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Use of Worenine as JNK2 Kinase Inhibitor and Treatment of Psoriasis

A technology of methyl coptisine and kinase inhibitor, which is applied in the field of methyl coptisine, can solve the problems of many active ingredients, limited wide application, unclear molecular target and the like

Active Publication Date: 2020-02-14
朱峰
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the pharmacological effects of Coptidis Rhizome are clear, its active ingredients are many, its molecular targets are unknown, and its mechanism of action is unclear, which limits its wide application.

Method used

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  • Use of Worenine as JNK2 Kinase Inhibitor and Treatment of Psoriasis
  • Use of Worenine as JNK2 Kinase Inhibitor and Treatment of Psoriasis
  • Use of Worenine as JNK2 Kinase Inhibitor and Treatment of Psoriasis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1 The binding ability and inhibitory activity of methyl berberine and JNK2 kinase

[0060] 1. Determination of the binding constant Kd of methyl berberine and JNK2 by micro-thermophoresis (MST)

[0061] (1) Purchase pGSTag Flag Jnk2a2 plasmid from addgene company, transfer it into BL21 bacteria for expression, culture at 37°C, induce with ITPG for 4 hours, separate and purify GST-JNK2a2 protein with GSH-beads.

[0062] (2) GST-JNK2a2 recombinant protein according to Monolith NT TM Protein Labeling Kit RED (Cat#L001) was used for labeling. Methyl berberine was configured into 50mM mother solution with DMSO, and was diluted with 20mM HEPES (pH7.4) assay solution containing 5% DMSO. The highest concentration was 2mM, and the lowest concentration was 0.14nM. A total of 16 diluted working solutions. GST-JNK2a2 protein at a concentration of 869.6nM was added to each working solution, and the equilibrium dissociation constant Kd was measured on a microcalorometer. T...

Embodiment 2

[0065] Example 2 Observing the effect and molecular mechanism of methyl berberine on inhibiting psoriasis in a psoriasis cell model

[0066] 1. MTT method to determine the concentration of 80% HaCat cell survival after the addition of methyl berberine

[0067] HaCat cells were digested and counted, and 7000 cells were inoculated into each well of a 96-well plate. After 24 hours, different concentrations of methyl coptisine (0 μM, 0.4 μM, 2 μM, 10 μM, 50 μM, 250 μM, 1250 μM) were added to 10 wells at each concentration. 24h and 48h after adding the drug, add 100μl of 0.5mg / ml MTT to each well, incubate at 37°C for 4 hours, discard the MTT solution, add 150μl DMSO, shake well to completely dissolve the crystals in the well, and measure the wavelength at 490nm with a microplate reader The absorbance value was used to analyze cell viability. Take 80% HaCat cell survival rate as the drug safety concentration, that is, 12.5μM, IC 50 = 175 μM.

[0068] 2. Establish a psoriasis cel...

Embodiment 3

[0070] Example 3 Methyl coptisine reduces the clinical manifestations and pathological changes of psoriasis induced by imiquimod (IMQ)

[0071] 1. Establishment of animal models of psoriasis

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PUM

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Abstract

The invention discloses the use of Worenine as JNK2 kinase inhibitor. The Worenine can specifically combine JNK2 kinase and the two have strong binding ability, and simultaneously inhibit JNK2 activity in a dose-dependent manner. Worenine has good therapeutic activity against psoriasis, which is closely related to the inhibition of JNK, STAT3 signal pathway activation and the expression of psoriasis marker S1007 by Worenine, so it can be used as an active ingredient to prepare drugs for treating psoriasis.

Description

technical field [0001] The present invention relates to the new use of methyl berberine, especially the new use as a JNK2 kinase inhibitor. The present invention also relates to the use of methyl berberine in the preparation of medicines for treating psoriasis and a medicine for treating psoriasis . Background technique [0002] c-jun N-terminal kinase [c-jun N-terminal kinases (JNK)] was first defined as stress-activated protein kinases [stress-activated protein kinases (SAPK)], is a serine threonine kinase, belongs to the mitogen Activated protein kinase [mitogen-activated protein kinase (MAPK)] family member. Mammalian JNKs are encoded by three different genes, namely JNK1, JNK2, and JNK3. After alternative splicing, there are more than ten kinds of protein products, with molecular weights ranging from 46kDa to 55kDa[1]. JNK1 and JNK2 are expressed in most tissues, while JNK3 expression is mainly restricted to the brain, heart and testis. The different distribution of ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4375A61K36/718A61P17/06
CPCA61K31/4375A61K36/718A61K9/0014A61P17/06
Inventor 朱峰段秋红路慧马腾飞倪小芳
Owner 朱峰
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