Application of aspidopterys obcordata extract in preparation of medicine for preventing and / or treating hyperlipidemia

Abstract

The invention discloses application of aspidopterys obcordata extract in preparation of a medicine for preventing and / or treating hyperlipidemia. Animal experiments prove that the aspidopterys obcordata diluted ethanol extract can reduce the indexes such as TC, HDL-C, LDL-C, HDL / TC, APOA, APOB, UREA, TP, GLB, ALB / GLB and the like in the blood of a hyperlipidemia model rat, can remarkably reduce the liver visceral organ coefficient and regenerate liver cells, can be used for treating hypercholesteremia in hyperlipidemia, and has a good clinical application prospect.

Description

Technical Field

[0001] The present invention specifically relates to the use of the extract of the Herba Lycopodii in preparing medicines for preventing and / or treating hyperlipidemia. Background Art

[0002] Hyperlipidemia is a disease of systemic metabolic abnormality caused by various reasons, in which the cholesterol, triglyceride and low-density lipoprotein levels in the plasma are elevated and the high-density lipoprotein levels are too low. Hyperlipidemia mainly includes four types: hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and low high-density lipoprotein cholesterol. Among them, hypercholesterolemia is an increase in cholesterol in the blood, which may cause vascular abnormalities and endanger life and health. It is the most common type of hyperlipidemia and the most dangerous one. Generally, lovastatin tablets, simvastatin tablets, atorvastatin calcium dispersible tablets and other cholesterol-lowering drugs are used. At present, these drugs for treating hyperlipidemia have obvious side effects, such as indigestion, muscle pain and weakness.

[0003] Aspidopterys obcordata Hemsl.var.obcordata is derived from the dried vine stems of the Malpighiaceae plant Aspidopterys obcordata Hemsl.var.obcordata, which is included in the Yunnan Province Traditional Chinese Medicine Standards - Dai Medicine (2005 edition). The efficacy and effects of Aspidopterys obcordata are clearing away heat and promoting diuresis; dispelling wind and unblocking meridians, and are mainly used to treat stranguria caused by heat; stranguria caused by stones; and rheumatism and heat arthralgia. So far, there has been no research on its application in the treatment of hyperlipidemia, especially hypercholesterolemia. Summary of the invention

[0004] In order to solve the above problems, the present invention provides the use of the extract of the Herba Lycopodii in the preparation of a medicine for preventing and / or treating hyperlipidemia.

[0005] Furthermore, the extract of the Herba Lycopodii is an extract obtained by extracting the Herba Lycopodii with dilute ethanol.

[0006] Furthermore, the extract of the Herba Lycopodii is an extract obtained by soaking the Herba Lycopodii in dilute ethanol, extracting, filtering and drying.

[0007] Furthermore, the extract of the Herba Lycopodii is obtained by soaking the Herba Lycopodii in 3 to 9 times v / w, ml / g dilute ethanol for 1 to 2 hours, then refluxing for 1 to 2 hours, extracting three times in total, filtering, combining the filtrates, and drying the filtrates.

[0008] Furthermore, the extract of the Herba Lycopodii is prepared by adding 9 times v / w, ml / g of dilute ethanol to Herba Lycopodii powder that has passed through a 40-mesh sieve, soaking it for 1 hour, then refluxing for extraction for 1 hour, extracting it 3 times in total, filtering, combining the filtrate, concentrating the filtrate to a relative density of 1.4 to 1.5 at 50°C, and then drying it at 80°C to obtain an extract.

[0009] Furthermore, the drug is a drug for treating hypercholesterolemia.

[0010] Even further, the drug has the effect of reducing body weight.

[0011] Even further, the drug has the effect of reducing TC, HDL-C, LDL-C, HDL / TC, APOA, APOB, UREA, TP, GLB, and ALB / GLB in the blood.

[0012] Even further, the drug has the effect of reducing the liver organ coefficient.

[0013] Even further, the drug has the effect of regenerating hepatocytes.

[0014] The "dilute ethanol" used in the present invention is an ethanol solution containing 49.5% - 50.5% (ml / ml) of C2H5OH at 20°C.

