Application of pinostrobin in preparation of medicine for treating gastric ulcer

Abstract

The invention provides application of pinostrobin in preparation of a medicine for treating gastric ulcer, and belongs to the technical field of biological medicine. The pinostrobin provided by the invention realizes the anti-gastric ulcer effect by improving the gastric mucosa blood flow volume, inhibiting inflammatory reaction, inhibiting oxidation reaction and maintaining the integrity of the gastric mucus barrier. Pinostrobin can reduce the gastric ulcer area of rats and increase the pain threshold value; the content of ET-1 in plasma is reduced, and the repairing effect of gastric mucosa is enhanced; the contents of TNF-alpha and IL-6 are reduced, the content of IL-10 is increased, and the anti-inflammatory effect is enhanced; the content of T-SOD in plasma is increased, the content of MPO is reduced, and the antioxidant effect is enhanced. The pinostrobin is expected to be used as a new medicine for treating gastric ulcer.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to the application of thiazolinone in the preparation of drugs for treating gastric ulcers. Background Technology

[0002] Gastric ulcer is a common digestive system disease with a high incidence and recurrence rate. Its main symptoms include abdominal pain, bloating, loss of appetite, belching, nausea, and vomiting. The pathogenesis of gastric ulcer is not fully understood, but the widely accepted theory is the imbalance between gastric mucosal attack factors (gastric acid and pepsin, etc.) and defense factors (mucus and bicarbonate, etc.). Furthermore, gastric ulcers can be activated by various factors, such as inflammatory mediators, nonsteroidal anti-inflammatory drugs (NSAIDs), and ethanol. Ethanol damages the gastric mucosa, induces microcirculatory disturbances and hypoxia, weakens mucosal resistance, makes the gastric mucosa susceptible to damage, and may even exacerbate the degree of gastric mucosal damage.

[0003] Clinically, commonly used drugs for treating gastric ulcers include proton pump inhibitors (omeprazole, lansoprazole), H2 receptor antagonists (ranitidine, cimetidine), and antacids. However, long-term use of these drugs can cause adverse reactions such as impotence, changes in hematopoietic function, arrhythmia, and gynecomastia in men. Therefore, it is necessary to provide a new drug for treating gastric ulcers. Summary of the Invention

[0004] The purpose of this invention is to provide the application of thiazolinone in the preparation of a drug for treating gastric ulcers, in order to provide a new drug for the treatment of gastric ulcers.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] This invention provides the use of pneumoconiol in the preparation of a medicament for treating gastric ulcers, wherein the structural formula of pneumoconiol is:

[0007]

[0008] Preferably, the globularin achieves its anti-gastric ulcer effect by improving gastric mucosal blood flow, inhibiting inflammatory response, inhibiting oxidative response, and maintaining the integrity of the gastric mucus barrier.

[0009] Preferably, the improvement in gastric mucosal blood flow is achieved by increasing gastric mucosal blood flow by reducing the content of ET-1 in plasma.

[0010] Preferably, the inhibition of the inflammatory response exerts its anti-inflammatory effect by reducing the levels of TNF-α and IL-6 and increasing the levels of IL-10.

[0011] Preferably, the inhibition of oxidation reaction is achieved by increasing the content of T-SOD and decreasing the content of MPO to exert an antioxidant effect.

[0012] Preferably, the gastric ulcer is a gastric ulcer caused by ethanol.

[0013] This invention, through observation of gastric tissue morphology in rats under different treatment groups, measurement of gastric ulcer index and ulcer inhibition rate, and determination of plasma levels of repair factor ET-1, inflammatory factors TNF-α, IL-6, IL-10, and oxidative factors T-SOD and MPO, found that compared with the model control group, globularisin reduced the area of ​​gastric ulcers and increased the pain threshold in rats; decreased plasma ET-1 levels, enhancing gastric mucosal repair; decreased TNF-α and IL-6 levels, increased IL-10 levels, enhancing anti-inflammatory effects; increased plasma T-SOD levels, decreased MPO levels, enhancing antioxidant effects. Therefore, globularisin can achieve its anti-gastric ulcer effect by improving gastric mucosal blood flow, inhibiting inflammatory responses, inhibiting oxidative responses, and maintaining the integrity of the gastric mucus barrier. Thus, globularisin shows promise as a new drug for treating gastric ulcers. Attached Figure Description

[0014] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0015] Figure 1 The results of morphological observation of the stomach tissue of rats in each treatment group in Example 1 are shown. Detailed Implementation

[0016] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention. The reagent kits used in the following embodiments were all purchased from Wuhan Elite Biotechnology Co., Ltd.

