A polyphenolic complex that inhibits the production of hydrogen sulfide in the intestine and its application

Abstract

This invention discloses a polyphenolic complex that inhibits the production of hydrogen sulfide in the intestine and its applications, belonging to the field of biotechnology. The plant polyphenolic complex of this invention is composed of three active plant polyphenols obtained through stepwise screening, namely gallic acid, baicalin, and curcumin, with a mass ratio of 0.5-3:1:0.5-5. This invention utilizes a three-stage screening system—in vitro anaerobic fermentation primary screening, molecular docking secondary screening, and in vivo validation in mice—to screen from 20 natural polyphenols for a complex that targets and inhibits the production of hydrogen sulfide in the intestine. The method is simple and reliable, balancing in vitro activity and in vivo efficacy. This invention elucidates the mechanism of action of its targeted inhibition of key enzymes in hydrogen sulfide synthesis, effectively reducing the content of hydrogen sulfide in the colon, providing technical support for the preparation of natural products that inhibit hydrogen sulfide production and protect the intestines, and has broad application prospects.

Description

Technical Field

[0001] This invention belongs to the field of biotechnology, and specifically relates to a natural plant polyphenol complex and its applications. Background Technology

[0002] Gut homeostasis is the core foundation for maintaining the normal physiological function of the human digestive system and ensuring metabolic and immune balance. Hydrogen sulfide, as a key gaseous metabolic signaling molecule in the gut, is synthesized primarily by sulfite reductase and cysteine ​​desulfurase. Normal physiological concentrations of hydrogen sulfide regulate intestinal motility, mucosal blood flow, and gut microbiota homeostasis. Excessive hydrogen sulfide disrupts gut homeostasis, causing intestinal epithelial cell toxicity; damages the intestinal mucosal barrier, inducing inflammation; and long-term accumulation increases the risk of intestinal dysfunction and chronic intestinal diseases such as ulcerative colitis and irritable bowel syndrome. Therefore, developing a naturally derived, safe, non-toxic, and highly effective targeted approach to improve hydrogen sulfide-induced intestinal damage is an urgent problem to be solved in the field of gut health intervention.

[0003] Plant polyphenols are natural active ingredients widely found in fruits, vegetables, grains, and medicinal and edible plants. They possess significant advantages such as natural safety, extremely low side effects, wide availability, and long-term consumption. Studies have shown that plant polyphenols have multiple biological activities, including antioxidant, anti-inflammatory, gut microbiota regulation, and intestinal mucosal barrier repair, demonstrating good application potential in intestinal damage intervention. For example, invention patent CN114831980A discloses a combination of baicalein and scutellarin and its application in the preparation of anti-colorectal cancer drugs, proving that the combination of baicalein and scutellarin has synergistic inhibitory activity against the proliferation of colorectal cancer cells; invention patent CN115120571A discloses the preparation and application of curcumin core-shell nanoparticles, indicating that curcumin core-shell nanoparticles can target the site of colitis inflammation and alleviate ulcerative colitis; and invention patent CN102482662A discloses catechins as inhibitors of hydrogen sulfide generating enzyme, exhibiting inhibitory activity against hydrogen sulfide generating enzyme.

[0004] Although the gut-protective effects of plant polyphenols are widely recognized, existing research largely focuses on the "passive binding" of polyphenols to already generated hydrogen sulfide or their "antagonistic effect" on hydrogen sulfide toxicity. It has not delved into the regulatory mechanisms of plant polyphenols on intestinal hydrogen sulfide metabolism. Whether they can target and regulate the activity of key enzymes in hydrogen sulfide synthesis and inhibit excessive hydrogen sulfide production in the intestine remains unclear. Furthermore, the synergistic effects of different polyphenols on hydrogen sulfide metabolic pathways are still under investigation.

