Use of mangiferin in preparing ferroptosis inhibitor

Abstract

Disclosed in the present invention is use of mangiferin in preparing a ferroptosis inhibitor. It has been discovered for the first time that the mangiferin can significantly reverse the levels of ferroptosis-related factors in bone tissue of bilateral ovariectomy-induced mouse model, can significantly reverse the levels of ferroptosis-related factors in bone tissue of iron dextran-induced mouse model, can significantly reverse the levels of ferroptosis-related factors in iron dextran-induced osteoblasts, and can significantly reverse the levels of ferroptosis-related factors of Erastin-induced osteoblasts, so that the ferroptosis-related factors are restored to normal levels, indicating that the mangiferin can effectively inhibit ferroptosis and can be used for preparing a ferroptosis inhibitor, thereby providing a new idea and a new approach for drug research of ferroptosis-related diseases.

Description

Application of mangiferin in the preparation of ferroptosis inhibitors Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the application of mangiferin in the preparation of a ferroptosis inhibitor. Background Art

[0002] Ferroptosis is a form of programmed cell death that is completely different from apoptosis, autophagy, and necrosis. When the cell nucleus is intact, the intracellular iron ion concentration increases, leading to mitochondrial damage including reduced cristae, changes in bilateral membrane density, and outer membrane rupture. Mitochondrial damage further leads to peroxidation of organelles such as the Golgi apparatus, lysosomes, and endoplasmic reticulum, ultimately leading to cell death.

[0003] Ferroptosis plays an important role in the occurrence and development of many diseases, such as pneumonia, osteoporosis, liver cancer, oral cancer, cardiovascular disease, etc.; and the mechanism is complex. Certain compounds such as erastin or clinical drugs such as sulfasalazine and sorafenib can induce cancer cells and certain normal cells (such as renal tubular cells, neurons, fibroblasts, T cells) to trigger ferroptosis.

[0004] Therefore, the development of ferroptosis inhibitors is of great significance for maintaining cell function. Mangiferin, also known as 2-c-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyflavone, is a tetrahydroxybenzopyrrolidone carbonyl glycoside belonging to the bisbenzopyrrolidone class of compounds with a molecular formula of C 19 H 18 O 11 Mangiferin is a natural compound found in the fruit, leaves, and bark of mango (Anacardiaceae), as well as in the rhizomes and aerial parts of Anemarrhena asphodeloides (Liliaceae). Mangiferin is a polyphenolic acid with strong antioxidant activity and multiple pharmacological activities, such as antitussive, expectorant, antiasthmatic, central nervous system regulation, anti-tumor, anti-inflammatory, antibacterial, antiviral, and immunomodulatory effects, and has promising development prospects. Currently, there are no reports on mangiferin's ability to inhibit ferroptosis. Technical issues

[0005] The purpose of the present invention is to provide the use of mangiferin in the preparation of ferroptosis inhibitors, providing new ideas and new approaches for the drug research of ferroptosis-related diseases. Technical Solutions

[0006] In order to achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0007] The application of mangiferin in the preparation of ferroptosis inhibitors, wherein the structural formula of mangiferin is as follows:

[0008] .

[0009] The present invention discovered for the first time that mangiferin can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, SLC7A11, GPX4, MDA and GSH / GSSG, etc.) in the bone tissue of bilaterally ovariectomized mice and restore them to normal levels; it can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, SLC7A11, GPX4, MDA and GSH / GSSG, etc.) in the bone tissue of mice modeled with dextran iron and restore them to normal levels; it can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, etc.) in osteoblasts modeled with dextran iron and restore them to normal levels; it can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, C11 BODIPY-labeled lipid peroxides and Mitosox-labeled mitochondrial reactive oxygen species, etc.) in osteoblasts modeled with Erastin, indicating that mangiferin can effectively inhibit ferroptosis.

[0010] It can be seen that mangiferin inhibits ferroptosis by improving the oxidative stress levels of cells and tissues. Therefore, on this basis, the present invention also provides the use of mangiferin in the preparation of GPX4 agonists.

