Mirabilis himalaica extract and application of chemical components of mirabilis himalaica extract in fatigue resistance

Abstract

The invention provides application of a mirabilis himalaica (MH) extract in preparation of drugs for tonifying primordial qi, resisting fatigue and preventing and treating deficiency syndromes. The mirabilis himalaica (MH) extract is proved to have excellent anti-fatigue activity through a plurality of fatigue experimental models (such as an exhaustion swimming model, a rotating rod test, a suspension test and a tail suspension test) and in-vivo biochemical index determination thereof. The invention provides application of compounds (such as Boeravinone A, Boeravinone B and Boeravinone E) shown in a formula I in preparation of drugs for tonifying primordial qi, resisting fatigue and preventing and treating deficiency syndromes. A fatigue experiment model and in-vivo biochemical index determination prove that the compound shown in the formula I has excellent anti-fatigue activity.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicines, and particularly relates to application of Himalayan Mirabilis jalapa extract and chemical components thereof in anti-fatigue. Background Art

[0002] Many situations can cause fatigue, including irregular nutrition, irregular work or relaxation, insufficient sleep or exercise, chronic mental stress and excessive psychological stress. Fatigue is a physiological state in which the body is slow to respond and has reduced work efficiency when excessive physical and mental consumption and physical labor or some other non-pathological reasons occur. The impact of fatigue is particularly prominent on some jobs that require concentration. For example, when drivers of motor vehicles such as cars, airplanes, and ships are in a fatigued driving state, it is easy to cause a series of adverse reactions in their physiology and psychology, greatly increasing the risk of accidents and even seriously threatening the safety of life and property. Fatigue not only causes immediate effects, but long-term fatigue can also lead to long-term effects. If fatigue is not recovered in time after it occurs, it may lead to a sub-healthy state, which not only has a negative impact on daily life and work, but also affects emotions and social relationships. In addition, persistent fatigue or severe fatigue can also lead to anxiety, depression, cognitive impairment, endocrine disorders, decreased immunity and organic diseases, becoming an important factor threatening human health.

[0003] At present, the research on drugs for the treatment of fatigue is mainly divided into the research and development of chemically synthesized small molecule anti-fatigue agents and traditional Chinese medicine-related anti-fatigue agents. Due to the slow efficacy, large side effects and high research and development costs of chemically synthesized anti-fatigue small molecule compounds, chemically synthesized anti-fatigue agents have not been widely used in clinical and daily life. For example, the small molecule compound Betaloc Zok developed by AstraZeneca Group plays an important role in anti-fatigue, but it has strong renal toxicity and is accompanied by metabolic acidosis and adverse reactions. In addition, the characteristics of traditional Chinese medicine with multiple components and multiple targets are an effective strategy for treating complex systems with multiple mechanisms and multiple causes of fatigue. Therefore, traditional Chinese medicine has the advantage of being an anti-fatigue agent.

[0004] In China, traditional Chinese medicine is the main treatment for sports fatigue and mental fatigue. Traditional Chinese medicine has significant efficacy in eliminating sports fatigue and improving athletic ability, but traditional Chinese medicine often has defects such as low anti-fatigue efficacy and long service life. In the context of the modernization of traditional Chinese medicine, combining traditional Chinese medicine with modern scientific and technological means can more efficiently explore monomer components with anti-fatigue activity in traditional Chinese medicine (a certain type or a certain class of substances with active ingredients extracted from traditional Chinese medicine), laying a good foundation for the clinical development of new drugs for pathological fatigue such as cancer-related fatigue and the development of anti-fatigue health products. Based on traditional Chinese medicine resources, the discovery of monomer components of traditional Chinese medicine with anti-fatigue activity has achieved phased achievements, such as Acanthopanax senticosus extract, Lycium barbarum polysaccharides, and Rosobrytin, but these substances still have the disadvantages of needing to improve anti-fatigue efficacy and a narrow treatment window. These deficiencies have further stimulated the research on faster, more efficient and safer anti-fatigue agents.

