Application of gastrodin in preparation of medicine for relieving muscle atrophy caused by dexamethasone
By using gastrodin to regulate the expression of proteins related to muscle atrophy and development, and preparing injectable or oral formulations, the problem of muscle atrophy caused by dexamethasone has been solved, and muscle function and morphology have been improved, filling the gap in clinical drugs for alleviating hormone-induced muscle atrophy.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HUAZHONG AGRI UNIV
- Filing Date
- 2026-03-30
- Publication Date
- 2026-05-12
AI Technical Summary
There is a lack of effective drugs in the current technology to alleviate muscle atrophy caused by dexamethasone, which seriously affects the quality of life of patients.
Using gastrodin as the active ingredient, it is prepared into injectable or oral formulations, with a preferred concentration of 8 mg/kg to 200 mg/kg body weight, to alleviate dexamethasone-induced muscle atrophy and regulate the expression of muscle atrophy-related and development-related proteins.
Gastrodin significantly improves muscle function, enhances muscle grip strength, increases the cross-sectional area of muscle fibers, specifically alleviates gastrocnemius muscle atrophy, and does not affect the natural recovery of weight, demonstrating good drug safety.
Smart Images
Figure FT_1 
Figure FT_2 
Figure FT_3
Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of gastrodin in the preparation of drugs to alleviate muscle atrophy caused by dexamethasone. Background Technology
[0002] Dexamethasone, a commonly used glucocorticoid in clinical practice, possesses various pharmacological effects such as anti-inflammatory, anti-allergic, and anti-shock properties, and is widely used in the treatment of autoimmune diseases and inflammatory diseases. However, long-term or high-dose use of dexamethasone can easily induce muscle atrophy, manifested as decreased muscle weight, reduced muscle function, and myofibril degeneration, becoming a significant adverse reaction in its clinical application and severely impacting patients' quality of life. Currently, there are no specific drugs to alleviate this type of muscle atrophy.
[0003] Gastrodin is the main active ingredient in Gastrodia elata. Existing studies have confirmed its sedative, anticonvulsant, microcirculation-improving, and neuroprotective effects, making it widely used in the treatment of nervous system diseases. However, its application in alleviating hormone-induced muscle atrophy has not yet been found. This invention, through animal experiments, demonstrates for the first time that gastrodin can effectively alleviate dexamethasone-induced muscle atrophy, improve muscle function, and does not affect the body's natural weight recovery, exhibiting good safety. This provides a new and effective drug for alleviating dexamethasone-induced muscle atrophy and expands the pharmaceutical application field of gastrodin. Summary of the Invention
[0004] The purpose of this invention is to provide a new use for gastrodin, specifically its application in the preparation of a drug to alleviate dexamethasone-induced muscle atrophy.
[0005] To achieve the above objectives, the present invention adopts the following technical solution: Application of gastrodin in the preparation of drugs to alleviate dexamethasone-induced muscle atrophy.
[0006] In the application described above, preferably, the effective concentration of gastrodin is 8 mg / kg to 200 mg / kg body weight.
[0007] Preferably, the effective concentration of gastrodin is 50 mg / kg to 100 mg / kg body weight.
[0008] In the application described above, preferably, the gastrodin is prepared into an injectable formulation using PBS as a solvent.
[0009] As described above, preferably, the drug is an injectable or oral formulation.
[0010] Further, preferably, the injectable preparation is an intraperitoneal injection, an intravenous injection, or an intramuscular injection.
[0011] Further, preferably, the oral preparation is a tablet, pill, granule, oral liquid, powder, or capsule.
[0012] As described above, the gastrodin is used to alleviate dexamethasone-induced gastrocnemius muscle atrophy, improve muscle grip strength in mice with muscle atrophy, and increase the average cross-sectional area of gastrocnemius muscle fibers in mice with muscle atrophy.