[0005] In summary, the development of polyphenolic complexes that can effectively inhibit the abnormal accumulation of hydrogen sulfide in the intestine has significant practical application value and scientific research significance, and also provides new research ideas for the development of technologies related to targeted intervention for intestinal damage. Summary of the Invention

[0006] This invention addresses the technical problem of the lack of targeted inhibitors for the generation of hydrogen sulfide in the intestine in the prior art, and proposes a polyphenol complex that inhibits the generation of hydrogen sulfide in the intestine and its application.

[0007] To achieve the above objectives, the technical solution of the present invention is implemented as follows:

[0008] In a first aspect, the present invention provides a polyphenolic complex that inhibits the production of hydrogen sulfide in the intestine, the polyphenolic complex being composed of gallic acid, baicalin and curcumin; wherein the mass ratio of gallic acid, baicalin and curcumin is 0.5-3:1:0.5-5.

[0009] Furthermore, the mass ratio of gallic acid, baicalein and curcumin is 0.5-3:1:0.5-3.

[0010] Furthermore, the mass ratio of gallic acid, baicalein, and curcumin is 1.5:1:2.

[0011] The three plant polyphenols are natural plant compounds that target the activity of sulfite reductase and cysteine ​​desulfurase, obtained through in vitro anaerobic fermentation primary screening, molecular docking simulation secondary screening, and in vivo verification in animal experiments. They inhibit the excessive synthesis of hydrogen sulfide in the intestine through the intestinal microbial pathway.

[0012] The polyphenol complex can reduce the hydrogen sulfide content in colonic contents.

[0013] Secondly, the present invention provides the use of the polyphenol complex in the preparation of a drug for inhibiting the generation of hydrogen sulfide in the intestine.

[0014] This invention provides the use of the aforementioned polyphenol complex in the preparation of a medicament for treating intestinal inflammation, ulcerative colitis, and irritable bowel syndrome caused by excessive hydrogen sulfide.

[0015] The inhibition of hydrogen sulfide production in the intestine is achieved by inhibiting the activity of hydrogen sulfide synthase in the intestine.

[0016] The intestinal hydrogen sulfide synthase is cysteine ​​desulfurase and sulfite reductase.

[0017] Thirdly, the present invention also provides a pharmaceutical composition comprising the aforementioned polyphenol complex and pharmaceutically acceptable excipients.

[0018] The amount of the polyphenol complex used is 1-200 mg / kg.

[0019] The pharmaceutically acceptable excipients include one or more of the following: carriers, diluents, binders, lubricants, and wetting agents.

[0020] The dosage form of the pharmaceutical composition includes tablets, granules, or capsules.

[0021] The beneficial effects of this invention are:

[0022] This invention employs a three-tiered screening system—in vitro anaerobic fermentation for initial screening, molecular docking for secondary screening, and in vivo validation in mice—to screen a complex that targets and inhibits the formation of hydrogen sulfide in the intestine from 20 natural polyphenols. The core components are gallic acid, baicalin, and curcumin. The method is simple and reliable, balancing in vitro activity and in vivo efficacy. Animal experiments show that the polyphenol complex of this invention can inhibit the production of hydrogen sulfide in the intestine, demonstrating good application potential. This invention elucidates the mechanism of action of its targeted inhibition of key enzymes in hydrogen sulfide synthesis, effectively reducing the content of hydrogen sulfide in the colon, providing technical support for the preparation of natural products that inhibit sulfur and protect the intestines, and has broad application prospects. Attached Figure Description

[0023] 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 some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 This is a diagram showing the molecular docking analysis of polyphenols and sulfite reductase in this invention.

[0025] Figure 2 This is a diagram showing the molecular docking analysis of polyphenols and cysteine ​​desulfurase in this invention.

[0026] Figure 3 This figure shows the effect of different mass ratios of gallic acid, baicalin, and curcumin on the inhibition rate of hydrogen sulfide production under simulated colonic fermentation conditions.

[0027] Figure 4 This is a graph showing the hydrogen sulfide content in the contents of the colon and cecum of mice in this invention.

