Use of Gastrodia elata-derived compounds in alleviating sarcopenia phenotypes

Abstract

The present invention discloses a use of a Gastrodia elata-derived compound for alleviating a sarcopenia phenotype. The Gastrodia elata-derived compound can effectively alleviate a sarcopenia phenotype caused by dexamethasone modeling and can be used to prevent sarcopenia.

Description

Technical Field

[0001] The present invention relates to the application of a compound derived from Gastrodia elata, in particular to the application of a compound derived from Gastrodia elata for alleviating sarcopenia phenotype. Background Art

[0002] Sarcopenia is an age-related geriatric syndrome characterized by decreased muscle mass, strength, and / or physical function. It severely impacts the mobility and quality of life of the elderly, significantly increasing their risk of falls, fractures, hospitalizations, disability, and death, and increasing the healthcare burden on society. Epidemiological data indicate that the global prevalence of sarcopenia is 6-12%, with a prevalence of 14-33% in those aged 65 and above. Epidemiological surveys of sarcopenia in the Chinese population indicate that the prevalence of sarcopenia in community-dwelling elderly people is 8.9-38.8%, and increases significantly with age, reaching as high as 67.1% in those aged 80 and above.

[0003] However, current clinical interventions for sarcopenia are primarily limited to nutrition and exercise, lacking effective drug interventions. Gastrodia elata is a commonly used Chinese herbal medicine, primarily used for sedation, hypnosis, anticonvulsant, and antianxiety. In recent years, it has been found to have anti-aging effects, but the effects of Gastrodia elata and its extracts on sarcopenia have not been studied.

[0004] There are no clear diagnostic indicators for sarcopenia in experimental mice, but phenotypes similar to human sarcopenia, such as muscle atrophy, decreased muscle strength, and decreased physical function, have been found in model mice such as elderly mice and dexamethasone-induced mice, and these mice can be used as animal models for sarcopenia research. Summary of the Invention

[0005] The present invention aims to provide a use of a compound derived from Gastrodia elata for alleviating the sarcopenia phenotype. The present invention can effectively alleviate the sarcopenia phenotype caused by dexamethasone modeling and can be used to prevent sarcopenia.

[0006] The technical solution of the present invention: Use of a compound derived from Gastrodia elata for alleviating the sarcopenia phenotype.

[0007] In the aforementioned use of the Gastrodia elata-derived compound for alleviating the sarcopenia phenotype, the sarcopenia phenotype is a sarcopenia phenotype caused by dexamethasone modeling.

[0008] Among the aforementioned uses of the Gastrodia elata-derived compound for alleviating the sarcopenia phenotype, the Gastrodia elata-derived compound is used in the preparation of a preparation for preventing and treating sarcopenia.

[0009] In the aforementioned use of the Gastrodia elata-derived compound for alleviating the sarcopenia phenotype, the Gastrodia elata-derived compound is parishin.

[0010] In the aforementioned use of the Gastrodia elata-derived compound for alleviating the sarcopenia phenotype, the Gastrodia elata-derived compound is gastrodin.

[0011] In the aforementioned use of the Gastrodia elata-derived compound for alleviating the sarcopenia phenotype, the Gastrodia elata-derived compound is parishin B.

[0012] In the aforementioned use of the Gastrodia elata-derived compound for alleviating the sarcopenia phenotype, the Gastrodia elata-derived compound is parishin C.

[0013] Compared with the existing technology, the compound parishin derived from Gastrodia elata and its analogues (such as gastrodin, parishin B, parishin C, etc.) can effectively alleviate the sarcopenia phenotype caused by dexamethasone modeling and can be used to prevent sarcopenia. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 This is a schematic diagram of the effects of the dexamethasone modeling group and the parishin intervention group on the body weight of mice;

[0015] Figure 2 This is a schematic diagram of the effects of the dexamethasone modeling group and the parishin intervention group on the grip strength of mice;

[0016] Figure 3 This is a schematic diagram of the effects of the dexamethasone modeling group and the parishin intervention group on the motor ability of mice;

[0017] Figure 4 This is a schematic diagram of the effects of the dexamethasone modeling group and the parishin intervention group on the expression of muscle tissue atrophy genes. DETAILED DESCRIPTION

[0018] The present invention will be further described below with reference to the accompanying drawings and examples, but they are not intended to limit the present invention.

[0019] Example: Use of a compound derived from Gastrodia elata for alleviating sarcopenia phenotype.

[0020] The alleviated sarcopenia phenotype is a sarcopenia phenotype caused by dexamethasone modeling.

[0021] Use of a compound derived from Gastrodia elata in preparing a preparation for preventing and treating sarcopenia.

[0022] The compound derived from Gastrodia elata is parishin and its similar structure.

[0023] The compound derived from Gastrodia elata is gastrodin, parishin B and / or parishin C.

