Use of plantain fruit extract in preparation of anticoagulant or antithrombotic drugs

Abstract

This invention relates to the field of biomedicine, specifically to the application of banana fruit extract in the preparation of anticoagulant or antithrombotic drugs. The banana fruit extract provided by this invention contains flavonoids, polyphenols, polysaccharides, hydroxyanthraquinones, triterpenoids, and other components. Flavonoids and polyphenols have been widely proven to have anti-inflammatory and antioxidant effects, which can synergistically enhance the anticoagulant effect. The high potassium content of banana fruit can indirectly improve vascular function by regulating sodium-potassium balance. The banana fruit extract provided by this invention can inhibit platelet production or promote platelet metabolism, prolong clotting time, and inhibit platelet aggregation. Its natural plant components interfere with platelet aggregation by inhibiting the production of thromboxane A2, achieving anticoagulant and antithrombotic effects. The mechanism of action of banana fruit extract differs from traditional anticoagulants such as heparin, reducing the risk of bleeding. Its natural component characteristics provide a direction for the development of novel plant-derived anticoagulant drugs.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to the application of banana fruit extract in the preparation of anticoagulant or antithrombotic drugs. Background Technology

[0002] Garlic, ginkgo leaves, and natto are among the most studied natural anticoagulant components. Garlic contains allicin and other sulfides that reduce clotting factors (such as fibrinogen) in the blood and inhibit platelet aggregation, thus reducing thrombus formation and preventing atherosclerosis and hypertension. Ginkgo leaves contain flavonoids and terpene lactones that can inhibit thrombin activity, promote fibrinolysis, and improve microcirculation; their anticoagulant effect is considered comparable to some modern drugs (such as warfarin). Natto (fermented soybeans) contains nattokinase, which directly breaks down fibrin, reduces clotting factor levels (such as prothrombin and fibrinogen), and significantly reduces the risk of cardiovascular disease; Japanese research suggests it may replace traditional anticoagulant drugs.

[0003] The advantage of natural ingredients is multi-target synergy, low risk of bleeding, and fewer side effects, making them suitable for long-term prevention (such as cardiovascular health). Banana (Musapientum) fruit extract can significantly inhibit pro-inflammatory cytokines and chemokines, and can be used for anti-inflammatory purposes, but there are currently no reports on the anticoagulant activity of banana fruit extract. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides the application of banana fruit extract in the preparation of anticoagulant or antithrombotic drugs. This invention reveals that banana fruit extract possesses significant anticoagulant activity, and its mechanism of action is closely related to the inhibition of thromboxane A2 formation, providing a new research direction for the development of natural anticoagulant drugs.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] This invention provides the application of banana fruit extract in the preparation of anticoagulant products.

[0007] Preferably, the banana fruit extract contains flavonoids, polyphenols, polysaccharides, enolone, hydroxyanthraquinone, triterpenoids, diterpenoids, steroids, potassium, sodium, lupinone, selenium, anthraquinones, palmitic acid, β-sitosterol, amino acids, coumarins, and saponins.

[0008] Preferably, the anticoagulant product inhibits platelet production or promotes platelet metabolism.

[0009] Preferably, the anticoagulant product inhibits platelet aggregation induced by arachidonic acid and collagen.

[0010] Preferably, the anticoagulant product inhibits the formation of thromboxane A2 and has no effect on the formation of cAMP and cGMP.

[0011] Preferably, the product includes a drug.

[0012] This invention provides the application of banana fruit extract in the preparation of antithrombotic drugs.

[0013] Preferably, the antithrombotic drug inhibits the formation of thromboxane A2.

[0014] Preferably, the antithrombotic drug inhibits platelet production or promotes platelet metabolism.

[0015] This invention provides an anticoagulant drug, the active ingredient of which includes banana fruit extract; the unit dose of the banana fruit extract in the drug is a dilution of 1 / 1000-1 / 2000 times.