[0011] At the same time, the present invention also provides the use of mangiferin in the preparation of bone health products, and the use of mangiferin in drugs for treating bone injuries. Beneficial effects

[0012] Compared with the prior art, the beneficial effects of the present invention are embodied in:

[0013] The present invention discovered for the first time that mangiferin can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, SLC7A11, GPX4, MDA and GSH / GSSG, etc.) in the bone tissue of bilaterally ovariectomized mice and restore them to normal levels; it can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, SLC7A11, GPX4, MDA and GSH / GSSG, etc.) in the bone tissue of mice modeled with dextran iron and restore them to normal levels; it can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, etc.) in osteoblasts modeled with dextran iron and restore them to normal levels; it can significantly reverse the levels of ferroptosis-related factors (including 4-HNE, C11 BODIPY-labeled lipid peroxides and Mitosox-labeled mitochondrial superoxides, etc.) in osteoblasts modeled with Erastin, indicating that mangiferin can effectively inhibit ferroptosis; based on this, the present invention provides the use of mangiferin in the preparation of ferroptosis inhibitors, providing new ideas and new approaches for the drug research of ferroptosis-related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 shows the effect of mangiferin on the level of MDA, a factor related to ferroptosis in bone tissue of ovariectomized mice;

[0015] OVX is bilateral ovariectomy; Mangiferin is mangiferin, L is a low dose of 10 mg / kg / d, and H is a high dose of 50 mg / kg / d; Estrodiol is estradiol, 100 μg / kg / d; administration duration is 12 weeks; ** indicates P < 0.01; the same below;

[0016] Figure 2 shows the effect of mangiferin on the levels of GSH / GSSG, a factor related to ferroptosis in bone tissue of ovariectomized mice;

[0017] Figure 3 shows the effect of mangiferin on the level of 4-HNE, a factor related to ferroptosis in bone tissue of ovariectomized mice;

[0018] Figure 4 shows the effect of mangiferin on the level of GPX4, a ferroptosis-related factor in bone tissue of ovariectomized mice;

[0019] Figure 5 shows the effect of mangiferin on the level of ferroptosis-related factor SLC7A11 in bone tissue of ovariectomized mice;

[0020] Figure 6 shows the effect of mangiferin on the level of MDA, a factor related to ferroptosis in bone tissue of mice induced by dextran iron model;

[0021] Iron refers to the iron dextran modeling method; Mangiferin refers to mangiferin; L refers to the low dose of 10 mg / kg / d, M refers to the medium dose of 50 mg / kg / d, and H refers to the high dose of 100 mg / kg / d; the administration duration is 12 weeks; ** indicates P < 0.01; the same below;

[0022] Figure 7 shows the effect of mangiferin on the levels of GSH / GSSG, a factor related to ferroptosis, in bone tissue of mice induced by dextran iron model;

[0023] Figure 8 shows the effect of mangiferin on the level of 4-HNE, a factor associated with ferroptosis in bone tissue of mice induced by dextran iron model;

[0024] Figure 9 shows the effect of mangiferin on the level of ferroptosis-related factor GPX4 in bone tissue of dextran iron model mice;

[0025] Figure 10 shows the effect of mangiferin on the level of ferroptosis-related factor SLC7A11 in bone tissue of dextran iron model mice;

[0026] FIG11 shows the effect of mangiferin on the level of 4-HNE, a factor related to ferroptosis in osteoblasts induced by iron overload;

[0027] FIG12 shows the effect of mangiferin on lipid peroxidation levels in dextran iron-induced osteoblasts;

[0028] Wherein, C11 BODIPY fluorescence (green / red, of control) represents the fluorescence intensity of C11 BODIPY fluorescent probe (green / red, with blank control group as reference); the same below;

[0029] FIG13 shows the effect of mangiferin on mitochondrial peroxidation levels in dextran iron-induced osteoblastic models;

