Application of nuezhenide G13 in preparation of medicine or medicine composition for treating or preventing ulcerative colitis

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of nuezhenide G13 in preparation of a medicine or a medicine composition for treating or preventing ulcerative colitis. It is found for the first time that the nuezhenide G13 can significantly improve the pathological symptoms of UC on an in-vivo animal model, the curative effect of the nuezhenide G13 is even superior to that of a clinical first-line drug salazosulfapyridine, and the invention also discloses a unique action mechanism of the nuezhenide G13 for repairing the intestinal mucosal barrier, which is not reported before for the first time. According to the invention, the in-vivo drug effect of the ligustroside G13 is evaluated through a recognized DSS-induced mouse UC model. When the ligustroside G13 is used for treating UC of a human body, the ligustroside G13 shows superior performance exceeding that of clinical standard treatment drugs.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and specifically relates to the use of privetin G13, an iridoid glycoside compound derived from osmanthus fruit, in the preparation of drugs or pharmaceutical compositions for the treatment or prevention of ulcerative colitis. Background Technology

[0002] Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory disease that primarily affects the rectal and colonic mucosa and submucosa. Its clinical features include persistent or recurrent diarrhea, bloody and mucous stools, and abdominal pain. In recent years, the incidence of UC has been steadily increasing worldwide, becoming a major health challenge for the digestive system.

[0003] Currently, clinical treatments for ulcerative colitis (UC) mainly include aminosalicylic acid preparations (such as sulfasalazine and mesalazine), glucocorticoids, immunosuppressants, and biologics (such as anti-TNF-α monoclonal antibodies). However, these treatments all have limitations to varying degrees: while conventional drugs can relieve symptoms, their long-term efficacy is poor, relapse rates are high, and their effectiveness is limited for moderate to severe patients; glucocorticoid and immunosuppressant treatments are accompanied by significant side effects; and emerging biologics are not only expensive, increasing the economic burden on patients, but their long-term safety and efficacy still need further evaluation. Therefore, the search for and development of novel small-molecule anti-UC drugs from natural products with significant efficacy, few side effects, and a clearly defined mechanism of action has urgent clinical needs and enormous social value.

[0004] Ligustrum lucidum glycoside G13 (molecular formula C) 48 H 64 O 27 Ligustrum lucidum glycoside G13 is an iridoid glycoside isolated from the dried, ripe fruit of Osmanthus fragrans (also known as Osmanthus seeds). Literature reports that ligustrum lucidum glycoside G13 possesses various activities, including antioxidant, anti-osteoporosis, antibacterial, anti-inflammatory, and antitumor effects. However, no studies have been reported on its role in alleviating ulcerative colitis (UC) symptoms, its in vivo tissue distribution and metabolism after administration, or its potential as a therapeutic agent for UC. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a new use of privetin G13 in the preparation of a medicament for the treatment or prevention of human ulcerative colitis.

[0006] The technical solution adopted by this invention to solve its technical problem is:

[0007] The use of a ligustrazine G13 in the preparation of a medicament or pharmaceutical composition for the treatment or prevention of ulcerative colitis.

[0008] This invention is the first to discover that privetin G13 can not only significantly improve the pathological symptoms of ulcerative colitis in an in vivo animal model, but its efficacy is even better than that of the first-line clinical drug sulfasalazine. Furthermore, this invention also reveals for the first time its unique and previously unreported mechanism of action in repairing the intestinal mucosal barrier.

[0009] Preferably, the ligustrazine G13 is derived from the fruit of a plant in the Oleaceae family, specifically Osmanthus fragrans.

[0010] Preferably, the drug or pharmaceutical composition is used to inhibit the expression of pro-inflammatory cytokines and / or promote the expression of anti-inflammatory cytokines. Another key aspect of this invention is the discovery of a unique anti-inflammatory regulatory mode of privetin G13. More specifically, the pro-inflammatory cytokines are selected from one or more of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); the anti-inflammatory cytokine is transforming growth factor-β1 (TGF-β1). Specifically, this invention has found that privetin G13 can promote the production of the key anti-inflammatory and tissue repair factor TGF-β1, which is crucial for inhibiting excessive inflammatory responses and promoting mucosal healing.

