Application of poplatin in preparation of medicine for treating muscle injury

Abstract

The invention discloses application of poplatin in preparation of a medicine for treating muscle injury. The research finds that the poplatin has the effects of promoting mouse myoblast differentiation and promoting mouse muscle regeneration under various pathological conditions such as acute injury, obesity, diabetes mellitus and hereditary dystrophy.

Description

Technical Field

[0001] The present invention relates to new indications of luteolin (TEC), and in particular to application of TEC in preparing medicines for treating muscle damage under various pathological conditions. Background Art

[0002] The structural formula of Tectochrysin (TEC) is shown in Formula I. It has multiple pharmacological activities and is mainly suitable for Alzheimer's disease. [1] In addition, there are related reports on anti-inflammatory, anti-oxidation, anti-tumor, lowering blood sugar, and improving insulin sensitivity. [2-5] .

[0003] Summary of the Invention

[0004] The inventors established multiple muscle injury pathology models: 1) toxin-induced acute injury model (CTX-injured mice), 2) diet-induced obesity model, 3) diabetes model (db / db mice), and 4) genetic dystrophy model (mdx mice with Duchenne muscular dystrophy). By observing muscle histopathological staining, treadmill fatigue test, grip strength test, and in situ muscle measurement, they found that:

[0005] TEC can treat muscle damage in various pathological conditions, promote myoblast differentiation, increase muscle fiber cross-sectional area, and does not affect satellite cell proliferation.

[0006] TECs can repair muscle damage and enhance muscle function in a variety of pathological conditions.

[0007] Based on the above findings, the present invention provides the use of jasminoidin for preparing a medicament for treating muscle damage, wherein the muscle damage is caused by acute injury or a chronic disease. The chronic disease is obesity, malnutrition, or diabetes. Optionally, the medicament is administered at a dosage of 20 mg / kg body weight. The medicament is administered orally. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 Figure 1 shows the effect of TEC on muscle damage in the acute injury mouse model. Figure A shows the HE staining results after vehicle and TEC treatment; Figure B shows the immunofluorescence staining results of cell membrane (WGA, green), new muscle fibers (eMYHC, red) and cell nuclei (DAPI, blue) of muscle tissue after vehicle and TEC treatment; Figure C shows the average muscle fiber cross-sectional area after vehicle and TEC treatment, the results are expressed as "mean ± standard deviation", n = 10, ***P < 0.001; Figure D shows the different cross-sectional areas (μm 2) Statistics of the proportion of central nuclei in muscle fibers, **P<0.01, *P<0.05; Figures EF are the qRT-PCR results of the mRNA expression levels of MyoD (E) and Myogenin (Myf3) in the control group and the CTX injection group for 5 days (5d) after vehicle and TEC treatment, respectively, ns indicates no significant difference, *P<0.05; Figure GI. is the Western blot results of the protein expression of eMYHC (G, H) and MYOG (myogenin, abbreviated as MFOG in the figure) in the control group and the CTX injection group for 5 days (5d) after vehicle and TEC treatment, with tubulin as the internal control; the quantitative results were normalized to tubulin, ns indicates no significant difference, *P<0.05, **P<0.01.

