Use of ferroptosis inhibitor-1 in the preparation of a phytotoxicity inhibitor and a pesticide composition

Abstract

The application relates to the technical field of plant protection, in particular to application of ferroptosis inhibitor-1 in preparation of a toxitant inhibitor of mycotoxin and a pesticide composition. The application finds that the ferroptosis inhibitor-1 can significantly improve the tolerance of plants to mycotoxin poisoning, has the effect of relieving the plants from mycotoxin poisoning, and helps the plants and seeds to normally germinate and grow under the condition of high-concentration mycotoxin.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of plant protection, in particular to an application of ferrostatin-1 in preparation of a tunicamycin plant toxicity inhibitor and a pesticide composition. BACKGROUND

[0002] Tunicamycin (TM) is a kind of nucleotide antibiotic produced by soil actinomycetes, which can inhibit the N-acetylglucosamine phosphotransferase (GPT) to block the N-glycosylation process in the endoplasmic reticulum (ER) of cells, leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen, triggering endoplasmic reticulum stress (ER stress) and cell death. Tunicamycin can inhibit gram-positive bacteria, yeast, fungi and viruses, and has anticancer activity, which has important research and application value.

[0003] The toxic effect of tunicamycin on animal cells can be alleviated by chemical chaperones, and the mechanism is that chemical chaperones can alleviate endoplasmic reticulum stress by helping unfolded proteins to form the correct conformation, reducing the response of unfolded proteins, and alleviating tunicamycin-induced cell death. However, for plant cells, no effective tunicamycin toxicity inhibitor has been found. It is necessary to further study the molecular mechanism of tunicamycin-induced cell death and to study tunicamycin plant toxicity inhibitors, which will help to help analyze the related mechanism and promote the precise targeted application of tunicamycin.

[0004] Ferrostatin-1 (Fer-1) is an artificially synthesized antioxidant, which is known as a ferroptosis inhibitor, and can inhibit Erastin-induced HT-1080 cell ferroptosis. It can prevent membrane lipid damage through a reduction mechanism, thereby inhibiting cell death. There is no report on the inhibition of tunicamycin activity by ferrostatin-1. SUMMARY

[0005] Based on this, one or more embodiments of the present application provide an application of ferrostatin-1 in preparation of a tunicamycin plant toxicity inhibitor and a pesticide composition, and the present application finds that ferrostatin-1 has the effect of alleviating the toxic damage of tunicamycin to plants, and can be used for soil detoxification in agricultural production.

[0006] The technical solution of the present application includes the following contents:

[0007] An application of ferrostatin-1 in preparation of a tunicamycin plant toxicity inhibitor, wherein the structure of the ferrostatin-1 is shown as formula (I):

[0008]

[0009] In some embodiments, the thaxtomin phytotoxicity inhibitor can be used to alleviate thaxtomin phytotoxicity.

[0010] In some embodiments, the thaxtomin phytotoxicity comprises at least one of inhibiting seed germination and inhibiting seedling growth.

[0011] In some embodiments, the plant comprises at least one of Brassicaceae, Poaceae, Fabaceae, Solanaceae, Cucurbitaceae, Rosaceae, Rutaceae, Umbelliferae.

[0012] A method of alleviating thaxtomin phytotoxicity in a plant, comprising:

[0013] treating a seed or a seedling of the plant with ferroptosis inhibitor-1;

[0014] The ferroptosis inhibitor-1 has a structure as shown in formula (I):

[0015]

[0016] A use of ferroptosis inhibitor-1 in preparation of a pesticide composition, the pesticide composition comprising the ferroptosis inhibitor-1 and a pesticide adjuvant;

[0017] The ferroptosis inhibitor-1 has a structure as shown in formula (I):

[0018]

[0019] In some embodiments, the pesticide composition can be used to alleviate thaxtomin phytotoxicity.

[0020] In some embodiments, the thaxtomin phytotoxicity comprises at least one of inhibiting seed germination and inhibiting seedling growth.

[0021] In some embodiments, the plant comprises Arabidopsis thaliana.