[0011] Preferably, the drug or pharmaceutical composition is used to regulate the level of oxidative stress in colonic tissue. More specifically, regulating the level of oxidative stress in colonic tissue includes: reducing the level of malondialdehyde (MDA), and / or increasing the activity of one or more of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT).

[0012] Preferably, the drug or pharmaceutical composition is used to upregulate the expression of intestinal barrier-related proteins, thereby repairing the intestinal barrier. More specifically, the intestinal barrier-related proteins are selected from one or more of Claudin-1, Occludin, and ZO-1. This invention is the first to discover that privetin G13 treats ulcerative colitis by repairing the intestinal barrier. The integrity of the intestinal mucosal barrier is crucial for maintaining intestinal health and preventing inflammation. This invention demonstrates that privetin G13 can significantly upregulate the expression of these key proteins, thereby rebuilding the intestinal physical barrier damaged by UC, which is an important mechanistic basis for its significant therapeutic effect.

[0013] Preferably, the pharmaceutical composition comprises a therapeutically effective amount of privetin G13 and one or more pharmaceutically acceptable excipients, carriers or diluents.

[0014] Preferably, the pharmaceutical composition is prepared into a dosage form suitable for oral administration, more preferably an enteric-coated formulation capable of targeted delivery of the drug to the colon.

[0015] Compared with the prior art, the present invention has the following outstanding advantages:

[0016] 1. A novel mechanism of action targeting key pathological aspects of ulcerative colitis (UC) has been discovered. This invention is the first to demonstrate in vivo, in animal models of the disease, that privetin G13 can repair and rebuild the damaged intestinal mucosal barrier by upregulating the expression of key proteins such as Claudin-1, Occludin, and ZO-1. Intestinal barrier dysfunction is a core element in the occurrence and development of UC. This invention reveals this novel mechanism of action for the first time, deepening our understanding of the pharmacological activity of privetin G13 and demonstrating its unique value as a therapeutic agent for UC.

[0017] 2. This invention evaluated the in vivo efficacy of privetin G13 using a recognized DSS-induced mouse UC model. Privetin G13 (40 mg / kg) significantly outperformed the first-line clinical drug sulfasalazine (264 mg / kg, SCC group) in several key efficacy indicators, including improving mouse body weight loss, reducing disease activity index (DAI) scores, and increasing colon length. Those skilled in the art could not have predicted that privetin G13 would exhibit such superior performance compared to first-line clinical drugs in improving UC symptoms.

[0018] 3. Pharmacokinetic studies of this invention show that privetin G13 exhibits high concentrations in the stomach, small intestine, and large intestine after oral administration, suggesting its effective reach of the lesion site—the colon—and its beneficial effect on local treatment. Simultaneously, it is normally metabolized and rapidly excreted in the body, reducing the risk of cumulative toxicity from long-term use. These favorable in vivo characteristics provide a solid scientific basis for its development as a safe and effective oral anti-UC drug. Attached Figure Description

[0019] Figure 1 These are macroscopic indicators of how privetin G13 improves DSS-induced UC mice, including (A) animal experiment diagrams, (B) colon photos of mice in each group (n=6), (C) weight changes of mice in each group (n=6), and (D) changes in DAI scores of mice in each group (n=6).

[0020] Figure 2Effects of privetin G13 on serum inflammatory factors and colonic oxidative stress markers in UC mice, including (A) the effect of privetin G13 on the activities of IL-1β, TGF-β1, IL-6, and TNF-α in serum of UC mice; and (B) the effect of privetin G13 on oxidative stress markers MDA, GSH-Px, SOD, and CAT in colonic tissue of UC mice (mean ± SD, #: compared with the control group, ####P < 0.0001; *: compared with the model group, ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05).