[0028] Figure 5 This is a relative abundance diagram of Desulfovibrio, the main hydrogen sulfide-producing bacterium, in the mouse colon contents of this invention. Detailed Implementation

[0029] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0030] Example 1

[0031] A method for screening polyphenol complexes, the specific steps of which are as follows:

[0032] (1) In vitro simulated colonic anaerobic fermentation experiment:

[0033] The basal culture medium consisted of: peptone (2.5 g), yeast extract (2.0 g), 0.5 g methionine, bile salts (0.5 g), ferrous heme (0.05 g), NaHCO3 (2.0 g), NaCl (0.1 g), CaCl2·6H2O (0.01 g), MgSO4·7H2O (0.01 g), K2HPO4 (0.04 g), KH2PO4 (0.04 g), vitamin K1 (10 μL), resazurite (0.01 g), and Tween 80 (2.0 mL). The solution was dissolved in 800 mL of deionized water, and the pH was adjusted to 7.0 with 1 mol / L NaHCO3. The solution was then sterilized and cooled before use.

[0034] Preparation of fecal microbial suspension: Samples were collected from 6 healthy volunteers (3 males and 3 females, aged 22-25 years, BMI 20-24 kg / m²). 2 Approximately 20.0 g of fresh feces (without intestinal disease and no antibiotic treatment in the past 3 months) was added to sterile PBS at a ratio of 1:9 (w / v) to prepare a 10% human fecal bacterial suspension. After vortexing for 5 min, the suspension was filtered through 3 layers of sterile gauze. The filtrate was centrifuged at 4°C and 5,000×g for 10 min to obtain the fecal bacterial suspension.

[0035] Preparation of polyphenol solution: Natural plant compounds ferulic acid, ellagic acid, kaempferol, hesperidin, epigallocatechin gallate, dihydromyricetin, hydroxytyrosol, gallic acid, naringin, luteolin, proanthocyanidins, tannic acid, rutin, baicalin, caffeic acid, quercetin, curcumin, chlorogenic acid, anthocyanins, and resveratrol were added to sterile PBS at a ratio of 1:9 (w / v) to prepare a 50 mg / mL polyphenol solution. After vortexing for 15 min, the polyphenol solution was obtained.

[0036] The fermentation system consisted of 8.0 mL of basal culture medium, 1.0 mL of 50 mg / mL polyphenol solution, and 1.0 mL of 10% (w / v) fecal bacterial suspension. After dispensing the basal culture medium, the mixture was first boiled to remove oxygen, each tube was then filled with nitrogen for 2 min, capped for sterilization, and then the polyphenol solution and bacterial suspension were added using a sterile syringe. The tubes were then placed in an anaerobic fermentation incubator containing an anaerobic gas generator and fermented anaerobicly at 37°C for 48 h.

[0037] Determination of hydrogen sulfide content in fermentation broth: The hydrogen sulfide content in the fermentation broth was determined using the methylene blue spectrophotometric method. Specifically, after fermentation, 1 mL of fermentation broth was transferred to a 2 mL EP tube, and 0.2 mL of 10% (w / v) zinc acetate solution was added. The mixture was gently mixed and allowed to stand for 5 min to allow the hydrogen sulfide to be completely converted into zinc sulfide precipitate. The tube was centrifuged at 4,000 × g for 10 min, the supernatant was discarded, and the bottom precipitate was retained. 1 mL of distilled water was added to the precipitate, and the tube was gently shaken and washed. The tube was then centrifuged again at 4,000 × g for 10 min, and the supernatant was discarded to reduce interference from other impurities in the fermentation broth on subsequent color development. 0.5 mL of 0.1% (w / v) N,N-dimethyl-p-phenylenediamine dihydrochloride solution and 0.5 mL of 0.1% (w / v) ferric chloride solution were added sequentially to the washed zinc sulfide precipitate. After thorough mixing, the tube was placed in a 25°C water bath in the dark for 30 min. After the reaction was completed, the absorbance was measured at a wavelength of 665 nm. The hydrogen sulfide content in the fermentation broth was determined by in vitro anaerobic fermentation, and the results are shown in Table 1.