[0009] Figure 2 The effect of TEC administration on muscle damage in the obese mouse model in Example 2 is shown in Figure A. Figure A shows the HE staining results of muscle tissue 5 days (5d) and 14 days (14d) after treatment with normal diet (NCD), HFD+Vehicle, and HFD+TEC. Scale bar = 50 μm. Figure B shows the average muscle fiber cross-sectional area statistics of muscle tissue after treatment in each group. The results are expressed as "mean ± standard deviation", n = 10, **P < 0.01 (compared with the HFD-Vehicle group); Figure C shows the different cross-sectional areas (μm 2 Figure 5 (a) shows the percentage of central nuclei in muscle fibers (with different cross-sectional areas as the abscissa). The curves represent the NCD-Vehicle, HFD-Vehicle, and HFD-TEC groups, respectively, n=6, **P<0.01, *P<0.05 (compared with the HFD-Vehicle group); Figure D shows the qRT-PCR results of the relative expression levels of Myog (myogenin) and Myh3 (myosin heavy chain 3) mRNA in muscle tissues of each group, n=6, ***P<0.001, **P<0.01, *P<0.05 (compared with the Figure E shows the results of immunofluorescence staining of muscle tissue after NCD, HFD-Vehicle, and HFD-TEC treatment, labeling cell membranes (WGA, green), newly formed myofibers (eMYHC, red), and cell nuclei (DAPI, blue). Scale bar = 50 μm. Figures FI and FI show the functional test results of mice after treatment in each group: Figure F shows running time (seconds), ***P<0.001, **P<0.01; Figure G shows grip strength (N / g), **P<0.01; Figure H shows single contraction force (mN / mm 2 ), ***P<0.001, **P<0.01; Figure I shows tetanic force (mN / mm 2 ), ***P<0.001, **P<0.01 (all compared with the HFD-Vehicle group).

[0010] Figure 3 The effect of TEC administration on muscle damage in diabetic db / db mice in Example 3 is shown. Figure A shows the HE staining results of muscle tissues in the wild-type (WT), db / db-Vehicle (vehicle-treated), and db / db-TEC (TEC-treated) groups. Scale bar = 50 μm; Figure B shows the average muscle fiber cross-sectional area statistics of muscle tissues in each group. Data are expressed as "mean ± standard deviation" (n = 6), **P < 0.01 (compared with the db / db-Vehicle group); Figure C shows the different cross-sectional areas (μm 2 ) The curves represent the WT-Vehicle, db / db-Vehicle, and db / db-TEC groups, **P<0.01, *P<0.05 (compared with the db / db-Vehicle group); Figure D shows the qRT-PCR results of the relative expression levels of Myog (myogenin) and Myh3 (myosin heavy chain 3) mRNA in the muscles of each group, **P<0.01, *P<0.05 (compared with the db / db-Vehicle group); Figure E shows the WT Immunofluorescence staining results of muscles in the db / db-Vehicle, db / db-TEC groups, labeling cell membranes (WGA, green), newly formed muscle fibers (eMYHC, red), and cell nuclei (DAPI, blue). Scale bar = 50 μm. Figures F–I are the results of muscle function tests in mice: Figure F is running time (seconds), P < 0.01 (compared with the db / db-Vehicle group); Figure G is grip strength (N / g), P < 0.01 (compared with the db / db-Vehicle group); Figure H is single contraction force (mN / mm 2 ), P < 0.01 (compared with the db / db-Vehicle group); Figure 1 shows the tetanic contraction force (mN / mm 2 ), P < 0.01 (compared with the db / db-Vehicle group).