[0022] A method of soil detoxification, comprising:

[0023] applying ferroptosis inhibitor-1 to the soil and turning over;

[0024] The ferroptosis inhibitor-1 has a structure as shown in formula (I):

[0025]

[0026] The present application provides a use of ferroptosis inhibitor-1 in preparation of a thaxtomin phytotoxicity inhibitor and a pesticide composition, and a method of alleviating thaxtomin phytotoxicity in a plant and a method of soil detoxification.

[0027] The ferroptosis inhibitor-1 of the embodiments of the present application can significantly improve the tolerance of plants to tunicamycin toxicity, and help plants and seeds to grow normally under high concentration of tunicamycin. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the specific embodiments or prior art of the present application, the drawings needed in the description of the specific embodiments or prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor on the basis of these drawings.

[0029] Figure 1 Figure 1 is a comparison chart of detoxification effects of 4-phenylbutyric acid, taurine deoxycholic acid, ferroptosis inhibitor CPX and ferroptosis inhibitor-1 on tunicamycin toxicity of Arabidopsis bzip28 / 60 double mutants in Example 1 of the present application.

[0030] Figure 2 Figure 2 is a comparison chart of detoxification effects of different concentrations of ferroptosis inhibitor-1 on tunicamycin toxicity of wild type Arabidopsis in Example 1 of the present application. Figure 2 Figure 3 is a comparison chart of growth states of wild type Arabidopsis under different treatment conditions. Figure 2 Figure 4 is a comparison chart of relative weight of wild type Arabidopsis under different treatment conditions.

[0031] Figure 3 Figure 5 is a comparison chart of detoxification effects of different concentrations of ferroptosis inhibitor-1 on tunicamycin toxicity of wild type Arabidopsis, Arabidopsis bzip28 / 60 double mutants and Arabidopsis nrt1.7-2 mutants in Example 1 of the present application.

[0032] Figure 4 Figure 6 is a comparison chart of UPR gene expression of wild type Arabidopsis under tunicamycin toxicity with and without the addition of ferroptosis inhibitor-1 in Example 1 of the present application.

[0033] Figure 5 Figure 7 is a comparison chart of detoxification effects of different concentrations of ferroptosis inhibitor-1 on tunicamycin toxicity of wild type Arabidopsis and Arabidopsis bzip28 / 60 double mutants in Example 1 of the present application.

[0034] Figure 6 Figure 8 is a comparison chart of detoxification effects of ferroptosis inhibitor-1 of Comparative Example 1 of the present application on wild type and tunicamycin hypersensitive yeast cells under tunicamycin toxicity. Figure 6Example 1: The detoxification effect of Ferrostatin-1 on wild-type yeast cells poisoned by tunicamycin; Figure 6 Example 2: The detoxification effect of Ferrostatin-1 on yeast cells hypersensitive to tunicamycin. DETAILED DESCRIPTION

[0035] The application will be further described below in connection with the embodiments and examples. It should be understood that these examples are only used to illustrate the application and not intended to limit the scope of the application. Furthermore, it should be understood that those skilled in the art can make various modifications or changes to the application after reading the content taught in the application, and these equivalent forms also fall within the protection scope of the claims of the application.

[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0037] Terminology

[0038] Unless otherwise indicated or unless the context clearly indicates otherwise, the terms or phrases used in this application have the following meanings:

[0039] The term "and / or" as used herein is intended to cover any and all combinations of one or more relevant items, and includes the possibility of any and all combinations of the relevant items. It should be noted that when at least two conjunctions selected from "and / or" are combined to connect at least three items, it should be understood that in this application, the technical solution undoubtedly includes the technical solution connected by "logical and", and also undoubtedly includes the technical solution connected by "logical or". For example, "A and / or B" includes three parallel solutions of A, B and A+B.

[0040] In this application, "further", "even further", "in particular" and the like are used for the purpose of description and indicate differences in content, but should not be understood as limiting the scope of protection of the application.