[0013] The beneficial effects of this invention are as follows: This invention provides a novel use for gastrodin: its application in the preparation of drugs to alleviate dexamethasone-induced muscle atrophy. This fills a gap in clinical drug treatment for hormone-induced muscle atrophy and expands the pharmaceutical applications of gastrodin. This invention reveals that gastrodin can significantly improve muscle function and grip strength in mice with muscle atrophy, while specifically alleviating gastrocnemius muscle atrophy and increasing the cross-sectional area of muscle fibers, thus improving muscle atrophy symptoms from both morphological and functional perspectives. Furthermore, gastrodin does not interfere with the natural recovery of body weight in mice with muscle atrophy while alleviating muscle atrophy, indicating good drug safety and no significant growth-inhibiting effect. Attached Figure Description
[0014] Figure 1 This is a schematic diagram of the experimental technical route in Embodiment 1 of the present invention.
[0015] Figure 2 This is a graph showing the statistical results of daily weight changes in mice in Example 1.
[0016] Figure 3 The image shows the gripping force test results of mice in each group during the experiment of this invention.
[0017] Figure 4 The figure shows the muscle weight test results of mice in each group in the experiment of this invention; where A is the weight of the tibialis anterior muscle, B is the weight of the quadriceps femoris muscle, C is the weight of the gastrocnemius muscle, and D is the total muscle weight; * indicates P<0.05, ** indicates P<0.01, and the difference between groups is statistically significant.
[0018] Figure 5 Figure 1 shows the expression and quantitative analysis results of proteins related to gastrocnemius muscle atrophy and development in mice in each group during the experiment of this invention; where A is a Western Blot protein expression electrophoresis diagram, and B is a graph of protein expression quantitative analysis results; * indicates P<0.05, ** indicates P<0.01, *** indicates P<0.001, and the difference between groups is statistically significant.
[0019] Figure 6 These are H&E stained sections of the gastrocnemius muscle of mice in each group during the experiments of this invention.
[0020] Figure 7 The results show the statistical results of the cross-sectional area of muscle fibers in different experimental groups in Example 3.
[0021] Figure 8 The cross-sectional distribution of muscle fibers in different experimental groups in Example 3 is shown. Detailed Implementation
[0022] This invention is the first to discover that gastrodin has a significant alleviating effect on dexamethasone-induced muscle atrophy. Experiments demonstrate that gastrodin can alleviate muscle atrophy by inhibiting the expression of muscle atrophy-related proteins Fbx32 and MURF1, and promoting the expression of muscle development-related proteins MyHC and MyoD. This indicates that gastrodin exerts its effect by regulating the expression of muscle atrophy and development-related proteins, with a clear mechanism of action, providing a theoretical basis for further in-depth research and clinical application. Simultaneously, it provides a new drug option for clinically alleviating hormone-induced muscle atrophy, solving the problem of the lack of effective drugs in current clinical practice.
[0023] The following embodiments are used to further illustrate the present invention, but should not be construed as limiting the present invention. Any modifications or substitutions made to the present invention without departing from its spirit and essence are within the scope of the present invention.
[0024] Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art. Unless otherwise specified, all reagents used in the examples are of analytical grade or higher. Gastrodin can be purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.
[0025] Example 1
[0026] 1. Forty 8-week-old C57BL / 6 mice with similar average weights (23g) were selected (purchased from the Experimental Animal Center of Huazhong Agricultural University). After approximately one week of acclimatization, they were randomly divided into four groups: a control group (PBS, intraperitoneal injection), a modeling group (25mg / kg dexamethasone, intraperitoneal injection), a low-concentration gastrodin group (50mg / kg gastrodin, intraperitoneal injection), and a high-concentration gastrodin group (100mg / kg gastrodin, intraperitoneal injection). For the first 14 days, the modeling group, low-concentration group, and high-concentration gastrodin group were injected with 25mg / kg dexamethasone to establish a muscle atrophy model. Subsequently, the low-concentration and high-concentration gastrodin groups were injected with 50mg / kg and 100mg / kg gastrodin, respectively. The grouping pattern is as follows: Figure 1 As shown, this study investigated the alleviating effect of gastrodin on muscle atrophy in mice. Specifically, the mouse groups were set up as follows: Control group (CON): Intraperitoneal injection of an equal volume of PBS buffer, continuously treated for 30 days; Model group (DEX): 25 mg / kg dexamethasone was injected intraperitoneally for the first 14 days to establish a muscle atrophy model, and an equal volume of PBS buffer was injected intraperitoneally for the next 16 days. Low concentration gastrodin group (DEX+50Gas): The model was established by intraperitoneal injection of 25mg / kg dexamethasone for the first 14 days, and then by intraperitoneal injection of 50mg / kg gastrodin for the next 16 days. High-concentration gastrodin group (DEX+100Gas): The model was established by intraperitoneal injection of 25mg / kg dexamethasone for the first 14 days, and then by intraperitoneal injection of 100mg / kg gastrodin for the next 16 days.