[0005] Mirabilis himalayana (MH) is a herb widely distributed in Shanxi, Gansu, Yunnan, Sichuan and Tibet, China. The dried root of MH is used as Tibetan medicine to treat nephritis, edema, gonorrhea, lumbago, joint pain, uterine tumors and bladder stones. However, as an important resource of traditional Chinese medicine, there are few reports on the pharmacology and chemical composition of MH at home and abroad. Therefore, it is necessary to explore the pharmacological activity of Mirabilis himalayana and to clarify the material basis of the efficacy of this plant. Summary of the invention

[0006] In order to improve the above technical problems, the present invention provides the use of Himalayan Mirabilis jalapa (MH) extract and its chemical components in the preparation of drugs for resisting fatigue, replenishing vital energy, and preventing and treating deficiency syndromes.

[0007] The invention provides application of Himalayan Mirabilis jalapa (MH) extract in preparing medicines for resisting fatigue, replenishing vital energy and preventing and treating deficiency syndromes.

[0008] According to an embodiment of the present invention, the preparation method of Himalayan Mirabilis jalapa (MH) extract is:

[0009] The Himalayan Mirabilis jalapa root is used as raw material, solvent extraction is performed, and the Himalayan Mirabilis jalapa (MH) extract is obtained after concentration.

[0010] According to an embodiment of the present invention, the preparation method of Himalayan Mirabilis jalapa (MH) extract is:

[0011] The root of Himalayan Mirabilis jalapa is used as raw material, solvent extraction is performed, and the Himalayan Mirabilis jalapa (MH) extract is obtained after concentration and removal of the solvent.

[0012] According to an embodiment of the present invention, the solvent is selected from one, two or more of water, methanol, ethanol, chloroform, dichloromethane, acetonitrile, etc.; preferably a mixed solvent of water and methanol, such as 75% methanol, 50% methanol, 25% methanol.

[0013] According to an embodiment of the present invention, the extraction method is selected from ultrasonic extraction, reflux extraction, immersion extraction and the like.

[0014] According to an embodiment of the present invention, Himalayan Mirabilis jalapa (MH) extract can replenish vital energy, resist fatigue, and prevent and treat deficiency symptoms in any one or more of the following ways:

[0015] 1) Reduce the lactic acid LD content,

[0016] 2) Increase the content of lactate dehydrogenase LDH;

[0017] 3) Reduce the content of malondialdehyde (MDA);

[0018] 4) Increase the content of superoxide dismutase SOD;

[0019] 5) Increase the content of glutathione peroxidase GSH-PX;

[0020] 6) Increase liver glycogen (HG) content;

[0021] 7) Increase muscle glycogen (MG) content.

[0022] According to an embodiment of the present invention, the administration method of the Mirabilis Himalayanus (MH) extract is selected from: oral administration, injection administration (eg, intravenous injection).

[0023] The present invention also provides an application of a pharmaceutical composition in the preparation of a drug for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes; the pharmaceutical composition comprises the above-mentioned Himalayan Mirabilis jalapa (MH) extract.

[0024] According to an embodiment of the present invention, the pharmaceutical composition may further comprise a pharmaceutically acceptable excipient.

[0025] According to an embodiment of the present invention, the pharmaceutical composition may further comprise other components having the effects of replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes.

[0026] The present invention also provides the use of the compound represented by formula I in the preparation of drugs for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes;

[0027]

[0028] wherein R1-R6 are the same or different and are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, OH, amino, nitro, cyano;

[0029] m is selected from any natural number between 0 and 4, such as 0, 1, 2, 3, or 4.

[0030] According to an embodiment of the present invention, C1-6 alkyl and C1-6 alkoxy are C1-4 alkyl and C1-4 alkoxy; for example, methyl, methoxy, ethyl, ethoxy and the like.

[0031] According to an embodiment of the present invention, halogen is fluorine, chlorine, bromine, iodine.

[0032] According to an embodiment of the present invention, R1 is hydroxyl.

[0033] According to an embodiment of the present invention, R2 is methyl.

[0034] According to an embodiment of the present invention, R3 is hydroxyl.

[0035] According to an embodiment of the present invention, R4 is hydrogen.

[0036] According to an embodiment of the present invention, R6 is each independently selected from hydrogen, hydroxyl; m is selected from 0 or 1.

[0037] According to an embodiment of the present invention, R5 is hydroxyl or methoxy.