[0041] In this application, the terms "first", "second", "third", "fourth" and the like are used for the purpose of description only and should not be understood as indicating or implying relative importance or quantity, nor should they be understood as implicitly indicating the importance or quantity of the technical features indicated. Moreover, "first", "second", "third", "fourth" and the like only serve the purpose of non-exhaustive enumeration and should be understood as not constituting a closed limitation on the quantity.

[0042] In the present application, the technical features described in an open manner include both the closed technical solutions consisting of the listed features and the open technical solutions containing the listed features.

[0043] In the present application, when referring to a numerical interval (i.e., a numerical range), unless otherwise specified, the optional numerical distribution within the numerical interval is considered to be continuous, and includes both numerical endpoints (i.e., the minimum value and the maximum value) of the numerical range and every numerical value between the two numerical endpoints. Unless otherwise specified, when a numerical interval refers only to integers within the numerical interval, it includes both the integer endpoints of the numerical range and every integer between the two endpoints. In addition, when multiple ranges are provided to describe a feature or characteristic, the ranges can be combined. In other words, unless otherwise indicated, the ranges disclosed herein are to be interpreted to include any and all subranges therein.

[0044] Ferrostatin-1 (Ferrostatin-1) is an artificially synthesized antioxidant known to be an effective and selective inhibitor of ferroptosis, which can inhibit Erastin-induced ferroptosis in HT-1080 cells. It can prevent membrane lipid damage through a reduction mechanism, thereby inhibiting cell death.

[0045] Ferrostatin CPX refers to Ciclopirox, which is an iron ion chelator.

[0046] Ferroptosis is an iron-dependent, active oxygen (ROS)-regulated form of programmed cell death, mainly characterized by the accumulation of intracellular lipid peroxides. The process of ferroptosis involves the participation of iron ions, which promote the production of lipid peroxides through Fenton reaction.

[0047] Tunicamycin is an antibiotic mainly derived from Streptomyces. The main function of tunicamycin is to inhibit the N-glycosylation process. It prevents the initial step of N-glycosylation by inhibiting N-acetylglucosamine-1-phosphotransferase, thereby interfering with the synthesis of glycoproteins and glycolipids in cells, affecting many physiological functions of cells, such as affecting the secretion function of cells, the function of cell membrane proteins, etc.

[0048] N-acetylglucosamine phosphotransferase (GPT) is a key enzyme involved in the N-glycosylation process. It catalyzes the transfer of N-acetylglucosamine-1-phosphate from UDP-N-acetylglucosamine to dolichol phosphate in the endoplasmic reticulum (ER), which is an important reaction in the initial step of N-glycosylation.

[0049] Endoplasmic reticulum (ER) is an important organelle in cells, which is a continuous membrane system of tubular, vesicular or flat sac-like structure surrounded by membrane. It is divided into rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). The surface of rough endoplasmic reticulum is attached to ribosomes, and its main function is to synthesize, process and transport proteins. After the newly synthesized proteins enter the lumen of endoplasmic reticulum, they will be modified by folding and glycosylation. The smooth endoplasmic reticulum is mainly involved in lipid synthesis, glycogen metabolism and detoxification.

[0050] N-glycosylation is a post-translational modification of proteins, which is the process of adding an oligosaccharide chain to the asparagine (Asn) residue of a protein. This process occurs in the endoplasmic reticulum and Golgi apparatus.

[0051] Endoplasmic reticulum stress (ER stress) refers to a series of adaptive responses initiated by the endoplasmic reticulum when protein processing, folding, transport and other processes in the endoplasmic reticulum are disturbed or overloaded.

[0052] Chemical chaperones are small molecule compounds that can help proteins in cells to fold correctly and alleviate endoplasmic reticulum stress. 4-phenyl butyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) are two known molecular chaperone compounds that can alleviate endoplasmic reticulum stress caused by unfolded proteins.

[0053] The present application found that ferroptosis inhibitor-1 can alleviate the toxic effect of tunicamycin on plants.

