Use of pyrroloquinoline quinone for inhibiting iron imbalance and preparation of an iron imbalance inhibiting drug

Abstract

The application discloses application of pyrroloquinoline quinone in inhibition of iron imbalance and preparation of an iron imbalance inhibition drug, the pyrroloquinoline quinone can be used as an iron homeostasis regulator or an iron imbalance inhibitor, can significantly maintain iron homeostasis in cells and / or tissue organs, inhibits iron imbalance in cells and / or tissue organs, and provides a new choice for research and development of safe and efficient iron homeostasis regulator and / or iron imbalance inhibitor related drugs.

Description

Technical Field

[0001] This invention specifically relates to the application of pyrroloquinoline quinone in inhibiting iron imbalance and in the preparation of iron imbalance inhibitory drugs, which can effectively inhibit iron imbalance and achieve regulation and improvement of iron homeostasis. Background Technology

[0002] Iron, as an essential trace element, plays a crucial role in oxygen transport. However, excessive Fe... 2+ Accumulation of iron can disrupt the redox system, leading to ferroptosis and contributing to aging and the development of various related diseases. Ferritin plays a crucial role in maintaining iron homeostasis by storing excess cellular iron. Ferritin is composed of ferritin heavy chains (FTH) and ferritin light chains (FTL). Abnormal expression of FTH and FTL can lead to the release of free iron within the cell. 2+ A sharp increase in reactive oxygen species and lipid peroxidation products leads to cell death and disease. Furthermore, research has found that activation of nuclear factor erythrocyte-associated factor 2 (Nrf2) plays a crucial role in regulating ferritin expression and maintaining iron homeostasis. Increasing evidence suggests that iron imbalance is involved in the development of various diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, acute liver and kidney injury, rhabdomyolysis, cardiovascular diseases, Parkinson's disease, sarcopenia, and cancer. Iron imbalance can also be induced by various compounds; for example, erastin or the clinical drug sorafenib can induce cellular iron imbalance and trigger ferroptosis. Therefore, in clinical practice, regulating iron homeostasis and inhibiting iron imbalance can not only effectively alleviate iron imbalance-related diseases but also reduce drug side effects. The development of highly effective iron homeostasis regulators and iron imbalance inhibitors will bring unprecedented opportunities for the treatment of these diseases.

[0003] Known iron imbalance inhibitors are mainly used in in vitro cell experiments, but their stability and efficacy in animals are insufficient. Typical iron imbalance inhibitors, such as Ferrostatin-1 (Fer-1), can inhibit ferroptosis caused by iron imbalance in RSL3 or Erastin-induced HT-1080 cells, but Fer-1 is metabolically unstable in vivo, resulting in poor inhibitory effects. While the iron imbalance inhibitor Liproxstatin-1 (Lip-1) has greater stability, its safety and efficacy are still far from clinical application standards. Therefore, the screening and development of iron homeostasis regulators and iron imbalance inhibitors has become one of the hot topics and challenges in related research fields. Thus, developing more effective and safer iron homeostasis regulators and iron imbalance inhibitors and their drugs for the treatment of diseases caused by iron imbalance is of great significance.

[0004] Recently, nutritional interventions for iron imbalance have gained popularity among researchers due to their safety, reliability, and ease of use. Pyrroloquinoline quinone (PQQ) is an essential nutrient for animal reproduction, growth, and development, and is also considered a bioactive substance with the strongest catalytic redox reaction capability. Its structural formula is as follows: Figure 1 PQQ is widely distributed in nature and is abundant in food sources. With a molecular weight of only 330, PQQ possesses unique physicochemical properties, exhibiting high thermal stability and water solubility, making it easily absorbed. A 90-day subchronic toxicity study found that rats supplemented with a maximum daily dose of 600 mg / kg of PQQ showed no significant abnormalities or changes in hematology, clinical chemistry, neurological assessments, thyroid function, reproductive hormone levels, sperm evaluation, vaginal cytology, endocrine function, organ weight, or pathology, indicating that PQQ has broad-spectrum safety for human consumption. Furthermore, PQQ's potent effects in scavenging free radicals, antioxidation, inhibiting inflammatory responses, regulating mitochondrial function and energy metabolism, nutrition, and promoting growth suggest promising applications and a broad market potential in medicine, food, and agriculture. However, there are no reports on the application of PQQ in regulating iron homeostasis, inhibiting iron imbalance, or in its drug preparation. Summary of the Invention

[0005] The purpose of this invention is to provide the application of pyrroloquinoline quinone in regulating iron homeostasis and in the preparation of drugs for regulating iron homeostasis, so as to solve the above-mentioned problems and put pyrroloquinoline quinone into new uses, while disclosing the role of pyrroloquinoline quinone in the treatment of diseases caused by iron imbalance.

