CN111202741B

CN111202741B - Application of lignan compound in preparation of medicine for treating and/or preventing nephropathy

Info

Publication number: CN111202741B
Application number: CN202010068887.3A
Authority: CN
Inventors: 欧阳冬生; 黄琪; 曾祥昌; 郭飞; 陈露露; 李超鹏; 陈思雨; 刘琼
Original assignee: Xiangya Hospital of Central South University
Current assignee: Xiangya Hospital of Central South University
Priority date: 2020-01-21
Filing date: 2020-01-21
Publication date: 2021-07-20
Anticipated expiration: 2040-01-21
Also published as: CN111202741A

Abstract

The invention discloses an application of a lignan compound in preparing a medicament for treating and/or preventing nephropathy, wherein the compound is Isoeucommin A and has the following structural formula:

the nephropathy comprises at least one of diabetic nephropathy, nephritis, toxic nephropathy, and nephrotic syndrome. The action mechanism of the compound for treating nephropathy is to play an antioxidation role by enhancing intracellular GSH expression and SOD enzyme activity, inhibiting MDA generation and inducing activation of Nrf2/HO-1 signal path, and the discovery of the action mechanism of the compound has important research value and application prospect for treating nephropathy.

Description

Application of lignan compound in preparation of medicine for treating and/or preventing nephropathy

Technical Field

The invention relates to the field of pharmaceutical chemistry, in particular to application of a lignan compound in preparing a medicament for treating and/or preventing nephropathy.

Background

Diabetic Nephropathy (DN) is the most severe and common microvascular complication of diabetes, accounting for 20-40% of the total diabetic patients. The clinical manifestations of DN are mainly proteinuria, hypertension and progressive injury to renal function, edema, etc., and eventually end-stage renal failure can develop. However, the existing effective DN treatment medicines and means are relatively lack, so that the development of a novel effective DN prevention and treatment medicine becomes an important subject facing the global medical and pharmaceutical fields at present. The pathogenesis of DN is complex and the etiology is not clear. The role played by several biochemical mechanisms associated with hyperglycemia in DN has been demonstrated, with the most focused being the Polyol Pathway (PP) and its rate-limiting enzyme, Aldose Reductase (AR), in the pathway. Imbalance in polyol pathways can lead to a series of chain reactions, including oxidative stress mechanisms (oxidative stress), protein non-enzymatic glycosylation (protein non-enzymatic), Protein Kinase C (PKC), and the like. Among them, AR plays an important pivotal role, and has become a popular target for developing drugs for preventing and treating DN. Currently, Aldose Reductase Inhibitors (ARIs) are mainly chemical drugs, mainly including hydantoins, carboxylic acids and heterocyclic compounds. However, many of the drugs have the problems of low selectivity, obvious toxic and side effects, low bioavailability, large clinical dosage and the like. Therefore, the search for novel ARIs with economy, high efficiency, low toxicity and strong specificity has great academic value and clinical significance.

Disclosure of Invention

The present invention is directed to solving at least one of the problems of the prior art. Therefore, the invention provides the application of the lignan compound in preparing the medicine for treating and/or preventing the nephropathy, and the lignan compound has a good treatment effect on the nephropathy.

The invention also provides a medicament for treating and/or preventing nephropathy.

The invention also provides a pharmaceutical composition for treating and/or preventing nephropathy.

According to a use of an embodiment of the first aspect of the invention, the compound has the following structural formula:

the application of the embodiment of the invention has at least the following beneficial effects: the compound provided by the invention can effectively inhibit the proliferation of human glomerular mesangial cells induced by high sugar and inhibit H₂O₂The compound has the action mechanism that the antioxidant effect is exerted by enhancing the intracellular GSH expression and the enzyme activity of SOD, inhibiting the MDA generation and inducing the activation of the Nrf2/HO-1 signal path, provides a good lead compound for developing a new medicine for preventing and/or treating the nephropathy, and has important research value and application prospect for treating the nephropathy.

According to some embodiments of the invention, the kidney disease comprises at least one of diabetic nephropathy, nephritis, toxic nephropathy, and nephrotic syndrome.

According to some embodiments of the invention, preferably, the renal disease comprises diabetic nephropathy.

A medicament according to an embodiment of the second aspect of the invention, comprising a compound as described above and/or a pharmaceutically acceptable salt thereof.

According to some embodiments of the invention, the pharmaceutical dosage form is a tablet, capsule or injection.