[0054] The technical scheme of the present application embodiment includes an application of ferroptosis inhibitor-1 in preparing a tunicamycin plant toxicity inhibitor. The structure of ferroptosis inhibitor-1 is shown in formula (I):

[0055]

[0056] In some embodiments, the tunicamycin plant toxicity inhibitor can be used to alleviate the toxic effect of tunicamycin on plants.

[0057] In some embodiments, the toxic effect of tunicamycin on plants includes at least one of inhibiting seed germination and inhibiting seedling growth.

[0058] In some embodiments, the plants include at least one of Brassicaceae plants, Poaceae plants, Leguminosae plants, Solanaceae plants, Cucurbitaceae plants, Rosaceae plants, Rutaceae plants, and Umbelliferae plants.

[0059] A method for alleviating the toxic effect of tunicamycin on plants includes:

[0060] treating seeds or seedlings of the plant with ferroptosis inhibitor-1;

[0061] Ferroptosis inhibitor-1 has the structure of formula (I):

[0062]

[0063] In some embodiments, the way of treating seeds or seedlings of the plant with ferroptosis inhibitor-1 comprises:

[0064] immersing roots of the seeds or seedlings of the plant in a solution of ferroptosis inhibitor-1.

[0065] In some embodiments, the way of treating seeds or seedlings of the plant with ferroptosis inhibitor-1 comprises:

[0066] preparing a plant culture medium containing ferroptosis inhibitor, and culturing seeds or seedlings of the plant with the plant culture medium.

[0067] It is understood that the plant culture medium containing ferroptosis inhibitor can be completely prepared by itself, or can be obtained by adding a certain proportion of ferroptosis inhibitor to a commercially available plant culture medium.

[0068] Use of ferroptosis inhibitor-1 in the preparation of a pesticide composition, the pesticide composition comprising ferroptosis inhibitor-1 and a pesticide adjuvant;

[0069] Ferroptosis inhibitor-1 has the structure of formula (I):

[0070]

[0071] In some embodiments, the pesticide composition can be used to alleviate the toxic effect of tunicamycin on plants.

[0072] In some embodiments, the toxic effect of tunicamycin on plants comprises at least one of inhibiting seed germination and inhibiting seedling growth.

[0073] In some embodiments, the plant comprises at least one of Brassicaceae, Poaceae, Fabaceae, Solanaceae, Cucurbitaceae, Rosaceae, Rutaceae, Umbelliferae.

[0074] A method for reducing the toxicity of soil, comprising:

[0075] applying ferroptosis inhibitor-1 to the soil, and turning over;

[0076] Ferroptosis inhibitor-1 has the structure of formula (I):

[0077]

[0078] In some implementations, the method of applying ferroptosis inhibitor-1 to the soil includes:

[0079] First, the pesticide is prepared. The pesticide consists of ferroptosis inhibitor-1 and pesticide adjuvants.

[0080] The pesticide is applied to the soil, and the application methods include spraying, irrigation, and other pesticide application methods commonly used in the agricultural field.

[0081] This application provides the use of iron death inhibitor-1 in the preparation of tunicamycin plant toxicity inhibitors and pesticide compositions, as well as methods for mitigating plant tunicamycin toxicity and soil detoxification methods.

[0082] Iron death inhibitor-1 in this application embodiment can significantly improve the plant's tolerance to tunicamycin toxicity, and help the plant and its seeds germinate and grow normally under high concentrations of tunicamycin.

[0083] In some implementations, a 1 μM iron death inhibitor-1 solution can alleviate plant growth inhibition and seed death after germination caused by 0.02–0.2 μM tunicamycin treatment.

[0084] The following are some specific examples.

[0085] For experimental parameters not specified in the following specific embodiments, please refer to the guidelines given in this application document first, or refer to experimental manuals or other experimental methods known in the art, or refer to the experimental conditions recommended by the manufacturer.

[0086] The raw materials and reagents involved in the following specific embodiments can be obtained commercially or prepared by those skilled in the art using known methods.

[0087] The Arabidopsis bzip28 / 60 double mutant and nrt1.7-2 mutant were constructed according to the method described in patent document CN113549645A. The bzip28 / 60 double mutant is a tunicamycin-sensitive mutant, and the nrt1.7-2 mutant is a tunicamycin-insensitive mutant.

