A method for treating sepsis with a medicament or formulation containing astragalin

Abstract

This invention relates to the pharmaceutical and food fields, and particularly to novel applications of astragaloside. This invention provides a method for treating sepsis using a drug or preparation containing astragaloside. Animal studies have shown that astragaloside can exert a therapeutic effect on sepsis. This invention discovers that astragaloside can be used to prepare drugs for treating sepsis.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceuticals and food, and particularly to the application of astragaloside in the treatment of sepsis. Background Technology

[0002] Sepsis is a systemic inflammation response syndrome (SIRS) caused by bacterial or other pathogenic microorganism infection. Its main symptoms include chills, palpitations, fever, and altered mental status, often accompanied by multiple organ dysfunction. It is characterized by high morbidity and mortality. Relevant clinical statistics show that more than 19 million people worldwide suffer from sepsis annually, with 6 million dying from it, resulting in a mortality rate exceeding 25%. According to international epidemiological surveys, the mortality rate of sepsis has surpassed that of myocardial infarction, becoming the leading cause of death among non-cardiac patients in intensive care units.

[0003] Astragalin (AST) is a natural flavonoid compound that has been isolated and identified from various plants, such as water lily, mulberry leaf, dodder seed, and astragalus. The chemical name of AST is 3-O-glucoside of kaempferol, and its molecular formula is C2. 21 H 20 O 11 It has a relative molecular mass of 448.39 and a melting point of 177-179℃. Its molecular structure is shown in Formula I.

[0004]

[0005] Currently, there are no reports of it being used to treat sepsis. Summary of the Invention

[0006] 1. This invention provides the application of astragalin in the treatment of sepsis. Animal experiments have shown that astragalin can exert a therapeutic effect on sepsis. This invention also reveals that astragalin can be used to prepare drugs for the treatment of sepsis.

[0007] 2. This invention provides a method for treating sepsis using a drug or preparation containing astragaloside.

[0008] 3. In some specific embodiments of the present invention, the treatment of sepsis includes any one of the following:

[0009] 1) Improves weight changes caused by sepsis;

[0010] 2) Reduce the level of high-mobility group box 1 (HMP-B1), a biomarker of sepsis, in the body;

[0011] 3) Improves liver, lung, and kidney damage caused by sepsis. Attached Figure Description

[0012] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0013] Figure 1 shows the changes in mouse body weight during modeling and drug administration. After randomization, 12 mice were placed in the sham operation group (hereinafter referred to as the Sham group), and another 36 mice underwent cecal ligation and perforation (hereinafter referred to as the Sepis group). Figure 1A shows the initial body weight of the two groups of mice; Figure 1B shows the body weight of the two groups of mice on day 2; on day 2, the Sepis group was randomly regrouped (divided into the Sepis group, Sepis+AST group, and Sepis+KAE group); Figure 1C shows the body weight of each group of mice on day 7; * indicates comparison between the Sham group and the Sepis group, # indicates comparison between the Sepis group and the Sepis+AST group and the Sepis+KAE group; * or #p<0.05, ** or ##p<0.01, *** or ###p<0.001; n>=8;

[0014] Figure 2 shows the results of Western blot analysis of the mouse hippocampus; Figure 2A shows the comparative analysis of protein content in the hippocampus of mice in different groups; Figure 2B shows the comparative analysis of HMGB1 protein content in the hippocampus of mice; * indicates comparison between the Sham group and the Sepis group, # indicates comparison between the Sepis group and the Sepis+AST group and the Sepis+KAE group; * or #p<0.05, ** or ##p<0.01, *** or ###p<0.001; n>=3;

[0015] Figure 3 shows the HE staining results of different groups of mouse liver tissue. HE staining shows its tissue structure and cellular composition.

[0016] Figure 4 shows the HE staining results of different groups of mouse lung tissue. HE staining shows its tissue structure and cellular composition.

[0017] Figure 5 shows the HE staining results of different groups of mouse kidney tissue. HE staining shows its tissue structure and cellular composition. Detailed Implementation

[0018] This invention discloses the application of astragaloside in the treatment of sepsis. Those skilled in the art can refer to this document and appropriately modify the process parameters to achieve the desired result. It is particularly important to note that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0019] In the application of astragaloside provided by this invention for the treatment of sepsis, the raw materials and reagents used are all commercially available.

[0020] The present invention will be further illustrated below with reference to the embodiments:

[0021] Example 1: Establishment and administration of a sepsis model in C57BL / 6J mice

[0022] Before modeling the experiment, the mice were first acclimatized for one week. After the mice adapted to the environment, 48 C57BL / 6J mice were randomly divided into a sham operation group (n=12, hereinafter referred to as the Sham group) and a sepsis group (n=36, which subsequently underwent cecal ligation and perforation, hereinafter referred to as the Sepsis group).

[0023] On day 1, cecal ligation and perforation were performed in the Sepsis group as follows: Mice were anesthetized by intraperitoneal injection of sodium pentobarbital (30 mg / kg). After complete anesthesia, the mice were fixed in a supine position on the operating table. After skin disinfection, an incision of approximately 2 cm was made along the midline of the lower abdomen to expose the cecum. The cecum was ligated at 20% of the distance between the distal end and the base of the cecum, and perforated twice with an 18-gauge needle. Then, gentle squeezing was performed to allow a small amount of intestinal contents to overflow into the peritoneal cavity. The cecum was returned to the peritoneal cavity, and the abdomen was closed with 3-0 sutures. In the Sham group, the abdominal cavity was opened to expose the cecum without ligation or perforation.