[0030] MitoSOX fluorescence (red, of control) represents the fluorescence intensity of the MitoSOX fluorescent probe (with the blank control group as a reference); the same below;

[0031] Figure 14 shows the effect of mangiferin on the level of 4-HNE, a ferroptosis-related factor in Erastin-induced osteoblasts;

[0032] FIG15 shows the effect of mangiferin on lipid peroxidation levels in Erastin iron-induced osteoblasts;

[0033] FIG16 shows the effect of mangiferin on mitochondrial peroxidation level in Erastin iron-induced osteoblasts. Best Mode for Carrying Out the Invention

[0034] The technical solution of the present invention is further described in detail below with reference to the accompanying drawings and specific implementation methods.

[0035] Example 1 Inhibitory effect of mangiferin on ferroptosis in bilaterally ovariectomized mice

[0036] (1) Mouse grouping and drug administration

[0037] C57BL / 6 female mice, each weighing 20±2 g, were randomly divided into five groups, with 10 mice in each group:

[0038] ① Sham operation group: partial fat was removed bilaterally and normal saline was given by gavage for 12 consecutive weeks;

[0039] ② Model group (OVX): bilateral ovarian removal and oral administration of normal saline for 12 consecutive weeks;

[0040] ③ Low-dose mangiferin group (Mangiferin-L): bilateral ovarian removal and oral administration of mangiferin (10 mg / kg / d) for 12 consecutive weeks;

[0041] ④ Mangiferin high-dose group (Mangiferin-H): bilateral ovarian removal and oral administration of mangiferin (50 mg / kg / d) for 12 consecutive weeks;

[0042] ⑤ Positive drug group (Estradiol): bilateral ovarian removal and oral administration of estradiol (100 μg / kg / d) for 12 consecutive weeks.

[0043] After 12 consecutive weeks of drug administration, bone tissues of mice in each group were collected for future use.

[0044] (2) MDA analysis

[0045] The MDA (malondialdehyde) content in the bone tissue of mice in each group was detected using an MDA kit (#A003-1-1, Nanjing Jiancheng). The test results are shown in Figure 1.

[0046] As shown in Figure 1, compared with the sham operation group, the MDA content in the bone tissue of the model group was significantly increased (P<0.01); compared with the model group, the low-dose mangiferin group, the high-dose mangiferin group and the positive drug group could effectively reduce the MDA content in the bone tissue (P<0.01); compared with the positive drug group, the MDA content in the high-dose mangiferin group was significantly lower (P<0.01).

[0047] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with 95% confidence intervals. The results showed that the AUC of the low-dose and high-dose mangiferin groups were both 1. Compared with the positive drug group, the AUC of the high-dose mangiferin group was 1.

[0048] The above results show that mangiferin can effectively reduce the level of MDA, a marker of ferroptosis activation, and its effect is better than that of the positive drug estradiol (P < 0.01).

[0049] (3) GSH / GSSG analysis

[0050] The GSH / GSSG level in the bone tissue of mice in each group was detected using a GSH / GSSG kit (#S0053, Beyotime). The test results are shown in Figure 2.

[0051] As shown in Figure 2, compared with the sham operation group, the GSH / GSSG level in the bone tissue of the model group was significantly decreased (P<0.01). Compared with the model group, the low-dose mangiferin group, the high-dose mangiferin group and the positive drug group could effectively increase the GSH / GSSG level in the bone tissue (P<0.01). Compared with the positive drug group, the GSH / GSSG level in the high-dose mangiferin group was significantly higher (P<0.01).

[0052] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the areas under the curve (AUC) of different groups with 95% confidence intervals. The results showed that compared with the model group, the AUC of the ROC curves of the low-dose and high-dose mangiferin groups were both 1; compared with the positive drug group, the AUC of the high-dose mangiferin group was 1.

[0053] The above results show that mangiferin can effectively increase the level of ferroptosis inhibition markers GSH / GSSH, and its effect is better than that of the positive drug estradiol (P < 0.01).