A pharmaceutical composition according to an embodiment of the third aspect of the invention comprises a compound as described above and/or a pharmaceutically acceptable salt thereof.

Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.

Drawings

FIG. 1 is a mass spectrum (HRESIMS) of the compound of example 1 of the present invention;

FIG. 2 shows a hydrogen spectrum of the compound of example 1 of the present invention (¹H NMR)；

FIG. 3 shows a carbon spectrum of a compound of example 1 of the present invention (¹³C NMR)；

FIG. 4 is a circular dichroism plot (CD) of the compound of example 1 of the present invention;

FIG. 5 shows the results of the compound of example 2 of the present invention inhibiting high glucose-induced HRMC cell proliferation;

FIG. 6 shows the induction of expression of normal cells Nrf2 and HO-1 by the compound of example 2;

FIG. 7 shows the induction of expression of high sugar-inducible cells Nrf2 and HO-1 by the compound of example 2 of the present invention;

FIG. 8 shows the effect of the compound of example 2 on the expression of SOD in HRMC cells induced by high sugar;

FIG. 9 shows the effect of the compound of example 2 on MDA expression in HRMC cells induced by high sugar;

FIG. 10 shows the compound pair H in example 3 of the present invention₂O₂The effect of proliferation of damaged primary tubular cells;

FIG. 11 shows the compound pair H in example 3 of the present invention₂O₂(ii) the effect of expression of SOD in damaged primary renal tubular cells;

FIG. 12 shows the compound pair H in example 3 of the present invention₂O₂The effect of MDA expression in damaged primary tubular cells;

FIG. 13 shows the compound pair H in example 3 of the present invention₂O₂Induction of Nrf2 and HO-1 expression in injured primary tubular cells;

FIG. 14 shows the compound pair H in example 3 of the present invention₂O₂The expression of GSH in injured primary tubular cells.

Detailed Description

In order to explain technical contents, achieved objects, and effects of the present invention in detail, the following description is made with reference to the accompanying drawings in combination with the embodiments.

MTT detection solution: 50mg of MTT powder was weighed, diluted with 10mL of PBS to 5mg/mL of assay solution, filtered through a 0.22 μm filter, dispensed, and stored at-20 ℃.

Glucose mother liquor: 0.26g D- (+) -glucose was dissolved in 8mL of PBS to prepare a 250mM glucose stock solution, which was filtered through a 0.22 μm filter and used as it was.

Culture medium: DMEM medium with different glucose concentrations of 10% FBS was prepared:

low-sugar DMEM medium (L-DMEM): 47.5mL, 500. mu.L of diabody, 500. mu.L of pyruvic acid, 500. mu.L of MEMNAEA, 500. mu.L of HEPES, 500. mu.L of FBS, and 5.6mM of glucose final concentration;

sugar-free DMEM medium (N-DMEM): 47.5mL, 500. mu.L of diabody, 500. mu.L of pyruvic acid, 500. mu.L of MEMNEAA, 500. mu.L of HEPES and 500. mu.L of FBS.

HRMC cell culture: HRMC cells were incubated at 37 deg.C with 5% CO₂And culturing for 2-3 days in a cell culture box with 100% relative humidity. And (3) when the cells grow to 80% confluence degree by adherence, digesting with 0.25% pancreatin for 1-2 minutes, sucking out the pancreatin, and adding a culture medium containing 10% FBS to terminate digestion. The cell suspension was aspirated into a centrifuge tube, centrifuged at 1000rpm for 5min, and the medium was removed. Cells were resuspended in fresh medium at a 1: 4, putting the mixture into a culture flask for continuous subculture.

And (4) performing data analysis by adopting Graphpad 7.0 software, and calculating the survival rate of each group of cells.

Example 1: confirmation of the Structure of the target Compound

1. Mass spectrum: HRESIMS M + Na 573.1972(calculated 573.1948); the mass spectrum is shown in FIG. 1.

2. Nuclear magnetism: the data tables for the hydrogen spectra (FIG. 2) and carbon spectra (FIG. 3) are shown in Table 1 below, with MeOH-d as the solvent₄Hydrogen spectrum 600MHz, carbon spectrum 150 MHz:

TABLE 1 assignment of hydrogen and carbon spectra signals (in ppm. delta.) of the target compounds

