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Application of Lei Tenshu in the preparation of medicines for treating non-alcoholic fatty liver disease

A fatty liver disease, non-alcoholic technology, applied in the field of pharmacotherapeutics, can solve the problems that the pathogenesis is not fully elucidated, and there is no effective marketed drug for treatment

Active Publication Date: 2021-10-08
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the occurrence of NAFLD is closely related to metabolic syndrome such as diabetes, obesity, and hypertension, its pathogenesis has not yet been fully elucidated, so there is no effective marketed drug for the treatment of this disease

Method used

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  • Application of Lei Tenshu in the preparation of medicines for treating non-alcoholic fatty liver disease
  • Application of Lei Tenshu in the preparation of medicines for treating non-alcoholic fatty liver disease
  • Application of Lei Tenshu in the preparation of medicines for treating non-alcoholic fatty liver disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0118] Example 1: Leitengshu relieves lipid accumulation and damage in the liver of NAFLD model mice

[0119] In the present invention, on the model mice of NAFLD induced by a high-fat and high-sugar diet, the influence of reitengshu on lipid accumulation and damage in the liver of the model mice is tested. Experiments have shown that Leitenshu can alleviate the lipid accumulation in the liver of NAFLD model mice, reduce the two important indicators of liver function, AST and ALT, and the liver damage caused by ballooning.

[0120] 1. Experimental principle:

[0121] High-fat and high-sugar diet-induced C57BL / 6J is a classic mouse model of NAFLD, which can relatively simulate the main clinical features, biochemical changes and morphological changes of NAFLD [Biomed Res Int. 2015:574832,2015]. The present invention uses this induction scheme as an animal model for evaluating the anti-type 2 diabetes of the compound.

[0122] 2. Experimental materials and methods

[0123] 1) ...

Embodiment 2

[0134] Example 2: Effect of Leitenshu on the types and contents of fatty acids in the liver of NAFLD model mice

[0135] The present invention uses gas chromatography-mass spectrometry to detect the types and contents of fatty acids in the liver of experimental animals, compares the differences in fatty acids between the Leitenshu administration group and the solvent control group, and infers its effect from Leitenshu on liver fatty acid metabolism. Possible mechanism for inhibition of lipid accumulation. The research results show that Leitenshu can significantly reduce the ratio of C16:1 / C16:0 fatty acid and the ratio of C16:0 / C18:2n6 fatty acid, indicating that the activity of SCD-1 and lipid regeneration are inhibited.

[0136] 1. Experimental principle:

[0137] The activity of some lipogenesis-related enzymes can be predicted by the ratio of different products to precursors of fatty acids, for example: the activity of SCD-1 can be characterized by the ratio of C16:1n-7 / C16...

Embodiment 3

[0148] Example 3: The effect of the tissue level test compound Leitenshu on SCD-1 in the liver

[0149] The present invention uses real-time quantitative fluorescent PCR technology to detect the effect of the compound Leitenshu on SCD-1 mRNA in liver tissue. The research results show that: high dose Leitenshu can significantly inhibit the mRNA of SCD-1 in liver tissue.

[0150] 1. Experimental materials and methods:

[0151] (1) RNA extraction from liver tissue: Accurately weigh 10 mg of liver tissue; add two steel beads to a centrifuge tube containing 10 mg of tissue, add 1 ml of Trizol, and homogenize with a homogenizer; centrifuge at 12,000 rpm for 5 min at 4°C, and take Transfer the clear liquid into a new 1.5ml centrifuge tube; add 200μL chloroform, mix by inverting for 2min, let stand for 5min, centrifuge at 12000rpm at 4°C for 10min; take 400μL of the upper aqueous phase into a clean centrifuge tube, add 200μL of absolute ethanol, mix well After that, let it stand for ...

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Abstract

The invention discloses the use of Leitenshu (LLDT‑8) in preparing medicine for treating nonalcoholic fatty liver disease. In the use, Leitenshu acts as a transcription inhibitor of SCD-1 and / or a transcription activator of genes related to fatty acid beta oxidation, including PPARα, ACADL, ACADM, ACOX1, and CPT1A. Leitenshu can inhibit the mRNA of SCD-1, thereby inhibiting the desaturation of fatty acids and inhibiting lipid regeneration; at the same time, it can also increase the mRNA of genes related to fatty acid β-oxidation, thereby increasing the β-oxidation of fatty acids and increasing the level of β-hydroxybutyrate in serum. The content of acid ultimately inhibits lipid accumulation in the liver by inhibiting lipid production and promoting lipid oxidative decomposition.

Description

technical field [0001] The invention relates to the field of drug therapy, in particular to the use of Leitenshu or its pharmaceutical composition in the treatment of non-alcoholic fatty liver disease. Background technique [0002] Triptolide ((5R)-5-hydroxytriptolide, LLDT-8) is a derivative of triptolide (Triptolide), an effective extract from the traditional Chinese medicine Tripterygium wilfordii Hook.f.TWHF. It also has immunosuppressive activity, but Less toxic. Current studies suggest that the anti-inflammatory effect of Leitenshu is mainly through inhibiting the production of Th1 cytokines (IFN-c, IL-2) and inflammatory cytokines (TNF-α, IL-6); reducing the production of nitric oxide (NO) This is achieved through regulatory mechanisms such as production and expression of inducible nitric oxide synthase (iNOS). In addition, Leitenshu has been reported to have anti-tumor biological activity. [0003] [0004] Nonalcoholic fatty liver disease (NAFLD) is a kind of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/585A61P1/16
CPCA61K31/585A61P1/16
Inventor 任进陆姮磊陈静董云霞戚新明李援朝
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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