[0038] Table 1. Inhibition rate of polyphenols on hydrogen sulfide in fermentation broth

[0039]

[0040] As shown in Table 1, compared with the control group, except for anthocyanins, naringin, and tannic acid, the other 17 polyphenols could significantly reduce the hydrogen sulfide content in the fermentation broth. Among them, the top five polyphenols with the best inhibitory effect were curcumin (74.34%), baicalein (69.72%), gallic acid (65.14%), chlorogenic acid (54.03%), and dihydromyricetin (53.60%).

[0041] (2) Molecular docking simulation

[0042] First, small molecule ligand structures were obtained from the PubChem database. Then, cysteine ​​desulfurase (PDB ID: 1P3W) and sulfite reductase (PDB ID: 2V4J) were screened from the RCSB PDB database as acceptor proteins for molecular docking. The molecular docking results were visualized using Discovery Studio 2019 and PyMOL 2.6 software, and two-dimensional and three-dimensional schematic diagrams of the interactions between the small molecule ligands and key amino acid residues of the protein were drawn. The binding energies of the candidate polyphenols and target proteins were calculated using AutoDockVina 1.2.2 software to determine the optimal binding conformation. The protein-ligand binding interface was analyzed using PLIP and LigPlus, and the interaction details were visualized using PyMOL 2.6.

[0043] Molecular docking technology was used to further screen polyphenols with better potential. For example... Figure 1 As shown, the docking results for cysteine ​​desulfurase showed that the binding energies of baicalin, gallic acid, curcumin, dihydromyricetin, and chlorogenic acid were -7.52, -6.45, -8.91, -5.75, and -5.31 kcal / mol, respectively, all exhibiting binding activity. Figure 1 As shown in Figure A, the interaction between baicalein and cysteine ​​desulfurase mainly includes: hydrogen bonds formed by residues such as PLP764 and ALA11; van der Waals forces formed by residues such as THR76, LYS206, and ASP109; hydrophobic interactions formed by ALA106 residues; and π-π interactions formed by LYS105 residues. Figure 1 As shown in B, gallic acid forms hydrogen bonds with residues such as HIS104 and PLP764; residues such as SER10, THR76, and LYS206 form van der Waals forces; as... Figure 1 As shown in C, curcumin forms hydrogen bonds with residues such as ASN155, ASP109, and ALA106; van der Waals forces with residues such as ALA11, LYS206, and GLN183; and hydrophobic interactions with residues such as LYS105 and PLP764. Figure 1 As shown in D, dihydromyricetin forms hydrogen bonds with residues such as PLP764 and ASN80; residues such as THR110, THR76, and ASP109 form van der Waals forces; and residues such as LYS105 and ALA106 form hydrophobic interactions; as shown in Figure D, dihydromyricetin forms hydrogen bonds with residues such as PLP764 and ASN80; residues such as THR110, THR76, and ASP109 form van der Waals forces; residues such as LYS105 and ALA106 form hydrophobic interactions; Figure 1As shown in E, chlorogenic acid forms hydrogen bonds with residues such as THR110, ASN80, and ASP109; and van der Waals forces with residues such as THR76, LYS105, and HIS205. These results suggest that curcumin may first form the strongest binding affinity through the lowest binding energy, relying on multiple binding mechanisms—hydrogen bonds, van der Waals forces, and hydrophobic interactions—to occupy the key active site of cysteine ​​desulfurase, thereby inhibiting enzyme activity. Secondly, baicalein and gallic acid may also show good inhibitory effects.

