Application of polycyclic polyisopentenyl phloroglucinol in preventing and treating ulcerative colitis

Abstract

The present invention relates to the field of medical technology, and specifically discloses the use of a polycyclic polyisopentenyl phloroglucinol as an active ingredient in the preparation of a drug for preventing and treating ulcerative colitis. The present invention's research shows that polycyclic polyisopentenyl phloroglucinol (Hypersampsonone H, HS-1) derived from Herba Lycopodii has an anti-ulcerative colitis effect. The present invention utilizes a mouse ulcerative colitis model to observe a series of experiments such as the therapeutic effect of HS-1 on ulcerative colitis, and explores the therapeutic effect of HS-1 on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice. It is revealed for the first time that HS-1 can resist ulcerative colitis, providing a new natural medicine option for preventing and treating ulcerative colitis, and has good application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to the use of polycyclic polyisopentenyl phloroglucinol as an active ingredient in the preparation of a medicine for preventing and treating ulcerative colitis. Background Art

[0002] Ulcerative colitis (UC) is a chronic, recurrent intestinal inflammatory disease caused by a variety of etiologies. Its main clinical manifestations include diarrhea, abdominal pain, weight loss, bloody stools, abscesses, etc., and its symptoms depend on the degree of progression of the disease. It is worth noting that the recurring and lengthy course of ulcerative colitis often leads to multiple complications, and the chance of cancer in patients is 5 to 10 times higher than that of normal people. In addition, ulcerative colitis is considered by the World Health Organization to be a difficult-to-cure disease that seriously affects the health and quality of life of patients. In recent years, the incidence of ulcerative colitis has shown a significant upward trend in developing countries in Asia, Africa and other regions.

[0003] Currently, the treatment of ulcerative colitis is primarily based on Western medicine, including steroidal and nonsteroidal drugs, such as glucocorticoids, aminosalicylic acids, antibiotics, and immunosuppressants. While these drugs can control ulcerative colitis, they also have various side effects, such as fever, vomiting, headache, and osteoporosis. Furthermore, these drugs require long-term use, and discontinuation can easily lead to a rebound effect. However, my country has abundant resources of traditional Chinese medicine, and Chinese herbal medicines are safe and effective. Therefore, there is an urgent need to find natural drugs for the treatment of ulcerative colitis from natural plants to meet urgent clinical needs. Summary of the Invention

[0004] To this end, the present invention provides a polycyclic polyisopentenyl phloroglucinol isolated from the Chinese herbal medicine Herba Lycopodii and its application in preparing a drug for preventing and treating ulcerative colitis, providing a new drug option for the prevention and treatment of ulcerative colitis.

[0005] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0006] A polycyclic polyisopentenyl phloroglucinol having the following structural formula:

[0007]

[0008] The polycyclic polyisopentenyl phloroglucinol of the present invention is isolated and obtained from the Chinese herbal medicine Herba Lycopodii. The inventors have found that the polycyclic polyisopentenyl phloroglucinol (Hypersampsonone H, HS-1) described in the above structural formula can effectively treat and alleviate the symptoms of DSS-induced ulcerative colitis, including significantly alleviating symptoms such as weight loss, colon shortening, splenomegaly, and diarrhea and bloody stools; can significantly reduce inflammatory cell infiltration in colon tissue and protect colon tissue structure; and can regulate the expression level of inflammatory factors. Therefore, HS-1 can be used as an effective therapeutic drug for ulcerative colitis.

[0009] Furthermore, the preparation method of the polycyclic polyisopentenyl phloroglucinol comprises the following steps:

[0010] S1: Mix Herba Cinnamomi powder with 8 volumes of 95% ethanol, heat under reflux and extract for 1 hour, extract three times, filter and combine the three extracts, and concentrate under reduced pressure until the solution is thick to obtain Herba Cinnamomi total extract;

[0011] S2: The total extract of Herba Coptidis was passed through a 200-300 mesh silica gel column and gradient eluted with pure petroleum ether: dichloromethane in a ratio from 1:0 to 0:1. The eluate in the petroleum ether: dichloromethane ratio of 3:2 was collected and concentrated by rotary evaporation to remove the solvent to obtain component A.