[0024] After modeling was completed (day 2), mice were randomly assigned to groups: mouse weight and mental state were used to evaluate whether the modeling was successful, and mice that did not successfully model were excluded. The Sepsis group mice that had successfully modeled in the previous step were randomly divided into three groups: Sepsis group, Sepsis+AST group, and Sepsis+KAE group (KAE is the flavonoid compound kaempferol), with 10 mice in each group. The Sepsis+AST group was administered 10 mg / kg AST by gavage, 200 μL / time (i.e., AST concentration of 50 μg / μL); the Sepsis+KAE group was administered 10 mg / kg KAE by gavage, 200 μL / time (i.e., KAE concentration of 50 μg / μL); the Sham group and Sepsis group were administered an equal volume of physiological saline by gavage. Drug administration began on day 3 and lasted for a total of 4 days. During the experiment, mouse weight data was recorded and photographed on day 0 (before modeling), day 2 (after modeling), and day 7 (after drug intervention).

[0025] Example 2: Astragaloside improves weight changes caused by sepsis

[0026] During the drug administration period, changes in mouse body weight and mental status were observed and monitored. As shown in Figure 1, after modeling, the weight gain of mice in the Sepis group and the Sepis+KAE group was significantly lower than that in the Sham group and the Sepis+AST group. During the observation period, mice in the Sham group and the Sepis+AST group showed high activity levels, good appetite, significant weight gain, smooth fur, and normal appetite, activity, and responsiveness. Mice in the Sepis group and the Sepis+KAE group showed significantly reduced activity, sluggish movement, significantly reduced food and water intake, significant weight loss, rough fur, and some mice exhibited unsteady gait. In conclusion, AST can improve weight changes caused by sepsis, while KAE has no such effect.

[0027] Data from Table 1 and Figure 1A

[0028]

[0029] Data in Table 3, Figure 1C

[0030]

[0031]

[0032] Example 3: Astragaloside reduces the level of high-mobility group B1, a biomarker of sepsis, in vivo.

[0033] High mobility group protein B1 (HMGB1) expression is upregulated during sepsis and is an important biomarker of sepsis. As shown in Figure 2, in brain tissue, the HMGB1 expression level in the Sepsis+AST group was significantly lower than that in the Sepsis group, while the HMGB1 expression level in the Sepsis+KAE group was not significantly different from that in the Sepsis group. In conclusion, AST can reduce the level of the sepsis biomarker HMGB1 in vivo, while KAE has no such effect.

[0034] Data from Table 4 and Figure 2

[0035]

[0036] Example 4: Astragaloside improves liver, lung, and kidney damage caused by sepsis.

[0037] Pathological sections and HE staining experiments of liver and small intestine tissues showed the following results:

[0038] In the Sham group (Figure 3), hepatocytes were neatly arranged in cords and radially distributed around the central vein. The lobular structure was intact, the nucleus structure was clear, the hepatic sinusoids were of average size, and there was no dilation, congestion, inflammatory cell infiltration, or pathological changes. In the Sepis group and the Sepis+KAE group, the lobular structure of the liver tissue was incomplete, the hepatocytes were irregularly arranged and there were a few punctate necrosis, the HE color was lighter, the borders of the hepatic cords were blurred, and there were pathological changes such as inflammatory cell infiltration around the central vein. In the Sepis+AST group, the hepatocytes were neatly arranged and basically orderly, distributed in cords and radially around the central vein. The lobular structure was basically intact, the nucleus structure was clear, the hepatic sinusoids were of average size, and there was no dilation, congestion, but there was still a few inflammatory cell infiltrations around the central vein.

[0039] The alveoli in the Sham group (Figure 4) had intact structure, neatly arranged cells, no dilation or congestion, no inflammatory cell infiltration, and no pathological changes; the alveoli in the Sepis group and the Sepis+KAE group collapsed, and there was inflammatory cell infiltration in the alveolar septa; the degree of alveolar collapse in the Sepis+AST group was reduced, and the number of inflammatory cells infiltrating the alveolar septa was decreased.

[0040] In the Sham group (Figure 5), the renal cells were tightly arranged, the renal tubules were clearly defined, the glomerular structure was normal, the gap between the glomeruli and Bowman's capsule was obvious, and the cells showed no obvious swelling, necrosis, or inflammatory cell infiltration. In the Sepis group and the Sepis+KAE group, the renal cells were loosely arranged, the renal tubules were healed in patches, most of the renal tubular epithelial cells were sloughed off, the tubular walls were thinned, the glomeruli changed from normal spherical shape to irregular shape, the gap between the glomeruli and Bowman's capsule was not obvious, and the cells showed obvious swelling, necrosis, and inflammatory cell infiltration. In the Sepis+AST group, the renal cells were basically normally arranged, the renal tubules did not heal, the renal tubular epithelial cells did not slough off significantly, the glomerular structure was partially abnormal, the gap between the glomeruli and Bowman's capsule was slightly indistinct, and the cells showed a small amount of swelling, necrosis, and inflammatory cell infiltration.

[0041] The above results indicate that AST has a significant effect on improving sepsis, while KAE, a precursor compound of flavonoids, has a limited effect on improving sepsis.

[0042] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Astragaloside is used to treat sepsis.

2. The application as described in claim 1, characterized in that, The drugs, preparations, foods, food additives, or beverages containing astragaloside are used to treat sepsis.

3. The application as described in claim 1, characterized in that, The treatment of sepsis includes any one of the following: 1) Improves weight changes caused by sepsis; 2) Reduce the level of high-mobility group box 1 (HMP-B1), a biomarker of sepsis, in the body; 3) Improves liver, lung, and kidney damage caused by sepsis.

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