[0021] Figure 3 The effects of privetin G13 on NF-κB pathway proteins and intestinal barrier proteins in DSS-induced UC mice were investigated. (A) The expression levels of NF-κB pathway proteins and intestinal barrier proteins in UC mice by privetin G13. (B) Quantitative analysis of the expression of NF-κB pathway proteins and intestinal barrier proteins (mean ± SD, #: compared with the control group, ####P < 0.0001; ##P < 0.01; *: compared with the model group, ****P < 0.0001, **P < 0.01, *P < 0.05).

[0022] Figure 4 This shows the tissue distribution of privetin G13 in rats at different time points.

[0023] Figure 5 The cumulative excretion curves of privetin G13 in the urine of rats at different time points after oral administration are shown.

[0024] Figure 6 The cumulative excretion curves of privetin G13 in the urine of rats at different time points after oral administration are shown.

[0025] Figure 7 The curves show the cumulative excretion of privetin G13 in the bile of rats at different time points after oral administration. Detailed Implementation

[0026] The technical solution of the present invention will be further described in detail below through specific embodiments. It should be understood that the implementation of the present invention is not limited to the following embodiments, and any modifications and / or alterations made to the present invention will fall within the protection scope of the present invention.

[0027] In this invention, unless otherwise specified, all parts and percentages are by weight, and the equipment and raw materials used are commercially available or commonly used in the art. Unless otherwise specified, the methods in the following embodiments are conventional methods in the art.

[0028] Unless otherwise specified, the reagents used in the following examples can be purchased from a regular biochemical reagent store.

[0029] Dextran sulfate sodium (DSS) is a sulfated polysaccharide. As a bioactive substance, it can disrupt the intestinal barrier and mimic the pathological process of ulcerative colitis (UC) by inducing immune cell infiltration and inflammatory responses. The anti-UC activity experimental data in the technical solution disclosed in this invention are provided by constructing a DSS-induced mouse UC model.

[0030] Example 1: The activity and mechanism of privetin G13 in alleviating DSS-induced UC

[0031] This embodiment aims to evaluate the therapeutic effect of privetin G13 in a DSS-induced UC mouse model and compare it with the positive control drug sulfasalazine, while exploring its mechanism of action.

[0032] 1.1 Laboratory Animals

[0033] Male C57BL / 6 mice, weighing 20±2 g, were housed in a professional experimental animal center. The temperature in the housing was controlled at 21-25℃, and the relative humidity at 50-60%, with a 12-hour light-dark cycle. They underwent a one-week acclimatization period. Weights were recorded, and mice were fasted for 12 hours before drug administration, but had free access to water. Animal experimental procedures were conducted in accordance with the "Regulations for the Management of Experimental Animals" and approved by the university's Animal Ethics and Use Committee.

[0034] 1.2 Experimental Scheme

[0035] Twenty-four mice were randomly divided into four groups of six each: control group (CON), DSS model group (DSS), privetin G13 treatment group (G13), and sulfasalazine colonic solvent group (SCC). After a week of acclimatization, from day 1 to day 7, all mice except the CON group were fed a 2.8% DSS aqueous solution. Once the model was successfully established, the mice were administered the drug. From day 8 to day 14, the privetin G13 group and the SCC group were administered privetin G13 aqueous solution (40 mg / kg) and sulfasalazine colonic solvent aqueous solution (264 mg / kg), respectively, by gavage. The CON and DSS groups were given an equal volume of saline. Mice were weighed and their fecal condition and bleeding were observed daily. The Disease Activity Index (DAI) was calculated based on a scoring system. On day 15, the mice were euthanized by enucleation to collect blood, and serum was obtained by centrifugation. Colon tissue was collected, its length was measured, and photographs were taken. The colon tissue was then frozen at -80°C for subsequent experimental analysis. The disease activity index scores of the mice are shown in Table 1.