[0011] Figure 4The effect of TEC administration on muscle damage in the hereditary malnutrition model mdx mice in Example 4 is shown in Figure A. A schematic diagram of the experimental process: 4-week-old mdx mice were intraperitoneally injected with DMSO (Vehicle) or TEC (20 mg / kg) daily for 28 days, and samples were collected and analyzed on the 28th day; Figure B on the left shows the HE staining results of the gastrocnemius muscle (GAS), tibialis anterior muscle (TA), and vastus intermedius muscle (DIA), observing muscle fiber morphology and centromeric distribution, scale = 50 μm; Figure B on the right shows the proportional distribution curve of centromeric muscle fibers in GAS, TA, and DIA and the average cross-sectional area (CSA) statistics, **P<0.01, *P<0.05 (mdx+TEC group vs. mdx+Vehicle group); Figure C shows the relative expression levels of Myog (myogenin) and Myh3 (myosin heavy chain 3) mRNA in muscle tissue (qRT-PCR detection), *P<0.05 (mdx+TEC group vs. mdx+Vehicle group, WT+Vehicle group as normal control); Figures D–F show the serum inflammatory factor concentrations (ELISA test) in the mdx+TEC group vs. the mdx+Vehicle group and the WT+Vehicle group, **P<0.01, *P<0.05: Figure D shows the serum TNF-α level; Figure E shows the serum IL-6 level; Figure F shows the serum IL-1β level; Figures G–H show macrophage infiltration analysis: Figure G shows the results of immunofluorescence staining of muscle tissue, marked as F4 / 80 + (macrophages, green), cell membrane (WGA, blue), observe the distribution of macrophages, scale bar = 20 μm; Figure H is F4 / 80 + Macrophage ratio statistics, **P<0.01, *P<0.05 (mdx+TEC group vs. mdx+Vehicle group); Figures I–L show muscle function test results of the mdx+TEC group vs. the mdx+Vehicle group and the WT+Vehicle group, n=12, **P<0.01: Figure I shows running time (seconds), reflecting endurance; Figure J shows grip strength (N / g), reflecting overall muscle strength; Figure K shows single contraction force (mN / mm 2 ), reflecting the ability of rapid contraction; Figure L is the tetanic contraction force (mN / mm 2 ), reflecting the ability to sustain contraction. Specific implementation plan

[0012] Unless otherwise specified, the scientific and technical terms used herein are understood according to the knowledge of ordinary technicians in the relevant fields.

[0013] Acute injuries and chronic diseases (such as obesity, diabetes, and hereditary muscular dystrophy) can lead to muscle damage, which manifests as muscle volume loss, fibrosis, and loss of function, ultimately reducing mobility and quality of life. [6-9]For example, in obese and diabetic patients, chronic hyperglycemia and insulin resistance disrupt the IGF1R / PI3K / AKT signaling axis, a key pathway for myoblast differentiation, leading to muscle damage. [10,11] Similarly, Duchenne muscular dystrophy (DMD), caused by a deficiency of anti-muscle damage proteins, leads to repeated muscle damage and failure to regenerate due to persistent inflammation and fibrosis.

[12] .

[0014] Glucocorticoids are often used in clinical practice for DMD.

[13] Or adjust the lifestyle of metabolic disorders to relieve symptoms.

[0015] This paper uses the following four muscle injury pathology models as research objects, which correspond to the four core pathogenic mechanisms of muscle injury:

[0016] Acute injury model: Cyclophosphamide (CTX)-induced acute muscle injury model in mice (simulating muscle injury caused by physical / chemical injury);

[0017] Diet-induced obesity model: (simulating muscle damage caused by metabolic abnormalities such as chronic inflammation in obese people);

[0018] Diabetic mouse model: (simulates muscle damage caused by metabolic abnormalities such as insulin resistance in diabetic patients);

[0019] Genetic muscular dystrophy model: X-linked muscular dystrophy (mdx) mouse model (simulates muscle damage caused by genetic defects).

[0020] The above models cover the four major causes of muscle damage - acute injury, obesity, diabetes and genetic defects, in order to systematically evaluate the therapeutic effects of target compounds on muscle damage under different pathological mechanisms.

[0021] It should be noted that the TEC used in the following examples was purchased from Chengdu Ruifens Biotechnology Co., Ltd. (PF-4708671). Its purity was ≥99% by HPLC and it could be diluted to 20 mg / kg in DMSO and saline. All cells were purchased from the National Laboratory Cell Resource Sharing Platform; C57BL / 6J mice were purchased from the Animal Center of Xi'an Jiaotong University (Xi'an, China); and classical mdx mice (strain number T003035) and db / db mice with a C57BL / 10SnJ genetic background were purchased from WuXi AppTec (Nanjing, China). The mice were acclimated for one week in the animal facility of Northwest Agriculture and Forestry University, fed with standard chow and water, and maintained in a 12-hour light / dark cycle. Unless otherwise specified, the experimental methods and related detection methods used in the following examples were based on methods known in the art.