[0017] Example 1

[0018] 1. Animal grouping and administration

[0019] Twenty healthy male SPF-grade SD rats weighing 180g±20g (purchased from Jinan Pengyue Experimental Animal Breeding Co., Ltd., Experimental Animal License No.: SCXK(Lu)2002-0006) were selected and acclimatized for 3 days in a 12h day and night alternation environment, with free access to water and food during the acclimatization period.

[0020] After the adaptive feeding period, the rats were randomly divided into 4 groups of 5 rats each: blank control group (KB), model control group (MX), globus buperidone group (QSS, 48.51 mg / kg), and WT (WT, positive control, 225.00 mg / kg). The QSS and WT groups were treated with the drug by gavage for 7 consecutive days, once a day. On the sixth day, the rats were fasted but allowed to drink water at 8 pm. The drug was administered 12 hours later. One hour after the drug administration, except for the blank control group, all rats were given an anhydrous ethanol at a dose of 5 mL / kg to create a gastric ulcer model.

[0021] Among them, the structural formula of pine oleoresin is shown in Formula 1. It was extracted and separated from cassia japonica and analyzed by high performance liquid chromatography. The purity was greater than 98%. Weitongning tablets were purchased from Henan Lingrui Pharmaceutical Co., Ltd., batch number 2301262. Anhydrous ethanol was purchased from Xinxiang Sanwei Disinfectant Preparation Co., Ltd.

[0022]

[0023] 2. Time to reach pain threshold in rats

[0024] Gastric ulcers can cause stomach pain, which falls under the category of stomach pain in Traditional Chinese Medicine. Therefore, this study aimed to verify whether globular pine resin could alleviate pain caused by gastric ulcers by measuring the pain threshold. The specific method involved administering anhydrous ethanol via gavage for 1 hour, then placing all rats on a thermal pain stimulation device to measure their pain threshold and recording the time it took for the rats to reach that threshold. The results are shown in Table 1.

[0025] Table 1. Time to reach pain threshold in rats of each treatment group (x±s, n=5)

[0026] Group Dosage (mg / kg) Pain threshold (s) KB 0.00 5.14±0.90 MX 0.00 <![CDATA[3.18±0.22 ## ]]> QSS 48.51 4.82±0.47** WT 225.00 3.92±0.44*

[0027] Wherein, ## indicates that compared with KB, P < 0.01, there is a significant difference; ** indicates that compared with MX group, P < 0.01, there is a significant difference; * indicates that P < 0.05, there is a difference.

[0028] As shown in Table 1, the time to reach the pain threshold in the MX group and the WT positive control group were (3.18±0.22)s and (3.92±0.44)s, respectively. Compared with the MX group, the time to reach the pain threshold in the QSS group was significantly increased (P<0.01), even longer than that in the WT group, indicating better efficacy. It is speculated that globular pine sulfate can effectively relieve pain caused by gastric ulcers.

[0029] 3. Observation of rat gastric tissue morphology and determination of ulcer index

[0030] After anesthetizing rats with isoflurane, the stomach and abdominal aorta were exposed by incision along the midline of the abdomen. Plasma was collected from the abdominal aorta using a lancet, centrifuged at 5000 g / min for 4 min at 4°C, and the supernatant was collected and stored at -80°C for later use. Next, the pylorus and cardia were ligated with sutures, and a small incision was made at the bottom of the greater curvature of the stomach to collect the gastric contents. The contents were centrifuged at 1000 r / min for 4 min at 4°C, and the supernatant was collected. The gastric fluid volume was recorded and stored at -80°C for later analysis. Finally, the stomach was cut open along the greater curvature, rinsed with physiological saline, unfolded, and photographed.