[0012] S3: Component A was separated by preparative HPLC using Rp-C18 reverse phase silica gel as a mobile phase with 85% acetonitrile to collect polycyclic polyisopentenyl phloroglucinol.

[0013] Furthermore, step S3 includes collecting the peak with a retention time of 15.2 min, concentrating by rotary evaporation, and removing the solvent to obtain polycyclic polyisopentenyl phloroglucinol. The purity of the polycyclic polyisopentenyl phloroglucinol is greater than 95%.

[0014] In other embodiments, the polycyclic polyisopentenyl phloroglucinol is used as an active ingredient in the preparation of drugs for preventing and treating ulcerative colitis.

[0015] Furthermore, the drug includes pharmaceutically acceptable excipients.

[0016] Furthermore, the drug is any one of a liquid preparation, a solid preparation, a semisolid preparation, and a gas preparation.

[0017] Furthermore, the dosage form of the drug is any one of oral solution, tablet, capsule, pill, granule or injection.

[0018] Furthermore, the drug is used in reducing the disease activity index of ulcerative colitis mice, restoring colon length and alleviating spleen enlargement.

[0019] Furthermore, the drug is used to reduce colon tissue structure damage, reduce the level of pro-inflammatory factors and promote the secretion of anti-inflammatory factors in mice with ulcerative colitis.

[0020] Furthermore, the effective dosage of the drug is 3 to 12 mg / kg / day.

[0021] The polycyclic polyisopentenyl phloroglucinol (HS-1) is formulated into a 0.5% sodium carboxymethylcellulose suspension. The method of using the suspension in mice is: daily gavage administration, the dosage is 3-12 mg / kg. The preparation method of the 0.5% sodium carboxymethylcellulose suspension of the drug is: weigh 5g of sodium carboxymethylcellulose (CMC-Na), take 1L of ultrapure water and heat it to about 70-80°C, add CMC-Na to the ultrapure water in small amounts and multiple times, stirring while adding, to obtain a 0.5% CMC-Na solution. Weigh 3mg, 6mg, and 12mg of HS-1 respectively and dissolve them in 10mL of 0.5% CMC-Na solution to obtain drug solutions with dosages of 3mg / kg, 6mg / kg, and 12mg / kg, respectively, and store them in a refrigerator at 4°C.

[0022] Figures in the specification

[0023] Figure 1 The weight changes of ulcerative colitis mice in different treatment groups provided in the embodiments of the present invention;

[0024] Figure 2 The disease activity index (DAI) scores of ulcerative colitis mice in different treatment groups provided in the examples of the present invention;

[0025] Figure 3 Representative colon images of ulcerative colitis mice in different treatment groups provided in the examples of the present invention;

[0026] Figure 4 The statistical analysis results of the colon length of ulcerative colitis mice in different treatment groups provided in the embodiments of the present invention;

[0027] Figure 5 Representative spleen images of ulcerative colitis mice from different treatment groups provided in the examples of the present invention;

[0028] Figure 6 Statistical analysis results of spleen index of ulcerative colitis mice in different treatment groups provided in the embodiments of the present invention;

[0029] Figure 7 HE staining results of colon tissues of ulcerative colitis mice in different treatment groups provided in the embodiments of the present invention;

[0030] Figure 8The histological pathological damage scores of the colon of ulcerative colitis mice in different treatment groups provided in the examples of the present invention;

[0031] Figure 9 The expression levels of inflammatory factor IL-6 in colon tissue of ulcerative colitis mice in different treatment groups provided in the embodiments of the present invention;

[0032] Figure 10 The expression levels of inflammatory factor TNF-α in colon tissue of ulcerative colitis mice in different treatment groups provided in the embodiments of the present invention;

[0033] Figure 11 The expression levels of the inflammatory factor IL-10 in the colon tissues of ulcerative colitis mice in different treatment groups provided in the examples of the present invention. DETAILED DESCRIPTION

