CN114177208A - Application of custard apple seed ethanol extract in preparation of lipid-lowering and weight-losing medicine - Google Patents
Application of custard apple seed ethanol extract in preparation of lipid-lowering and weight-losing medicine Download PDFInfo
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A61K2236/50—Methods involving additional extraction steps
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Abstract
The invention relates to a new application of an ethanol extract of custard apple, namely the application in preparing a medicament for reducing fat and losing weight. The extract has simple preparation method, can remarkably reduce serum total cholesterol and triglyceride, and reduce body weight, and has remarkable effect and no toxic and side effects. The invention provides the new medical application of the custard apple ethanol extract, can obviously increase the economic additional value of custard apple, and has good economy; but also provides a new idea for treating hyperlipidemia and obesity, and has good social benefit.
Description
Technical Field
The invention relates to application of an ethanol extract of custard Galangal, in particular to application of the ethanol extract of custard Galangal in preparing a lipid-lowering and weight-losing medicine.
Background
A higher than normal level of one or more lipids in plasma due to abnormal fat metabolism or movement is called hyperlipidemia. Hyperlipidemia is usually more secret and generally can not be found, and is more serious when finding. Hyperlipidemia is a major risk factor for atherosclerotic diseases in humans. Like common atherosclerotic diseases are: coronary heart disease (including myocardial infarction, angina pectoris and sudden death), cerebral infarction and peripheral vascular thromboembolic diseases. The cardiovascular and cerebrovascular diseases have high morbidity, great harm and serious disease progression, and the death rate of the cardiovascular and cerebrovascular diseases accounts for about half of the total death rate of human beings. Obesity refers to a condition of excess accumulation of body fat, especially triglycerides, due to a degree of significant overweight and an excessively thick fat layer. Excessive accumulation of fat in the body due to excessive food intake or altered metabolism of the body causes excessive weight gain and causes pathological, physiological changes or latency in the human body. The World Health Organization (WHO) has formally defined obesity as a disease for a long time. According to research data, the incidence rate and the growth speed of overweight and obesity in China are at the first place in the world, and the number of people who are overweight and obese is at the first place in the world. In the adults in China, on average, one overweight patient exists in every 5 adults, and one obese patient exists in every 9 adults in clinical significance. In 2019, overweight/obesity is the sixth leading lethal and disabling risk factor in our country. Obesity not only affects body beauty and brings inconvenience to life, but also increases the risk of cardiovascular diseases, affects the functions of the digestive system and the endocrine system, and increases the risk of cancer. Therefore, the lipid-lowering weight-losing medicine has good market prospect and social benefit.
The lipid-lowering drugs which are commonly used clinically at present comprise: (1) statins: statins are the best drugs for treating hypercholesterolemia and combined hyperlipidemia, but have common side effects, such as rise of transaminase, liver damage, myopathy, rise of blood sugar and increase of incidence rate of diabetes, and memory and cognitive dysfunction caused by long-term statin administration; (2) nicotinic acids: nicotinic acid drugs are the oldest lipid regulating drugs, are the drugs with the best effect of increasing high density lipoprotein cholesterol, and are particularly suitable for reducing the high density lipoprotein cholesterol or increasing combined triglyceride. But the adverse reactions are more, including liver poisoning, hyperglycemia, peptic ulcer, ventilation and the like can occur; (3) the fibrate drugs are lipid regulators which are widely applied at present, are lipid-lowering drugs with the best effect of lowering triglyceride, have slight side effects after short-term administration, mainly cause gastrointestinal reactions such as abdominal distension, diarrhea and the like, and occasionally have symptoms such as headache, hypodynamia, rash, blurred vision and the like, and can increase transaminase and increase the incidence rate of gallstones after long-term administration. Patients with liver, gallbladder or severe kidney diseases should not use the original drugs.