[0022] Example 1: The inventors found that TEC can treat muscle damage in mice under acute injury pathological conditions

[0023] plan:

[0024] Eight-week-old C57BL / 6J male mice were used as research subjects, and the specific protocol was as follows:

[0025] Grouping: C57BL / 6J mice were induced with CTX and divided into a DMSO vehicle-treated group and a TEC-treated group (20 mg / kg dose), with 12 mice in each group.

[0026] CTX modeling

[14] ① Modeling at 8 weeks of age, subcutaneous injection of buprenorphine anesthesia: grab the mouse, with the abdomen facing up, disinfect the injection site (lower abdomen, 1 cm from the midline of the abdomen) with an alcohol cotton ball, and slowly push buprenorphine solution (0.05 mg / kg). Deep anesthesia usually occurs 5-10 minutes after administration and lasts for about 2-3 hours. The degree of anesthesia is monitored by the disappearance of the limb withdrawal reflex; ② Positioning of the tibialis anterior (TA) muscle: The TA muscle is located on the anterior side of the tibia of the mouse hind limb. It is long and starts from the proximal end of the tibia and ends at the ankle. Pinch the skin of the hind limb with the thumb and index finger, stretch and fix it, and the outline of the TA muscle can be seen through the skin (assisted by a stereomicroscope if necessary); ③ Disinfect the skin at the injection site (1 cm below the knee joint) with an alcohol cotton ball, hold a microinjector (30G needle), pierce the skin at a 45° angle, advance about 2-3 mm toward the muscle (the needle enters 1 / 2 depth of the muscle), and slowly inject 30 μL ④ Place the mouse on a heating pad (37°C) until it wakes up to avoid hypothermia after anesthesia; ⑤ Keep the mouse individually housed for the first 3 days after surgery to reduce secondary damage to the injured area caused by group fighting; ⑥ Record the mouse's daily activity, food and water intake, and whether the injection site is red, swollen, or infected. Typical injury manifestations include: TA muscle swelling within 24 hours after injection, and gradual appearance of muscle fibrosis and induration (perceptible by palpation) after 48 hours.

[0027] Administration: After CTX modeling, mice were administered DMSO vehicle and TEC by oral gavage. The TEC dose was 20 mg / kg, i.e., each mouse was given 20 mg / kg TEC and the same volume of DMSO per day (the DMSO vehicle group was given the same volume of DMSO). The administration was done once a day for two weeks, ensuring that the time period of each administration and the surgery time were the same.

[0028] The following tests and analyses were further performed on the above groups:

[0029] Muscle histopathological staining: ① Mice were killed by overdose of anesthesia; ② After disinfection, the bilateral TA muscles (including the injured side and the contralateral uninjured control) were completely dissected; ③ The TA was fixed with 4% paraformaldehyde for more than 72 hours and then dehydrated and embedded; ④ 2 to 4 μm thick muscle paraffin sections were obtained for H&E staining and immunofluorescence staining.

[0030] Immunofluorescence staining: Muscle sections and cultured cells were fixed with 4% formaldehyde for 10 minutes, permeabilized with 0.2% Triton X-100 on ice for 20 minutes, and then blocked with 3% bovine serum albumin in PBS for 1 hour. Samples were then blocked with 5% BSA for 2 hours at room temperature. The primary antibodies listed in Table S1 were incubated in blocking buffer overnight at 4°C. Subsequently, samples were washed with PBS and stained with the appropriate fluorescent-conjugated secondary antibody (fluorescein isothiocyanate or rhodamine) for 1 hour at room temperature. After washing with PBS, cell nuclei were stained with DAPI (C0060, Solarbio, Beijing, China) for 3 minutes. For immunostaining of muscle sections, whole-slide digital images were collected using a Pannoramic DESK scanner (P-MIDI, P250, 3D HISTECH). The cross-sectional area of ​​new myofibers was calculated from slice images obtained from TA muscles using ImageJ software. For immunostaining of cultured cells, images were acquired using BioTEK gen 5 software, and total nuclei and nuclei within myotubes were counted using ImageJ. The distribution of nuclei and fusion index of each myotube (MYHC with at least 3 nuclei) + cells) were calculated as the number of nuclei in the myotubes divided by the total number of nuclei counted.