[0006] The technical solution of the present invention is as follows:

[0007] One of the objectives of this invention is to provide the application of pyrroloquinoline quinone in inhibiting iron imbalance. The pyrroloquinoline quinone is an iron imbalance inhibitor that can effectively inhibit iron imbalance and tissue fibrosis induced by excessive exercise, and maintain the normal expression levels of ferritin FTH, FTL and nuclear factor erythrocyte-associated factor 2 (Nrf2).

[0008] Furthermore, the iron imbalance refers to an iron imbalance in cells and / or tissues and organs.

[0009] Furthermore, the iron imbalance is motion-induced iron imbalance.

[0010] The present invention further provides the use of pyrroloquinoline quinone in the preparation of therapeutic drugs for diseases caused by iron imbalance. The pyrroloquinoline quinone, as an iron imbalance inhibitor, can be used in or used to prepare therapeutic drugs for diseases caused by iron imbalance and related diseases, including but not limited to renal / hepatic / cardiac ischemia-reperfusion, neurodegenerative diseases, or acute liver and kidney injury.

[0011] Furthermore, the iron imbalance refers to an iron imbalance in cells and / or tissues and organs.

[0012] Furthermore, the iron imbalance is motion-induced iron imbalance.

[0013] The present invention also provides the use of pyrroloquinoline quinone in the preparation of iron homeostasis-regulating drugs, wherein the pyrroloquinoline quinone is an iron homeostasis regulator.

[0014] Furthermore, the iron homeostasis is the iron homeostasis of cells and / or tissues and organs.

[0015] Furthermore, the iron homeostasis refers to the iron homeostasis during the movement process and / or the iron homeostasis related to the expression of ferritin and nuclear factor erythrocyte-associated factor 2.

[0016] Furthermore, the drug contains a pharmaceutically acceptable carrier or excipient, and for mammals, the drug dosage is 10 mg / kg·d.

[0017] Compared with existing technologies, the beneficial effects of this invention are as follows: the highly safe nutritional factor pyrroloquinoline quinone in this invention can effectively inhibit iron imbalance induced by excessive exercise, maintain the normal expression levels of ferritin FTH, FTL and nuclear factor erythrocyte-associated factor 2 (Nrf2), avoid iron imbalance caused by decreased expression of FTH, FTL and Nrf2, and has excellent iron imbalance inhibition effect. At the same time, pyrroloquinoline quinone can significantly inhibit exercise-induced myocardial fibrosis; providing a new option for the development of safe and efficient iron homeostasis regulators and iron imbalance inhibitors. Attached Figure Description

[0018] Figure 1 This is a diagram showing the results of PQQ regulating iron steady state and significantly suppressing typical characteristics of iron imbalance in the embodiment;

[0019] Among them, (A): PQQ significantly inhibited Fe 2+ (B): PQQ significantly inhibited the excessive accumulation of malondialdehyde (MDA), a lipid peroxidation product induced by iron imbalance; NC: normal control group; E: excessive exercise-induced iron imbalance group; ME: excessive exercise-induced iron imbalance + 10 mg / kg / day PQQ intervention group; ##P<0.01, vs. NC group; *P<0.05, **P<0.01, vs. E group;

[0020] Figure 2 This is a graph showing the results of PQQ significantly inhibiting the decrease in ferritin expression levels in the examples;

[0021] Among them, (A): PQQ significantly inhibited the decrease in ferritin heavy chain (FTH) expression level; (B): PQQ significantly inhibited the decrease in ferritin light chain (FTL) expression level; NC: normal control group; E: excessive exercise-induced iron imbalance group; ME: excessive exercise-induced iron imbalance + 10 mg / kg / day PQQ intervention group; ##P<0.01, vs. NC group; **P<0.01, vs. E group;

[0022] Figure 3 This is a graph showing the results of PQQ significantly inhibiting the decrease in Nrf2 protein expression levels in the examples;

[0023] Among them, NC: normal control group; E: excessive exercise-induced iron imbalance group; ME: excessive exercise-induced iron imbalance + 10mg / kg / day PQQ intervention group; ##P<0.01, vs. NC group; **P<0.01, vs. E group;

