Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on OATP1B1 and OATP1B3

A compound, the technology of Polygonum multiflorum, is applied in the field of screening of hepatotoxic compounds in Polygonum multiflorum, which can solve the problems of time-consuming, high cost, and unclear targets of hepatotoxic components.

Pending Publication Date: 2021-09-10
NAT INST FOR FOOD & DRUG CONTROL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The screening method using in vitro cell and microtissue experiments has the problem of unclear targets of hepatotoxic components, and the screening method using animal experiments has problems such as time-consuming and high cost

Method used

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  • Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on OATP1B1 and OATP1B3
  • Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on OATP1B1 and OATP1B3
  • Rapid screening method for hepatotoxic compounds in polygonum multiflorum based on OATP1B1 and OATP1B3

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 Computer Molecular Docking Screening of Hepatotoxic Compounds

[0061] The main components of Radix Polygoni Multiflori were collected through literature and database retrieval, and a total of 49 molecules were obtained. DiscoveryStudio2.5 was used to preprocess these molecules. The preprocessing mainly included the following operations: three-dimensional structure generation, structure optimization, and repeated structure deletion. 49 molecules were obtained. Chemical structures, based on which ligand libraries are constructed and subsequently used for virtual screening.

[0062]Collect the primary sequence data of OATP1B1 / OATP1B3 protein from the uniprot database, input the sequence into trRossetta (https: / / yanglab.nankai.edu.cn / trRosetta / ) to construct the homology modeling structure of OATP1B1 / OATP1B3, and use the Laplace diagram And the Verify-3D algorithm evaluates the accuracy of the structure. Its structure and Laplace diagram are as follows figure 1...

Embodiment 2

[0089] Example 2 Hepatotoxicity investigation

[0090] In order to further verify the accuracy of the method in Example 1 and the correlation between OATP1B1 / 3 inhibition and liver toxicity, this example conducted a liver cytotoxicity investigation.

[0091] HepaRG cells in the logarithmic growth phase were digested and adjusted to 5×10 4 cells / mL, inoculate about 5000 cells per well in a 96-well plate, and administer after incubation for 18-24 hours. A blank control group (without HepaRG cells), a vehicle control group (0.5% DMSO), a positive control bilirubin group and different concentrations of target compound administration groups were set up. Firstly, a preliminary experiment was carried out according to the solubility of the compound in the solvent, and the concentration range of each target compound was preliminarily determined, and then further toxicity tests were carried out according to the results of the preliminary experiment to determine the half-inhibitory conc...

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Abstract

The invention relates to a method for screening hepatotoxic compounds in polygonum multiflorum based on a computer molecular docking technology. The method comprises the following steps: (1) obtaining a three-dimensional chemical structure of at least one compound to be detected in the polygonum multiflorum; (2) constructing a protein homologous modeling structure of the OATP1B1 and the OATP1B3, and respectively determining active sites of the OATP1B1 and the OATP1B3; (3) respectively carrying out computer molecular docking on the compound to be detected and a positive compound serving as a common substrate of OATP1B1 and OATP1B3 and the active sites to obtain docking scores; and (4) judging the to-be-detected compound as the hepatotoxic compound under the condition that the docking score of the to-be-detected compound reaches a docking judgment value. The screening method disclosed by the invention is rapid, economical and simple to operate, and can realize high-throughput screening of numerous compounds.

Description

technical field [0001] The invention relates to a rapid screening method for hepatotoxic compounds in Radix Polygoni Multiflori, in particular to an organic anion transporting polypeptide 1B1 (organic anion transporting polypeptide 1B1, OATP1B1) and an organic anion transporting polypeptide 1B3 (organic anion transporting polypeptide 1B3) based on molecular docking technology , OATP1B3) as a screening method for hepatotoxic compounds in Polygonum multiflorum multiflorum L. Background technique [0002] Polygonum multiflorum is the dry tuber root of Polygonum multiflorum Thunb., which has the functions of nourishing liver and kidney, nourishing essence and blood, and black hair. Recently, the toxicity of Polygonum multiflorum has become increasingly prominent. The Adverse Reaction Monitoring Center of the State Food and Drug Administration (SFDA) has collected more than 20,000 adverse reaction reports of Polygonum multiflorum preparations (involving more than 1,000 kinds) in ...

Claims

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Application Information

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IPC IPC(8): G16C20/64G16C20/30G16C20/90G16C20/20G16C20/50G16C10/00G16B15/30G16B50/30
CPCG16C20/64G16C20/30G16C20/90G16C20/20G16C20/50G16C10/00G16B15/30G16B50/30
Inventor马双成汪祺文海若李勇杨建波于建东姚令文
OwnerNAT INST FOR FOOD & DRUG CONTROL