[0031] result:

[0032] The therapeutic effect of TEC on muscle damage in mice with acute CTX injury is as follows Figure 1 As shown in (AI), the area of ​​newly regenerated muscle fibers in the tibialis anterior (TA) muscle increased significantly after TEC treatment ( Figure 1 A), damaged muscle fibers and fibrous tissues were significantly reduced ( Figure 1 D); eMYHC in mouse muscle after TEC treatment + The amount and size of recycled fibers increased significantly ( Figure 1 BC); The expression levels of myogenic differentiation markers Myog and Myh3 in mouse muscles were significantly upregulated after TEC treatment ( Figure 1 EF), the protein levels of eMYHC and MYOG were significantly increased ( Figure 1 GI).

[0033] Example 2: The inventors found that TEC can treat muscle damage in mice under pathological conditions of obesity.

[0034] Eight-week-old C57BL / 6J male mice were used as research subjects, and the specific protocol was as follows:

[0035] Grouping: C57BL / 6J mice were divided into normal chow (NCD) group, HFD+vehicle group and HFD+TEC group (20 mg / kg dose), with 12 mice in each group.

[0036] High-fat diet (HFD) obesity model was established: ① The mice were weighed and randomly assigned to the HFD group and the NCD group according to their weight, ensuring that there was no significant difference in the average body weight between the two groups (P>0.05); ② The HFD group was provided with fresh HFD daily, and the NCD group was provided with ordinary feed, with free access to food and water; ③ Body weight was monitored and recorded regularly (at a fixed time each week), fasting weighing was performed (fasting for 4 hours before weighing), and individual body weight was recorded (accurate to 0.1g); ④ TEC treatment and control experiments were performed after induction for 16 weeks.

[0037] Vehicle-treated group and TEC-treated group: Obese mice were given DMSO vehicle and TEC by oral gavage at a TEC dose of 20 mg / kg. That is, each mouse was given 20 mg / kg TEC and the same volume of DMSO once a day for two weeks, ensuring that the time period of each administration and the surgery time were the same.

[0038] The following tests and analyses were further performed on the above groups:

[0039] Muscle tissue pathological staining and immunofluorescence staining were the same as those in Example 1.

[0040] Treadmill fatigue test: Mice were tested for fatigue using a treadmill. Each run-to-fatigue test estimated maximal exercise capacity based on two parameters: running duration (seconds) and running distance (meters). Exercise capacity was determined by averaging two trials.

[0041] Grip strength test: As described in previous studies, the forelimb strength of mice was measured using a handgrip dynamometer (Columbus Instruments, USA). Each mouse was allowed to grasp a horizontal bar connected to the handgrip dynamometer and gently pull its tail horizontally until the bar was released. This process was repeated, and the peak force exerted by each mouse was recorded.

[0042] In situ muscle strength measurement: In situ strength measurement of the TA muscle was performed using a BL-420F Biofunctional Laboratory System (Tymon Software, Chengdu, China). Electrical stimulation was initiated with 50 Hz pulses via two electrodes placed on either side of the muscle, eliciting single twitches or tetanic contractions. At the end of the measurement, the optimal length and wet weight of the TA muscle were measured to calculate the physiological cross-sectional area (muscle mass / optimal length × muscle density (1.06 g / cm)). 3 )), then used to gain isometric twitching and limb strength.

[0043] result:

[0044] The therapeutic effect of TEC on muscle damage in obese mice Figure 2As shown in (AE), on the 5th day after injury, the muscle fiber area of ​​obese mice treated with TEC increased significantly, the expression levels of Myog and Myh3 in the muscles of obese mice treated with TEC increased significantly, and the expression of eMYHC + The amount and volume of recycled fibers increased significantly.