[0024] Figure 4 This is a diagram showing the results of PQQ significantly inhibiting movement-induced tissue fibrosis in the examples;

[0025] Among them, NC: normal control group; E: excessive exercise-induced iron imbalance group; ME: excessive exercise-induced iron imbalance + 10mg / kg / day PQQ intervention group. Detailed Implementation

[0026] To illustrate the possible application scenarios, technical principles, implementable specific solutions, and achievable objectives and effects of this application in detail, the following description, in conjunction with the listed specific embodiments and accompanying drawings, provides a detailed explanation. The embodiments described herein are merely illustrative of the technical solutions of this application and are therefore intended to limit the scope of protection of this application.

[0027] Unless otherwise defined, the technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0028] In this invention, the term "PQQ" refers to pyrroloquinoline quinone;

[0029] In this invention, the term "FTH" refers to ferritin heavy chain;

[0030] In this invention, the term "FTL" refers to ferritin light chain;

[0031] In this invention, the term "MDA" refers to malondialdehyde.

[0032] In this invention, the term "Nrf2" refers to nuclear factor erythroid 2-like 2.

[0033] The reagents used in this invention and their sources are shown in Table 1;

[0034] The main instruments used in this invention and their sources are shown in Table 2;

[0035] Table 1. Main reagents and their sources

[0036]

[0037]

[0038] Table 2. Main Instruments and Their Sources

[0039]

[0040]

[0041] The preparation methods for the main solutions used in the following examples are as follows:

[0042] (1) PQQ: Prepare a 2μM stock solution with ultrapure water, dispense it, store at -20℃, and dilute to the required concentration before use;

[0043] (2) 0.01mol / L PBS: KCl 0.20g, NaCl 8.00g, KH2PO4 0.24g, Na2HPO4·12H2O 2.9g, pH adjusted to 7.2, add ddH2O to bring the volume to 1L;

[0044] (3) 1M Tris-HCl (pH 6.0, 6.8, 8.0): Dissolve 121.1g Tris in deionized water, adjust the pH, and bring to volume.

[0045] (4) 30% (W / V) polyacrylamide: 290g acrylamide dissolved in ddH2O, diluted to 1L, filtered through a 0.45μM filter membrane, dispensed into brown bottles, and stored at 4℃;

[0046] (5) SDS-PAGE buffer (5×): Bromophenol Blue 25mg, SDS 0.5g, 1M Tris-HCl (pH 6.8) 1.25mL, Glycerol 2.5mL, dissolved in deionized water, brought to a final volume of 5mL, dispensed, stored at 4℃, and added 50μL 2-mercaptoethanol / 1mL (2-ME) before use;

[0047] (6) Transfer buffer (1×Transfer Buffer): Glycine 2.9g, SDS 0.37g, Tris 5.8g, dissolved in ddH2O, and diluted to 1L with an appropriate amount of methanol;

[0048] (7) TBST solution (10×): NaCl 8.8g, 1M Tris-HCl (pH 8.0) 20ml, dissolved in H2O, add 500μL L between 20, make up to 1L, store at 4℃;

[0049] (8) Blocking solution: TBST solution + 55% BSA.

[0050] Example 1

[0051] In this embodiment, pyrroloquinoline quinone is applied to inhibit motility-induced iron imbalance in cells and / or tissues and organs; a typical characteristic of iron imbalance is that tissue iron overload leads to lipid peroxidation. Therefore, this embodiment observes the iron content in tissues... 2+ The effects of pyrroloquinoline quinone were verified by changes in concentration and lipid peroxidation product MDA; the specific experimental methods are as follows:

[0052] (1) 28 SPF mice (purchased from Shanghai Slack Laboratory Animal Co., Ltd.) were selected and housed in cages according to national standards, with 5 mice per cage. The relative humidity was maintained at 45-55%, the room temperature was 22±2℃, and the mice had free access to food and water. They were fed under 12 hours of light per day and were given an acclimatization period of 1 week before the formal experiment.

[0053] (2) Before the experimental intervention, mice were given an adaptive swimming period of 20 minutes each day for three days, and mice that were not adapted to swimming were eliminated.

[0054] (3) The remaining 24 mice were randomly divided into three groups according to their body weight, with 8 mice in each group: normal control group (NC group), excessive exercise-induced ferroptosis group (E group), and excessive exercise-induced ferroptosis + PQQ intervention group (ME group).