[0038] According to an embodiment of the present invention, the compound represented by formula I is selected from the following compounds:

[0039]

[0040] According to the embodiment of the present invention, the compound shown in Formula I can replenish vital energy, resist fatigue, and prevent and treat deficiency syndromes in any one or more of the following ways:

[0041] 1) Increase liver glycogen (HG) content;

[0042] 2) Increase muscle glycogen (MG) content.

[0043] According to an embodiment of the present invention, the administration method of the compound represented by Formula I is selected from: oral administration, injection administration (eg, intravenous injection).

[0044] The present invention also provides an application of a pharmaceutical composition in the preparation of a drug for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes; the pharmaceutical composition comprises the compound represented by the above formula I.

[0045] According to an embodiment of the present invention, the pharmaceutical composition may further comprise a pharmaceutically acceptable excipient.

[0046] According to an embodiment of the present invention, the pharmaceutical composition may further comprise other components having the effects of replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes.

[0047] Beneficial Effects

[0048] The present invention provides the use of Himalayan Mirabilis jalapa (MH) extract in the preparation of a drug for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes. The present invention proves through multiple fatigue experimental models (such as an exhaustive swimming model, a rotating rod test, a suspension test, and a tail suspension test) and in vivo biochemical index determination that the Himalayan Mirabilis jalapa (MH) extract has excellent anti-fatigue activity.

[0049] The present invention provides the use of a compound represented by formula I (e.g., Boeravinone A, B, E) in the preparation of a drug for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes. The present invention proves through a fatigue experimental model and in vivo biochemical index determination that the compound represented by formula I has excellent anti-fatigue activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 UPLC-Q-TOF / MS BPI chromatograms of MH extracts under different extraction solvents. The positive ion mode chromatograms of metabolites are shown. The metabolomics spectra of MH extracts under pure water extraction conditions, 50:50 (methanol: water) extraction conditions, and 75:25 (methanol: water) extraction conditions are shown in order.

[0051] Figure 2 (a) Effects of MH on running time in the rotarod test *p≤0.05, **p≤0.01, compared with the control group. (b) Effects of MH on immobility time in the TST ****p≤0.001, compared with the control group. (c) Effects of MH on falling time in the hanging test. *p≤0.05, ***p≤0.001, compared with the control group. (d) Effects of MH on running distance in the forced running test **p≤0.01, ***p≤0.001, compared with the control group #p≤0.05. (e) Effects of MH on running time in the forced swimming test *p≤0.05, compared with the control group.

[0052] Figure 3 Effects of the rotarod test on fatigue-related biomarkers in mice. (a) LD, (b) LDH. Significant changes in the control group are marked with *p<0.05 and **p<0.01, while significant differences in the Rhodiola rosea group are marked with ## p<0.01.

[0053] Figure 4 Effects of the rotarod test on oxidation-related biomarkers in mice. (a) MDA, (b) SOD, and (c) GSH-Px. Significant differences compared with the control group are marked with *p<0.05, ***p<0.001.

[0054] Figure 5Effects of the exhaustive swimming test on oxidation-related biomarkers in mice. (a) MDA, (b) SOD, and (c) GSH-Px. Significant differences compared with the control group are marked with *p<0.05, **p<0.01.

[0055] Figure 6 Effects of overfatigue on fatigue-related biomarkers in mice. (a) MG, (b) HG. Significant differences from the control group are marked by **p<0.01, ***p<0.001.

[0056] Figure 7 (a) Effects of Boeravinone A, B, and E on the running time of the forced swim test *p ≤ 0.05 compared with the control group. (b) HG, (c) MG. Significant differences from the control group are marked with **p < 0.01, ***p < 0.001.

[0057] All experimental data were determined and presented as mean ± SEM. Multiple comparisons were performed using one-way analysis of variance (ANOVA) to determine statistical significance, followed by Dunnett's test for individual comparisons between groups. Changes with a p value of less than 0.05 were considered statistically significant in the investigation. DETAILED DESCRIPTION

[0058] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0059] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0060] Example 1 Preparation of MH extract

[0061] Screening of extraction solvents: The dried roots of Himalayan Mirabilis jalapa were ground into fine powder and then ultrasonically extracted in different solvents (75% methanol, 50% methanol, 25% methanol and pure water) for 2 hours, and then concentrated and dried under reduced pressure after filtration to remove the solvent to obtain a black extract.