[0015] The use of the extract of Aspidopterys obcordata in the preparation of a drug for preventing and / or treating hyperlipidemia, through a hyperlipidemia animal model, has confirmed that the dilute ethanol extract of Aspidopterys obcordata can effectively reduce indicators such as TC, HDL-C, LDL-C, HDL / TC, APOA, APOB, UREA, TP, GLB, and ALB / GLB in the blood of rats, and can significantly reduce the liver organ coefficient and regenerate stem cells. It can be used for the treatment of hypercholesterolemia in hyperlipidemia and has good clinical application prospects.

[0016] Obviously, based on the above content of the present invention, according to the common general knowledge and customary means in the art, without departing from the above basic technical idea of the present invention, various other forms of modifications, substitutions, or changes can be made.

[0017] The following is a further detailed description of the above content of the present invention through specific embodiments in the form of examples. However, this should not be understood as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention belong to the scope of the present invention. Description of the Drawings

[0018] Figure 1 Normal control group: After HE staining of liver tissue, normal hepatocyte morphology can be seen under the microscope;

[0019] Figure 2 Model control group: After HE staining of liver tissue, it can be seen under the microscope that hepatocytes show balloon-like changes, lipid droplets of different sizes can be seen in the cytoplasm, and focal necrosis and punctate necrosis can be seen locally;

[0020] Figure 3Positive control group: After HE staining of liver tissues, obvious ballooning changes of hepatocytes were visible under the microscope, and obvious macrovesicular and microvesicular steatosis were observed.

[0021] Figure 4 Aspidopterys obcordata W. T. Wang group: After HE staining of liver tissues, a small number of regenerated hepatocytes were partially visible under the microscope, and focal necrosis was observed locally, and lipid droplets of different sizes were visible. Specific implementation manners

[0022] The reagents and equipment in the specific implementation manners of the present invention are all obtained by purchasing commercially. Among them, the dilute ethanol extract of Aspidopterys obcordata W. T. Wang is prepared according to the method recorded in the patent of the previous research result CN202110605339.4. Specifically, the Aspidopterys obcordata W. T. Wang is passed through a 40-mesh medicinal powder, and 9 times the amount of the medicinal material of dilute ethanol (that is, the material-liquid ratio is 1:9, 1000 g of medicinal powder is added with 9000 ml of solvent) is added and soaked for 1 h, then heated under reflux for 1 hour, and filtered; the medicinal residues are added with 9 times the amount of the medicinal material of dilute ethanol and heated under reflux for 1 hour, filtered, and finally the medicinal residues are added with 9 times the amount of the medicinal material of dilute ethanol and heated under reflux for 1 hour, filtered. The three filtrates are combined, ethanol is recovered, and concentrated to a thick paste with a relative density of 1.4 - 1.5 (50 °C), dried below 80 °C to obtain a dry extract, pulverized, and passed through an 80-mesh sieve to obtain a dry extract powder.

[0023] Example 1 Comprehensive pharmacodynamic evaluation of the dilute ethanol extract of the Dai medicine Aspidopterys obcordata W. T. Wang on regulating blood lipid (lowering cholesterol) in hyperlipidemic rats

[0024] 1. Experimental scheme

[0025] 1.1 Grouping of experimental animals

[0026] Modeling stage: 50 male SD rats were randomly divided into 4 groups. Among them, 10 rats in the normal control group were fed with a basal diet; the remaining 40 rats were fed with a high-fat diet (2% cholesterol, 10% lard, 0.2% methylthiouracil, 0.2% sodium cholate, 87.6% basal diet) for modeling. After 4 weeks of modeling, the rats were anesthetized by intraperitoneal injection of pentobarbital sodium, and blood was taken from the orbital cavity to detect total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Compared with the normal control group, the animals with elevated cholesterol (more than 20% higher than the average cholesterol value of the blank control group) were selected to continue the experiment. According to the cholesterol level, the modeled animals were randomly stratified and grouped into a model control group (14 rats), a positive control group (13 rats), and an Aspidopterys obcordata W. T. Wang group (13 rats).