[0055] (4) Excessive exercise and PQQ intervention: The ME group was given 10 mg / kg of PQQ by gavage every morning, while the NC and E groups were given an equal volume of physiological saline by gavage. The NC group did not receive exercise intervention. The mice in the other two groups were given lead weights of 3% of their body weight on their tails and were put into a plastic barrel with a height of 60 cm, a diameter of 55 cm, a water depth of 40 cm, and a water temperature of 32±2℃ for exhaustive swimming exercise (each time should be no less than 2 hours). During this period, the animals' physical condition was carefully observed. If any abnormal behavior was found, the animals were immediately taken out of the water, their fur was dried, and they were prevented from drowning or getting sick. The supplementation and exercise intervention continued for 2 weeks, 6 days / week, with a 1-day rest in between. The exhaustion time on the last day was recorded.

[0056] The criteria for judging exhaustion are: the mouse’s head sinks for more than 10 seconds in three consecutive consecutive times and cannot emerge from the water; after being pulled out, it is unable to support its body and cannot complete the righting reflex.

[0057] (5) After blood collection, the thoracic cavity of the mouse is opened and sterile saline is infused using a perfusion instrument. The success is indicated by the outflow of bloodless liquid. The heart tissue of the mouse is removed, washed again with saline, and excess water is absorbed by filter paper. After being flash-frozen in liquid nitrogen, it is transferred to an ultra-low temperature freezer at -80℃ for later use.

[0058] (6) Organize free Fe 2+ The activity assay kit for MDA was purchased from Nanjing Jiancheng, and the assay was performed strictly in accordance with the kit instructions.

[0059] like Figure 1 As shown, compared to the normal control group, excessive exercise led to increased tissue Fe... 2+ The MDA concentration increased sharply, and PQQ intervention at 10 mg / kg / day significantly alleviated these changes, indicating that excessive exercise induces tissue iron imbalance, while PQQ at 10 mg / kg / day can significantly inhibit iron imbalance, with excellent effect. This further demonstrates that pyrroloquinoline quinone in this invention can effectively inhibit iron imbalance induced by excessive exercise, thereby regulating iron homeostasis in cells and / or tissues and organs. Pyrroloquinoline quinone can be used to prepare therapeutic drugs for diseases caused by iron imbalance.

[0060] Example 2

[0061] Ferritin plays a central role in maintaining iron homeostasis and inhibiting iron imbalance by storing excess cellular iron. Therefore, in this embodiment, the protein expression levels of ferritin heavy chain (FTH) and ferritin light chain (FTL) were measured to verify the role of pyrroloquinoline quinone in inhibiting exercise-induced iron imbalance in cells and / or tissues and organs. The specific experimental methods are as follows:

[0062] (1) The grouping, intervention, and material collection of experimental animals were the same as in Example 1;

[0063] (2) Extract total protein;

[0064] ①Tissue lysis: Weigh 20mg of heart tissue, add 300uL of RIPA lysis buffer (with added PMSF protease inhibitor), cut on ice, grind the tissue with a manual grinder, and let stand on ice for 5min;

[0065] ② Centrifugation: 4℃, 13500r, 10min;

[0066] ③ Collect the supernatant: Transfer the protein supernatant into a new EP tube;

[0067] ④ Preparation of standard curve: Dilute 25 mg / mL BSA to 1 mg / mL, and add 0, 1, 2, 4, 8, 10, 12, 16, and 20 μL of BSA (1 mg / mL) to each well of a 96-well plate, respectively. Then add PBS to make the total volume 20 μL, resulting in final BSA concentrations of 0, 1, 2, 4, 8, 10, 12, 16, and 20 μg. Add 1 μL of the protein to be tested to each sample well, and repeat for two wells. Prepare BCA working solution at a ratio of 50:1 (reagent A: reagent B). Add 180 μL of BCA working solution to each well of the standard curve and 190 μL of BCA working solution to each well of the sample plate, for a final volume of 200 μL per well. Incubate at 37°C for 30 min.

[0068] ⑤ Determine protein concentration: Place the 96-well plate into the microplate reader, select the BCA assay option, measure the absorbance (OD value) at a wavelength of 562 nm, obtain the curve equation, and calculate the protein concentration.