3. Circular dichroism spectrum: the spectrum of the ECD is shown in FIG. 4.

The known compound Isoeutommin A is obtained by analyzing the nuclear magnetism and mass spectrum data, and the structural formula is as follows:

example 2: isoeutomomin A (in the figure, labeled P16 to avoid over-space labeling) anti-hyperglycemia-induced human mesangial cell (HRMC) proliferation study

Construction of high-sugar induced HRMC cell proliferation model

1. Taking HRMC cells which are well proliferated and are in logarithmic phase, discarding culture solution, dispersing by digestive juice of 0.25% pancreatin and EDTA half, and counting to prepare cell suspension;

2. adjusting the cell density to 1X 10 with L-DMEM medium⁴Inoculating to 96-well plate at 80 μ L/well, standing at 37 deg.C and 5% CO₂Pre-culturing for 24h in an incubator with 100% relative humidity;

3. adding 20 mu L/well L-DMEM into Blank group and Control group, adding culture medium (the final concentration of Glucose is 30mM) prepared by mixing 20 mu L/well L-DMEM with 250mM Glucose mother liquor into Glucose group, and continuously culturing for 24 h;

4. isoeutomomin A with different concentrations is added to make the final concentration of 250 μm, 125 μm, 62.5 μm, 31.25 μm,15.63 μm, 7.8 μm, 3.9 μm and 1.9 μm, and the cell viability is detected by using an MTT method after the continuous culture for 24 h.

The result of the cell survival rate is shown in figure 5, and the result proves that the compound Isoeutomomin A can effectively inhibit the proliferation of human glomerular mesangial cells induced by high sugar, has obvious dose effect, and has obvious effect when the dose is not less than 31.25 mu m.

II, regulation and control of Nrf2 and HO-1 protein level downstream of Nrf2 pathway

1. Regulation of normal HRMC cells Nrf2 and HO-1 by target compounds

1) Sample preparation

a) Taking HRMC cells which are well proliferated and are in logarithmic phase, discarding culture solution, washing with PBS once, digesting with digestive juice of 0.25% pancreatin and EDTA half, stopping with fresh culture medium, blowing, dispersing and counting to prepare cell suspension;

b) adjusting the cell density to 3X 10 with L-DMEM medium⁵Cells/well, inoculated into 6-well plate, 2 mL/well, placed at 37 ℃ with 5% CO₂Culturing for 24 hours in an incubator with 100% relative humidity;

c) the Blank group, the Control group and the administration group were cultured in L-DMEM (2 ml/well) for 24 hours.

d) The blank group was added with 2. mu.L of DMSO, the administration group was added with 2. mu.L of the objective compound at different concentrations so that the final concentrations were 31.25. mu.M, 62.5. mu.M and 125. mu.M, respectively, and the mixture was subjected to CO treatment₂Culturing for 24h in the incubator to collect cell samples;

e) removing culture medium supernatant, washing with PBS once, digesting with 0.25% pancreatin, stopping digestion with 1mL culture medium, centrifuging at low speed, collecting cells, and washing with PBS once again;

f) each 1 × 10⁶Adding 100 mu L of RIPA lysate into each cell, fully suspending, and placing on ice for cracking for 15-30 min; centrifuging at 12000g for 10min at 4 ℃;

g) and sucking a little supernatant for BCA quantification, and adding the A solution: preparing a detection working solution according to the proportion of 50:1 of the solution B, adding 5 mu L of supernatant or standard substance, incubating at 37 ℃ for 30min, and detecting the absorbance at the wavelength of 562 nm;

h) the total protein concentration in the supernatant was calculated and configured to the appropriate concentration using Buffer, plotted as a linear plot against the standard concentration. Adding 4 xSDS loading buffer solution according to the ratio of 3:1, boiling in a metal bath for 10min, and storing at-80 ℃.

2) Electrophoresis

a) Loading on the prepared gel;

b) electrophoresis: adjusting the voltage to 60V, adjusting the voltage to 120V after the protein is concentrated until the bromophenol blue front edge reaches the gel bottom, and ending electrophoresis;

c) film transfer: electrifying, keeping constant voltage, rotating the die for 2h at 18V;

d) and (3) sealing: placing the lower membrane in 5% skimmed milk powder sealing solution, and sealing for 1 hr at room temperature under shaking on a shaking table;

e) primary antibody incubation: dripping primary antibody according to the required dilution concentration, and incubating at 4 ℃ overnight or incubating at 37 ℃ for 3 h;

f) and (3) secondary antibody incubation: the PVDF membrane was removed and washed three times with TBST for 10min each. And adding the secondary antibody dropwise according to the required dilution concentration, and incubating for 1h at room temperature. Taking out the membrane, and washing with TBST for 10min for three times;

g) and opening the developing instrument, preparing an ECL developing solution, uniformly coating the ECL developing solution on the film, and developing.