[0062] LC-MS metabolomics analysis: The extracts obtained by extraction with different solvents were analyzed by LC-MS metabolomics. The chemical characteristics of MH extracts with different extraction solvents are as follows: Figure 1As shown. The results show that the extract prepared by ultrasonic extraction using 75% methanol (v / v) as the extraction solvent contains the most types of chemical components and can more comprehensively and effectively reflect the chemical composition of the extract. Therefore, ultrasonic extraction using 75% methanol (v / v) was finally selected as the optimal extraction condition for preparing crude samples.

[0063] Example 2 Anti-fatigue experiment of MH extract

[0064] 1. Forced running test (FRT)

[0065] Mice were administered MH extract (0.6 mg / kg), Rhodiola rosea granules (0.6 g / kg) (purchased from Beijing Tong Ren Tang Co., Ltd.), and saline (control group) by oral gavage for 22 consecutive days, with n=8 per group. 30 minutes after the last administration, the endurance of mice was evaluated using FRT using a treadmill (JY-YLS-10B, China). First, adaptive running was performed at a speed of 16 r / min and 20 r / min for 15 minutes, respectively, for a total of 30 minutes; finally, 24 r / min was used for testing. Mice rested more than 4 times within 60 minutes as a fatigue index. When the mice were exhausted, the running distance at a speed of 24 r / min was recorded.

[0066] The experimental results are as follows Figure 2 As shown in Figure d, in the forced running test, mice treated with MH extract and positive control Rhodiola rosea showed a long running distance, which was significantly (p≤0.05) greater than that of normal mice. Compared with the positive control group of Rhodiola rosea, mice treated with MH extract also showed a significant anti-fatigue effect.

[0067] 2. Rotarod Test

[0068] The rotarod test was performed using a constant speed device (KW-6C, China). Mice were dosed for 22 consecutive days, and MH extract (0.6 mg / kg), Rhodiola rosea granules (0.6 mg / kg), and saline (control group) were administered to mice by gavage, with n=8 in each group. 30 minutes after the last gavage, the mice were immediately placed on the rotarod to put the muscles in a static stress state. Before the formal experiment, the mice were pre-trained for 5 minutes each time, for a total of 4 times. The speed of the rotarod was set to 40 revolutions per minute, and the time required for each group of mice to fall off due to muscle fatigue was measured. Only mice that were able to stay on the rod for 300 seconds in four consecutive trials were used for the formal experiment. Four formal experiments were conducted at the same time, and the rest time of the mice on the rotarod was recorded.

[0069] The results of the resting time of mice on the rotating rod showed that the mice treated with MH extract and Rhodiola rosea showed a significant increase in time compared with the saline group (p≤0.05); the doses of MH extract and Rhodiola rosea showed extremely significant effects ( Figure 2 b).

[0070] 3. Suspension test

[0071] The Hanged test was conducted using a thin line. Mice were given MH extract (0.6 mg / kg), Rhodiola rosea extract (0.6 mg / kg), and saline (control group) by oral gavage for 22 consecutive days, with n=8 in each group. The test began 30 minutes after the last oral gavage. A thin line was hung on two iron frames, and the mouse was placed on the thin line. The mouse fell from the thin line due to exhaustion. The time it took for its forelimbs and hindlimbs to grab the thin line until it fell due to exhaustion was recorded. The test was carried out three times at the same time.

[0072] The experimental results are as follows Figure 2 As shown in c, in the hanging test, the mice treated with MH extract showed a significantly longer descent time than the mice in the normal group (p≤0.05). At the same time, the effect of MH extract was better than that of the positive control Rhodiola rosea.

[0073] 4. Tail suspension test (TST)

[0074] Mice were administered MH extract (0.6 mg / kg), Rhodiola rosea extract (0.6 mg / kg), and saline (control group) by oral gavage for 22 consecutive days, with n=8 in each group. TST was performed on the experimental animals 30 minutes after the last administration. The immobility time of each mouse was recorded for a duration of 6 minutes. TST was performed by placing in a quiet room, and the mice were hung upside down with their tails taped about 1 cm from the tip. The mice wanted to change their unusual body posture, but showed intermittent immobility after a period of time. The immobility time within 6 minutes was taken as the exhaustion time of the mice.