[0069] ⑥ Prepare protein loading buffer: Calculate the required protein volume, the protein amount is 4 mg / uL, add 5X protein loading buffer, and make up the final volume with PBS to 200 uL, mix thoroughly; use a regular PCR instrument, 99℃ for 10 min, and store at -80℃ for later use;

[0070] (3) SDS-PAGE electrophoresis;

[0071] ① Prepare clean Western blot glass plates and combs. Use a frame to clamp the glass plates and fix them on the glue applicator.

[0072] ② Gel preparation: Prepare the lower separating gel, pour it into a glass plate, add 500uL of isopropanol, press the liquid, let it stand for about 20 minutes, pour off the isopropanol, wash the isopropanol in the plate with running water, and absorb the excess water with filter paper; prepare the upper concentrating gel as shown in Table 1-9, pour it into a glass plate, insert a comb, and let it stand for about 20 minutes.

[0073] ③ Electrophoresis: Place the glass plate in the inner electrophoresis tank, pour in the freshly prepared SDS-PAGE electrophoresis buffer, carefully remove the comb, add the protein sample, add the markers to both ends of the sample, and fill the outer electrophoresis tank with electrophoresis buffer; adjust the electrophoresis apparatus to S1 program, 80V, 20min, then switch to S2 program, 120V, 60min, the end sign is when the blue protein on the buffer reaches the bottom of the gel;

[0074] ④ Transfer: Remove the glass plate from the electrophoresis tank, separate the glass plate with a plate lifter, and remove excess gel as needed; pour methanol into a small box, place the PVDF membrane in, and activate for 1 min; pour transfer buffer into the tray, place the sandwich clamp with the black plate facing down, wet the sponge, wet the 4 pre-prepared filter papers and place them on the sponge, place the gel on the filter paper, cover with the PVDF membrane, and then cover with 4 more wet filter papers. Use a small roller to remove air bubbles, cover the filter paper with a sponge, align and assemble the sandwich clamp, place it in the transfer tank, 400mA, 30 min;

[0075] ⑤ Washing the membrane: Transfer the membrane to a small box with the front side facing up, pour in an appropriate amount of TBST washing solution, shake on a shaker for 10 minutes, and repeat three times;

[0076] ⑥ Blocking: Pour in an appropriate amount of 5% BSA blocking solution, shake on a shaker, for 2 hours;

[0077] ⑦ Washing the membrane: Pour in an appropriate amount of TBST washing solution, shake on a shaker for 10 minutes, and repeat three times;

[0078] ⑧ Primary antibody incubation: Wrap the PVDF membrane with plastic wrap, cut the target band as needed, place it in the prepared primary antibody solution, and incubate overnight at 4°C on a shaker.

[0079] ⑨ Washing the membrane: Pour in an appropriate amount of TBST washing solution, shake on a shaker for 10 minutes, and repeat three times;

[0080] ⑩ Secondary antibody incubation: Use a fluorescent secondary antibody compatible with the primary antibody, at room temperature, on a shaker, for 2 hours;

[0081] Washing membrane: Pour in an appropriate amount of TBST washing solution, shake on a shaker for 10 minutes, repeat three times;

[0082] Scanning: Transfer the PVDF film to a dual-color infrared laser imager, scan it, and save the image;

[0083] (4) Data statistics are the same as in Example 1;

[0084] like Figure 2 As shown, Western blot data revealed that excessive exercise significantly reduced the levels of FTH and FTL proteins in tissues; however, supplementation with 10 mg / kg / day of PQQ significantly reversed this reduction. This indicates that PQQ can significantly inhibit iron imbalance by suppressing the decrease in ferritin, maintain the expression levels of FTH and FTL proteins in tissues, and thus regulate iron homeostasis in cells and / or tissues and organs. Pyrroloquinoline quinone can be used as an iron imbalance inhibitor in the preparation of drugs for the treatment of diseases caused by iron imbalance due to decreased ferritin, or as an iron homeostasis regulator in the preparation of drugs for regulating iron homeostasis.

[0085] Example 3

[0086] Activation of nuclear factor erythrocyte-associated factor 2 (Nrf2) plays an important role in regulating ferritin expression and maintaining iron homeostasis. In this example, the expression level of the key protein Nrf2 was measured to verify the role of pyrroloquinoline quinone in regulating iron homeostasis of cells and / or tissues and organs during movement. The specific experimental method is as described in Example 2.