The experimental result is shown in fig. 6, the compound Isoeucommin a can significantly induce the expression of Nrf2 and HO-1 of normal HRMC, wherein Tublin is tubulin.

2. Regulation of high sugar-induced HRMC cells Nrf2 and HO-1 by target compounds:

a) taking HRMC cells which are well proliferated and are in logarithmic phase, discarding culture solution, dispersing by digestive juice of 0.25% pancreatin and EDTA half, and counting to prepare cell suspension;

b) adding 2 mL/hole L-DMEM into Blank group and Control group, adding 2 mL/hole L-DMEM into Glucose group, adding a culture medium (the final concentration of Glucose is 30mM) prepared by mixing 250mM Glucose mother liquor into Glucose group, and continuously culturing for 24 h;

c)2 μ L DMSO was added to the blank group and the Glucose group, 2 μ L target compound was added to the administration group at different concentrations to give final concentrations of 62.5 μ M and 125 μ M, respectively, and CO was added₂Culturing for 24h in the incubator to collect cell samples;

other processing steps and detection methods have the same regulating effect of the target compound on normal HRMC cells Nrf2 and HO-1.

The experimental result is shown in fig. 7, and it can be seen from the figure that the expression of Nrf2 in HRMC cells is significantly reduced under the induction of high sugar, and it is found that the phosphorylation modification level of GSK-3 β is significantly enhanced after isoeucomin a action, and the protein stability of GSK3 β is reduced, so that the inhibition effect of GSK 353 β on Nrf2 is weakened, thereby significantly enhancing the protein expression levels of Nrf2 and HO-1, and exerting an antioxidant effect, further inhibiting the proliferation of mesangial cells in a high sugar environment, and reducing the damage effect of high sugar on kidneys.

Third, detection of superoxide dismutase (SOD) Activity

2. adding 2 ml/hole L-DMEM into Blank group and Control group, adding 2 ml/hole L-DMEM into Glucose group, adding a culture medium (the final concentration of Glucose is 30mM) prepared by mixing 250mM Glucose mother liquor into Glucose group, and continuously culturing for 24 h;

3. the blank group and the Glucose group were added with 2. mu.L DMSO, and the administration group was added with Isoeutomomin A2. mu.L at different concentrations to give final concentrations of 31.25. mu.M, 62.5. mu.M and 125. mu.M, respectively, and placed in CO₂Culturing for 24h in the incubator to collect cell samples;

4. the cells were collected by trypsinization, washed 1-2 times with pre-cooled PBS, added with 40. mu.L PBS and disrupted with liquid nitrogen. Centrifuging at 7500rpm at 4 deg.C for 10min, and collecting supernatant as sample to be tested;

5. sample detection method

1) Preparing WST-8/enzyme working solution: an appropriate amount of WST-8 enzyme working solution was prepared in a volume of 160. mu.L per reaction. 151 mu LSOD detection buffer solution, 8 mu LWST-8 and 1 mu L enzyme solution are uniformly mixed to prepare 160 mu L WST-8/enzyme working solution, and the prepared working solution is prepared as soon as possible.

2) Preparing a reaction starting working solution: dissolving the reaction starting solution of 40X, uniformly mixing, adding 1 mu L of the reaction starting solution (40X) into 39 mu L of SOD detection buffer solution, diluting, and uniformly mixing to obtain the reaction starting working solution.

3) And (3) sample determination:

a. the sample wells and various blank control wells were set using a 96-well plate with reference to table 2 below, and the sample and the working solution were added in sequence. Adding the reaction starting liquid and fully mixing the mixture.

TABLE 2 reaction System

	Sample (I)	Blank control 1	Blank control 2	Blank control 3
					Sample to be tested	20μL	—	—	20μL
SOD detection buffer solution	—	20μL	40μL	20μL
					WST-8/enzyme working solution	160μL	160μL	160μL	160μL
Reaction starting working solution	20μL	20μL	—	—

b.37 ℃ for 30 minutes, and the absorbance at 450 nm.