[0016] Beneficial effects:

[0017] This invention provides the application of banana fruit extract in the preparation of anticoagulant products. The banana fruit extract provided by this invention contains flavonoids, polyphenols, polysaccharides, hydroxyanthraquinones, triterpenoids, and other components. Among these, flavonoids and polyphenols have been widely proven to have anti-inflammatory and antioxidant effects, which can synergistically enhance the anticoagulant effect. The high potassium content of banana fruit can indirectly improve vascular function by regulating sodium-potassium balance. The banana fruit extract provided by this invention can inhibit platelet production or promote platelet metabolism, prolong clotting time, and inhibit platelet aggregation. Its natural plant components interfere with platelet aggregation by inhibiting the production of thromboxane A2, achieving anticoagulant and antithrombotic effects. The mechanism of action of banana fruit extract differs from traditional anticoagulants such as heparin, reducing the risk of bleeding. Its natural component characteristics provide a direction for the development of novel plant-derived anticoagulant drugs. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0019] Figure 1 This diagram illustrates the mechanism of action of banana fruit extract in inhibiting platelet aggregation and thrombus formation. Detailed Implementation

[0020] This invention provides the application of banana fruit extract in the preparation of anticoagulant products.

[0021] As one implementation method, the banana fruit extract used in this invention was provided by Guangxi Xiupeikeling Biotechnology Co., Ltd.

[0022] In one embodiment, the banana fruit extract contains flavonoids, polyphenols, polysaccharides, enolone, hydroxyanthraquinone, triterpenoids, diterpenoids, steroids, potassium, sodium, lupinone, selenium, anthraquinones, palmitic acid, β-sitosterol, amino acids, coumarins, and saponins.

[0023] In one implementation, the anticoagulant product inhibits platelet production or promotes platelet metabolism.

[0024] In one embodiment, the anticoagulant product inhibits platelet aggregation induced by arachidonic acid and collagen.

[0025] In one implementation, the anticoagulant product inhibits the formation of thromboxane A2 but has no effect on the formation of cAMP and cGMP.

[0026] In one implementation, the product includes a drug.

[0027] This invention provides the application of banana fruit extract in the preparation of antithrombotic drugs.

[0028] In one embodiment, the antithrombotic drug inhibits the formation of thromboxane A2.

[0029] In one implementation, the antithrombotic drug inhibits platelet production or promotes platelet metabolism.

[0030] This invention provides an anticoagulant drug, the active ingredient of which includes banana fruit extract; the unit dose of the banana fruit extract in the drug is a dilution of 1 / 1000-1 / 2000 times.

[0031] This invention involves diluting banana fruit extract to 1 / 1000, 1 / 1200, 1 / 1500, and 1 / 2000 times, and orally administering it to Wistar rats at a dose of 1 ml / kg daily for 14 consecutive days. Its anticoagulant activity was assessed by measuring prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count (PLT), and platelet aggregation reaction. Simultaneously, the levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) were measured to determine its mechanism of action. Results showed that banana fruit extract significantly prolonged PT and APTT at higher concentrations (p<0.01) and inhibited platelet aggregation. Its mechanism of action is primarily through inhibiting the production of thromboxane A2 (TXB2) (p<0.01), rather than through the cAMP or cGMP pathway. This invention has discovered that banana fruit extract has significant anticoagulant activity, and its mechanism of action is closely related to the inhibition of thromboxane A2 production, providing a new research direction for the development of natural anticoagulant drugs.

[0032] The banana fruit extract provided by this invention contains flavonoids, polyphenols, polysaccharides, hydroxyanthraquinones, triterpenoids, and other components. Flavonoids and polyphenols have been widely proven to have anti-inflammatory and antioxidant effects, which can synergistically enhance anticoagulant effects. The high potassium content of banana fruit can indirectly improve vascular function by regulating sodium-potassium balance. The banana fruit extract provided by this invention can inhibit platelet production or promote platelet metabolism, prolong clotting time, and inhibit platelet aggregation. Its natural plant components interfere with platelet aggregation by inhibiting the production of thromboxane A2, achieving anticoagulant and antithrombotic effects. The mechanism of action of banana fruit extract differs from traditional anticoagulants such as heparin, reducing the risk of bleeding. Its natural component characteristics provide a direction for the development of novel plant-derived anticoagulant drugs.

