, and some animals died, with a mortality rate of 42.1%. The above-mentioned symptoms were significantly improved in the positive group and each dose group of Cistanche glycosides, and the number of animal deaths were reduced. There was a significant difference compared with the model group, indicating that Cistanche glycosides can significantly improve the general condition of Yang deficiency mice caused by hydrocortisone and reduce the mortality of mice
2.2 improvement of learning and memory impairment in Yang deficiency model mice induced by hydrocortisone.
After 8 days of administration of hydrocortisone, the latency of the platform jumping test in the model group was significantly shortened and the number of errors was significantly increased compared with the normal group, indicating that the model mice had learning and memory dysfunction. Compared with the model group, the latency of the platform jumping test was significantly prolonged and the number of errors was significantly reduced in the positive group and the total glycosides of Cistanche 8 days after administration of hydrocortisone, indicating that total glycosides of Cistanche can resist the learning and memory dysfunction of mice caused by hydrocortisone.
After stopping hydrocortisone for 10 days, the latency and error times of the platform jumping test in the model group recovered significantly, and there was no significant difference between the model group and the normal group. After stopping hydrocortisone and continuing Administration for 10 days, the latency and error times of the platform jumping test in the positive group and Cistanche glycosides groups were still improved to a certain extent compared with the model group, but there was no significant difference.

3 Discussions
Learning and memory are advanced functions of the brain and an element of intelligence. Learning and memory impairment is a common symptom of a variety of brain diseases, with a high incidence and a variety of causes, such as hyperactivity disorder in childhood, chorea in youth, lobar atrophy, neurasthenia, cerebrovascular sclerosis in the elderly, insufficient cerebral blood supply, dementia and so on. Modern medical research has proved that learning and memory impairment is closely related to the disorder of synaptic transmission in the brain and the metabolic abnormalities of neurotransmitters, brain substances, and energy. Traditional Chinese medicine believes that there are two kinds of reasons for intellectual impairment, most of which belong to deficiency syndrome, especially deficiency of heart, kidney, and spleen qi. Clinical and experimental studies show that many traditional Chinese medicines and prescriptions with tonic effects can improve learning and memory dysfunction to a certain extent. According to the physiological and biochemical basis of learning and memory, various memory damage models are often caused by chemicals such as m-choline receptor blocker, central nervous system inhibitor, brain protein synthesis inhibitor, and brain hypoxia agent. Cerebral ischemia, electric shock, stress, and other methods can also cause learning and memory damage. In addition, various animal models of "deficiency syndrome" in traditional Chinese medicine, such as Qi deficiency, blood deficiency, yin deficiency, and yang deficiency, especially the models of spleen deficiency and kidney deficiency, also show different degrees of learning and memory dysfunction, which is more suitable for the study of tonic drugs. In this experiment, in addition to the typical appearance of Yang deficiency, the mice were given hydrocortisone by gavage for 8 days also showed obvious learning and memory impairment, which further confirmed that the Yang deficiency model mice can be used as a model of learning and memory impairment.
Cistanche deserticola is a traditional tonic and aphrodisiac medicine, which has the functions of Tonifying the kidney, filling essence, and moistening intestines. Zhu Zhiming and others analyzed the drug composition of 46 compound prescriptions for the treatment of senile dementia published in relevant magazines from 1990 to 1999 and found that Cistanche deserticola is one of the commonly used drugs. Animal experiments also confirmed that Cistanche deserticola has an anti-dementia effect. In this experiment, the total glycosides of Cistanche deserticola can significantly improve the learning and memory dysfunction of kidney yang deficiency model mice induced by hydrocortisone, further confirming that Cistanche deserticola has the effect of promoting intelligence, and indicating that the total glycosides of Cistanche deserticola may be the active component of Cistanche deserticola for tonifying kidney, filling essence and benefiting intelligence.






