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Application of dihydrotanshinone I in preparation of medicines for resisting hepatic fibrosis

A technology of dihydrotanshinone and anti-hepatic fibrosis, applied in the field of medicine

Inactive Publication Date: 2016-01-06
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The anti-hepatic fibrosis effect of dihydrotanshinone I described in this experiment has not been reported so far at home and abroad.

Method used

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  • Application of dihydrotanshinone I in preparation of medicines for resisting hepatic fibrosis
  • Application of dihydrotanshinone I in preparation of medicines for resisting hepatic fibrosis
  • Application of dihydrotanshinone I in preparation of medicines for resisting hepatic fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] "Example 1" Dihydrotanshinone I inhibits the main markers of liver fibrosis in LX-2 cells induced by TGFβ1 at the mRNA and protein levels

[0026] 1.1 TGFβ1 induces LX-2 cells, and cultures LX2 cells in DMEM (Gibco) medium containing 10% fetal bovine serum at 37°C and 5% CO2. Follow 1 x 10 per well 5 The cells were plated in a 6-well plate, and after culturing for 24 hours, the original medium in the 6-well plate was removed using a vacuum pump and DMEM (Gibco) medium without 10% fetal bovine serum was added. After 24 hours of starvation culture, TGF-β1 (2ng / ml) was added to induce, and at the same time, dihydrotanshinone I (CAS number: 87205-99-0) was added in a gradient concentration, the concentrations were 1 μmmol / L, 5 μmmol / L, 10 μmmol / L , and set up a control group (no TGF-β1 induction) and a TGF-β1 induction group (only TGF-β1 induction).

[0027] 1.2 After continuing to cultivate for 24 hours, discard the medium and follow the instructions of AZfresh TM Total...

Embodiment 2

[0029] "Example 2" SD rat common bile duct ligation-induced liver fibrosis model preparation

[0030]Select 22 SD male rats with a body weight of 180-220g, and randomly divide them into a sham operation group, a model group, and a dihydrotanshinone I administration (25 mg / kg) group, wherein 6 in the sham operation group, 8 in the model group, and 2 8 rats in group I of hydrotanshinone. After fasting without food and water for 12 hours before the animal experiment, the animals were anesthetized with isoflurane for surgery. Among them, the model group and the treatment group underwent common bile duct ligation (BDL). In the aseptic operating table, a midline incision was made on the upper abdomen, the liver margin was raised, the duodenum was opened, and the common bile duct was separated by 2-3 cm. Two 000 surgical sutures were ligated at the place near the duodenum and near the porta hepatis, and the common bile duct was cut from the middle. In the sham operation group, only...

Embodiment 3

[0031] "Example 3" the inhibitory effect of dihydrotanshinone I on the elevation of serum ALT / AST / γ-GT levels in rats induced by BDL

[0032] The rats were fasted without food and water for 12 hours before sampling, and the rats were anesthetized with 10% chloral hydrate, and abdominal aortic blood was collected. After centrifugation at 1500 rpm for 10 min, the serum was collected for detection of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyltransferase (γ-GT). The results showed that dihydrotanshinone I could significantly inhibit the contents of ALT, AST and γ-GT in rat serum (Table 1), indicating that dihydrotanshinone I could improve rat liver function.

[0033] Table 1. Effect of dihydrotanshinone I on BDL-induced serum ALT / AST / γ-GT levels in rats

[0034]

[0035] *p<0.05 vs. BDL group; #p<0.05 vs. sham group.

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Abstract

The invention belongs to the field of medicines, and relates to application of dihydrotanshinone I in preparation of anti-hepatic fibrosis medicines. Systematic researches on the inhibiting effect on the mRNA and protein level of fibrosis main markers (COL1A1, TGFB1, ACTA2 and MMP2) in a TGF beta 1 induced LX-2 cell, influence on contents of ALT and AST in the serum of a BDL rat, improvement on the pathological change of liver tissues of the BDL rat, influence on the content of hydroxyproline of liver tissues of the BDL rat, inhibition on the mRNA and protein level of fibrosis main markers of liver tissues of a rat, influence on the hepatic fibrosis degree of the rat prove that the dihydrotanshinone I has excellent anti-hepatic fibrosis activity, and is expected to be developed into novel anti-hepatic fibrosis medicines.

Description

Technical field: [0001] The invention belongs to the field of medicine, and relates to the application of dihydrotanshinone I, an active ingredient of salvia miltiorrhiza, in the preparation of anti-hepatic fibrosis drugs. Background technique: [0002] Hepatic fibrosis is a tissue repair compensatory response secondary to liver injury caused by various etiologies. When liver fibrosis occurs, hepatic stellate cells (HSCs) are abnormally activated and proliferated, leading to a large amount of extracellular matrix (ECM) synthesis and secretion, ECM synthesis and degradation imbalance, and damage to the normal structure and function of the liver. Hepatic fibrosis (hepatic fibrosis, HF) is a necessary pathological process for the development of chronic liver disease to liver cirrhosis and even primary liver cancer. Therefore, all the factors that lead to liver cirrhosis injury are also the cause of liver fibrosis. The most common clinical causes are viral infection, excessive...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/58A61P1/16
Inventor 邵荣光葛茂旭何红伟赵双双李娜仁张镱萱
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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