[0045] The muscle function of obese mice was significantly improved after TEC treatment. Figure 2 As shown in (FI), the running time and forelimb grip strength of obese mice were significantly improved after TEC treatment, and the specific twitch force and tetanic force of obese mice were significantly increased.

[0046] Example 3: The inventors found that TEC can treat muscle damage in mice under diabetic pathological conditions

[0047] plan:

[0048] Eight-week-old db / db mice were used as research subjects.

[0049] Grouping: db / db mice were divided into WT+vehicle, HFD+vehicle and HFD+TEC groups (20 mg / kg dose), with 12 mice in each group.

[0050] Vehicle-treated group and TEC-treated group: db / db mice were administered with drugs (DMSO vehicle and TEC were administered by oral gavage, with a TEC dose of 20 mg / kg, i.e., each mouse was administered with 20 mg / kg TEC and the same volume of DMSO once a day for two weeks, ensuring that the time period of each administration and the surgery time were the same).

[0051] The following tests and analyses were further performed on the above groups: muscle tissue pathological staining and immunofluorescence staining were the same as in Example 1; treadmill fatigue test, grip strength test and in situ muscle strength measurement were the same as in Example 2.

[0052] result:

[0053] The therapeutic effect of TEC on muscle damage in diabetic mice (db / db mice) is as follows Figure 3 As shown in (AC), the average cross-sectional area of ​​TA increased significantly after TEC treatment. In addition, TEC treatment had a significant effect on muscle regeneration function in diabetic mice, as shown in Figure 3 As shown in (DE), the expression levels of Myog and Myh3 in TA were significantly increased after TEC treatment, and eMYHC + The fiber size increased significantly. The muscle function of obese mice was significantly improved after TEC treatment, such as Figure 3As shown in (FI), the running time and forelimb grip strength of diabetic mice were significantly improved after TEC treatment, and the specific twitch force and tetanic force of diabetic mice were significantly enhanced.

[0054] Example 4: The inventors found that TEC can treat muscle damage in mice under pathological conditions of genetic malnutrition

[0055] plan:

[0056] Eight-week-old C57BL / 6J male mice and mdx mice were used as research subjects.

[0057] Grouping: C57BL / 6J mice were set as the control group, and mdx mice were divided into a vehicle group and a TEC group (20 mg / kg dose), with 12 mice in each group.

[0058] TEC treatment group: mdx mice were administered TEC (TEC was administered by oral gavage at a dose of 20 mg / kg, i.e., each mouse was administered 20 mg / kg TEC once daily for two weeks, ensuring that the time period of each administration and the surgery time were the same); the WT+Vehicle group and the mdx+Vehicle group were treated with the same volume of vehicle by oral gavage.

[0059] Muscle tissue pathological staining and immunofluorescence staining were the same as in Example 1; treadmill fatigue test, grip strength test and in situ muscle strength measurement were the same as in Example 2.

[0060] result:

[0061] The therapeutic effect of TEC on muscle damage in genetic dystrophy mice Figure 4 As shown in (AC), the average cross-sectional area of ​​myofibers in mdx mice increased significantly after TEC treatment, and the mRNA levels of myogenic regulatory factors Myog and Myh3 were significantly upregulated. At the same time, TEC treatment reduced systemic inflammation, as shown in Figure 4 (DH) As shown, the levels of proinflammatory cytokines TNFα, IL-1β, and IL-6 were significantly decreased in mdx mice after TEC treatment. Immunofluorescence staining showed that F4 / 80 + The proportion of macrophages decreased.

[0062] Muscle function of mdx mice was significantly improved after TEC treatment. Figure 4 As shown in (IL), TEC treatment significantly enhanced the running time and grip strength of mdx mice, and significantly increased the twitch force and tetanic force of TA muscles.