The weight loss drugs currently on the market fall into two broad categories, pancreatic lipase inhibitors and appetite suppressants acting on the central nervous system. Appetite suppressants are limited in use because they cause adverse reactions in the nervous system, and the pancreatic lipase inhibitor orlistat is used for weight reduction by inhibiting pancreatic lipase activity and thus inhibiting the decomposition and absorption of fat in food. But it can cause fat diarrhea and can cause fat-soluble vitamin deficiency. It has also recently been reported to cause liver function damage. Although the central nervous system appetite suppressants lorcaserin and Qsymia became the first approved weight loss drugs by FDA for 13 years, they still have safety uncertainties in the central brain and cardiovascular system.
Therefore, the search for safe and effective lipid-lowering and weight-losing drugs is always an important task for medical workers.
Annona squamosa Linn, Annona squamosa, is a small tree of Annona squamosa, Annona, and is cultivated in Zhejiang, Taiwan, Fujian, Guangdong, Guangxi, Hainan, and Yunnan provinces. The fruit is edible, is a famous fruit in tropical regions, and contains 2.34% of protein, 0.3% of fat and 20.42% of carbohydrate; the oil content of the seeds reaches 20 percent. The bark fiber can be used for making paper. The medicine can be used for treating acute dysentery, mental depression and spinal cord osteopathia; the fruit can be used for treating sore and swelling pain, and invigorating spleen. The custard apple has the effect of activating brain cells and is commonly used for treating encephalatrophy outside China. In addition, the custard apple has high fiber content, can effectively promote intestinal peristalsis and remove stubborn stool accumulated in intestines, and is also the best antioxidant fruit, so that the custard apple can effectively delay skin aging and whiten skin. Inside the custard apple there are many black seeds, which are usually discarded. The custard does not contain toxic substances, and even if the custard is eaten by mistake, the custard does not cause toxic reaction. Besides being used for raising seedlings, making hand strings and serving as fertilizer, the research and development on the pharmacological activity and application of the custard apple is still blank, and the custard apple with relatively high price is a waste of resources.
Disclosure of Invention
Aiming at the situations, in order to overcome the defects of the prior art, the invention aims to develop the new application of the custard, realize waste utilization and provide a new lipid-lowering and weight-losing therapeutic drug.
In order to achieve the purpose, the invention provides the application of the ethanol extract of custard apple in preparing the lipid-lowering and weight-losing medicines.
The invention solves the technical scheme that the application of the custard apple nuclear ethanol extract in preparing the lipid-lowering and weight-losing medicine is characterized in that the custard apple nuclear ethanol extract is obtained by adopting the following extraction method: taking custard, drying, crushing, sieving, placing in a round-bottom flask, adding 12 times of 75% ethanol by volume, heating and refluxing for 3h, filtering to obtain filtrate, placing in a rotary evaporator to recover ethanol until no ethanol smell exists, continuing to concentrate into extract, and drying under reduced pressure to obtain brown yellow powder.
Compared with the prior art, the invention has the following advantages:
the invention provides the application of the ethanol extract of the custard apple in preparing the lipid-lowering and weight-losing medicines, the raw materials are rich, the preparation method is simple, the total cholesterol and triglyceride in serum can be obviously reduced, the weight is reduced, the effect is obvious, and no toxic or side effect exists. The invention provides a new medical application of the custard apple ethanol extract, can realize waste utilization, obviously increases the economic additional value of custard apple, and has good economic benefit; but also provides a new idea for treating hyperlipidemia and obesity, and has good social benefit.
Drawings
FIG. 1 shows the effect of ethanol extract of custard apple on the tissue structure of heart, liver, spleen, lung and kidney of mice.
Detailed Description
The present invention will be described in detail with reference to specific examples.