[0044] like Figure 2 As shown, the docking results with sulfite reductase showed that the binding energies of baicalin, gallic acid, curcumin, dihydromyricetin, and chlorogenic acid were -8.03, -7.60, -8.67, -5.09, and -6.14 kcal / mol, respectively, all exhibiting binding activity. Figure 2 As shown in Figure A, the interaction between baicalein and sulfite reductase mainly includes: hydrogen bonds formed by residues such as ARG172, ARG101, and ARG83; van der Waals forces formed by residues such as LYS213, GLY168, and SER167; and hydrophobic interactions formed by residues such as ILE81 and ILE70. Figure 2 As shown in B, gallic acid forms hydrogen bonds with residues such as ARG83, GLY69, and GLY82; residues such as ILE70, GLY78, and SER167 form van der Waals forces; and residues such as ILE81 form hydrophobic interactions; as... Figure 2 As shown in C, curcumin forms hydrogen bonds with residues such as TYR76, ARG101, and VAL73; and forms van der Waals forces with residues such as LYS213, GLY168, and ILE70; as shown in Figure C, curcumin forms hydrogen bonds with residues such as TYR76, ARG101, and VAL73; and forms van der Waals forces with residues such as LYS213, GLY168, Figure 2 As shown in D, dihydromyricetin forms hydrogen bonds with residues such as VAL71, GLY77, and ARG83; residues such as GLY72, GLY168, and LYS213 form van der Waals forces; and residues such as ILE81 form hydrophobic interactions; as shown in Figure D, dihydromyricetin forms hydrogen bonds with residues such as VAL71, GLY77, and ARG83; residues such as GLY72, GLY168, and LYS213 form van der Waals forces; and residues such as ILE81 form hydrophobic interactions. Figure 2 As shown in E, chlorogenic acid forms hydrogen bonds with residues such as VAL80, GLY79, and GLY77, while residues such as GLY82, ARG101, and SER167 form van der Waals forces. These results suggest that curcumin may first rely on the synergistic effect of hydrogen bonds and van der Waals forces to bind to key residue sites of sulfite reductase, anchoring the enzyme's active region and restricting its conformational freedom; while baicalin utilizes a multi-factor molecular force network of hydrogen bonds, van der Waals forces, and hydrophobic interactions, and gallic acid binds through hydrogen bonds, van der Waals forces, and hydrophobic interactions.

[0045] In summary, the inhibitory effects of the five polyphenols on hydrogen sulfide-producing enzymes, from strongest to weakest, are curcumin, baicalin, gallic acid, chlorogenic acid, and dihydromyricetin. Based on in vitro anaerobic fermentation experiments and molecular docking simulations, curcumin, baicalin, and gallic acid were selected for further experimental verification.

[0046] Example 2

[0047] The preparation methods for polyphenol complexes with different mass ratios are as follows:

[0048] According to the mass ratios of gallic acid, baicalin, and curcumin as 0.5:1:1, 1:1:1, 1.5:1:1, 2:1:1, 2.5:1:1, 3:1:1, 1.5:0.5:1, 1.5:1:1, 1.5:1.5:1, 1.5:2:1, 1.5:2.5:1, 1.5:3:1, 1.5:1:0.5, 1.5:1:1, 1.5:1:1.5, 1.5:1:2, 1.5:1:2.5, and 1.5:1:3, the corresponding proportions of gallic acid, baicalin, and curcumin were weighed out and mixed evenly to obtain polyphenol complexes with different mass ratios.

[0049] Example 3

[0050] A method for preparing a polyphenol complex with a mass ratio of 1.5:1:2, the specific steps of which are as follows:

[0051] According to the mass ratio of gallic acid, baicalin and curcumin of 1.5:1:2, 15 g of gallic acid, 10 g of baicalin and 20 g of curcumin were weighed and mixed evenly to obtain the polyphenol complex.