[0034] Hypericum sampsonii Hance is a Chinese herbal medicine used to treat enteritis, hematemesis, and the like. Previous studies have shown that an ethyl acetate extract of Hypericum sampsonii Hance has anti-inflammatory activity, but there are no reports of its use in the treatment of ulcerative colitis. Therefore, the inventors investigated the effects of an ethyl acetate extract of Hypericum sampsonii Hance on ulcerative colitis and found that the ethyl acetate extract can improve symptoms such as weight loss, bloody stools, shortened colon, and histopathological damage in mice with experimental ulcerative colitis. Therefore, the ethyl acetate extract of Hypericum sampsonii Hance contains an active ingredient that can be used to prepare drugs for preventing and treating colitis, particularly those for preventing and treating ulcerative colitis.

[0035] In order to find the active ingredient in the ethyl acetate extract of Herba Truncatum that plays a role in preventing and treating colitis, the inventors conducted the following screening process:

[0036] First, the components of the ethyl acetate extract of Herba Lycopodii were isolated and identified, yielding 35 polycyclic polyisopentenyl phloroglucinol compounds. The compounds were then tested for cytotoxicity and anti-inflammatory activity in LPS-inflamed RAW264.7 macrophages, resulting in the identification of polycyclic polyisopentenyl phloroglucinol compounds with low cytotoxicity and high anti-inflammatory activity. Finally, a mouse model of ulcerative colitis was established using a DSS solution. The mice were then treated with polycyclic polyisopentenyl phloroglucinol compounds with strong anti-inflammatory activity. After eight days of continuous administration, the mice were evaluated for general clinical symptoms, DAI scores, colon length, spleen index, colon histopathological scores, and expression of inflammatory factors. This identified a polycyclic polyisopentenyl phloroglucinol (Hypersampsonone H, HS-1) with potential for the prevention and treatment of ulcerative colitis.

[0037] Furthermore, the present invention provides an application of polycyclic polyisopentenyl phloroglucinol (HS-1) in the preparation of a drug for preventing and treating ulcerative colitis.

[0038] The molecular formula of the polycyclic polyisoprene phloroglucinol (HS-1) of the present invention is: 38 H 50 O4, molecular weight is 609.4, and its structural formula is as follows:

[0039]

[0040] The polycyclic polyisopentenyl phloroglucinol (HS-1) of the present invention can be prepared according to the following preparation method, which specifically comprises the following steps: mixing Herba Lycopodii Truncatum powder and 95% ethanol, heating and refluxing for extraction, filtering, and concentrating to obtain a crude extract; passing the crude extract through a silica gel column, performing gradient elution using petroleum ether and dichloromethane as solvents, collecting the eluate, performing rotary evaporation concentration, and then collecting HS-1 through the preparative liquid phase.

[0041] Compound HS-1 of the present invention can be used alone or in the form of a pharmaceutical composition. The pharmaceutical composition comprises compound HS-1 of the present invention as an active ingredient and a pharmaceutically acceptable carrier. Preferably, the pharmaceutical composition of the present invention contains 0.1-99.9% by weight of compound HS-1 of the present invention as the active ingredient. A "pharmaceutically acceptable carrier" does not impair the pharmaceutical activity of compound HS-1 of the present invention, and its effective amount (i.e., the amount required to function as a pharmaceutical carrier) is non-toxic to the human body.

[0042] The pharmaceutically acceptable carriers include, but are not limited to, lecithin, aluminum stearate, aluminum oxide, ion exchange materials, self-emulsifying drug delivery systems, Tween or other surfactants, serum proteins, buffer substances such as phosphates, aminoacetic acid, sorbic acid, water, salts, electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, magnesium silicate, partial glyceride mixtures of saturated fatty acids, and the like.

[0043] Other commonly used pharmaceutical excipients include binders (such as microcrystalline cellulose), fillers (such as starch, glucose, anhydrous lactose and lactose beads), disintegrants (such as cross-linked PVP, cross-linked sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose), lubricants (such as magnesium stearate), as well as absorption enhancers, adsorption carriers, flavoring agents, sweeteners, excipients, diluents, wetting agents, etc.