[0036] Table 1. Disease Activity Index Scores for Mice

[0037] fecal state Blood in stool score normal none 0 soft Slightly red 1 soft stool Mild bleeding 2 loose stool Moderate bleeding 3 watery stool Severe bleeding 4

[0038] 1.3 ELISA Detection and Analysis

[0039] The activities of IL-1β, TGF-β1, IL-6, and TNF-α in mouse serum samples were detected using the Enzyme-Linked Immunosorbent Assay (ELISA) kit.

[0040] 1.4 Analysis of Oxidative Stress Indicators

[0041] Accurately weigh 100 mg of colon sample, add ice-cold 0.9% physiological saline at a ratio of 1:9 (m / V), grind with a grinder to prepare a 10% homogenate, centrifuge at 4℃ and 3000 r / min for 10 min, collect the supernatant, and determine the content of MDA, GSH-Px and the activities of SOD and CAT in the colon tissue homogenate.

[0042] 1.5 Western blot analysis

[0043] Accurately weigh 100 mg of colon tissue from each group, add lysis buffer at a ratio of 1:9 (m / V), grind using a homogenizer, centrifuge at 12000 r / min for 10 min, collect the supernatant, determine the protein concentration, and heat to denature the protein. Protein samples were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to an NC membrane, and blocked at room temperature for 1.5 h with 5% skim milk added. Antibodies against β-actin (1:1000), Claudin-1, Occludin, ZO-1, NF-κB, and IκBα were added, and the membrane was incubated overnight at 4℃. The next day, the membrane was washed 5 times with TBST. Horseradish peroxidase-labeled goat anti-rabbit / mouse IgG (H+L) (1:1000) was added to 5% skim milk, and the membrane was incubated at room temperature for 1 h. After washing 5 times with TBST, the bands were exposed using an ultrasensitive chemiluminescent reagent, and the expression levels of each protein were analyzed using ImageJ software.

[0044] 1.6 Statistical Analysis

[0045] Experimental data were statistically analyzed using GraphPad Prism 9.0.0 software. All results are expressed as Mean ± SD. Student's t-test was used to compare two groups, and one-way ANOVA was used to analyze the significance of more than two groups.

[0046] 1.7 Results and Analysis: Study on the activity and mechanism of privetin G13 in alleviating DSS-induced UC

[0047] 1.7.1 Privet G13 improves DSS-induced UC in mice

[0048] Depend on Figure 1 Changes in colon length, body weight, and DAI score were observed in each group of mice. It was observed that the colonic structure of mice in the CON group was intact, while the colonic structure of mice in the DSS group was disrupted, with shortened colon length, significantly decreased body weight, and increased DAI score. The colon of mice in the privetin G13 group showed no significant changes. Compared to the DSS group, the colonic length and body weight of mice in the privetin G13 and sulfasalazine (SCC) groups were significantly increased, and the DAI score was significantly decreased. It should be noted that, regarding the core efficacy indicator of DAI score, the improvement effect of the privetin G13 group was superior to that of the positive control drug sulfasalazine (SCC) group.

[0049] 1.7.2 Privet G13 alleviates DSS-induced UC by regulating inflammatory factors.

[0050] Figure 2(A) shows that privetin G13 can regulate the activity of cytokines in the serum of UC mice, significantly inhibit the overexpression of pro-inflammatory cytokines II-1β, II-6 and TNF-α in the serum of UC mice, and significantly promote the production of TGF-β1, thereby reducing the inflammatory response in UC mice and alleviating the symptoms of ulcerative colitis.

[0051] 1.7.3 Privet glycoside G13 reduces colonic oxidative stress levels in DSS-induced UC mice.