[0052] Example of implementation effect 1

[0053] The optimal mass ratio was investigated using polyphenol complexes prepared in Example 2 at different mass ratios, as detailed below:

[0054] Using the in vitro anaerobic fermentation experiment simulating colonic fermentation described in Example 1, polyphenol complexes prepared in Example 2 at different mass ratios were added to the culture medium, and anaerobic fermentation was carried out at 37°C for 48 h. The hydrogen sulfide content in the fermentation broth was then measured, and the inhibition rate of hydrogen sulfide production was calculated.

[0055] The results are as follows Figure 3As shown, under the condition that the ratio of baicalein to curcumin is fixed, with the increase of the ratio of gallic acid, the inhibition rate of hydrogen sulfide production first increases and then decreases, and the optimal inhibition rate ratio is 1.5:1:1; under the condition that the ratio of gallic acid to curcumin is fixed, with the increase of the ratio of baicalein, the inhibition rate of hydrogen sulfide production first increases and then decreases, and the optimal inhibition rate ratio is 1.5:1:1; under the condition that the ratio of gallic acid to baicalein is fixed, with the increase of the ratio of curcumin, the inhibition rate of hydrogen sulfide production first increases and then decreases, and the optimal inhibition rate ratio is 1.5:1:2. The above results show that the optimal mass ratio of gallic acid, baicalein and curcumin to inhibit hydrogen sulfide production is 1.5:1:2. Therefore, a polyphenol complex with a mass ratio of 1.5:1:2 was selected for subsequent in vitro fermentation and in vivo animal experiments.

[0056] Example of implementation effect 2

[0057] In vivo animal experiments were carried out using the polyphenol complex prepared in Example of implementation 3, as follows:

[0058] All experimental animals required for this application were purchased from the Animal Experiment Center of Zhengzhou University, a total of 60, and the specific information is as follows: the breed is C57BL / 6J mice, the gender is male, the age is 8 weeks old, the level is specific pathogen free (SPF) level, and the weight range is 21-23 g; the experimental animal production license number is: SCXK (Yu) 2022-0001.

[0059] Before the experiment, all mice were fed adaptively for 7 days to adapt to the experimental environment. During this period, standard feed was fed, and the mice were allowed to eat and drink freely. After the adaptive feeding ended, the mice were randomly divided into 6 groups (n = 10), namely: normal group, high methionine group, gallic acid group, baicalein group, curcumin group and polyphenol complex group. The ratio of gallic acid, baicalein and curcumin in the polyphenol complex is 1.5:1:2. The gavage dose of the four polyphenol intervention groups was 50 mg / kg body weight, and continuous gavage treatment was carried out for twelve weeks. After twelve weeks of dietary intervention, all experimental animals were fasted for 12 h. On the day of the experiment, the mice were anesthetized by inhaling 3% isoflurane, and the mice were dissected to take their colon and cecal contents.

[0060] Accurately weigh 600 mg of colon and cecal contents respectively, homogenize with 1.2 mL of phosphate buffer (pH 7.3), and centrifuge at 4°C and 16,000×g for 15 min. The supernatant was filtered through a 0.22 μm nylon filter membrane. Take 500 μL of fecal water sample, mix it with 500 μL of phosphate buffer (pH = 7.3) and 50 μL of sulfide reagent 1, and incubate for 5 seconds. Subsequently, 50 μL of sulfide reagent 2 was added, and the mixture was incubated for 5 minutes. The colorimetric product was analyzed spectroscopically using an ultraviolet spectrophotometer, and its optimal detection wavelength was determined to be 450 nm.

[0061] like Figure 4 As shown, compared with the normal group of mice, the hydrogen sulfide content in the colon and cecum of mice in the high-methionine group was significantly increased (p<0.05). Compared with the high-methionine group, the hydrogen sulfide content in the colon and cecum of mice in the gallic acid, baicalin, curcumin, and polyphenol complex groups was significantly decreased (p<0.05). Further comparison revealed that the hydrogen sulfide content in the colon and cecum of mice in the polyphenol complex group was significantly decreased compared with the gallic acid, baicalin, and curcumin groups (p<0.05). The reduction effect of the four intervention groups, from highest to lowest, was: polyphenol complex group > curcumin > baicalin > gallic acid. These results indicate that gallic acid, baicalin, curcumin, and polyphenol complex can all significantly reduce the hydrogen sulfide content in the colon contents of mice on a high-methionine diet, with the polyphenol complex showing a more significant reduction effect.

