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Application of cortex periplocae C21 sterides in preparation of IDO inhibitor

A technology of fragrant peel and inhibitor, which is applied in the field of fragrant peel C21 steroids in the preparation of IDO inhibitors

Active Publication Date: 2018-11-13
CATCH BIO SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] For this reason, the technical problem to be solved in the present invention is the problem in the prior art that C21 steroids are used for the preparation of IDO inhibitors without Perfume, thereby providing the purposes of C21 steroids in the preparation of IDO inhibitors

Method used

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  • Application of cortex periplocae C21 sterides in preparation of IDO inhibitor
  • Application of cortex periplocae C21 sterides in preparation of IDO inhibitor
  • Application of cortex periplocae C21 sterides in preparation of IDO inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1 Preparation of C21 steroids from Persica chinensis

[0051] Take xiangjiapi, crush it, add 3 times the weight of ethanol aqueous solution with a volume concentration of 95%, heat and reflux for extraction 3 times, extract for 2 hours each time, combine the extracts, concentrate under reduced pressure until there is no alcohol smell, and get xiangjiapi extract ;

[0052] Suspend the extract of Cyanorrhizae bark in 1 times the weight of water, then use chloroform as the extractant to extract twice, collect the organic phase of the extract, and then concentrate under reduced pressure to obtain the extract of the chloroform extraction part of Xiangjiapi;

[0053] Take the extract from the chloroform extraction part of Xiangjiapi and purify it by AB-8 macroporous resin column chromatography (the diameter of the macroporous resin column is 8cm, and the column volume is 3.5L), using water as mobile phase A and ethanol as mobile phase B , carry out gradient elution ...

experiment example 1

[0057] Experimental example 1 Study on the Inhibitory Activity of C21 Steroids of Cortex Persicae of the Present Invention on IDO

[0058] 1. Purpose of the experiment

[0059] The plasmid pcDNA3.1-IDO was used to transfect HEK293 cells to make it highly express IDO, and then the inhibitory activity of C21 steroids of the present invention at the cell level to IDO was determined.

[0060] 2. Experimental method

[0061] HEK 293 cells were seeded in a 96-well plate at a density of 2.5X104 cells / well, cultured in DMEM medium (containing 10% fetal bovine serum, 50 U / mL penicillin and 50 mg / mL streptomycin), placed at 37 ° C, humidity 95%, 5% CO 2 cultured in an incubator. After culturing for 24 hours, liposome Lipofectamin 2000 was used to mediate pcDNA3.1-hIDO plasmid transfection, and they were divided into positive control group and experimental group 1-9.

[0062] Positive control group is with 1-methyltryptophan (1-MT) as test product, and experimental group 1-9 groups...

experiment example 2

[0073] Experimental example 2 Therapeutic effect of Cinnabar cortex C21 steroids of the present invention on ankylosing spondylitis

[0074] 1. Purpose of the experiment

[0075] The mouse model of ankylosing spondylitis was established by using proteoglycan immunization method, then gavage C21 steroids of the present invention, and ELISA method was used to detect inflammatory markers serum TNF-α and NF-кB receptor activator ligand (RANKL ) level, and detect the serum IDO activity (Kyn / Trp), verify the curative effect of the present invention C21 steroid for ankylosing spondylitis.

[0076] 2. Experimental method

[0077] 2.1 Experimental animals

[0078] Thirty-two healthy male BALB / c mice, weighing (18±2) g, aged 4-5 weeks, were purchased from Shanghai SLAC.

[0079] 2.2 Drugs to be tested

[0080] The salivaside C and salivaside Q prepared in Example 1 were used as the test drugs.

[0081] 2.3 Experimental grouping and modeling

[0082] After the mice were adaptivel...

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Abstract

The invention belongs to the field of drugs or health care products, and particularly relates to application of cortex periplocae C21 sterides in preparation of an IDO inhibitor. Through research, inhibition activity of periplocin C, periplocin D, periplocin O, periplocin P, periplocin Q, periplocin R, periplocin S, periplocin M and periplocin N to IDO in cells is superior to inhibition activity of positive control drug 1-methyltryptophan (1-MF) to IDO in cells, and the cortex periplocae C21 sterides have remarkable IDO inhibition activity, and can be used for treating cancers, an alzheimer disease, an autoimmune disease, ankylosing spondylitis, bacterial infection, cataract, mood disorder, depression or anxiety disorder.

Description

technical field [0001] The invention belongs to the field of medicines or health care products, and in particular relates to the use of C. citronella C21 steroids in the preparation of IDO inhibitors. Background technique [0002] IDO (indoleamine-2, 3-dioxygenase) is the only rate-limiting enzyme that catalyzes the metabolism of tryptophan along the kynurenine pathway (KP) outside the liver. , can decompose tryptophan into various metabolites such as L-kynurenine, picolinic acid and quinolinic acid. L-Tryptophan is an amino acid necessary to maintain cell activation and proliferation in the human body, and is also an indispensable component of protein. Its deficiency will lead to abnormal function of some important cells. Since it was discovered in 1967, the mechanism of IDO inhibiting the proliferation of pathogenic microorganisms by degrading tryptophan, and the relationship between IDO and nervous system diseases have been gradually clarified; and studies have confirmed...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/58A61P35/00A61P37/00A61P25/28A61P31/04A61P27/12A61P19/00A61P25/22A61P25/24
CPCA61K31/58
Inventor 张黎明
Owner CATCH BIO SCI & TECH
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