[0052] Figure 2 (B) indicates that privetin G13 can significantly reduce the level of lipid peroxidation product MDA in the colonic tissue of UC mice by regulating oxidative stress indicators in colonic tissue, thereby reducing lipid peroxidation damage and increasing the activity of antioxidant enzymes GSH-Px, SOD and CAT, enhancing the antioxidant capacity of colonic tissue, thereby alleviating the damage of oxidative stress to colonic tissue and improving the pathological state of UC mice.

[0053] 1.7.4 Effects of privetin G13 on NF-κB pathway proteins and intestinal barrier proteins in DSS-induced UC mice

[0054] like Figure 3 As shown, the expression levels of P-NF-κB and P-IκBα were increased in the colon tissue of UC mice (P < 0.001).

[0055] Western blot results showed that, compared with the DSS model group, treatment with privetin G13 significantly increased the protein expression levels of tight junction proteins Claudin-1, Occludin, and ZO-1 in the colonic tissue of UC mice (P < 0.01, P < 0.001), while the positive control group (SCC) had no significant effect on the expression level of Occludin protein (P > 0.05). This result demonstrates that privetin G13 has a strong function in repairing the intestinal physical barrier.

[0056] Example 2: Tissue distribution and metabolism of privetin G13 in SD rats

[0057] 2.1 Laboratory Animals

[0058] Male Sprague-Dawley (SD) rats, weighing 200±20 g, SPF grade. All rats were housed in a professional laboratory animal center with the temperature controlled at 21-25℃ and relative humidity at 50-60%, maintaining a 12-hour light-dark cycle. They underwent a one-week acclimatization feeding period, and their weight was recorded. All rats were fasted for 12 hours before drug administration, but had free access to water. Animal experiments were conducted in accordance with the "Regulations for the Management of Laboratory Animals" and approved by the university's Animal Ethics and Use Committee.

[0059] 2.2 LC-MS Analysis Conditions

[0060] An InfinityLab Poroshell 120 Aq-C18 column (4.6 × 150 mm, 2.7-Micron) was used. The mobile phase consisted of an organic phase of acetonitrile solution and an aqueous phase of 0.1% formic acid and 5 mmol / L ammonium acetate aqueous solution. The column temperature was 35℃, the flow rate was 0.4 mL / min, and the injection volume was 5 μL.

[0061] Detection method: Multiple reaction monitoring (MRM); Electrospray ion source: Positive ion; Nebulizer temperature: 325℃; Nebulizer flow rate: 6 L / min; Sheath gas temperature: 350℃; Sheath gas flow rate: 12 L / min; Privetin G13 ion pair: 1090.39→165.1 m / z; Privetin G13 collision energy: 72 eV; Rhodioloside ion pair: 318→256 m / z; Rhodioloside collision energy: 20 eV; Genipin ion pair: 406→227 m / z; Genipin collision energy: 4 eV.

[0062] 2.3 Preparation of Standard Solutions

[0063] Accurately weigh 10 mg of rhodioloside into a 10 mL amber volumetric flask, dissolve in acetonitrile, and dilute to the mark. Shake well to obtain a 1 mg / mL rhodioloside standard solution. Perform serial dilutions with acetonitrile to prepare working solutions for the rhodioloside standard curve with concentrations of 0.001, 0.0025, 0.005, 0.01, 0.025, 0.05, 0.08, 0.1, 0.2, 0.25, 0.5, 0.8, and 1 ng / mL, and working solutions for low, medium, and high concentrations of quality control (QC) with concentrations of 0.01, 0.1, and 0.8 ng / mL. Accurately weigh 10 mg of genipin, the internal standard, into a 10 mL amber volumetric flask, dissolve in acetonitrile, and dilute to the mark. Shake well to obtain a 1 mg / mL genipin internal standard solution, and then dilute with acetonitrile to a working internal standard solution with a concentration of 5 µg / mL. All obtained solutions must be stored in a refrigerator at 4°C, protected from light, for later use.