[0024] This application conducted corresponding experiments on the use of compounds derived from Gastrodia elata in alleviating the sarcopenia phenotype. The detailed experiments are as follows:

[0025] (1) Dexamethasone modeling and drug intervention:

[0026] Dexamethasone is a synthetic glucocorticoid with anti-inflammatory, anti-allergic, and anti-shock effects. However, long-term use can cause side effects, including weight loss and muscle atrophy. Its mechanism is related to promoting muscle degradation and inhibiting muscle protein synthesis. An imbalance between muscle protein synthesis and degradation is a key factor in the pathogenesis of sarcopenia, so intraperitoneal injection of dexamethasone can be used as a method to establish a sarcopenic phenotype in mice. Forty six-week-old C57BL / 6 mice were purchased and, after two weeks of acclimation, randomly divided into four groups (10 mice each): a normal control group (intraperitoneal injection of 0.9% saline + 30% PEG400; oral gavage of 0.9% saline), a dexamethasone modeling group (intraperitoneal injection of 20 mg / kg / d dexamethasone dissolved in 0.9% saline + 30% PEG400; oral gavage of 0.9% saline), a parishin intervention group (intraperitoneal injection of 20 mg / kg / d dexamethasone; oral gavage of 30 mg / kg / d parishin), and a positive control group (intraperitoneal injection of 20 mg / kg / d dexamethasone combined with treadmill training (12 m / min, 0.5 h / d, 4 days / week). Sarcopenia phenotype-related tests were performed 18 days after modeling and drug intervention.

[0027] (2) Sarcopenia phenotype detection:

[0028] Body weight: During the modeling and intervention process, the daily body weight changes of mice were recorded.

[0029] Grip strength: The grip strength of mice was tested using a YLS-13A rat grip strength tester. Each mouse was tested 10 times and the average value was taken to evaluate the changes in mouse muscle strength.

[0030] Gait analysis: Gait analysis of mice was performed using the Catwalk XT animal gait analysis system. As the mice moved freely through the glass corridor, cameras below recorded their footprints, automatically analyzing indicators such as the mice's average speed, steps per second, dwell time, contact time, and contact intensity to assess changes in their physical functions.

[0031] Detection of expression of atrophy genes in mouse muscle tissue: After the mice were anesthetized and killed, the leg muscles were separated, and RNA was extracted using Trizol-chloroform. After reverse transcription into cDNA, fluorescence quantitative PCR was performed to analyze whether there were differences in the expression levels of atrophy-related genes Atrogin-1 and MuRF-1 among the groups, thereby verifying at the molecular level whether parishin can improve muscle atrophy caused by dexamethasone modeling.

[0032] Body weight: After 18 days of modeling and intervention, the weight loss of mice in the dexamethasone model group was significantly higher than that in the control group. Parishin intervention can significantly reduce the weight loss caused by modeling, and its effect is comparable to that of the positive control exercise intervention group (e.g. Figure 1 shown).

[0033] Figure 1 The results showed that after 18 days of dexamethasone (DM) intervention, the weight loss was greater than that of the control group (Control), while parishin intervention (DM+PA) could inhibit this decline, and its effect was comparable to that of the positive control group - exercise intervention (DM+Running).

[0034] Grip strength: After the intervention, the grip strength of mice in each group was tested, and it was found that dexamethasone modeling could significantly reduce the grip strength of mice, while parishin intervention could improve the decrease in grip strength caused by dexamethasone modeling ( Figure 2 ), revealing that it has an improving effect on decreased muscle strength.

[0035] Figure 2 The results showed that after 18 days of dexamethasone (DM) intervention, the grip strength of mice decreased significantly, while parishin intervention could significantly inhibit the effect of dexamethasone modeling on the grip strength of mice, and its effect was even better than that of the positive control exercise intervention group.

[0036] Gait analysis: After the intervention, the gait analysis of each group of mice was performed using the Catwalk animal gait analysis system. It was found that the average walking speed (average speed) and steps per second (steps / s) of the model group mice decreased, while the parishin intervention group could improve these two indicators, and its effect was even better than the positive control - the exercise intervention group ( Figure 3 AB); The duration of the model group mice was longer than that of the control group, while parishin intervention could reduce their duration, and its effect was equivalent to that of the exercise intervention group ( Figure 3 C). Analysis of various indicators of the four paws (including right front RF, right rear RH, left front LF, and left rear LH) showed that the swing speed of each foot of the model group mice decreased compared with the control group, while parishin intervention could increase its speed, and its effect was better than that of the exercise intervention group ( Figure 3 D); The maximum contact area (max contact area) and the average strength of the maximum contact surface of the mice in the modeling group were lower than those in the control group, while parishin intervention could improve these two indicators, and its effect was significantly better than that of the exercise intervention group ( Figure 3 EF).

[0037] Figure 3 Results: After the intervention with dexamethasone and parishin, analysis of the mice's gait revealed that parishin can improve a variety of movement-related indicators.

[0038] Muscle atrophy gene detection: After the above tests, the mice were anesthetized and killed, and the muscle tissue was isolated. The expression of atrophy genes Atrogin-1 and MuRF-1 in muscle tissue was detected by qPCR technology. It was found that dexamethasone modeling could significantly increase the expression levels of the two genes, while parishin intervention could reduce the expression of Atrogin-1 and MuRF-1 ( Figure 4 ).

[0039] Figure 4 The results showed that dexamethasone modeling could lead to a significant increase in the expression of atrophy genes Atrogin-1 and MuRF-1, while parishin intervention could reduce their expression.

Claims

1. Use of a compound derived from Gastrodia elata in preparing a preparation for preventing and treating sarcopenia, characterized in that: The compound derived from Gastrodia elata is parishin.

2. Use of the compound derived from Gastrodia elata according to claim 1 in preparing a preparation for preventing and treating sarcopenia, characterized in that: The sarcopenia is caused by dexamethasone modeling.

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