4) Calculation of total SOD activity in samples:

percent inhibition ═ 100% for [ (a blank 1-a blank 2) - (a sample-a blank 3) ]/(a blank 1-a blank 2) ×;

the SOD enzyme activity unit in the sample to be detected is the SOD enzyme activity unit in the detection system is the inhibition percentage/(1-inhibition percentage) units.

The experimental results are shown in fig. 8, and the results show that the expression of SOD in HRMC cells is remarkably reduced under the induction of high sugar, and the expression level of SOD can be enhanced after Isoeutomin A acts, so that the anti-oxidation effect is exerted.

Detection of Malondialdehyde (MDA) expression level

2. adding 2 ml/hole L-DMEM into Blank group and Control group, adding 2 ml/hole L-DMEM into Glucose group and adding 250mM Glucose mother liquor (the final concentration of Glucose is 30mM), and continuously culturing for 24 h;

3. 2 μ L DMSO was added to the blank group and the Glucose group, and Isoeutomomin A2 μ L was added to the administration group to give final concentrations of 31.25 μ M, 62.5 μ M and 125 μ M, respectively, and CO was added₂Culturing for 24h in the incubator to collect cell samples;

4. and (3) sample determination:

1) preparing TBA storage solution: weighing a proper amount of thiobarbituric acid (TBA), and preparing TBA storage solution with the concentration of 0.37% by using TBA preparation solution.

2) And (3) preparing an MDA detection working solution, namely dissolving 4X TBA solution, uniformly mixing, adding 150 mu L TBA diluent into 50 mu L TBA storage solution to dilute, adding 3 mu L antioxidant, and uniformly mixing to obtain the MDA detection working solution.

3) Adding 0.1ml of appropriate solution such as homogenate, lysate or PBS as blank control into a centrifuge tube or other appropriate container, adding 0.1ml of the standard substance with different concentrations for preparing standard curve, and adding 0.1ml of sample for determination; subsequently 0.2ml of MDA assay working solution was added.

a. The detection reaction system can be set up with reference to table 3 below:

TABLE 3 reaction System

	Blank control	Standard article	Sample (I)
				Homogenate, lysate or PBS	0.1ml	－	－
Standard article	－	0.1ml	－
				Sample to be tested	－	－	0.1ml
MDA detection working solution	0.2ml	0.2ml	0.2ml

b. After mixing, heating for 15 minutes at 100 ℃ or in a boiling water bath.

c. The water bath was cooled to room temperature and 1000g was centrifuged at room temperature for 10 min. 200. mu.l of the supernatant was added to a 96-well plate, followed by measurement of absorbance at 532nm with a microplate reader. If it is not convenient to measure the absorbance at 532nm, the absorbance between 530 nm and 540nm may also be measured. The dual wavelength measurement can be performed by setting 450nm as a reference wavelength.

d, calculating the MDA content: the molar concentration of MDA was calculated from the standard curve.

The experimental result is shown in fig. 9, and the result shows that the expression of MDA in the HRMC cell is significantly increased under the induction of high sugar, and the induced expression of MDA can be reduced after the Isoeucommin a acts, so that the anti-oxidation effect is exerted.

Example 3: research on oxidation signal path in Isoeutommin A anti-SD rat primary renal tubular cells

First, target Compound Pair H₂O₂Effect of injury of primary renal tubular cells in SD rats:

a) inoculating the well-propagated primary renal tubular cells to a 96-well plate at a density of 1500 cells/well, respectively, placing at 37 deg.C and 5% CO₂And pre-culturing for 24h in a 100% relative humidity cell culture box.

b) 10% FBS RPMI L-DMEM was added to Blank, Control and Model groups, and Isoeutommin A was added to the administration group so that the final concentrations were 31.25. mu.m, 62.5. mu.m and 125. mu.m. After shaking and mixing, the culture was continued for 24 h.

c) After 24h, the Blank and Control groups were changed to L-DMEM, Model and administration groups to 400. mu. mol/L H₂O₂The L-DMEM is cultured for 2 hours at 37 ℃ in an incubator. Adding 100 μ L of luminous cell activity detection reagent into each well, placing in a constant temperature oscillator, oscillating at room temperature for 15min, and detecting at 500nm of a microplate reader. The cell growth rate of each group was defined as (observed OD value-blank OD value)/(control OD value-blank OD value) × 100%. The experiment was repeated 3 times and the average was taken.

The results of cell activity experiments are shown in FIG. 10, and the compound Isoeutomomin A can effectively inhibit H₂O₂Killing primary renal tubules in a dosage effect.