[0087] The results are as follows Figure 3 As shown, Western blot data revealed that excessive exercise significantly reduced myocardial Nrf2 protein levels; however, supplementation with 10 mg / kg / day of PQQ significantly reversed this reduction. This indicates that PQQ can significantly inhibit ferroptosis by suppressing the decrease in Nrf2 and maintain a stable expression level of myocardial Nrf2 protein. Therefore, pyrroloquinoline quinone can be used as an iron imbalance inhibitor in the preparation of drugs for treating diseases caused by iron imbalance due to decreased ferritin levels, or as an iron homeostasis regulator in the preparation of drugs for regulating iron homeostasis.

[0088] Example 4

[0089] Tissue fibrosis refers to the disordered repair response after tissue injury, characterized by an increase in fibrous connective tissue within organs. In this embodiment, microscopic images were used to observe changes in myocardial fibrosis in tissues to verify the role of pyrroloquinoline quinone in inhibiting exercise-induced myocardial fibrosis. The specific experimental method is as follows.

[0090] (1) The grouping and intervention of experimental animals were the same as in Example 1;

[0091] (2) After blood collection, the thoracic cavity of the mice was opened and sterile saline was infused using a perfusion instrument. The success was determined by the outflow of bloodless liquid. The heart tissue of the mice was removed and washed again with saline. The excess water was absorbed by filter paper. Some heart tissue was used for Masson staining and fixed in EP tubes pre-filled with 4% paraformaldehyde.

[0092] (3) Paraffin section preparation and staining

[0093] Preparation of sections:

[0094] ① Embedding: Fresh heart tissue was placed in 4% paraformaldehyde and fixed for 24 hours. Then, the tissue was embedded in paraffin using conventional histopathological methods.

[0095] ② Sectioning: Use a paraffin microtome to cut the wax block into 4µm thin slices, unfold the slices, transfer them to glass slides, mount and bake the slides, and store at room temperature for later use;

[0096] ③ Dewaxing: sequentially pass through xylene I for 20 min; xylene II for 20 min; anhydrous ethanol I for 15 min; anhydrous ethanol II for 15 min; 75% alcohol for 5 min, followed by rinsing with running water;

[0097] Masson staining:

[0098] ①Immerse the slices completely in Masson A solution overnight, then rinse with running water;

[0099] ② Place the slices in the mixed solution (Masson B solution and Masson C solution in a 1:1 ratio), soak for 1 minute, rinse with running water, differentiate with 1% hydrochloric acid alcohol, and rinse with running water;

[0100] ③Immerse in Masson E solution for 1 minute, no rinsing required;

[0101] ④ Drain the liquid from the slices slightly and place them directly into Masson F stain for 30 seconds;

[0102] ⑤ Anhydrous ethanol III, 5 min; xylene, 5 min; neutral resin mounting;

[0103] ⑥ Microscope image acquisition;

[0104] The results are as follows Figure 4 Masson staining images of paraffin sections showed that excessive exercise induced myocardial fibrosis; however, supplementation with 10 mg / kg / day of PQQ significantly reduced myocardial fibrosis, indicating that PQQ can significantly inhibit exercise-induced tissue fibrosis by suppressing iron imbalance. Therefore, pyrroloquinoline quinone can be used as an iron imbalance inhibitor in the preparation of drugs for the treatment of diseases caused by iron imbalance.

[0105] In summary, PQQ can effectively regulate iron homeostasis, inhibit iron imbalance, decreased ferritin expression, and related tissue fibrosis and diseases, and can be used to prepare drugs that combat iron imbalance, decreased ferritin expression, and related tissue fibrosis and diseases.

[0106] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural or procedural transformations made based on the content of the present invention specification, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. The use of pyrroloquinoline quinone in the preparation of drugs that inhibit exercise-induced myocardial fibrosis, wherein the pyrroloquinoline quinone is an iron imbalance inhibitor.

2. The application of pyrroloquinoline quinone in the preparation of drugs for maintaining iron homeostasis, wherein the pyrroloquinoline quinone is an iron homeostasis regulator.

3. The application according to claim 2, characterized in that, The iron stability refers to the iron stability of cells and / or tissues and organs.

4. The application according to claim 2, characterized in that, The iron homeostasis refers to the iron homeostasis during the movement process and / or the iron homeostasis related to the expression of ferritin and nuclear factor erythrocyte-associated factor 2.

5. The application according to claim 1 or 2, characterized in that, The drug contains a pharmaceutically acceptable carrier or excipient, and for mammals, the drug dose is 10 mg / kg·d.

Images