[0075] The experimental results are as follows Figure 2 As shown in a, the immobility time of the MH extract group was significantly lower than that of the control group (p≤0.05). In addition, the immobility time of the MH extract-treated mice was significantly shorter than that of the Rhodiola rosea-positive group (p≤0.05).

[0076] 5. Exhaustive Swim Test

[0077] The endurance of mice was evaluated by the weighted forced swimming test (WFST). Mice were administered with saline, Rhodiola rosea granules (0.6 g / kg), and MH extract (0.6 mg / kg) once a day for 22 days. Mice were taught to swim twice a week for 30 minutes each time. The animals were placed in a swimming pool (area 50 cm × 50 cm × 40 cm) with a water depth of 70 cm and a temperature of 30 ± 1 °C. The endurance of mice was measured from the start of swimming to fatigue, which was defined as the inability to return to the top within 10 seconds.

[0078] The experimental results are as follows Figure 2 As shown in e, in the forced swimming test, the swimming time of mice treated with MH extract and positive control Rhodiola rosea was significantly (p≤0.05) longer than that of animals in the control group.

[0079] 6. Determination of fatigue-related biomarkers

[0080] The mice were euthanized after the above 2. Rotarod test and 5. Exhaustive swimming test. Their liver, gastrocnemius muscle, and blood samples were taken. The blood samples were centrifuged at 2500 rpm for 10 minutes to obtain serum samples, which were then stored at -80 °C for further study. Fatigue-related biomarkers were assessed using commercially available kits, including blood lactate LD, lactate dehydrogenase LDH, malondialdehyde MDA, superoxide dismutase SOD, glutathione peroxidase GSH-Px, liver glycogen (HG), and muscle glycogen (MG).

[0081] 6.1 Determination of biomarkers related to lactate accumulation

[0082] Lactic acid LD is a key marker of anaerobic metabolism, and the accumulation of LD is an important cause of fatigue. Lactate dehydrogenase LDH is essential for the clearance of LD. Under standard conditions, lactate dehydrogenase is mainly present in muscle tissue; however, after prolonged exercise or fatigue, it can penetrate into the blood, resulting in high activity of lactate dehydrogenase in the blood. Therefore, LDH activity plays a key role in anti-fatigue effects and is also a key indicator for measuring anti-fatigue effects.

[0083] The experimental results are as follows Figure 3 As shown in a, during the rotarod test, the blood LD levels of mice in the MH extract group and the Rhodiola rosea group were significantly (p≤0.05) lower than those in the normal control mice. Figure 3 As shown in b, the LDH activity of mice in the MH extract group and the Rhodiola rosea group was significantly higher than that of the normal control mice (p≤0.05); compared with the Rhodiola rosea group, the LDH activity of mice treated with MH extract was also significantly increased (p≤0.05).

[0084] These results indicate that MH extract improved the diffusion of lactate dehydrogenase from muscle to blood and enhanced the activity of lactate dehydrogenase in the blood of mice, thereby accelerating the metabolism of lactate and reducing blood lactate levels.

[0085] 6.2 Determination of biomarkers related to free radical damage induced by exercise

[0086] It has been demonstrated that reactive oxygen species (ROS) play a crucial role in exercise-induced protein oxidation and contribute greatly to muscle fatigue. Excessive production of ROS can unbalance the redox state of cells and may lead to irreversible tissue damage. Therefore, the activities of antioxidant enzymes (superoxide dismutase SOD and glutathione peroxidase GSH-Px) and oxidative damage indicators (MDA content) in mouse serum were measured; malondialdehyde (MDA) is one of the end products of membrane lipid peroxidation, and its content can be used as one of the indicators to examine the severity of cell stress, and its main damage is to cause membrane lipid peroxidation).

[0087] The experimental results of the rotating rod test are as follows Figure 4 As shown. In the rotating rod test, the serum MDA content of the mice treated with Rhodiola rosea and MH extracts was much lower than that of the control group, showing a significant difference (3a); and in the rotating rod test, the MDA content in the blood of the mice treated with MH extract was lower than that of the mice treated with Rhodiola rosea. In addition, in the rotating rod test, the SOD and GSH-Px activities of the mice treated with MH extract and Rhodiola rosea were higher than those of the control group, also showing a significant difference ( Figure 4 b, 4c).