Example 1 preparation of Annona Sakyamuni Kernel ethanol extract
Taking custard, drying, weighing 100g, crushing, sieving, placing in a 2000mL round-bottom flask, adding 1200mL of ethanol with 75% volume fraction, placing on an electric heating jacket, heating, refluxing and extracting for 3h, filtering with gauze to obtain filtrate, placing in a rotary evaporator, recovering ethanol until no alcohol smell exists, continuing to concentrate into extract, and drying under reduced pressure to obtain 12.3g of brown yellow powder.
The invention further describes the effect of reducing fat and losing weight through test examples, and has good safety.
Test example 1 therapeutic Effect of Annona squamosa Kernel ethanol extract on acute hyperlipidemic mouse
1. Test materials
The ethanol extract of custard Galamina prepared by the embodiment is respectively dissolved by normal saline to prepare solutions of 0.5mg/mL, 1mg/mL and 2 mg/mL;
poloxamer 407, basf, germany;
serum Total Cholesterol (TC) and Triglyceride (TG)2 kit, Nanjing institute of bioengineering;
clean-grade Kunming mice, with the body mass of 18-22 g and half male and female, are provided by Qingdao Daren Fucheng livestock Limited and are used for experiments after being fed for 7 days in an adaptive manner.
2. Test method
40 mice were randomly assigned to 5 groups (n-8): control group, hyperlipemia group, small, medium and large dosage group of custard apple seed ethanol extract. The small, medium and large dose of the ethanol extracts of the custard apple are respectively gavaged with 0.5mg/mL, 1mg/mL and 2mg/mL of the ethanol extracts of the custard apple 0.1mL/10g for 1 time per day for 3 days, and the mice of the control group and the poloxamer group are gavaged with the same amount of physiological saline. After the last administration for 3h, except for the control group which is injected with normal saline with the same amount, other groups of mice are injected with 30mg/mL poloxamer 4070.1mL/10g in the abdominal cavity. Fasting is carried out on the day, blood is taken from the eye orbit of the mouse after 24h, serum is taken by centrifuging at 3500r/min for 10min, and the TC and TG contents of the serum are determined by adopting a kit.
The experimental data are expressed as mean ± standard deviation, and single factor analysis of variance using SPSS17.0, P <0.05 is considered statistically significant.
3. Test results
The test results are shown in Table 1. The experiment adopts a method of injecting poloxamer 407 into the abdominal cavity to prepare a mouse acute hyperlipidemia model, and the result shows that the TC and TG levels of serum of a mouse in a hyperlipidemia group are obviously increased (P is less than 0.01) compared with those of a control group after injecting poloxamer 407 into the abdominal cavity, thereby prompting the successful establishment of the hyperlipidemia model. After mice are given with different doses of the ethanol extract of the custard apple tree seeds, the serum TC and TG levels are reduced to different degrees (compared with a hyperlipemia group, P is less than 0.01), and a dose dependence relationship is shown, wherein the large dose of the ethanol extract of the custard apple tree seeds has no significant difference (P is more than 0.05) compared with a control group.
TABLE 1 Effect of Annona squamosa Kernel ethanol extract on the blood lipid level of hyperlipidemic mice
Note: compared with the control group, the compound of the formula,*P<0.05，**P<0.01; compared with the group with high blood fat,△P<0.01; compared with the group of small dose,▲P<0.01; in comparison with the medium dose group,#P<0.01。
4. conclusion
The ethanol extract of Annona squamosa has blood lipid reducing activity, and can be used for treating hyperlipidemia.
Test example 2 therapeutic Effect of Annona squamosa Kernel ethanol extract on obese mice
1. Test materials
The ethanol extract of custard Galamina prepared by the embodiment is respectively dissolved by normal saline to prepare solutions of 0.5mg/mL, 1mg/mL and 2 mg/mL;
the high-fat feed is prepared by self, and the formula of the high-fat feed is as follows: 88% basal feed + 2% cholesterol + 10% lard;
cholesterol, food grade, Jiangsu Xin and Source Biotech, Inc.;
lard, which is prepared by boiling commercial fat pork;
basal feed, livestock limited of great-grained great-chang of Qingdao;
serum Total Cholesterol (TC) and Triglyceride (TG) kit, Nanjing institute of bioengineering;
clean-grade Kunming mice, with the body mass of 18-22 g and half male and female, are provided by Qingdao Daren Fucheng livestock Limited and are used for experiments after being fed for 7 days in an adaptive manner.