[0054] (4) Analysis of 4-HNE

[0055] The levels of 4-HNE (4-hydroxynonenal) in the bone tissues of mice in each group were detected by western blot. The primary antibodies were 4-HNE (#ab46545, Abcam) and GAPDH (#BK7021, Boster). GAPDH was used as the internal control. The grayscale of the bands was analyzed using ImageJ software. The detection results are shown in Figure 3.

[0056] As shown in Figure 3, compared with the sham group, the expression level of 4-HNE in bone tissue of the model group was significantly increased (P < 0.01). Compared with the model group, both the low-dose and high-dose mangiferin groups effectively reduced the level of 4-HNE in bone tissue (P < 0.01).

[0057] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with 95% confidence intervals. The results showed that compared with the model group, the AUC of the ROC curve of the low-dose and high-dose mangiferin groups was 1.

[0058] The above results show that mangiferin can effectively reduce the level of 4-HNE, a marker of ferroptosis activation.

[0059] (5) Analysis of SLC7A11 and GPX4

[0060] Western blot analysis was performed to analyze the expression levels of SLC7A11 and GPX4 proteins. The primary antibodies were GPX4 (#DF6701, Affinity) and SLC7A11 (#BM5318, Boster), with GAPDH as the internal control. ImageJ software was used to analyze the grayscale of the bands. The results are shown in Figures 4 and 5.

[0061] As shown in Figures 4 and 5, compared with the sham operation group, the SLC7A11 and GPX4 levels in the bone tissue of the model group were significantly decreased (P < 0.01). Compared with the model group, the low-dose mangiferin group, the high-dose mangiferin group, and the positive drug group were able to effectively increase the levels of SLC7A11 and GPX4 in the bone tissue (P < 0.01). Moreover, compared with the positive drug group, the SLC7A11 level in the high-dose mangiferin group was significantly higher (P < 0.01).

[0062] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that compared with the model group, the AUC of the ROC curve of the low-dose and high-dose mangiferin groups were both 1; compared with the positive drug group, the AUC of the high-dose mangiferin group was 1.

[0063] The above results show that mangiferin can effectively increase the levels of ferroptosis inhibition markers SLC7A11 and GPX4.

[0064] Example 2 Inhibitory effect of mangiferin on iron overload-induced ferroptosis in mice

[0065] (1) Grouping of mice

[0066] C57BL / 6 female mice, each weighing approximately 20 ± 2 g, were randomly divided into five groups, with 10 mice in each group:

[0067] ①Blank control group: intraperitoneal injection of normal saline and oral administration of normal saline for 12 consecutive weeks;

[0068] ② Model group: intraperitoneal injection of iron dextran 100 mg / kg / week and oral administration of normal saline for 12 consecutive weeks;

[0069] ③ Low-dose mangiferin group: intraperitoneal injection of iron dextran 100 mg / kg / week and oral administration of mangiferin (10 mg / kg / d) for 12 consecutive weeks;

[0070] ④ Medium-dose mangiferin group: intraperitoneal injection of iron dextran 100 mg / kg / week and oral administration of mangiferin (50 mg / kg / d) for 12 consecutive weeks;

[0071] ⑤ High-dose mangiferin group: intraperitoneal injection of iron dextran 100 mg / kg / week and oral administration of mangiferin (100 mg / kg / d) for 12 consecutive weeks.

[0072] After 12 consecutive weeks of drug administration, bone tissues of mice in each group were collected for future use.

[0073] (2) MDA analysis

[0074] The MDA content in the bone tissue of each group of mice was detected using the same method as in Example 1. The detection results are shown in FIG6 .

[0075] As shown in Figure 6, compared with the blank control group, the MDA content in bone tissue of the model group was significantly increased (P < 0.01). Compared with the model group, the low-dose, medium-dose, and high-dose mangiferin groups all effectively reduced the MDA content in bone tissue (P < 0.01).

[0076] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that compared with the model group, the AUC of the ROC curve of the low-dose, medium-dose, and high-dose mangiferin groups were all 1.