[0062] Example of implementation effect 3

[0063] The composition and distribution of the microbial community in colonic contents were analyzed using the polyphenol complex prepared in Example 3, as detailed below:

[0064] 16S rDNA high-throughput sequencing was used to analyze the microbial community composition and distribution in colon contents. DNA was extracted from colon contents samples using a kit. Using 20-50 ng of DNA as a template, the V3 / V4 variable region of prokaryotic 16S rDNA was amplified by PCR. After verifying the 600 bp target fragment by 1.5% agarose gel electrophoresis, a next-generation sequencing library was constructed and sequenced to obtain raw data. Bioinformatics analysis was performed using R 3.1.1 and QIIME 1.9.1 software, and bar charts were generated for differentially abundant bacteria.

[0065] like Figure 5 As shown, compared with the normal group of mice, the abundance of Desulfovibrio, a hydrogen sulfide-producing bacterium, in the colonic contents of mice in the high-methionine group was significantly increased (p<0.05). Compared with the high-methionine group of mice, the abundance of Desulfovibrio in the colonic contents of mice in the gallic acid, baicalein, curcumin, and polyphenol complex groups was significantly decreased (p<0.05). Further comparison revealed that compared with the gallic acid, baicalein, and curcumin groups, the abundance of Desulfovibrio in the colonic contents of mice in the polyphenol complex group was significantly decreased (p<0.05). The reduction effect of the four intervention groups, from highest to lowest, was: polyphenol complex group > curcumin > baicalein > gallic acid. These results are consistent with the trend of changes in intestinal hydrogen sulfide content. The above results indicate that gallic acid, baicalin, curcumin, and polyphenol complex can all significantly reduce the abundance of Desulfovibrio, a hydrogen sulfide-producing bacterium, in the colonic contents of mice on a high-methionine diet, with the polyphenol complex showing a more significant reduction effect.

[0066] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A polyphenolic complex that inhibits the production of hydrogen sulfide in the intestine, characterized in that: The polyphenol complex is composed of gallic acid, baicalin and curcumin; the mass ratio of gallic acid, baicalin and curcumin is 0.5-3:1:0.5-5.

2. The method for preparing the polyphenol complex according to claim 1, characterized in that: The mass ratio of gallic acid, baicalein and curcumin is 1.5:1:

2.

3. The use of the polyphenol complex according to claim 1 or 2 in the preparation of a medicament for inhibiting the generation of hydrogen sulfide in the intestine.

4. The use of the polyphenol complex according to claim 1 or 2 in the preparation of a medicament for treating intestinal inflammation, ulcerative colitis, and irritable bowel syndrome caused by excessive hydrogen sulfide production in the intestine.

5. The application according to claim 3, characterized in that: The inhibition of hydrogen sulfide production in the intestine is achieved by inhibiting the activity of hydrogen sulfide synthase in the intestine.

6. The application according to claim 5, characterized in that: The intestinal hydrogen sulfide synthase is cysteine ​​desulfurase and sulfite reductase.

7. A pharmaceutical composition, characterized in that: The product comprises a therapeutically effective amount of the polyphenol complex of claim 1 or 2 and pharmaceutically acceptable excipients.

8. The pharmaceutical composition according to claim 7, characterized in that: The dosage of the polyphenol complex is 1-200 mg / kg.

9. The pharmaceutical composition according to claim 8, characterized in that: The pharmaceutically acceptable excipients include one or more of the following: carriers, diluents, binders, lubricants, and wetting agents.

10. The pharmaceutical composition according to claim 9, characterized in that: The dosage form of the pharmaceutical composition includes tablets, granules, or capsules.

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