[0027] Mice in each group were given the drug once a day for a total of 30 days.
[0028] C57BL / 6 mice were housed under standard conditions at a temperature of 22±1℃, with free access to food and water. Mouse weight was measured daily during the rearing period, and one-way ANOVA was performed using Graphpad Prism 10.1.2 software to examine differences in body weight among groups.
[0029] The average body weight of mice in each group is as follows: Figure 2 As shown in the results, there was no significant difference in body weight among the groups before the experiment. After the first 14 days of dexamethasone injection, the body weight of mice in the model group, low-concentration gastrodin group, and high-concentration gastrodin group was significantly lower than that of the control group, indicating that the dexamethasone-induced muscle atrophy model was successfully established. After the dexamethasone injection was stopped, the body weight of mice in each group gradually increased naturally. The body weight of mice in the low-concentration and high-concentration gastrodin groups was not significantly different from that of the model group, indicating that gastrodin does not affect the natural recovery of mouse body weight in the process of alleviating muscle atrophy and has good drug safety.
[0030] Example 2
[0031] To investigate the effect of gastrodin on muscle function in mice with muscular atrophy, the grip strength of the mice was measured using a mouse grip strength meter. Following Example 1, after the experiment, the grip strength of the mice was measured as follows: The mice were placed horizontally above a grid, while keeping their trunks horizontal. The maximum grip strength value displayed on the screen when the mouse's tail was pulled was recorded. This procedure was repeated three times to obtain three grip strength measurements, and the average value was calculated. One-way ANOVA was performed using Graphpad Prism 10.1.2 software to detect differences in grip strength among the groups.
[0032] The results are as follows Figure 3 As shown in the figure, * indicates a significant difference at the P<0.05 level, *** indicates P<0.001, and **** indicates P<0.0001. The muscle grip strength of the model group mice was significantly lower than that of the control group (P<0.0001), indicating that dexamethasone-induced muscle atrophy led to a significant decline in muscle function in mice. The grip strength of mice in the low-concentration and high-concentration gastrodin groups was significantly higher than that of the model group, indicating that gastrodin can effectively improve dexamethasone-induced muscle function decline and improve muscle grip strength in mice with muscle atrophy.
[0033] Example 3
[0034] To investigate the effect of gastrodin on muscle weight in mice with muscular atrophy, we sampled and weighed the tibialis anterior (TA), quadriceps femoris (QU), and gastrocnemius (Gas) muscles. Following Example 1, after the experiment, the mice were fasted for 12 hours and anesthetized by intraperitoneal injection of 1% sodium pentobarbital (50 mg / kg). After complete anesthesia, the corneal reflex disappeared, the muscles relaxed, and the mice were fixed to a dissection table. The skin and fascia of the right leg were cut open, and the muscle tissue, including the tibialis anterior (TA), quadriceps femoris (QU), and gastrocnemius (Gas) muscles, was separated layer by layer and weighed. One-way ANOVA was performed using Graphpad Prism 10.1.2 software to detect the differences in muscle weight among the three groups.
[0035] The weight test results of mice in each test group are as follows: Figure 4 As shown in the figure, A: Tibialis anterior muscle weight; B: Quadriceps femoris muscle weight; C: Gastrocnemius muscle weight; D: Total muscle weight. * indicates P < 0.05, ** indicates P < 0.01.
[0036] The results showed that the gastrocnemius muscle weight of mice in the model group was significantly lower than that in the control group, while the weight of the tibialis anterior, quadriceps femoris, and the total weight of the three muscles did not differ significantly among the groups. The gastrocnemius muscle weight of mice in the low-concentration and high-concentration gastrodin groups was significantly higher than that in the model group, indicating that gastrodin can specifically alleviate dexamethasone-induced gastrocnemius muscle atrophy and has no significant effect on the tibialis anterior and quadriceps femoris muscles.