[0027] Administration phase: Each group of animals was administered by oral gavage once every morning and weighed once a week. After 4 consecutive weeks of administration in each treatment group, the animals were fasted but allowed water for 12 hours, weighed, anesthetized by intraperitoneal injection of sodium pentobarbital, and then sacrificed by blood collection. Indexes such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A, apolipoprotein B, lipoprotein a, liver function, and renal function were measured; the liver was weighed to calculate the liver organ coefficient, and the liver was fixed in 10% neutral formaldehyde solution, embedded in paraffin, sectioned, stained with hematoxylin and eosin, and then dehydrated, cleared, and sealed for pathological histological examination. The differences between groups were statistically analyzed.

[0028] 1.2 Dose setting and administration protocol

[0029] Normal control group: Given drinking water by gavage, with a dosage volume of 20 ml / kg

[0030] Model control group: Given drinking water by gavage, with a dosage volume of 20 ml / kg

[0031] Positive control group: Given atorvastatin calcium tablets by gavage, with a dosage of 4 mg / kg (20 mg was made into 100 ml of solution), a dosage volume of 20 ml / kg, which was about 3 times the adult clinical dosage (80 mg / day / person, calculated based on 60 kg / person).

[0032] Securidaca inappendiculata group: Given the dilute ethanol extract of Securidaca inappendiculata by gavage, with a dosage of 7.0 g of crude drug / kg (concentration 0.35 g of crude drug / ml, dosage volume of 20 ml / kg)

[0033] 1.3 Data processing and analysis

[0034] The experimental results were expressed as mean ± standard deviation (x±s). The experimental data were processed by t-test to compare the differences between groups.

[0035] 2 Experimental results

[0036] 2.1 Effect of the dilute ethanol extract of Securidaca inappendiculata on the body weight of hyperlipidemic rats

[0037] The specific results are shown in Table 1.

[0038] Table 1 Effect of the dilute ethanol extract of Securidaca inappendiculata on the body weight of hyperlipidemic rats (x±s)

[0039]

[0040] Note: Normal control group, n = 10; model control group, n = 14; positive control group, n = 13; Aspidopterys obcordata group, n = 13. Compared with the normal control group, *P < 0.05, **P < 0.01; compared with the model control group, ▲P < 0.05, ▲▲P < 0.01.

[0041] As shown in Table 1, from the start of drug administration intervention to the 4th week, compared with the model control group, the body weight of the positive control group increased significantly at the 4th week after drug administration (▲▲P < 0.01), and the body weight of the Aspidopterys obcordata group decreased significantly from the 2nd to the 4th week after drug administration (▲P < 0.05 or ▲▲P < 0.01). There was no significant difference in body weight change between the positive control group in the 1st - 3rd week and the Aspidopterys obcordata group in the 1st week and the model control group (▲▲P > 0.05).

[0042] 2.2. Effects of Aspidopterys obcordata on blood lipids, serum apolipoproteins, liver function, and kidney function in hyperlipidemic rats

[0043] The specific results are shown in Table 2

[0044] Table 2 Effects of dilute ethanol extract of Aspidopterys obcordata on blood lipids, serum apolipoproteins, liver function, and kidney function in hyperlipidemic rats (x±s)

[0045]

[0046] Note: Normal control group, n = 10; model control group, n = 14; positive control group, n = 13; Aspidopterys obcordata group, n = 13. Compared with the normal control group, *P < 0.05, **P < 0.01; compared with the model control group, ▲P < 0.05, ▲▲P < 0.01

[0047] The results in Table 2 show that after 4 weeks of drug administration in rats of each group, compared with the model control group, TC, HDL - C, LDL - C, HDL / TC, ALT, AST, UREA, CR, TP, ALB, and GLB in the positive control group were all significantly decreased (▲P < 0.05 or ▲▲P < 0.01), but TG, GLU, and ALB / GLB were significantly increased (▲P < 0.05 or ▲▲P < 0.01); TC, HDL - C, LDL - C, HDL / TC, APOA, APOB, UREA, TP, GLB, and ALB / GLB in the Aspidopterys obcordata group were all significantly decreased (compared with the model control group, ▲P < 0.05 or ▲▲P < 0.01), and LPA in the Aspidopterys obcordata group showed an upward trend (compared with the model control group, ▲P < 0.05).