[0033] To further illustrate the present invention, the application of the banana fruit extract provided by the present invention in the preparation of anticoagulant or antithrombotic drugs is described in detail below with reference to embodiments and accompanying drawings, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0034] Example 1

[0035] The banana fruit extract used in this invention was provided by Guangxi Xiupeikeling Biotechnology Co., Ltd., and the banana fruit extract was subjected to the following experiments:

[0036] 1.1 Chemical composition detection

[0037] 1.1.1 Testing standards: JIS K0133-2007 General rules for high-frequency plasma mass spectrometry analysis; JY / T007-1996 General rules for superconducting pulsed Fourier transform nuclear magnetic resonance spectroscopy; GB / T35959-2018 General rules for liquid chromatography-mass spectrometry analysis; GB / T 16631-2008 General rules for high performance liquid chromatography.

[0038] 1.1.2 Detection Instruments: Bruker AVANCENEO 400M nuclear magnetic resonance spectrometer; ultra-high performance liquid chromatography-ion mobility-quadrupole time-of-flight mass spectrometer; Thermo Fisher Scientific Evolution201 UV-Vis spectrophotometer; PerkinElmer Nexion 300D inductively coupled plasma mass spectrometer; Thermo Fisher Scientific Ultimate 3000 high performance liquid chromatograph.

[0039] 1.1.3 Test items: Flavonoids, polyphenols, polysaccharides, enolones, hydroxyanthraquinones, triterpenoids, diterpenoids, steroids, potassium, sodium, lupinone, selenium, anthraquinones, palmitic acid, β-sitosterol, amino acids, coumarins, and saponins.

[0040] 1.2 Anticoagulant activity test

[0041] 1.2.1 Experimental animals: Eight-week-old male Wistar rats were housed in an environment with a room temperature of 25±1℃ and 12 hours of light and 12 hours of darkness, with free access to food and water.

[0042] 1.2.2 Feeding method: The banana fruit extract was diluted with purified water to 1 / 1000, 1 / 1200, 1 / 1500 and 1 / 2000 times, and fed twice a day at a fixed time for 14 consecutive days. After the experiment, rats were anesthetized with phenobarbital, and blood was drawn from the femoral vein for hematological testing.

[0043] 1.2.3 Hematological examination: Red blood cells (RBC), white blood cells (WBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin level (MCH), and platelet count (PLT) were measured using a fully automated blood analyzer (Sysmex F-800, Japan).

[0044] 1.2.4 Anticoagulation Activity Tests: (1) Prothrombin Time (PT) Test. Measured using a Coatron M2 blood coagulation analyzer. Take 10 μl of test solution of different concentrations and add it to 50 μl of rat plasma. React at 37℃ for 1-2 minutes. Add 25 μl of PT reagent (TEClot PT, TECO GMBH Co. Ltd., Germany) preheated for 10 minutes and record the plasma coagulation time. (2) Activated Partial Thromboplastin Time (APTT) Test. Measured using a Coatron M2 blood coagulation analyzer. Take 10 μl of sample solution of different concentrations and add it to 25 μl of rat plasma. React at 37℃ for 1-2 minutes. Add 25 μl of APTT reagent (TEClot APTT, TECO GMBH Co. Ltd., Germany) and continue the reaction for 3 minutes. Finally, add 0.025M CaCl2 (25 μl) and record the plasma coagulation time.

[0045] 1.3 Anticoagulant activity mechanism test

[0046] 1.3.1 Platelet Agglutination Test: Venous blood from rats was anticoagulated with EDTA and centrifuged to obtain platelet-rich plasma. Platelet aggregation was measured using a Lumi-aggregometer (Chrono-Log Co., USA) and observed for 6 minutes.

[0047] 1.3.2 Determination of TXB2, cAMP, and cGMP released from platelets: After 6 minutes of platelet agglutination reaction, the platelet suspension was removed, heated, centrifuged, and the concentrations of TXB2, cAMP, and cGMP were determined using an ELISA kit.