[0037] Example 4
[0038] To investigate the effects of gastrodin on muscle atrophy and muscle development-related proteins in mice with muscular atrophy, this example uses Western blotting experiments on the gastrocnemius muscle of mice. Detection methods: Gastrocnemius muscle tissue from each group of mice in Example 3 was collected, and total protein was extracted. Western blotting was used to detect the expression of muscle atrophy-related proteins Fbx32 and MURF1, and muscle development-related proteins MyHC, MyoD, and MyoG, with Hsp90 as an internal control protein. ImageJ software was used for grayscale quantitative analysis of protein bands, and Graphpad Prism 10.1.2 software was used for T-tests to detect differences in protein expression among groups. The detection reagents MyHC (A4963), Fbx32 (A3699), and HSP90 (A5027) were purchased from ABclonal, MURF1 (55456-1-AP) from ProteinTech, and MyoD (sc-377460) and MyoG (sc-12732) from Santa Cruz Biotechnology.
[0039] The results are as follows Figure 5 As shown, the expression of atrophy-related proteins Fbx32 and MURF1 in the gastrocnemius muscle of mice in the model group was significantly higher than that in the control group, while the expression of muscle development-related protein MyoD was significantly lower than that in the control group. This indicates that dexamethasone induces muscle atrophy by upregulating atrophy-related proteins and downregulating development-related proteins, suggesting that dexamethasone can inhibit muscle development in mice, leading to muscle atrophy. In contrast, the expression of Fbx32 and MURF1 in the gastrocnemius muscle of mice in the low-concentration gastrodin group was significantly lower than that in the model group, while the expression of MyHC and MyoD was significantly higher than that in the model group. This suggests that gastrodin alleviates muscle atrophy by inhibiting the expression of muscle atrophy-related proteins and promoting the expression of muscle development-related proteins.
[0040] Example 5
[0041] To investigate the effect of gastrodin on the area of muscle fibers in mice with muscle atrophy, this example involved H&E staining of the gastrocnemius muscle of mice. Detection method: Gastrocnemius muscle tissue from each group of mice in Example 3 was collected, frozen sections were prepared, and stained using an H&E staining kit. Images were observed and acquired under an inverted fluorescence microscope. The cross-sectional area of muscle fibers was measured and statistically analyzed using ImageJ software. The distribution characteristics of the muscle fiber cross-sectional area were analyzed. Statistical analysis was performed using Graphpad Prism 10.1.2 software for one-way ANOVA to detect the differences in the cross-sectional area of muscle fibers among the groups.
[0042] H&E staining results of gastrocnemius muscle are as follows Figure 6 As shown, the statistical results of the cross-sectional area of muscle fibers are as follows: Figure 7 The cross-sectional integral distribution of muscle fibers is as follows Figure 8 As shown in the figure, **** indicates P < 0.0001. The results showed that the average cross-sectional area of the gastrocnemius muscle in the model group was significantly lower than that in the control group, indicating that dexamethasone-induced muscle atrophy is accompanied by morphological changes in muscle fibers. The average cross-sectional area of the muscle fibers in the low-concentration and high-concentration gastrodin groups was significantly higher than that in the model group, and the distribution of the muscle fiber cross-sectional area was closer to that in the control group, indicating that gastrodin can effectively alleviate the reduction in muscle fiber cross-sectional area caused by dexamethasone and improve the morphological damage of muscle tissue.
Claims
1. Application of gastrodin in the preparation of drugs to alleviate dexamethasone-induced muscle atrophy.
2. The application according to claim 1, characterized in that, The effective concentration of gastrodin is 8 mg / kg to 200 mg / kg body weight.
3. The application according to claim 1, characterized in that, The gastrodin was prepared into an injectable formulation using PBS as a solvent.
4. The application according to claim 1, characterized in that, The drug is an injectable or oral formulation.
5. The application according to claim 4, characterized in that, The injectable preparation is an intraperitoneal injection, an intravenous injection, or an intramuscular injection.
6. The application according to claim 4, characterized in that, The oral preparations include tablets, pills, granules, oral liquids, powders, and capsules.