[0031] Observe all the images of gastric tissue taken, and compare the morphology of gastric ulcer edges, ulcer surfaces, and mucosal folds in each group of rats. Using ImageJ software under the same conditions, calculate the gastric ulcer index and ulcer inhibition rate, as shown below:

[0032] Ulcer Index = (Area of ​​Gastric Ulcers) / (Total Area of ​​Stomach) × 100%

[0033] Ulcer inhibition rate = (Ulcer index of model group - Ulcer index of treatment group) / (Ulcer index of model group) × 100%

[0034] The results of morphological observation of stomach tissue in rats in different treatment groups are as follows: Figure 1 As shown in Table 2, the results of the gastric ulcer index and ulcer inhibition rate measurements are as follows.

[0035] Table 2. Gastric ulcer index and ulcer inhibition rate in rats of each treatment group (x±s, n=5)

[0036] Group Dosage (mg / kg) Ulcer index (%) Inhibition rate (%) KB 0.00 - - MX 0.00 5.08±0.80## - QSS 48.51 0.34±0.04** 93.31 WT 225.00 1.78±1.51** 64.96

[0037] Wherein, ## indicates that compared with KB, P < 0.01, there is a significant difference; ** indicates that compared with MX group, P < 0.01, there is a significant difference.

[0038] Depend on Figure 1 It can be seen that the gastric mucosa in the KB group was normal in color and smooth in surface, without ulcers or bleeding points; the gastric mucosa in the MX group had a large number of clearly visible hemorrhagic lesions. According to the data in Table 2, the rat gastric ulcer model induced by anhydrous ethanol was successfully established; the QSS group had only a few punctate hemorrhages visible to the naked eye, showing a better therapeutic effect compared with the WT group, indicating that globularisin has a good therapeutic effect on gastric ulcers.

[0039] Table 2 shows that the gastric ulcer index of the MX group was significantly different from that of the KB group (P < 0.01), proving the successful establishment of the anhydrous ethanol-induced gastric ulcer model in rats. The QSS group and WT group also showed significant differences compared to the MX group (P < 0.01), indicating that both groups had significant therapeutic effects on gastric ulcers. The ulcer inhibition rate more directly demonstrates the therapeutic effect of globularisin.

[0040] 4. Determination of ET-1 content in plasma

[0041] ET-1 is an active polypeptide with a strong and long-lasting vasoconstrictive effect. Its vasoconstrictive effect can lead to a decrease in blood flow to the gastric mucosa, which can cause severe ulceration.

[0042] The ET-1 content in the plasma of rats in each treatment group was determined using an enzyme-linked immunosorbent assay (ELISA) kit, following the instructions in the kit's manual. The results are shown in Table 3.

[0043] Table 3. ET-1 content in rat plasma of each treatment group (x±s, n=5)

[0044] Group Dosage (mg / kg) ET-1 (pg / mL) KB 0.00 5.30±0.17 MX 0.00 <![CDATA[7.49±0.83 ## ]]> QSS 48.51 4.96±0.19** WT 225.00 6.23±0.98**

[0045] Wherein, ## indicates that compared with KB, P < 0.01, there is a significant difference; ** indicates that compared with MX group, P < 0.01, there is a significant difference.

[0046] As shown in Table 3, compared with the MX group, the plasma ET-1 content in both the QSS group and the WT group was reduced, and the differences were significant (P<0.01). This indicates that globular pine syrup can increase gastric mucosal blood flow and promote gastric mucosal repair by reducing plasma ET-1 content, thereby achieving the effect of treating gastric ulcers.

[0047] 5. Measurement of inflammatory factor levels in plasma

[0048] Gastric ulcers are always accompanied by inflammation. After an inflammatory response occurs, macrophages secrete the pro-inflammatory factor TNF-α, which in turn promotes the production of other inflammatory factors such as IL-6. These factors collectively promote the aggregation of neutrophils at the site of inflammation, exacerbating the severity of the gastric ulcer. IL-10 is a multifunctional negative regulator that inhibits and antagonizes the production and action of pro-inflammatory factors, thereby suppressing the inflammatory response.

[0049] The levels of inflammatory factors TNF-α, IL-6, and IL-10 in the plasma of rats in each treatment group were determined using an ELISA kit, following the instructions in the kit's manual. The results are shown in Table 4.