[0077] The above results indicate that mangiferin can effectively reduce the level of MDA, a marker of ferroptosis activation, in the bone tissue of iron-overloaded mice.

[0078] (3) GSH / GSSG analysis

[0079] The GSH / GSSG levels in the bone tissues of the mice in each group were detected using the same method as in Example 1. The detection results are shown in FIG7 .

[0080] As shown in Figure 7, compared with the blank control group, the GSH / GSSG level in the bone tissue of the model group was significantly decreased (P < 0.01); and compared with the model group, the low-dose, medium-dose, and high-dose mangiferin groups could effectively increase the GSH / GSSG level in the bone tissue (P < 0.01).

[0081] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that the AUC of the ROC curve was 1 compared with the low-dose, medium-dose, high-dose and model groups of mangiferin.

[0082] The above results indicate that mangiferin can effectively increase the level of GSH / GSSG, a ferroptosis inhibition marker, in iron-overloaded mice.

[0083] (4) Analysis of 4-HNE

[0084] The same method as in Example 1 was used to detect the 4-HNE levels in the bone tissues of the mice in each group. The detection results are shown in FIG8 .

[0085] As shown in Figure 8, compared with the blank control group, the 4-HNE level in the bone tissue of the model group was significantly increased (P < 0.01); and compared with the model group, the low-dose, medium-dose, and high-dose mangiferin groups could effectively reduce the 4-HNE level in the bone tissue (P < 0.01).

[0086] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that the AUC of the ROC curve was 1 compared with the low-dose, medium-dose, high-dose and model groups of mangiferin.

[0087] The above results indicate that mangiferin can effectively reduce the level of 4-HNE, a marker of ferroptosis activation, in the bone tissue of iron-overloaded mice.

[0088] (5) Analysis of SLC7A11 and GPX4

[0089] The expression levels of SLC7A11 and GPX4 proteins in the bone tissues of mice in each group were detected using the same method as in Example 1. The detection results are shown in Figures 9 and 10.

[0090] As shown in Figures 9 and 10, compared with the blank control group, the levels of SLC7A11 and GPX4 in the bone tissue of the model group were significantly decreased (P < 0.01). Compared with the model group, the low-dose, medium-dose, and high-dose mangiferin groups could effectively increase the levels of SLC7A11 and GPX4 in the bone tissue (P < 0.01).

[0091] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that the AUC of the ROC curve was 1 compared with the low-dose, medium-dose, high-dose and model groups of mangiferin.

[0092] The above results indicate that mangiferin can effectively increase the levels of ferroptosis-inhibiting markers SLC7A11 and GPX4 in the bone tissue of iron-overloaded mice.

[0093] Example 3 Inhibitory effect of mangiferin on iron overload-induced ferroptosis

[0094] (1) Cell grouping

[0095] Osteoblasts were taken and divided into 5 groups. The experiment was repeated six times in each group:

[0096] ①Blank control group: culture cells in normal DMEM medium for 48 h;

[0097] ② Model group: cultured in DMEM cell culture medium containing 50 μM iron dextran, administration time 48 hours;

[0098] ③ Low-dose mangiferin group: containing 50 μM iron dextran and 10 μM mangiferin -3 μM in DMEM cell culture medium, and the administration time was 48 h;

[0099] ④ Mangiferin medium dose group: containing 50 μM iron dextran and 10 μM mangiferin -2 μM in DMEM cell culture medium, and the administration time was 48 h;

[0100] ⑤ High-dose mangiferin group: containing 50 μM iron dextran and 10 μM mangiferin -1 The cells were cultured in DMEM culture medium with a concentration of 5 μM and the administration time was 48 h.

[0101] After the culture is completed, the cells are collected and set aside.

[0102] (2) 4-HNE analysis

[0103] Western blot was used to detect the 4-HNE (4-hydroxynonenal) levels in osteoblasts of each group. The primary antibodies were 4-HNE (#ab46545, Abcam) and GAPDH (#BK7021, Boster). GAPDH was used as an internal control. ImageJ software was used to analyze the grayscale of the bands. The detection results are shown in Figure 11.