[0044] Compound HS-1 and its pharmaceutical compositions of the present invention can be prepared according to conventional methods in the art and can be administered enterally, parenterally, or topically. Oral formulations include capsules, tablets, oral solutions, granules, pills, powders, pills, and ointments; parenteral formulations include injections; and topical formulations include creams, patches, ointments, and sprays. Oral formulations are preferred.

[0045] The compound HS-1 and the pharmaceutical composition thereof of the present invention can be administered orally, sublingually, transdermally, intramuscularly or subcutaneously, through the skin and mucous membranes, intravenously, urethrally, vaginally, etc.

[0046] The present invention will be further described below with reference to specific embodiments.

[0047] Example 1

[0048] (1) Preparation of polycyclic polyisoprenylated phloroglucinol (HS-1)

[0049] S1: Take the whole herb of dried Herba Cinnamomi truncatum, crush it, add 8 times the amount of 95% ethanol, heat and reflux to extract, extract three times, each extraction for 1 hour, filter, combine the three alcohol extracts, and concentrate under reduced pressure until the solution is thick to obtain the Herba Cinnamomi truncatum total extract;

[0050] S2: The total extract of Herba Coptidis was passed through a 200-300 mesh silica gel column and gradient eluted with pure petroleum ether: dichloromethane (ratio from 1:0 to 0:1). The petroleum ether: dichloromethane (3:2) eluate was collected and concentrated by rotary evaporation to remove the solvent. After concentration, a slightly yellow oily substance A was obtained.

[0051] S3: Component A was separated by preparative HPLC using Rp-C18 reverse-phase silica gel as the mobile phase with 85% acetonitrile. The peak with a retention time of 15.2 min was collected and concentrated by rotary evaporation to remove the solvent to obtain a yellow oil with a purity of more than 95%.

[0052] S4: The yellow oil was analyzed by high-resolution mass spectrometry and nuclear magnetic resonance data, and was identified as a new polycyclic polyisoprenoyl phloroglucinol structure, named Hypersampsonone H (HS-1).

[0053] (2) Observation of mouse physical signs and disease activity index (DAI) scoring

[0054] A 0.5% sodium carboxymethylcellulose (CMC-Na) solution of polycyclic polyisopentenyl phloroglucinol (HS-1) at concentrations of 3 mg / kg, 6 mg / kg, and 12 mg / kg, a 0.5% CMC-Na solution of 5-aminosalicylic acid (5-ASA) at 200 mg / kg, and a 3% aqueous solution of dextran sulfate sodium (DSS) were prepared. The present invention does not specifically limit the specific sources of the above reagents; any commercially available products in the art can be used.

[0055] SPF-grade male BALB / c mice weighing 16 - 18 g were purchased from the Experimental Animal Center of Guangzhou University of Chinese Medicine, with the animal certificate number: SCXK(Guangdong)2018 - 0034. The experimental animals were housed in an SPF-grade animal room at a temperature of 22 ± 2°C with a 12-hour day-night cycle. The animals were adaptively fed for one week before the experiment, and they had free access to food and water during the feeding period.

[0056] The mice were randomly divided into six groups of six mice each, namely the control group (administered 0.5% CMC-Na solution by gavage daily while given distilled water), the dextran sulfate sodium (DSS) model group (administered 3% DSS solution by gavage daily while given 0.5% CMC-Na solution), the positive control group (administered 200 mg / kg 5-ASA by gavage daily while given 3% DSS solution), the low-dose HS-1 group (administered 3 mg / kg HS-1 by gavage daily while given 3% DSS solution), the medium-dose HS-1 group (administered 6 mg / kg HS-1 by gavage daily while given 3% DSS solution), and the high-dose HS-1 group (administered 12 mg / kg HS-1 by gavage daily while given 3% DSS solution). They were continuously gavaged for 8 days and then sacrificed after 8 days.