[0048] 1.4 Statistical Methods

[0049] Experimental data are expressed as mean ± standard deviation (mean ± SD). One-way ANOVA was used to analyze the variance, and Scheffe's multiple comparison test was used to determine the significance of differences. P < 0.05 was considered significant.

[0050] 2. Test Results and Discussion

[0051] 2.1 The results of the chemical composition analysis are shown in Table 1.

[0052] The results showed that banana fruit extract contains abundant flavonoids, polyphenols, polysaccharides, enolone, hydroxyanthraquinone, triterpenoids, diterpenoids, steroids, potassium, sodium, lupinone, selenium, anthraquinones, palmitic acid, β-sitosterol, amino acids, coumarins, saponins, and other components.

[0053] Table 1. Component analysis results of banana fruit extract

[0054] Serial Number Test Project Test unit Test Results Detection limit 1 Flavonoids mg / 100mL 177.5 0.05 2 Polyphenols mg / 100mL 60.5 0.10 3 polysaccharides mg / 100mL 433.2 0.05 4 Enoxone mg / 100mL 10.0 0.05 5 Hydroxyanthraquinone mg / 100mL 13.3 0.50 6 Triterpenoids mg / 100mL 22.5 0.50 7 Diterpenoids mg / 100mL 17.7 0.50 8 steroids mg / 100mL 6.5 0.10 9 Potassium mg / 100mL 55.2 1.0 10 sodium mg / 100mL 507.7 1.0 11 Lupinone mg / 100mL 100.5 0.5 12 selenium mg / 100mL 6.7 1.0 13 Anthraquinone mg / 100mL 76.4 0.05 14 Palmitic acid mg / 100mL 88.6 1.0 15 β-sitosterol mg / 100mL 3.5 1.0 16 amino acids mg / 100mL 355.8 0.1 17 Coumarin mg / 100mL 61.0 1.0 18 saponins mg / 100mL 41.3 1.0

[0055] 2.2 Anticoagulation test

[0056] Male Wistar rats were orally administered banana fruit extracts at doses of 1 / 1000, 1 / 1200, 1 / 1500, and 1 / 2000 of their original concentration at a dose of 1 ml / kg body weight daily. Male Wistar rats administered aspirin (10 mg / kg body weight) in the same manner served as the positive control group. The rats grew well during the experiment, and there were no significant differences in body weight, food intake, and water consumption between the experimental and control groups (see Table 2).

[0057] Table 2. Changes in body weight, food intake, and water consumption in Wistar rats after 14 days of continuous oral administration of banana fruit extract.

[0058]

[0059]

[0060] Note: The solvent treatment group received 1 ml / kg of purified water orally; 1 / 1000, 1 / 1200, 1 / 1500 and 1 / 2000 are the dilution factors of banana fruit extract, and the same applies to the table below; the data for each group are the results obtained from 10 experimental Wistar rats, and are expressed as mean ± SD.

[0061] As shown in Table 2, there was no statistically significant difference in the data obtained at the same time point between the banana fruit extract treatment group and the solvent treatment group.

[0062] After 14 days of feeding, the blood of the banana fruit extract treatment group was examined. The results showed that the values ​​of white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), and mean corpuscular volume (MCV) were all within the normal range of the control group. However, the platelet count (PLT) decreased significantly with increasing concentration, indicating that the extract can inhibit platelet production or promote platelet metabolism (see Table 3).

[0063] Table 3. Blood test values ​​of Wistar rats after 14 days of continuous oral administration of banana fruit extract.

[0064]

[0065] Note: The solvent treatment group received 1 ml / kg of purified water orally; data for each group were obtained from 10 experimental Wistar rats and are expressed as mean ± SD; compared with the data obtained from the solvent treatment group... a p<0.05, b p<0.01.

[0066] The prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged with increasing extract concentration, indicating that it has anticoagulant activity (see Table 4).

[0067] Table 4. Analysis of coagulation-related values ​​in Wistar rats after 14 days of continuous oral administration of banana fruit extract.

