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Application of betulinic acid as leptin sensitizer in preparation of related drugs for treating leptinresistance

A technology of betulinic acid and a sensitizer, applied in the field of pharmaceutical preparation, can solve problems such as unknown therapeutic effect of metabolic diseases, and achieve the effects of improving liver lipid deposition, inhibiting obesity process, correcting insulin resistance and hyperlipidemia

Inactive Publication Date: 2019-07-09
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The effects of betulinic acid in the treatment of tumors, anti-viruses, anti-infections and anti-parasites are well known, but the therapeutic effects on metabolic diseases are still unknown

Method used

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  • Application of betulinic acid as leptin sensitizer in preparation of related drugs for treating leptinresistance
  • Application of betulinic acid as leptin sensitizer in preparation of related drugs for treating leptinresistance
  • Application of betulinic acid as leptin sensitizer in preparation of related drugs for treating leptinresistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Effects of betulinic acid on body weight in high-fat diet-induced obese mice, ob / ob mice and db / db mice:

[0040] After one week of adaptive feeding with common feed, the mice were randomly divided into two groups, 15 in each group, and the average initial body weight of the two groups of mice was guaranteed to be the same. The mice were fed with high-fat diet and high-fat diet plus betulinic acid for two months, and the mice were weighed every three days. There was no difference in the initial body weight of the two groups of mice, but the difference in body weight between the high-fat mice and the high-fat plus betulinic acid mice began to appear on the 7th day of administration, and the body weight of the high-fat plus betulinic acid group was lower than that of the high-fat group (P figure 2 a).

[0041] After one week of adaptive feeding with common feed, the ob / ob mice were randomly divided into two groups, 15 in each group, and the average initial body weight of ...

Embodiment 2

[0045] Effects of betulinic acid on serum leptin concentrations in high-fat diet-induced obese mice:

[0046] Decreased serum leptin concentration is one of the important signs of relief of leptin resistance. Therefore, the serum of mice in the high-fat and high-fat drug-added groups was collected respectively, and the serum leptin concentration was detected by ELISA method.

[0047]The specific detection method is as follows: first prepare mouse serum leptin standard (provided by the kit) according to the doubling dilution method; prepare 500ml of 1×HRP Wash Buffer for washing the plate; take the plate, add 300 μl of 1×HRP WashBuffer to each well, Wash three times and set aside; add 30 μl Assay Buffer to the background well and standard well respectively, add 40 μl Assay Buffer to the sample well, then add 30 μl Matrix Solution to the background well and standard well respectively; next, add 10 μl to the background well Assay Buffer, add 10 μl mouse leptin standard substance...

Embodiment 3

[0051] Effects of betulinic acid on liver tissue of high-fat mice:

[0052] Non-alcoholic fatty liver disease (NAFLD) is generally caused by lipid deposition in the liver, and triglyceride is the most important indicator. Therefore, at the end of the experiment, the mouse liver tissue was taken for liver TG determination.

[0053] The specific measurement method is as follows: Firstly, homogenate the tissue, add 500ul of 5% NP40 into a 1.5ml EP tube, take out about 30mg of liver specimen and put it in (record the specific weight). Grind twice at 45s*60HZ in an ice bath to make a homogenate. Then transfer all the sample supernatant to a 1.5mL centrifuge tube. Then put the 1.5ml EP tube in a 95-degree water bath for 5 minutes (a white precipitate formed), and let it stand at room temperature for 10 minutes; then put it in a 95-degree water bath for 5 minutes, and then let it stand at room temperature for 10 minutes. The maximum speed is 13300g, centrifuge for 2 minutes, room ...

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Abstract

The invention discloses application of betulinic acid as a leptin sensitizer in preparation of related drugs for treating leptin resistance. According to the invention, high-fat, ob / ob and db / db obesemice are taken as research objects and treated with the betulinic acid, and the weight, serum leptin concentration, liver triglyceride, insulin tolerance and glucose tolerance tests and blood fat indexes are measured. The results show that the betulinic acid can significantly reduce the weight, improve the leptin resistance, lower the liver triglyceride, improve the insulin resistance and lower the blood fat in the high-fat obese mice, the ob / ob and db / db mice treated with the betulinic acid can not reduce the weight and improve the metabolism of glycolipid, and the cellular level proves thatthe combination of the betulinic acid and the leptin can enhance the expression of p-STAT3. The invention provides a basis for treating obesity, a non-alcoholic fatty liver disease, type 2 diabetes and hyperlipidemia by using the betulinic acid as the leptin sensitizer, and also provides a new treatment direction for developing more natural active pharmaceutical ingredients for treating diseasesrelated to the leptin resistance.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and particularly relates to the use of betulinic acid as a leptin sensitizer to prepare medicines related to leptin resistance. Background technique [0002] Leptin (leptin) is a protein product expressed by obesity genes, and it plays a role mainly by binding to leptin receptors. Leptin receptors are widely present on the cell surfaces of tissues and organs such as the hypothalamus, liver, kidney, heart, and lung. Leptin mainly plays its role in the central nervous system by binding to the hypothalamus leptin receptors: reducing body weight, reducing appetite, reducing Energy intake and increase energy consumption; the peripheral effects of leptin include regulating the balance of glucose metabolism, inhibiting fat synthesis and promoting fat decomposition, participating in the regulation of hematopoiesis and immune function, and promoting growth. Leptin binds to the extracellular ...

Claims

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Application Information

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IPC IPC(8): A61K31/56A61P3/04A61P3/06A61P3/10A61P1/16
CPCA61K31/56A61P1/16A61P3/04A61P3/06A61P3/10
Inventor 宁光张志国张翼飞穆倩童蕾
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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