[0088] The wild-type yeast strain is INVSc1 wild-type strain, and the yeast strain hypersensitive to tunica mycin is a self-constructed strain overexpressing tunica mycin transporter protein. The strain characteristics and construction method are described in the literature: [Liu C, Hao D, Sun R, Zhang Y, Peng Y, Yuan Y, Jiang K, Li W, Wen X, Guo H. Arabidopsis NPF2.13 functions as a critical transporter of bacterial natural compound tunicamycin in plant-microbe interaction. New Phytol. 2023 Apr; 238(2): 765-780. doi: 10.1111 / nph.18752. Epub 2023 Feb 9. PMID: 36653958.]

[0089] Example 1

[0090] This example provides an application of the ferroptosis inhibitor-1 of the present application in the preparation of a tunica mycin plant toxicity inhibitor, which includes the following content:

[0091] (1) The detoxification effect of the small molecule compound to be tested on tunica mycin toxic Arabidopsis

[0092] In 1 / 2MS medium containing 20nM and 50nM tunica mycin, no small molecule compound was added, 1μM of 4-phenylbutyric acid (PBA), taurine deoxycholic acid (TUDCA), ferroptosis inhibitor CPX (CPX) and ferroptosis inhibitor-1 (Fer-1) were added to prepare experimental medium, and the germination and seedling phenotype of Arabidopsis bzip28 / 60 double mutants in the experimental medium were observed and recorded.

[0093] Figure 1 The comparative diagram of the detoxification effect of 4-phenylbutyric acid, taurine deoxycholic acid, ferroptosis inhibitor CPX and ferroptosis inhibitor-1 on tunica mycin toxic Arabidopsis bzip28 / 60 double mutants in Example 1 of the present application. Figure 1 TM in the above table refers to tunica mycin, mock refers to a blank control group of tunica mycin toxicity without adding any small molecule, PBA refers to a 4-phenylbutyric acid group, TUDCA refers to a taurine deoxycholic acid group, CPX refers to a ferroptosis inhibitor CPX group, and Fer-1 refers to a ferroptosis inhibitor-1 group.

[0094] (2) The detoxification effect of ferroptosis inhibitor-1 on tunica mycin toxic Arabidopsis

[0095] The iron death inhibitor-1 (Fer-1) of 0 μM, 0.1 μM and 1 μM was added respectively in the 1 / 2MS medium without tunicamycin and the 1 / 2MS medium containing 0.2 μM tunicamycin to prepare the experimental medium, and the germination and seedling phenotype of the tunicamycin hypersensitive mutant bzip28 / 60 on the experimental medium were observed and recorded.

[0096] Figure 2 Figure 1 is a comparison chart of detoxification effects of different concentrations of iron death inhibitor-1 on tunicamycin poisoning of the wild type of Arabidopsis thaliana in Example 1 of the present application; Figure 2 Figure 1A is a comparison chart of growth states of the wild type of Arabidopsis thaliana under different treatment conditions;

[0097] Figure 2 Figure 1B is a comparison chart of relative weight of the wild type of Arabidopsis thaliana under different treatment conditions. Figure 2 The values under the Fer-1 label in Figure 1A represent different concentrations of iron death inhibitor-1, mock represents the 1 / 2MS medium without tunicamycin, and 0.2 μM TM represents the 1 / 2MS medium containing 0.2 μM tunicamycin. Figure 2 The ordinate of Figure 1B refers to the relative weight, and the groups represented from left to right in the abscissa are the 1 / 2MS medium without tunicamycin added with 0 μM, 0.1 μM and 1 μM iron death inhibitor-1, and the 1 / 2MS medium containing 0.2 μM tunicamycin added with 0 μM, 0.1 μM and 1 μM iron death inhibitor-1.

[0098] According to Figure 2 , the iron death inhibitor-1 alone treatment has a slight inhibitory effect on plant growth, indicating that the use of iron death inhibitor-1 under normal circumstances may interfere with the redox homeostasis of cells.