2. Test method
40 mice were taken and randomly divided into 5 groups (n ═ 8): control group, obesity group, small, medium and large dosage group of custard apple seed ethanol extract. The small, medium and large dose mice of the custard apple nuclear ethanol extract are respectively gavaged with 0.5mg/mL, 1mg/mL and 2mg/mL of the custard apple nuclear ethanol extract 0.1mL/10g, and the mice of the control group and the obese group are gavaged with the same amount of normal saline for 1 time per day for 8 weeks. During the period, the group was fed with high fat diet except for the basal diet of the control group. Fasting the mice for 12h after the last administration, weighing, taking blood from eye sockets, centrifuging at 3500r/min for 10min, taking serum, and determining the content of TC and TG in the serum by using a kit; after the mice die after dislocation, the heart, liver, spleen and kidney are taken, the wet weight is weighed after the blood is sucked dry, and the organ coefficient is calculated by the following formula: organ coefficient is organ wet weight/body weight.
The experimental data are expressed as mean ± standard deviation, and single factor analysis of variance using SPSS17.0, P <0.05 is considered statistically significant.
3. Test results
The test results are shown in tables 2 and 3. According to the experiment, a mouse obesity model is established by adopting a high-fat feed feeding method, and the results show that after the mouse is fed with the high-fat feed for 8 weeks, the serum TC and TG levels of mice in an obesity group are obviously increased (compared with a control group, P is less than 0.01), the body weight is obviously increased (compared with the control group, P is less than 0.01), the organ coefficients of the heart, the liver, the spleen and the kidney are all increased (compared with the control group, P is less than 0.01), and the success of establishing the obesity model is prompted. After the mice are fed with high-fat feed and simultaneously fed with different doses of the ethanol extract of the custard's nits, the serum TC and TG levels of the mice are obviously reduced (P <0.01) compared with the obese mice, the body weight is obviously reduced (P <0.01), the coefficients of various organs are reduced to different degrees (P <0.05 or P <0.01), and the dose-dependent relationship is shown, wherein the large-dose ethanol extract of the custard's nits has no obvious difference (P >0.05) compared with the control group.
TABLE 2 Effect of Annona squamosa Kernel ethanol extract on blood lipid levels in obese mice
Note: compared with the control group, the compound of the formula,*P<0.01; in comparison with the obese group,△P<0.01; compared with the group of small dose,▲P<0.01; in comparison with the medium dose group,#P<0.05。
TABLE 3 Effect of Annona squamosa Kernel ethanol extract on body weight and organ coefficients of obese mice
Note: compared with the control group, the compound of the formula,*P<0.05，**P<0.01; in comparison with the obese group,△P<0.05，△△P<0.01; compared with the small-dose custard water extract group,▲P<0.05，▲▲P<0.01; comparing with the middle-dose custard water extract group,#P<0.05，##P<0.01。
4. conclusion
The ethanol extract of custard Galamina can inhibit the increase of blood lipid level, weight gain and organ enlargement of obese mice, and can be used for treating obesity.
Test example 3 acute toxic Effect of Annona squamosa Kernel ethanol extract on mice
1. Test materials
The ethanol extract of custard apple prepared by the embodiment is dissolved by normal saline, and the maximum concentration of the liquid medicine of the ethanol extract of custard apple, which is difficult to absorb but not impossible to absorb, is 0.35g/mL by a gastric lavage needle test.
Clean-grade Kunming mice, with the body mass of 18-22 g and half male and female, are provided by Qingdao Daren Fucheng livestock Limited and are used for experiments after being fed for 7 days in an adaptive manner.