[0088] The results of the exhaustive swimming test are as follows Figure 5 As shown. In the exhaustive swimming test, the serum MDA content of the mice treated with Rhodiola rosea and MH extracts was also much lower than that of the control group, showing a significant difference. In the exhaustive swimming test, the MDA content in the blood of the mice treated with MH extract was lower than that of the mice treated with Rhodiola rosea ( Figure 5 a). In addition, in the exhaustive swimming test, the SOD and GSH-Px activities of the mice groups treated with MH extract and Rhodiola rosea were higher than those of the control group, showing a significant difference ( Figure 5 b, 5c).

[0089] These results indicated that the MH extract-treated mouse group reduced the oxidative level mainly by increasing the activities of the antioxidant enzymes SOD and GSH-Px.

[0090] 6.3 Effects on liver glycogen (HG) and muscle glycogen (MG) concentrations

[0091] The experimental results are as follows Figure 6a, 6b. When liver glycogen and muscle glycogen concentrations were measured in an exhaustive swimming test, the liver glycogen and muscle glycogen levels in the MH extract and Rhodiola rosea treatment groups were significantly increased relative to normal control mice (p≤0.05). In this study, the results showed that mice in the control group that swam for a longer time consumed more glycogen to provide sufficient power for swimming. Mice in the MH extract treatment group also consumed more HG and MG compared to the positive control Rhodiola rosea.

[0092] These results suggest that intragastric administration of MH extract can increase the storage of MG and HG, thereby enhancing the anti-fatigue ability of mice.

[0093] Based on the above experimental results, MH extract shows outstanding anti-fatigue activity. Its excellent anti-fatigue ability can be explained by at least the following three reasons: first, it reduces the accumulation of lactic acid, thereby delaying the occurrence of fatigue or accelerating the recovery of fatigue; second, MH extract reduces the oxidation level and lipid peroxidation MDA in mice by increasing the activity of SOD and GSH-Px; finally, it can enhance the storage of muscle glycogen for more intense exercise. MH extract can increase the activity of glutathione peroxidase in mice and the activity of defensive antioxidant enzymes, thereby reducing reactive oxygen and preventing irreversible tissue damage, which helps to fight fatigue. MH extract has excellent anti-fatigue activity and has the potential for development and utilization.

[0094] Example 3 Evaluation of the anti-fatigue effect of Boeravinone A, B, and E in vivo

[0095] The main components of Himalayan Mirabilis jalapa extract are Boeravinone A, B, and E, which were purchased from Beijing BetterKang Biotechnology Co., Ltd. with a purity of more than 98%.

[0096] The exhaustive swimming test model was used for evaluation, and experiments on glycogen levels were conducted on tissues. All compounds were administered by single tail vein injection. The test compounds (Boeravinone A, B, E) and positive drug (adenosine) groups were administered at 5 mg / kg body weight, respectively. The blank group was saline. 0.5 h after administration or saline, each group of mice was subjected to 5. Exhaustive swimming test in Example 2. After WFST, the mice were euthanized, and their liver and gastrocnemius muscle samples were immediately removed. Glycogen analysis was performed in liver tissue and gastrocnemius muscle tissue.

[0097] To verify that Boeravinone A, B, and E, the representative compounds in the Himalayan Mirabilis jalapa extract, are pharmacological substances, the anti-fatigue activities of the three components were evaluated in in vivo behavioral experiments and biochemical index tests.

[0098] The results of the fatigue swimming pharmacology model experiment are as follows Figure 7 Compared with the blank control group and the positive drug adenosine group, the Boeravinone A, B and E test groups all showed significant anti-fatigue effects in the fatigue swimming pharmacological model ( Figure 7 a). The anti-fatigue activity of Boeravinone A and E is significantly better than that of the positive drug adenosine, while the anti-fatigue effect of Boeravinone B is similar to that of the positive drug.