[0099] The iron death inhibitor-1 (Fer-1) of 0 μM, 0.1 μM, 1 μM and 5 μM was added respectively in the 1 / 2MS medium without tunicamycin and the 1 / 2MS medium containing 0.2 μM tunicamycin to prepare the experimental medium, and the germination and seedling phenotype of the wild type of Arabidopsis thaliana, the bzip28 / 60 double mutant of Arabidopsis thaliana and the nrt1.7-2 mutant of Arabidopsis thaliana on the experimental medium were observed and recorded.

[0100] Figure 3 Figure 1 is a comparison chart of detoxification effects of different concentrations of iron death inhibitor-1 on tunicamycin poisoning of the wild type of Arabidopsis thaliana, the bzip28 / 60 double mutant of Arabidopsis thaliana and the nrt1.7-2 mutant of Arabidopsis thaliana in Example 1 of the present application; Figure 3Fer-1 in the figure represents different concentrations of ferroptosis inhibitor-1, WT, bzip28 / 60 and nrt1.7-2 in the figure represent the germination and seedling phenotype of Arabidopsis wild type, Arabidopsis bzip28 / 60 double mutant and Arabidopsis nrt1.7-2 mutant on the medium, wherein mock represents 1 / 2MS medium without tunicamycin, and TM represents 1 / 2MS medium containing 0.2 μM tunicamycin.

[0101] The results are as shown in the following table: Figure 3 The ferroptosis inhibitor CPX does not show the effect of reducing or enhancing the toxicity of tunicamycin when the plant is treated with tunicamycin at the same time. When tunicamycin and ferroptosis inhibitor-1 are applied at the same time, the toxicity of tunicamycin to double mutants and wild type plants is significantly inhibited, showing normal seed germination and normal development of cotyledon and true leaf of seedling.

[0102] According to the results of the above experiments, it can be found that the toxicity of tunicamycin to Arabidopsis wild type plants can be significantly inhibited by the ferroptosis inhibitor-1, and the toxicity of tunicamycin to Arabidopsis bzip28 / 60 double mutant plants can also be significantly inhibited by the ferroptosis inhibitor-1. Figure 3 It can also be found that the toxicity of tunicamycin at a very high concentration cannot be alleviated by a higher concentration of ferroptosis inhibitor-1, indicating that there is a certain range of working concentration and action limit for ferroptosis inhibitor-1.

[0103] (3) Effect of ferroptosis inhibitor-1 and tunicamycin on UPR gene expression in Arabidopsis

[0104] After 7-day-old Arabidopsis wild type seedlings were transferred to liquid MS medium containing DMSO, 1 μM ferroptosis inhibitor-1, 0.1 μM tunicamycin, 1 μM ferroptosis inhibitor-1 and 0.1 μM tunicamycin for 72 hours, the plants were collected to extract RNA, and qPCR was performed after reverse transcription to detect the expression level of UPR marker genes BiP1 / 2, CNX1 and CRT1.

[0105] Figure 4 The comparison results of UPR gene expression of Arabidopsis wild type plants treated with tunicamycin with and without the addition of ferroptosis inhibitor-1 in Example 1 of the present application are as follows: Figure 4 In the figure, mock represents the blank control group medium added with DMSO, Fer-1, TM and TM+Fer-1 represent the experimental group medium added with 1 μM ferroptosis inhibitor-1, 0.1 μM tunicamycin, 1 μM ferroptosis inhibitor-1 and 0.1 μM tunicamycin, respectively, Figure 4 In the figure, A, B and C represent the expression level of UPR marker genes BiP1 / 2, CNX1 and CRT1 of Arabidopsis wild type seedlings cultured in each group of medium.