[0050] Table 4. Plasma levels of TNF-α, IL-6, and IL-10 in rats from each treatment group (x±s, n=5)

[0051]

[0052] Wherein, ## indicates that compared with KB, P < 0.01, there is a significant difference; ** indicates that compared with MX group, P < 0.01, there is a significant difference; * indicates that P < 0.05, there is a difference.

[0053] As shown in Table 4, the levels of TNF-α, IL-6, and IL-10 in plasma were significantly different between the MX group and the KB group (P < 0.01). Compared with the MX group, the levels of TNF-α and IL-6 were decreased and the level of IL-10 was increased in the QSS group, indicating that globularisin can exert an anti-inflammatory effect by reducing the levels of TNF-α and IL-6 and increasing the level of IL-10, thereby treating gastric ulcers.

[0054] 6. Determination of antioxidant factor content in plasma

[0055] Oxidative stress refers to an increase in the level of intracellular reactive oxygen species (ROS). These unpaired molecules play a crucial physiological role in cellular homeostasis. They damage lipids, proteins, and DNA, leading to lipid peroxidation, cell death, and tissue damage. T-SOD is an important antioxidant widely present in organisms. Its main function is to resist and prevent damage to cells from oxygen free radicals and to scavenge the oxidation products of oxygen free radicals. MPO is a major component of neutrophil cytoplasmic granules and can promote inflammation, quantitatively reflecting the degree of inflammatory damage.

[0056] The levels of T-SOD and MPO in the plasma of each treatment group were determined using a colorimetric assay kit, following the instructions in the kit's manual. The results are shown in Table 5.

[0057] Table 5. Plasma levels of T-SOD and MPO in rats from each treatment group (x±s, n=5)

[0058]

[0059] Wherein, ## indicates that compared with KB, P < 0.01, there is a significant difference; ** indicates that compared with MX group, P < 0.01, there is a significant difference.

[0060] As shown in Table 5, compared with the MX group, the levels of T-SOD and MPO in the plasma of both the QSS and WT groups were increased, while the levels were decreased, with significant differences (P < 0.01). This indicates that under the influence of globular pinellitine, the levels of T-SOD and MPO in rat plasma increased, and the antioxidant effect was enhanced. Therefore, globular pinellitine can exert a therapeutic effect on gastric ulcers through its antioxidant properties.

[0061] As can be seen from the above embodiments, this invention provides the application of globin in the preparation of drugs for treating gastric ulcers. Through observation of gastric tissue morphology in rats under different treatment groups, determination of gastric ulcer index and ulcer inhibition rate, and measurement of plasma levels of repair factor ET-1, inflammatory factors TNF-α, IL-6, IL-10, and oxidative factors T-SOD and MPO, this invention found that, compared with the model control group, globin could reduce the gastric ulcer area and increase the pain threshold in rats; decrease plasma ET-1 levels, enhancing gastric mucosal repair; decrease TNF-α and IL-6 levels, increase IL-10 levels, enhancing anti-inflammatory effects; increase plasma T-SOD levels, decrease MPO levels, enhancing antioxidant effects. Therefore, globin can achieve its anti-gastric ulcer effect by improving gastric mucosal blood flow, inhibiting inflammatory responses, inhibiting oxidative responses, and maintaining the integrity of the gastric mucus barrier.

[0062] 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. Use of taxifolin for the preparation of a medicament for the treatment of gastric ulcer, characterized in that, The structural formula of the podocarpin is:

2. Use according to claim 1, wherein The podocarpin realizes the anti-gastric ulcer effect by improving the gastric mucosa blood flow, inhibiting the inflammatory reaction, inhibiting the oxidation reaction and maintaining the integrity of the gastric mucus barrier.

3. Use according to claim 2, wherein the compound is ###0002### The improvement of the gastric mucosa blood flow is to increase the gastric mucosa blood flow by reducing the content of ET-1 in the blood plasma.

4. The use according to claim 2, wherein the compound is ###0002### The inhibition of the inflammatory reaction is to play the anti-inflammatory effect by reducing the contents of TNF-α and IL-6 and increasing the content of IL-10.

5. The use according to claim 2, wherein the compound is ###0002### The inhibition of the oxidation reaction is to play the anti-oxidation effect by increasing the content of T-SOD and reducing the content of MPO.

6. Use according to any one of claims 1 to 5, characterized in that, The gastric ulcer is the gastric ulcer caused by ethanol.

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