[0099] The liver and gastrocnemius muscles of mice after exhaustive swimming were taken and the glycogen content of each group was measured after tissue grinding. The experimental results are as follows: Figure 7 b, 7c. Boeravinone A, B and E have the effect of maintaining the energy reserve in the body and reducing the degradation of liver glycogen (HG) and muscle glycogen (MG). These results show that MH extract can increase the storage of MG and HG, thereby enhancing the anti-fatigue ability of mice.

[0100] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. Application of Himalayan Mirabilis jalapa (MH) extract in the preparation of drugs for anti-fatigue, vital energy replenishment, and prevention and treatment of deficiency syndromes.

2. The use according to claim 1, characterized in that: The preparation method of the Himalayan Mirabilis jalapa (MH) extract comprises the following steps: using the root of the Himalayan Mirabilis jalapa as a raw material, extracting with a solvent, and concentrating the root to obtain the Himalayan Mirabilis jalapa (MH) extract; Preferably, the preparation method of the Himalayan Mirabilis jalapa (MH) extract is: using the root of Himalayan Mirabilis jalapa as a raw material, extracting with a solvent, and concentrating and removing the solvent to obtain the Himalayan Mirabilis jalapa (MH) extract; Preferably, the solvent is selected from one, two or more of water, methanol, ethanol, chloroform, dichloromethane, acetonitrile, etc.; preferably, a mixed solvent of water and methanol, such as 75% methanol, 50% methanol, 25% methanol; Preferably, the extraction method is selected from ultrasonic extraction, reflux extraction, immersion extraction and the like.

3. The use according to claim 1 or 2, characterized in that: Himalayan Mirabilis jalapa (MH) extract can replenish vitality, fight fatigue, and prevent and treat deficiency symptoms in any one or more of the following ways: 1) Reduce the lactic acid LD content, 2) Increase the content of lactate dehydrogenase LDH; 3) Reduce the content of malondialdehyde (MDA); 4) Increase the content of superoxide dismutase SOD; 5) Increase the content of glutathione peroxidase GSH-PX; 6) Increase liver glycogen (HG) content; 7) Increase muscle glycogen (MG) content.

4. The use according to any one of claims 1 to 3, characterized in that: The administration method of the Himalayan Mirabilis jalapa (MH) extract is selected from: oral administration and injection administration.

5. Use of a pharmaceutical composition in the preparation of a drug for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes; the pharmaceutical composition comprises the Himalayan Mirabilis jalapa (MH) extract according to any one of claims 1 to 4; Preferably, the pharmaceutical composition may further comprise a pharmaceutically acceptable excipient. Preferably, the pharmaceutical composition may further comprise other components having the effects of replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes.

6. Use of the compound represented by formula I in the preparation of drugs for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes; in, R1-R6 are the same or different and are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, OH, amino, nitro, cyano; m is selected from any natural number between 0 and 4, such as 0, 1, 2, 3, 4; Preferably, the C1-6 alkyl group and the C1-6 alkoxy group are C1-4 alkyl group and C1-4 alkoxy group; for example, methyl group, methoxy group, ethyl group, ethoxy group and the like.

7. The use according to claim 6, characterized in that: Halogen is fluorine, chlorine, bromine, iodine; and / or, R1 is hydroxyl; and / or, R2 is methyl; and / or, R3 is hydroxyl; and / or, R4 is hydrogen; and / or, R6 are each independently selected from hydrogen, hydroxyl; and / or, m is selected from 0 or 1; And / or, R5 is hydroxyl or methoxy.

8. The use according to claim 6 or 7, characterized in that: The compound represented by formula I is selected from the following compounds:

9. The use according to any one of claims 6 to 8, characterized in that: The compound shown in Formula I can replenish vital energy, resist fatigue, and prevent and treat deficiency syndromes by any one or more of the following methods: 1) Increase liver glycogen (HG) content; 2) Increase muscle glycogen (MG) content; And / or, the administration method of the compound represented by Formula I is selected from: oral administration, injection administration (such as intravenous injection).

10. Use of a pharmaceutical composition in the preparation of drugs for replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes; the pharmaceutical composition comprises the compound represented by the above formula I. According to an embodiment of the present invention, the pharmaceutical composition may further comprise a pharmaceutically acceptable excipient. According to an embodiment of the present invention, the pharmaceutical composition may further comprise other components having the effects of replenishing vital energy, resisting fatigue, and preventing and treating deficiency syndromes.

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