[0106] According to the results of the above experiments, it can be found that the toxicity of tunicamycin to Arabidopsis wild type plants can be significantly inhibited by the ferroptosis inhibitor-1, and the toxicity of tunicamycin to Arabidopsis bzip28 / 60 double mutant plants can also be significantly inhibited by the ferroptosis inhibitor-1. Figure 4It can be seen that the up-regulation of UPR gene expression caused by tunicamycin treatment is not affected by the addition of ferroptosis inhibitor-1, indicating that tunicamycin can effectively enter cells and produce toxic effects, suggesting that the detoxification function of ferroptosis inhibitor-1 is not achieved by directly acting on the degradation of tunicamycin or preventing it from entering cells.

[0107] (4) Relief effect of ferroptosis inhibitor-1 on Arabidopsis thaliana poisoned by other endoplasmic reticulum stress inducers

[0108] In the MS medium without ferroptosis inhibitor-1 and the MS medium containing 1 μM ferroptosis inhibitor-1, gradient concentrations of dithiothreitol (DTT) (0 μM, 1.2 μM, 1.5 μM) and proline analogue L-azetidine-2-carboxylic acid (AZC) (0 μM, 50 μM, 100 μM) were added, respectively, and the seeds of wild-type Arabidopsis thaliana and Arabidopsis thaliana bzip28 / 60 double mutants were cultured in the above-mentioned medium for 10 days, and the germination and growth phenotypes were recorded by taking pictures.

[0109] Figure 5 For the comparison of the detoxification effects of different concentrations of ferroptosis inhibitor-1 on dithiothreitol (DTT) and proline analogue L-azetidine-2-carboxylic acid (AZC) poisoning of wild-type Arabidopsis thaliana and Arabidopsis thaliana bzip28 / 60 double mutants in Example 1 of the present application, the comparison chart is shown in FIG. 1. Figure 5 The values under the DTT label in FIG. 1 represent different concentrations of dithiothreitol, and the figures under the WT and bzip28 / 60 labels represent the germination and seedling phenotypes of wild-type Arabidopsis thaliana and Arabidopsis thaliana bzip28 / 60 double mutants on the medium, respectively, wherein mock is the MS medium without ferroptosis inhibitor-1, and Fer-1 is the MS medium containing 1 μM ferroptosis inhibitor-1.

[0110] According to Figure 5 It can be seen that ferroptosis inhibitor-1 cannot alleviate the growth inhibition of L-azetidine-2-carboxylic acid on seedlings, and ferroptosis inhibitor-1 aggravates the toxic effects of dithiothreitol on the growth inhibition of Arabidopsis thaliana seedlings.

[0111] Comparative Example 1

[0112] This comparative example studies the detoxification effect of ferroptosis inhibitor-1 on tunicamycin-poisoned yeast cells, and the steps are as follows:

[0113] 1 μM ferroptosis inhibitor-1, 0.2 μM tunicamycin, 0.2 μM tunicamycin and 1 μM ferroptosis inhibitor-1 were added to the SG-U medium, respectively, and an equal volume of blank solvent (DMSO) was added as a control group, and the wild-type yeast cells were cultured in the above-mentioned medium. After 48 h of culture, the OD600 (OD600 refers to the absorbance value of the solution at 600 nm wavelength) was measured.

[0114] Add 1 μM ferroptosis inhibitor-1, 0.02 μM tunicamycin, 0.02 μM tunicamycin and 1 μM ferroptosis inhibitor-1 to SG-U medium, respectively. Take another group as the control group with an equal volume of blank solvent (DMSO). Culture tunicamycin-sensitive yeast cells in the above medium and measure OD600 after 48 h.

[0115] Figure 6 This is a comparison diagram showing the detoxification effect of the ferroptosis inhibitor-1 of Comparative Example 1 of this application on wild-type and tunicamycin-sensitive yeast cells. Figure 6 In the figure, A represents the detoxification effect of ferroptosis inhibitor-1 on wild-type yeast cells poisoned by tunicamycin; mock represents the control group with an equal volume of blank solvent (DMSO); Fer-1, TM, and TM+Fer-1 represent the experimental groups with 1 μM ferroptosis inhibitor-1, 0.2 μM tunicamycin, 1 μM ferroptosis inhibitor-1, and 0.2 μM tunicamycin, respectively. Figure 6 In the figure, B represents the detoxification effect of ferroptosis inhibitor-1 on tunicamycin-sensitive yeast cells. The mock is the control group with an equal volume of blank solvent (DMSO). Fer-1, TM, and TM+Fer-1 are the experimental groups with 1 μM ferroptosis inhibitor-1, 0.02 μM tunicamycin, 1 μM ferroptosis inhibitor-1, and 0.02 μM tunicamycin, respectively.