[0068]

[0069] Note: The solvent treatment group received 1 ml / kg of purified water orally; data for each group were obtained from 10 experimental Wistar rats and are expressed as mean ± SD; compared with the data obtained from the solvent treatment group... a p<0.05, b p<0.01.

[0070] The banana fruit extract significantly inhibited arachidonic acid and collagen-induced platelet aggregation and had a significant inhibitory effect on TXB2 production, but had no significant effect on cAMP and cGMP production (see Tables 5 and 6). This indicates that its anticoagulant mechanism is mainly through the inhibition of thromboxane production, rather than through the cAMP or cGMP pathway.

[0071] Table 5. Evaluation of the inhibitory effect of banana fruit extract on platelet aggregation induced by arachidonic acid (AA) or collagen in Wistar rats after 14 days of continuous oral administration.

[0072]

[0073] Note: Solvent treatment group received 1 ml / kg of purified water orally; data for each group were obtained from 10 experimental Wistar rats and are expressed as mean ± SD. a p<0.05, b p<0.01 compared to the data obtained from the solvent treatment group; c p<0.05, d p<0.01 compared to the data obtained in the aspirin treatment group.

[0074] Table 6. Results of platelet release of TXB2, cAMP, and cGMP in Wistar rats after 14 days of continuous oral administration of banana fruit extract.

[0075]

[0076] Note: Solvent treatment group received 1 ml / kg of purified water orally; data for each group were obtained from 10 experimental Wistar rats and are expressed as mean ± SD. a p<0.05, b p<0.01 compared to the data obtained from the solvent treatment group; c p<0.05, d p<0.01 compared to the data obtained in the aspirin treatment group; the mechanism of action of banana fruit extract in inhibiting platelet aggregation and thrombus formation is shown in the figure. Figure 1 .

[0077] In summary, the banana fruit extract provided by this invention contains flavonoids, polyphenols, polysaccharides, hydroxyanthraquinones, triterpenoids, and other components. Flavonoids and polyphenols have been widely proven to have anti-inflammatory and antioxidant effects, which can synergistically enhance anticoagulant effects. The high potassium content of banana fruit can indirectly improve vascular function by regulating sodium-potassium balance. The banana fruit extract provided by this invention can inhibit platelet production or promote platelet metabolism, prolong clotting time, and inhibit platelet aggregation. Its natural plant components interfere with platelet aggregation by inhibiting the production of thromboxane A2, achieving anticoagulant and antithrombotic effects. The mechanism of action of banana fruit extract differs from traditional anticoagulants such as heparin, reducing the risk of bleeding. Its natural component characteristics provide a direction for the development of novel plant-derived anticoagulant drugs.

[0078] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. Application of banana fruit extract in the preparation of anticoagulant products.

2. Use according to claim 1, characterized in that, The banana fruit extract contains flavonoids, polyphenols, polysaccharides, enolone, hydroxyanthraquinone, triterpenoids, diterpenoids, steroids, potassium, sodium, lupinone, selenium, anthraquinones, palmitic acid, β-sitosterol, amino acids, coumarins, and saponins.

3. Use according to claim 1, characterized in that, The anticoagulant product inhibits platelet production or promotes platelet metabolism.

4. The application according to claim 1, characterized in that, The anticoagulant product inhibits platelet aggregation induced by arachidonic acid and collagen.

5. The application according to claim 1, characterized in that, The anticoagulant product inhibits the formation of thromboxane A2 but has no effect on the formation of cAMP and cGMP.

6. The application according to any one of claims 1 to 5, characterized in that, The products include pharmaceuticals.

7. Application of banana fruit extract in the preparation of antithrombotic drugs.

8. The application according to claim 7, characterized in that, The antithrombotic drug inhibits the formation of thromboxane A2.

9. The application according to claim 7 or 8, characterized in that, The antithrombotic drugs inhibit platelet production or promote platelet metabolism.

10. An anticoagulant drug, characterized in that, The active ingredient includes banana fruit extract; the unit dose of banana fruit extract in the drug is a dilution of banana fruit extract of 1 / 1000 to 1 / 2000 times.

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