Application of albiflorin as indoleamine 2,3-dioxygenase (IDO) inhibitor

A technology of paeonifloride glycosides and uses, applied in the field of paeonifloride glycosides as indoleamine 2,3-dioxygenase inhibitors, can solve side effects and other problems, achieve enhanced immune function, prevent and alleviate the formation and development of , the effect of preventing tumor cell escape

Inactive Publication Date: 2017-12-22
张作光
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The pathogenesis of depression is still unknown. Most of the existing antidepressants are developed on the basis of the monoamine hypothesis. The response rate of the drugs is only 50% to 60%, and they all have different degrees of side effects. According to statistics, "continuously receiving 6 Less than 25% of patients are treated with antidepressants for 1 month, and a considerable proportion are discontinued because of side effects of sex and sleep" (Andrew Solomon "Melancholy" P085) Due to the existence of a large number of unmet medical needs, people We have been working hard to find antidepressants with new biological targets and new mechanisms of action, among which IDO inhibitors have been the focus of global medical circles in recent years

Method used

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  • Application of albiflorin as indoleamine 2,3-dioxygenase (IDO) inhibitor
  • Application of albiflorin as indoleamine 2,3-dioxygenase (IDO) inhibitor
  • Application of albiflorin as indoleamine 2,3-dioxygenase (IDO) inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Effect of IDO inhibitor paeonifloride of the present invention on IDO overexpression and depression-like behavior induced by chronic stress rat model (CUMS)

[0058] 1. In the hippocampal tissue of chronic unpredictable mild stress model (CUMS) rats, the secretion of IDO was significantly increased, and the melatonin receptor 1 (MT1) was significantly decreased. After 7 days of paeonifloride administration (7mg / day, 14mg / day), the IDO activity in the rat hippocampus was significantly inhibited (Pfigure 1 :

[0059] Effects of paeonifloride on indoleamine-2,3-dioxygenase (IDO) in rat hippocampus

[0060] Effect of melatonin receptor 1 (MT1) (Mean±SE)

[0061]

[0062] (# indicates an increase in P<0.05 compared with the model group, ## indicates an increase in P<0.01 compared with the model group, ** indicates a decrease in P<0.01 compared with the model group)

[0063] 2. The anabolic pathway of serotonin in the hippocampus of rats with chronic unpredictable mild s...

Embodiment 2

[0065] Effects of IDO inhibitor paeonifloride of the present invention on LPS-induced IDO activation, inflammatory depression-like behavior and cognitive dysfunction in mice

[0066] The mice were randomly divided into 6 groups (16 in each group): blank group, model group, positive drug fluoxetine hydrochloride group (10mg / kg), low-dose paeonifloride group (3.5mg / kg), middle-dose Group (7mg / kg), high-dose group (14mg / kg), continuous intragastric administration for 7 days.

[0067] 1. Experiment and testing content

[0068] 1. Behavioral experiments: forced swimming (FST), tail suspension (TST) and open field test (OFT)

[0069] After administration on the 7th day, intraperitoneal injection of LPS (0.83mg / kg) was used to establish the model, and 16 hours after the injection, the open field test (OFT) was performed; 24 hours after the injection, the forced swimming test (FST) and the tail suspension test (TST) were performed; after that , the eyeballs were picked to get blood,...

Embodiment 3

[0091] Embodiment 3. Molecular docking experiment of IDO1 inhibitor paeonifloride and IDO1 protein using MOE2016 software

[0092] 1. Selection of IDO1 crystal structure

[0093] At present, there are 20 crystal structures of IDO protein reported. After considering multiple factors such as biological source, resolution, and ligand small molecule structure, the crystal structure numbered 4PK5 was finally determined as the molecular docking structure of IDO1 protein.

[0094] 2. Small molecular structure, paeoniflorin (Albiflorin), the structure is as follows:

[0095] 3. Molecular docking experiments

[0096] The docking experiments and other related calculations were completed using the MOE2016 software package.

[0097] step:

[0098] Prepare the acceptor structure, correct errors in the structure, complete partial charge calculations and protonation procedures. Choose an appropriate subunit as the receptor and delete the rest.

[0099] Using the Flexible Alignment funct...

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PUM

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Abstract

The invention provides an application of albiflorin, or a pharmaceutically acceptable salt thereof, as an IDO inhibitor. The albiflorin or the pharmaceutically acceptable salt thereof herein is used as the IDO inhibitor for preparing medicines, foods, healthcare products, food additives or nutritious supplements, which are used for preventing and treating pathological feature diseases with tryptophan metabolic pathway, which are induced by IDO over-activation; herein, the diseases are selected from one or more of cancer, depression, Alzheimer's disease and Parkinson's disease.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to the use of paeoniflorin (Albiflorin), and more specifically relates to the use of paeoniflorin as an indoleamine 2,3-dioxygenase (IDO) inhibitor. Background technique [0002] Indoleamine 2,3-dioxygenase (IDO) is an enzyme that contains heme in cells. It is the only enzyme outside the liver that can catalyze the metabolism of tryptophan and decompose it along the kynurenine pathway to produce quinoline Rate-limiting enzyme for a series of metabolites including acids. In recent years, studies have fully proved that overactivation of IDO causes the microenvironment of tryptophan deficiency in the body by degrading tryptophan, which may induce cancer, depression, Alzheimer's disease and other diseases closely related to tryptophan deficiency. Disease occurs. [0003] Specifically, the increase in IDO activity can cut off the activation of T cells by degrading tryptophan, thereby inhibiting t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7048A61P35/00A61P25/28A61P25/16A61P25/14A61P25/24A61P27/12A61P27/02A61P37/02A61P1/16A61P13/12A23L33/125
CPCA23L33/125A61K31/7048A61P25/16A61P25/24A61P25/28A61P27/12A61P35/00A61P37/00
Inventor 张作光
Owner 张作光
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