[0116] according to Figure 6 As a result, ferroptosis inhibitor-1 had no significant detoxification effect on yeast cells poisoned by tunicamycin, and even at high doses (1 μM), it could not restore the severe inhibition of yeast cell growth by tunicamycin.

[0117] In summary, the experimental results show that, unlike compound molecular chaperones which are applicable to animal cells, ferroptosis inhibitor-1 is a small molecule inhibitor of tunicamycin toxicity that is specific to plants.

[0118] All references to this application are incorporated herein by reference as if each document were individually incorporated herein by reference. Unless they conflict with the purpose and / or technical solution of this application, all cited references are incorporated herein by reference in their entirety and for all purposes. When references are cited in this application, the definitions of relevant technical features, terms, nouns, phrases, etc., are also incorporated herein by reference. Examples and preferred embodiments of the cited technical features may also be incorporated herein by reference, but only to the extent that they enable the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, this application shall prevail or modifications shall be made adaptably to the description in this application.

[0119] Each of the technical features of the above-described embodiments and examples can be combined in any suitable manner, and, for the sake of brevity, not all possible combinations are described, but it is to be understood that the scope of the present specification includes all possible combinations.

[0120] The above-described embodiments are merely illustrative of several embodiments of the present application and do not limit the scope of the patent application. It should be noted that, for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present application, and these are all within the scope of the present application. Furthermore, it should be understood that, after reading the above teachings of the present application, those skilled in the art can make various modifications or improvements to the present application, and the equivalent forms are also within the scope of the present application. It should also be understood that, based on the technical solutions provided by the present application, those skilled in the art can obtain technical solutions through logical analysis, reasoning or limited experiments, and these are all within the scope of the claims of the present application. Therefore, the scope of the patent application of the present application should be subject to the appended claims, and the description can be used to explain the content of the claims.

Claims

1. Use of an ferroptosis inhibitor-1 in the manufacture of a mycotoxin phytotoxicity inhibitor, the ferroptosis inhibitor-1 having a structure according to Formula (I): ###0001### Formula (I) for the preparation of a mycotoxin phytotoxicity inhibitor. （I）。 2. Use according to claim 1, wherein The mycotoxin phytotoxicity inhibitor can be used to alleviate the toxic effects of mycotoxins on plants.

3. Use according to claim 2, wherein the compound is ###0002### The toxic effects of mycotoxins on plants include at least one of inhibiting seed germination and inhibiting seedling growth.

4. Use according to claim 2 or 3, characterized in that, The plants include at least one of Brassicaceae plants, Poaceae plants, Fabaceae plants, Solanaceae plants, Cucurbitaceae plants, Rosaceae plants, Rutaceae plants, Umbelliferae plants.

5. A method of alleviating the toxic effects of austin toxin on a plant, comprising, including: treating seeds or seedlings of the plants with the ferroptosis inhibitor-1; The ferroptosis inhibitor-1 has a structure according to Formula (I): ###0001### Formula (I) （I）。 6. Use of a ferroptosis inhibitor-1 in the preparation of a pesticidal composition for alleviating the toxic effects of a tunicamycin on a plant, characterized in that, The pesticide composition includes the ferroptosis inhibitor-1 and a pesticide adjuvant. The ferroptosis inhibitor-1 has a structure according to Formula (I): ###0001### Formula (I) （I）。 7. Use according to claim 6, wherein The toxic effects of mycotoxins on plants include at least one of inhibiting seed germination and inhibiting seedling growth.

8. Use according to claim 6 or 7, wherein the compound is ###0002### The plants include Arabidopsis thaliana.

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