II, H₂O₂Effect of Isoeucommin A on intracellular SOD, MDA, GSH and Nrf2 signaling pathways after Effect in injury model

1) Taking primary kidney tubule cells with good proliferation at 3X 10⁵The density of each well is inoculated to 6-well plate, and the plate is placed at 37 ℃ and 5% CO₂And pre-culturing for 24h in a 100% relative humidity cell culture box.

2) The Blank, Control and Model groups were added with 10% FBS RPMI L-DMEM, the administration group was added with Isoeutommin A to give final concentrations of 31.25 μm, 62.5 μm and 125 μm, and the mixture was shaken and mixed, and then cultured for 24 h.

3) After 24h, the Blank and Control groups were changed to L-DMEM, Model and administration groups to 400. mu. mol/L H₂O₂The L-DMEM is evenly mixed by shaking and cultured in an incubator at 37 ℃ for 2 hours. Collecting cells and detecting SOD, MDA, GSH and Western-Blot by the same method.

The SOD enzyme activity detection result is shown in FIG. 11, and Isoeutomomin A can effectively enhance H after acting₂O₂SOD enzyme activity in the damaged primary renal tubular cells presents dose effect; the results of MDA expression level detection are shown in FIG. 12, and H is effectively inhibited after Isoeucommin A acts₂O₂MDA production in damaged primary tubular cells, in a dose-effect; the expression results of the proteins Nrf2 and HO-1 are shown in FIG. 13, FIG. 13(a) is the result of Western-Blot protein gel electrophoresis, it can be clearly seen that when the dosage is increased, the protein contents of Nrf2 and HO-1 are increased, FIGS. 13(b) and (c) are the protein expression difference of Nrf2 and HO-1 under different dosages, respectively, and when the dosage is not less than 31.25 μ M, the difference is significant, therefore, the Isoeutominin A can effectively enhance H after the action₂O₂Protein expression of Nrf2 and HO-1 in injured primary tubular cells, in a dose-response.

The GSH detection operation process is as follows:

a) sample preparation:

washing with precooled PBS for 1-2 times, resuspending each cell sample with 60 μ L5% sulfosalicylic acid (SSA), quickly freezing with liquid nitrogen, repeatedly and rapidly freezing and thawing in 37 deg.C water bath for 2 times to lyse cells, standing on ice for 10min, centrifuging at 10000rpm for 10min, and collecting supernatant as sample to be tested;

b) sample detection:

1) preparing a working solution: mu.L of glutathione reductase was diluted to 250. mu.L with 1X of the assay solution, i.e., enzyme solution. Adding 228 mu L of enzyme solution and 228 mu L of DTNB stock solution into 8mL of 1X detection solution, and uniformly mixing;

2) preparing an NADPH solution: sucking 10 μ L of NADPH original solution, adding into 2.5mL of 1 × detection solution, and mixing;

3) and (3) glutathione standard substance: diluting GSH stock solution 200 times with 5% sulfosalicylic acid (SSA) to obtain 50 μ M standard 1, diluting 2 times of standard 1 to obtain standard 2, and sequentially diluting 2 times to obtain standard 5;

4) the samples and desired solutions were added as specified in table 4 below:

TABLE 4

The average absorbance change per 5min was measured with a microplate reader at a wavelength of 412 nm.

From the results shown in FIG. 14, Isoeutommin A was effective in enhancing H after the action₂O₂GSH expression in injured primary tubular cells, in a dose-response.

In conclusion, the compound Isoeutommin A provided by the invention can effectively inhibit the proliferation of human glomerular mesangial cells induced by high sugar and inhibit H₂O₂Further inhibits the apoptosis of the kidney cells by the damage effect on the primary renal tubular cells. The action mechanism of the compound Isoeutomomin A is that the compound Isoeutomomin A plays an antioxidation role by enhancing the expression of GSH in cells, the enzyme activity of SOD, inhibiting the generation of MDA and inducing the activation of Nrf2/HO-1 signal channel, provides a good lead compound for developing a new medicament for preventing and/or treating nephropathy, and has important research value and application prospect for treating nephropathy.

The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all equivalent changes made by using the contents of the present specification and the drawings, or applied directly or indirectly to the related technical fields, are included in the scope of the present invention.

Claims

1. Use of a lignan compound in the manufacture of a medicament for the treatment and/or prevention of a kidney disease, wherein the compound has the formula:

the nephropathy is diabetic nephropathy.