[0063] References

[0064] [1]He B,Xu F,Yan T,et al.Tectochrysin from Alpinia OxyphyllaMiq.alleviates Abeta(1-42)induced learning and memory impairments in mice[J].Eur J Pharmacol,2019,842:365-372.

[0065] [2]Zhang J,Wu J,Shi X,et al.A Propolis-Derived Small MoleculeTectochrysin Ameliorates Type 2Diabetes in Mice by Activating InsulinReceptor beta[J].Mol Nutr Food Res,2024,68(1):e2300283.

[0066] [3]Ijaz M U,Alvi K,Hamza A,et al.Curative effects of tectochrysin onparaquat-instigated testicular toxicity in rats:A biochemical andhistopathological based study[J].Heliyon,2024,10(3):e25337.

[0067] [4]Wu I T,Kuo C Y,Su C H,et al.Pinostrobin and Tectochrysin ConquerMultidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase[J].Pharmaceuticals(Basel),2023,16(2).

[0068] [5]Fang L,Yan Y,Xu Z,et al.Tectochrysin ameliorates murine allergicairway inflammation by suppressing Th2 response and oxidative stress[J].Eur JPharmacol,2021,902:174100.

[0069] [6]Zhuang S,Russell A,Guo Y,et al.IFN-gamma blockade after geneticinhibition of PD-1aggravates skeletal muscledamage and impairs skeletalmuscle regeneration[J].Cell Mol Biol Lett,2023,28(1):27.

[0070] [7]Kalinkovich A,Livshits G.Sarcopenic obesity or obese sarcopenia:Across talk between age-associated adipose tissue and skeletal muscleinflammation as a main mechanism of the pathogenesis[J].Ageing Res Rev,2017,35:200-221.

[0071] [8]Song J,Liu J,Cui C,et al.Mesenchymal stromal cells amelioratediabetes-induced muscle atrophy through exosomes by enhancing AMPK / ULK1-mediated autophagy[J].J Cachexia Sarcopenia Muscle,2023,14(2):915-929.

[0072] [9]Pelosi L,Berardinelli M G,De Pasquale L,et al.Functional andMorphological Improvement of Dystrophic Muscle by Interleukin 6 ReceptorBlockade[J].EBioMedicine,2015,2(4):285-293.

[0073]

[10] Huang X,Liu G,Guo J,et al.The PI3K / AKT pathway in obesity andtype 2diabetes[J].Int J Biol Sci,2018,14(11):1483-1496.

[0074]

[11] Kim T Y,Park K T,Choung S Y.Codonopsis lanceolata and its activecomponent Tangshenoside I ameliorate skeletal muscle atrophy via regulatingthe PI3K / Akt and SIRT1 / PGC-1alpha pathways[J].Phytomedicine,2022,100:154058.

[0075]

[12] Russell A J,DuVall M,Barthel B,et al.Modulating fast skeletalmuscle contraction protects skeletal muscle in animal models of Duchennemuscular dystrophy[J].J Clin Invest,2023,133(10).

[0076]

[13] Morrison-Nozik A,Anand P,Zhu H,et al.Glucocorticoids enhancemuscle endurance and ameliorate Duchenne muscular dystrophy through a definedmetabolic program[J].Proc Natl Acad Sci U S A,2015,112(49):E6780-E6789.

[0077]

[14] Liao Z,Lan H,Jian X,et al.Myofiber directs macrophages IL-10-Vav1-Rac1efferocytosis pathway in inflamed muscle following CTX myoinjury byactivating the intrinsic TGF-beta signaling[J].Cell Commun Signal,2023,21(1):168.

Claims

1. Use of jasminoidin for preparing a drug for treating muscle damage, wherein the muscle damage is acute damage or muscle damage caused by chronic disease.

2. The use according to claim 1, characterized in that The chronic disease is obesity, malnutrition or diabetes.

3. The use according to claim 1 or 2, characterized in that The dosage of the drug is 20 mg / kg body weight.

4. The use according to claim 1 or 2, characterized in that The drug is administered orally.

Images