[0104] As shown in Figure 11, compared with the blank control group, the 4-HNE content of the model group cells was significantly increased (P < 0.01); compared with the model group, the low-dose, medium-dose, and high-dose mangiferin groups could effectively reduce the 4-HNE content of the cells (P < 0.01).

[0105] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that the AUC of the ROC curve was 1 compared with the low-dose, medium-dose, high-dose and model groups of mangiferin.

[0106] The above results show that at the cellular level, mangiferin can also effectively reduce the level of 4-HNE, a marker of ferroptosis activation.

[0107] (3) Lipid and mitochondrial peroxidation levels

[0108] Lipid peroxides were detected using C11 BODIPY (#D3861), and mitochondrial superoxide was detected using Mitosox (#M36008). The results are shown in Figures 12 and 13.

[0109] As shown in Figures 12 and 13, compared with the blank control group, the levels of lipid peroxides and mitochondrial superoxides in the model group were significantly increased (P < 0.01); compared with the model group, the mangiferin group could effectively reduce the levels of lipid peroxides and mitochondrial superoxides in the cells (P < 0.01).

[0110] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that the AUC of the ROC curve was 1 compared with the mangiferin group and the model group.

[0111] Example 4 Inhibitory effect of mangiferin on erastin-induced ferroptosis in osteoblasts

[0112] (1) Cell grouping

[0113] Osteoblasts were taken and divided into 3 groups. The experiment was repeated six times in each group:

[0114] ①Blank control group: cultured in normal DMEM cell culture medium for 48 h;

[0115] ② Model group: cultured in DMEM cell culture medium containing 1 μM Erastin, administration time 48 hours;

[0116] ③ Mangiferin group: containing Erastin 1 μM and mangiferin 10 -1 The cells were cultured in DMEM culture medium with a concentration of 5 μM and the administration time was 48 h.

[0117] (2) 4-HNE analysis

[0118] The 4-HNE levels in the osteoblasts of each group were detected. The detection results are shown in FIG14 .

[0119] As shown in Figure 14, compared with the blank control group, the 4-HNE content of the cells in the model group was significantly increased (P < 0.01); and compared with the model group, the mangiferin group could effectively reduce the 4-HNE content of the cells (P < 0.01).

[0120] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that the AUC of the ROC curve was 1 in both the mangiferin group and the model group.

[0121] The above results show that at the cellular level, mangiferin can also effectively reduce the level of 4-HNE, a marker of ferroptosis activation.

[0122] (3) Lipid and mitochondrial peroxidation levels

[0123] Lipid peroxides were detected using C11 BODIPY (#D3861), and mitochondrial superoxides were detected using Mitosox (#M36008). The results are shown in Figures 15 and 16 .

[0124] As shown in Figures 15 and 16, compared with the blank control group, the levels of lipid peroxides and mitochondrial superoxide in the model group were significantly increased (P < 0.01). Compared with the model group, the mangiferin group effectively reduced the levels of lipid peroxides and mitochondrial superoxide in the model group (P < 0.01).

[0125] The ROC curve was applied, and the Wilson / Brown method was used to perform pairwise comparisons of the area under the curve (AUC) of different groups with a 95% confidence interval. The results showed that the AUC of the ROC curve was 1 compared with the mangiferin group and the model group.

Claims

1. Application of mangiferin in the preparation of ferroptosis inhibitors.

2. The use according to claim 1, characterized in that The structural formula of mangiferin is as follows: 。 3. Application of mangiferin in the preparation of GPX4 agonists.

4. The use according to claim 3, characterized in that The structural formula of mangiferin is as follows: 。 5. Application of mangiferin in the preparation of bone health products.

6. The use according to claim 5, characterized in that The structural formula of mangiferin is as follows: 。 7. Application of mangiferin in drugs for the treatment of bone injuries.

8. The use according to claim 7, characterized in that The structural formula of mangiferin is as follows: 。

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