[0064] 2.4 Collection and processing of tissue samples

[0065] Thirty rats were randomly divided into 5 groups of 6 rats each. One group served as a control group (no drug administration), while the other four groups were administered 20 mg / kg of privetin G13 by gavage. Rats were sacrificed at 0.5, 1, 3, and 6 hours post-mortem examination, and tissue samples were obtained from the heart, liver, spleen, lung, kidney, stomach, pancreas, testis, large intestine, and small intestine, respectively. All tissue samples were washed with physiological saline, blotted dry with filter paper, and stored at -80°C for later use. 100 mg of each tissue sample was weighed and homogenized in 400 µL of physiological saline to prepare homogenates. Six replicates were prepared for each tissue sample at each time point. Take 100 µL of rat tissue homogenate samples from each time point, add 300 µL of acetonitrile and 100 µL of genipin internal standard working solution, vortex to mix, let stand for 2 min, centrifuge at 12000 r / min for 5 min, collect the supernatant, blow dry with nitrogen, reconstitute with 150 µL of 80% methanol-water, vortex to mix, repeat the above conditions and centrifuge, and take the supernatant for UPLC-MS / MS analysis.

[0066] 2.5 Standard tissue sample processing

[0067] The tissue samples were ground to prepare blank tissue homogenates at a ratio of 1:4 with physiological saline. 100 µL of each blank rat tissue homogenate was added, along with 100 µL of each concentration of rhodioloside standard curve working solution, 300 µL of acetonitrile, and 100 µL of genipin internal standard working solution to prepare standard tissue samples and low, medium, and high QC tissue samples. Three samples were prepared for each concentration. After vortexing and mixing, the samples were allowed to stand for 2 min, centrifuged at 12000 r / min for 5 min, and the supernatant was collected. The samples were dried under nitrogen, reconstituted with 150 µL of 80% methanol-water, vortexed, and centrifuged again under the same conditions. The supernatant was then analyzed by UPLC-MS / MS.

[0068] 2.6 Methodological Validation

[0069] Method validation was performed on the UPLC-MS / MS method for the determination of rhodioloside and internal standard genipin, including specificity, stability, precision and accuracy, linear range and limit of quantitation, extraction recovery, and matrix effect.

[0070] 2.7 Results and Analysis: Study on the tissue distribution and metabolism of privetin G13 in SD rats.

[0071] 2.7.1 Results of tissue distribution of privetin G13 in rats

[0072] Depend on Figure 4It is evident that, within 0.5 hours, the concentration of privetin G13 in the stomach was significantly higher than in other tissues, indicating that privetin G13 accumulates in the stomach immediately after entering the body. The concentration of privetin G13 also gradually increased in the small and large intestines, suggesting that the drug may have some retention in the intestines. The high distribution of privetin G13 in the stomach, small intestine, and large intestine indicates that it can effectively reach the lesion site in the colon.

[0073] Over time, privetin G13 showed a significant increase in the liver and kidneys, indicating that these are likely the primary organs for its metabolism and excretion. Furthermore, the distribution of privetin G13 in the lungs was relatively low, possibly related to its penetration ability. After 6 hours, the concentration of privetin G13 in the body was consistently below 50 ng / g, suggesting a short residence time and rapid elimination after exerting its effects.

[0074] 2.7.2 Results of excretion of privetin G13 in rat urine

[0075] The cumulative excretion of privetin G13 in urine samples from rats after oral administration at different time points is shown in the figure. Figure 5 It can be seen that within 36 hours of gavage, the cumulative excretion of privetin G13 was 1.76 ± 0.69 ng.

[0076] 2.7.3 Results of excretion of privetin G13 in rat feces

[0077] The cumulative excretion amounts of privetin G13 in fecal samples from rats after oral administration are shown in the table below. Figure 6 It can be seen that within 36 hours of gavage, the cumulative excretion of privetin G13 was 1.87 ± 0.75 ng.

[0078] 2.7.4 Results of excretion of privetin G13 in rat bile

[0079] The cumulative excretion amounts of privetin G13 in bile samples from rats after oral administration are shown in the table below. Figure 7 It can be seen that within 36 hours of gavage, the cumulative excretion of privetin G13 was 0.24 ± 0.09 ng.