[0057] The stools of the experimental animals were observed daily, and their weights were recorded. The disease activity index (DAI) scores for the changes in mouse body weight and fecal characteristics were evaluated according to relevant literature: 1) Body weight change scoring criteria: 0 points - no change or increase in body weight; 1 point - 0 - 5% (including 5%) decrease in body weight; 2 points - 5 - 10% (including 10%) decrease in body weight; 3 points - 10 - 20% (including 20%) decrease in body weight; 4 points - more than 20% decrease in body weight; 2) Fecal characteristics scoring criteria: 0 points - normal; 1 point - softer stools; 2 points - wet and soft stools; 3 points - semi-liquid stools; 4 points - liquid stools; 3) Fecal occult blood scoring criteria: 0 points - no fecal blood; 1 point - positive; 2 points - occult blood; 4 points - visible fecal blood. The results were as Figure 1-2 shown. On the last day of the experiment, the mice were sacrificed by cervical dislocation, and the colon and spleen were dissected. The colon length was measured and the spleen was weighed. The results were as Figure 3-6 shown.

[0058] Refer to Figure 1 . The body weights of the mice in the control group continued to increase steadily. The body weights of the mice in the model group increased in the first 4 days of modeling and then showed a downward trend after the 4th day. After the modeling was completed, the body weights of the mice in the model group were significantly different from those in the control group (P < 0.01). The body weights of the mice in the HS-1 treatment group also decreased, but compared with the model group, the downward trend of the body weights of the mice in the HS-1 treatment group was improved, and the difference was statistically significant (P < 0.05 or P < 0.01). At the same time, it was found during the modeling period that the mice in the model group had severe fecal blood, while the fecal blood in the mice was significantly alleviated after HS-1 treatment. Refer to Figure 2 Compared with the control group, the DAI score of the model group was significantly increased (P<0.01), while the DAI scores of the mice in the medium-dose HS-1 and high-dose HS-1 groups were significantly decreased (P<0.05). Therefore, HS-1 treatment can significantly alleviate the symptoms of weight loss, diarrhea, and bloody stools in DSS mice.

[0059] See Figure 3 and Figure 4 , Figure 3 Representative colon images of mice in each treatment group. Figure 4 The results of statistical analysis of the colon length of mice in each treatment group were shown in Table 2. Compared with the control group, the colon length of mice induced by DSS was significantly shortened (P<0.01), while the colon length of mice treated with HS-1 or 5-ASA was significantly improved (P<0.01), and the effect of high-dose HS-1 on improving the colon length of DSS mice was better than that of 5-ASA (P<0.01). Figure 5 、 Figure 6 As shown in the figure, compared with the control group, the spleen of mice after DSS modeling was significantly enlarged, while HS-1 or 5-ASA treatment could significantly alleviate the enlargement of the spleen in mice (P<0.05 or P<0.01).

[0060] (3) Colon pathological observation and histological pathological scoring

[0061] The terminal colon was sliced ​​and stained with hematoxylin-eosin (HE). The HE-stained colon specimens were subjected to pathological histological observation and histological pathology (HS) scoring: 1) Inflammation degree scoring criteria: 0 points - no inflammation; 1 point - inflammation limited to the mucosal layer; 2 points - inflammation gradually penetrates into the submucosa; 3 points - inflammation penetrates into the muscularis; 4 points - transmural inflammation; 2) Neutrophil infiltration scoring criteria: 0 points - no inflammatory infiltration; 1 point - mildly obvious; 2 points - moderately diffuse; 3 points - severely diffuse; 3) Crypt damage: 0 points - no damage; 1 point - basal 1 =1 point - lesions on the basal 2 / 3; 2 points - lesions on the basal 2 / 3; 3 points - all lesions; 4 points - all lesions and ulcers; 4) Crypt swelling: 0 point - no swelling; 1 point - mildly evident; 2 points - moderately diffuse; 3 points - severely diffuse; 5) Epithelial mucosal swelling: 0 point - no swelling; 1 point - mildly evident; 2 points - moderately diffuse; 3 points - severely diffuse; 6) Goblet cell loss: 0 point - no loss; 1 point - mild; 2 points - moderate; 3 points - severe; 7) Reactive epithelial hyperplasia: 0 point - no hyperplasia; 1 point - mildly evident; 2 points - moderately diffuse; 3 points - severely diffuse. The results are as follows: Figure 7 、 Figure 8 shown.