Serum alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), urea nitrogen (BUN) and creatinine (Cr) kit, Nanjing institute of bioengineering;
HE staining kit: beijing Boaosen Biotechnology Ltd.
2. Test method
Because the experiment does not show LD50 due to the limitation of drug concentration and volume, the maximum dose method is adopted. 20 mice were taken and randomly divided into two groups: control group and administration group. After fasting and water prohibition for 12h, mice in the administration group were gavaged with the maximum gavage concentration of the ethanol extract of custard's nuclear (0.35g/mL) according to the maximum administration volume (0.4mL/10g), and the control group was given with the same amount of physiological saline for 1 time. After administration, mice were observed for activity, diet, feces, respiration, body weight and death for 14 days. 14d, fasting for 12h, weighing, taking blood from an orbit, taking a drop of whole blood, counting the number of Red Blood Cells (RBC), White Blood Cells (WBC) and Platelets (PLT) by using a blood cell counting plate, centrifuging the rest blood at 3500r/min for 10min, taking serum, and measuring the content of serum alanine Aminotransferase (ALT), glutamic-oxalacetic transaminase (AST), urea nitrogen (BUN) and creatinine (Cr) by using the kit; mice are dislocated and sacrificed, the thoracic cavity and the abdominal cavity are opened, the appearance change of important visceral organs is observed, the heart, the liver, the spleen, the lung and the kidney are subjected to routine paraffin section HE staining, and the pathological change is observed.
The experimental data are expressed as mean ± standard deviation, with independent sample t-test using SPSS17.0, P <0.05 considered statistically significant.
3. Test results
The test results are shown in table 4, table 5 and fig. 1. The results show that the ethanol extract of the custard apple with the maximum dose is given to the mice, the mice do not die, the general states of the mice are good, the food, respiration, stool and urine and the body weight are not abnormal, the RBC, WBC and PLT counts of the mice have no obvious change, the ALT, AST, BUN and Cr levels of the serum have no obvious change, and the paraffin sections of the heart, liver, spleen, lung and kidney of important organs have no obvious pathological damage.
TABLE 4 Effect of Annona squamosa Kernel ethanol extract on mouse blood routine
TABLE 5 Effect of Annona squamosa Kernel ethanol extract on blood biochemical index of mice
4. Conclusion
The ethanol extract of the custard apple has no obvious damage to mice and good safety.
Claims (1)
1. The application of the ethanol extract of custard Galangal in preparing the lipid-lowering and weight-losing medicine is characterized in that the ethanol extract of custard Galangal is obtained by adopting the following extraction method: taking custard, drying, crushing, sieving, placing in a round-bottom flask, adding 12 times of 75% ethanol by volume, heating and refluxing for 3h, filtering to obtain filtrate, placing in a rotary evaporator to recover ethanol until no ethanol smell exists, continuing to concentrate into extract, and drying under reduced pressure to obtain brown yellow powder.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140056987A1 (en) * | 2011-04-29 | 2014-02-27 | Laila Nutraceuticals | Compositions comprising extracts or fractions derived from annona squamosa for the prevention, treatment or control of inflammatory and metabolic disorders |
| CN111317750A (en) * | 2020-02-17 | 2020-06-23 | 江苏卫生健康职业学院 | Application of sweetsop seed total lactone in preparing medicine for preventing and treating diabetes |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140056987A1 (en) * | 2011-04-29 | 2014-02-27 | Laila Nutraceuticals | Compositions comprising extracts or fractions derived from annona squamosa for the prevention, treatment or control of inflammatory and metabolic disorders |
| CN111317750A (en) * | 2020-02-17 | 2020-06-23 | 江苏卫生健康职业学院 | Application of sweetsop seed total lactone in preparing medicine for preventing and treating diabetes |
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| 唐迪等: "番荔枝籽中脂肪酸的提取和气相色谱-质谱联用分析", 《食品科学》 * |
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