[0080] in conclusion

[0081] 1. Privet glycoside G13 can increase colon length, body weight, and decrease DAI score in DSS-induced UC mice, promoting the restoration of normal colon morphology, with better effects than the positive control drug sulfasalazine. Privet glycoside G13 inhibits pro-inflammatory responses by regulating the activity of cytokines in the serum of DSS-induced UC mice, inhibiting the expression of pro-inflammatory cytokines II-1β, II-6, and TNF-α, and promoting the production of TGF-β1. In addition, privet glycoside G13 can also exert a protective effect against UC by regulating oxidative stress indicators in colonic tissue, reducing MDA levels, alleviating oxidative damage, and increasing the activity of GSH-Px, SOD, and CAT. Specifically, privet glycoside G13 inhibits inflammatory responses, protects the intestinal epithelial barrier, and repairs intestinal damage by attenuating the expression of NF-κB pathway proteins and increasing the expression of intestinal barrier proteins.

[0082] 2. The distribution of privetin G13 in the body exhibits significant tissue selectivity. Its accumulation in the stomach and intestines is related to its efficacy, while its distribution in the liver and kidneys is related to its metabolic excretion process. Furthermore, privetin G13 has the advantage of a short residence time in the body and is rapidly excreted after exerting its effects. Within 36 hours of gavage, the cumulative excretion in urine was 1.76 ± 0.69 ng, in feces 1.87 ± 0.75 ng, and in bile 0.24 ± 0.09 ng, indicating moderate metabolic and excretion efficiency. Comparative analysis revealed that the primary excretion route of privetin G13 is fecal excretion, and it is rapidly eliminated from the body.

[0083] In summary, privetin G13, an iridoid glycoside derived from Osmanthus fragrans fruit, exhibits significant protective activity against DSS-induced ulcerative colitis (UC) intestinal damage, and demonstrates good in vivo tissue distribution and metabolic excretion behavior. This invention confirms the great potential and unique mechanism of action of privetin G13 in the treatment of human ulcerative colitis, providing a valuable lead molecule for the development of novel, highly effective, and safe anti-UC drugs.

Claims

1. Use of a genistin G13 in the preparation of a medicament or a pharmaceutical composition for treating or preventing ulcerative colitis.

2. Use according to claim 1, characterized in that, The genistin G13 is derived from mature fruits of a plant of the genus Osmanthus of the Oleaceae family, and the plant is Osmanthus fragrans.

3. Use according to claim 1, characterized in that, The medicament or the pharmaceutical composition is used for inhibiting the expression of pro-inflammatory cytokines and / or promoting the expression of anti-inflammatory cytokines.

4. Use according to claim 3, characterized in that, The pro-inflammatory cytokines are selected from one or more of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); and the anti-inflammatory cytokine is transforming growth factor-β1 (TGF-β1).

5. The use according to claim 1, characterized in that, The medicament or the pharmaceutical composition is used for modulating the level of oxidative stress in colonic tissues.

6. Use according to claim 5, characterized in that, The modulation of the level of oxidative stress in colonic tissues comprises: reducing the level of malondialdehyde (MDA), and / or increasing the activity of one or more of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT).

7. The use according to claim 1, characterized in that, The medicament or the pharmaceutical composition is used for up-regulating the expression of intestinal barrier-related proteins.

8. Use according to claim 7, characterized in that, The intestinal barrier-related proteins are selected from one or more of Claudin-1, Occludin and ZO-1.

9. The use according to claim 1, characterized in that, The pharmaceutical composition comprises a therapeutically effective amount of the genistin G13 and one or more of pharmaceutically acceptable excipients, carriers or diluents.

10. Use according to claim 9, characterized in that, The pharmaceutical composition is prepared into a dosage form suitable for oral administration.

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