[0062] See Figure 7 , Figure 7The following are the results of HE staining of the colon tissue pathology sections of mice in each treatment group. The colon tissue structure of the control group mice was intact, with no obvious neutrophil infiltration, neatly arranged goblet cells, complete morphology, and normal crypt structure. The integrity of the colon wall of the model group mice was destroyed, with severe and diffuse neutrophil infiltration, severe loss of goblet cells, complete damage to the crypt structure, significant thickening of the mucosal and serosal layers, and disordered arrangement of the muscularis mucosa cells. Compared with the model group, after HS-1 or 5-ASA treatment, the colon tissue structure and morphology of the mice were significantly improved, inflammatory cell infiltration was significantly reduced, and the integrity of the intestinal mucosal epithelial cells was improved. Figure 8 , Figure 8 Colon histopathological scores of mice in each treatment group were significantly higher in the model group (P<0.01) compared to the control group, and significantly lower in the HS-1-treated group (P<0.05 or P<0.01) compared to the model group. Therefore, HS-1 treatment can significantly alleviate the symptoms of weight loss, diarrhea, and bloody stools in DSS mice.

[0063] (4) RT-PCR detection of mRNA expression of related inflammatory factors

[0064] Approximately 50 mg of colon tissue was collected, 1 mL of total RNA extraction reagent was added, and the sample was homogenized in a homogenizer. Subsequently, the sample was centrifuged at 12,000 g for 10 minutes at 4°C. The supernatant was removed and 200 μL of chloroform was added. The sample was vortexed vigorously for 15 seconds, allowed to stand at room temperature for 5 minutes, and centrifuged at 12,000 g for 15 minutes at 4°C. The solution separated into three layers, and 500 μL of the upper aqueous phase was aspirated. An equal volume of 500 μL of isopropanol was added, the sample was vortexed thoroughly, allowed to stand at room temperature for 5-10 minutes, and centrifuged at 12,000 g for 10 minutes at 4°C. The supernatant was discarded. 1 mL of 75% ethanol was added, and the bottom of the tube was gently flicked to resuspend the pellet. After thorough vortexing, the sample was centrifuged at 7,500 g for 5 minutes at 4°C.

[0065] Take 1 μL of RNA sample and measure the OD value on an ultraviolet spectrophotometer (NanoDrop 2000, Thermo Fisher Scientific). An OD260 / OD280 ratio between 1.8 and 2.2 indicates that the RNA sample is relatively pure and free of contamination. After the sample is tested, the total RNA concentration is quantified to 1 μg / μL using DEPC water.

[0066] Refer to Table 1. Add template RNA and 5X gDNA Clean Reaction Mix to a PCR tube. Make up to 20 μL with sterile double-distilled water. Mix thoroughly, incubate the tube at 42°C for 2 minutes, and store at 4°C. Refer to Table 2. Then, add 5X Evo M-MLV RT Reaction Mix and sterile double-distilled water to the completed PCR tube, mix thoroughly, and perform a reverse transcription reaction at 37°C for 15 minutes, 85°C for 5 seconds, and store at 4°C. Collect the cDNA product from the reverse transcription reaction for subsequent qPCR reactions or store at -80°C for long-term storage.

[0067] Table 1 Genome removal system

[0068]

[0069] Table 2 Reverse transcription system

[0070]

[0071] According to the operating instructions of the fluorescence quantitative PCR instrument, the cDNA obtained by reverse transcription was subjected to qPCR amplification detection, and GAPDH was used as the internal reference. -ΔΔCt The relative mRNA expression levels of the target genes were calculated using the PCR method. The primer sequences of the target genes are shown in Table 3, and the qPCR reaction system is shown in Table 4.