[0048] 2.3. Effects of Aspidopterys obcordata on the ratio of liver mass to body mass in hyperlipidemic model rats. The specific results are shown in Table 3.

[0049] Table 3 Effects of Aspidopterys obcordata on liver organ coefficient in hyperlipidemic rats (x±s)

[0050]

[0051] Note: Normal control group, n = 10; model control group, n = 14; positive control group, n = 13; Aspidopterys obcordata group, n = 13. Compared with the normal control group, *P < 0.05, **P < 0.01; compared with the model control group, ▲P < 0.05, ▲▲P < 0.01

[0052] The results in Table 3 showed that: compared with the normal control group, the liver organ indices in the model control group, positive control group, and Aspidopterys obcordata group all increased significantly (**P < 0.01); after 4 weeks of administration, compared with the model control group, there was no significant difference in the liver organ coefficient in the positive control group (P > 0.05), while the liver organ coefficient in the Aspidopterys obcordata group decreased significantly (▲P < 0.05).

[0053] 2.4. Histopathological examination of liver

[0054] Results of liver histopathology: Compared with the normal control group, the livers of the experimental rats in the model control group, positive control group, and Aspidopterys obcordata group all showed varying degrees of fatty changes. After 4 weeks of administration, compared with the model control group, a small number of regenerated hepatocytes were visible in the livers of some rats in the Aspidopterys obcordata group, focal necrosis was visible locally, and lipid droplets of different sizes were visible. See specifically Figures 1 to 4 。

[0055] 3. Experimental conclusions

[0056] The results of this experimental study showed that: the dilute ethanol extract of Aspidopterys obcordata had a significant effect on reducing cholesterol in the blood of hyperlipidemic rats and repairing damaged liver tissue, mainly manifested as: reducing the levels of TC, HDL-C, LDL-C, HDL / TC, APOA, APOB, UREA, TP, GLB, ALB / GLB, etc. in the blood of hyperlipidemic model rats, and significantly reducing the liver organ coefficient. Moreover, liver histopathological examination showed that: compared with the model control group, a small number of regenerated hepatocytes were visible in the livers of some rats in the Aspidopterys obcordata group.

Claims

1. Use of the extract of Aspidopterys obcordata in the preparation of a medicament for preventing and / or treating hyperlipidemia.

2. The use according to claim 1, wherein: The extract of Aspidopterys obcordata is an extract obtained by extracting Aspidopterys obcordata with dilute ethanol.

3. The use according to claim 2, characterized in that: The extract of Aspidopterys obcordata is an extract obtained by soaking Aspidopterys obcordata with dilute ethanol, extracting, filtering, and drying.

4. Use according to claim 3, characterized in that: The extract of Aspidopterys obcordata is an extract obtained by soaking Aspidopterys obcordata with 3 - 9 times the volume / weight (ml / g) of dilute ethanol for 1 - 2 hours, then refluxing for 1 - 2 hours, extracting 3 times in total, filtering, combining the filtrates, and drying the filtrates.

5. The use according to claim 4, wherein: The extract of Aspidopterys obcordata is an extract obtained by soaking the powder of Aspidopterys obcordata passing through a 40 - mesh sieve with 9 times the volume / weight (ml / g) of dilute ethanol for 1 hour, then refluxing for 1 hour, extracting 3 times in total, filtering, combining the filtrates, concentrating the filtrates to a relative density of 1.4 - 1.5 at 50°C, and then drying at 80°C.

6. The use according to claim 1, characterized in that: The medicament is a medicament for treating hypercholesterolemia.

7. The use according to claim 6, wherein: The medicament has the effect of reducing body weight.

8. The use according to claim 6, characterized in that: The medicament has the effect of reducing TC, HDL - C, LDL - C, HDL / TC, APOA, APOB, UREA, TP, GLB, and ALB / GLB in the blood.

9. The use according to claim 6, wherein: The medicament has the effect of reducing the liver organ coefficient.

10. The use according to claim 6, wherein: The medicament has the effect of regenerating hepatocytes.

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