[0072] Table 3 Primer sequences of target genes

[0073]

[0074] Table 4 PCR reaction system

[0075]

[0076] like Figure 9-11 As shown, the mRNA expression levels of proinflammatory cytokines (IL-6 and TNF-α) in the colon tissue of model mice were significantly increased compared with those in the control group, while the mRNA expression level of the anti-inflammatory cytokine (IL-10) was significantly decreased compared with the control group (P < 0.05 or P < 0.01). After treatment with HS-1 or 5-ASA, the mRNA expression of proinflammatory cytokines was significantly decreased, while the mRNA expression of anti-inflammatory cytokines was significantly increased (P < 0.05 or P < 0.01). These results indicate that HS-1 can effectively improve the inflammatory symptoms of DSS-induced ulcerative colitis in mice and has an anti-ulcerative colitis effect.

[0077] In summary, the present invention establishes a DSS-induced acute ulcerative colitis mouse model and detects the general clinical symptoms, DAI score, colon length, spleen index, colon histopathological score, and inflammatory factor expression of DSS mice treated with polycyclic polyisopentenyl phloroglucinol (HS-1). It is found that polycyclic polyisopentenyl phloroglucinol compounds (HS-1) can effectively alleviate the inflammatory symptoms of ulcerative colitis, including reducing weight loss, diarrhea, bloody stools, colon shortening, and splenomegaly, as well as inhibiting the excessive production of proinflammatory factors and increasing the expression of anti-inflammatory factors. This suggests that polycyclic polyisopentenyl phloroglucinol compounds (HS-1) may alleviate ulcerative colitis by protecting colon tissue structure, reducing colon inflammation, and improving colon damage, which may provide a new option for the treatment of ulcerative colitis.

[0078] The above-described embodiments are merely preferred embodiments for the purpose of fully illustrating the present invention, and the scope of protection of the present invention is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are within the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

Claims

1. Use of polycyclic polyisopentenyl phloroglucinol as an active ingredient in the preparation of a drug for preventing and treating ulcerative colitis, characterized in that: The polycyclic polyisopentenyl phloroglucinol has the following structural formula:

2. The use according to claim 1, characterized in that The preparation method of the polycyclic polyisopentenyl phloroglucinol comprises the following steps: S1: Mix Herba Cinnamomi powder with 8 volumes of 95% ethanol, heat under reflux and extract for 1 hour, extract three times, filter and combine the three extracts, and concentrate under reduced pressure until the solution is thick to obtain Herba Cinnamomi total extract; S2: The total extract of Herba Coptidis was passed through a 200-300 mesh silica gel column and gradient eluted with petroleum ether:dichloromethane as the solvent in a ratio from 1:0 to 0:

1. The eluate in the petroleum ether:dichloromethane ratio of 3:2 was collected and concentrated by rotary evaporation to remove the solvent to obtain component A. S3: Component A was separated by preparative HPLC using Rp-C18 reverse phase silica gel as a mobile phase with 85% acetonitrile to collect polycyclic polyisopentenyl phloroglucinol.

3. The use according to claim 2, characterized in that Step S3 includes collecting the peak with a retention time of 15.2 min, concentrating by rotary evaporation, and removing the solvent to obtain polycyclic polyisopentenyl phloroglucinol.

4. The use according to claim 3, characterized in that The drug includes pharmaceutically acceptable excipients.

5. The use according to claim 4, characterized in that The medicine is any one of a liquid preparation, a solid preparation, a semisolid preparation, and a gaseous preparation.

6. The use according to claim 5, characterized in that The dosage form of the drug is any one of oral solution, tablet, capsule, dripping pill, granule or injection.

7. The use according to claim 1, characterized in that The drug is used in reducing the disease activity index of ulcerative colitis mice, restoring colon length and alleviating spleen enlargement.

8. The use according to claim 1, characterized in that The drug is used in reducing colon tissue structure damage in ulcerative colitis mice, reducing the level of pro-inflammatory factors and promoting the secretion of anti-inflammatory factors.

9. The use according to any one of claims 4 to 8, characterized in that: The effective dosage of the drug is 3 to 12 mg / kg / day.

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