Application of furanodienone in preparation of medicine for treating inflammatory bowel disease

Abstract

The invention relates to the technical field of medicines, in particular to application of furanodienone in preparation of medicines for treating inflammatory bowel diseases. In-vivo animal experiments find that furanodienone can effectively inhibit the disease degree of a DSS-induced C57BL / 6J mouse colitis model, alleviate the phenomena of colon shortening, mouse hemafecia, weight loss and the like, effectively inhibit the activation of an NF-kappa B pathway in the mouse colon and the level of downstream inflammatory factors, and can alleviate intestinal mucosal barrier injury caused by DSS. The PXR agonist-furanodienone is separated and identified from a natural product, the raw materials are rich and easy to obtain, the price is low, preparation is easy, side effects are small, and the PXR agonist-furanodienone is suitable for clinical application and popularization and can be used for preparing the medicine for treating the inflammatory bowel disease.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to the application of furandienone in the preparation of medicines for treating inflammatory bowel disease. Background Art

[0002] In recent years, due to the influence of environment and eating habits, intestinal health issues have received great attention. As a natural barrier for the human body to defend against pathogens, the intestine is easily affected by various external stimuli and produces inflammatory responses. Inflammatory bowel disease (IBD) is a chronic, recurrent intestinal inflammatory disease. Abnormal immune response and mucosal barrier destruction in the intestine play an important role in the disease process. With the increasing incidence of IBD in my country, the study of new therapeutic drugs is one of the key breakthroughs in the study of this disease. At present, the pathogenesis and treatment of IBD are mainly explored through the study of animal models. Dextran sulphate sodium (DSS) is a sulfated polysaccharide that can increase intestinal permeability, destroy the intestinal mucosal barrier, lead to intestinal flora disorders, activate inflammatory signaling pathways, and thus induce colitis in mice. DSS-induced colitis in mice is similar to human IBD in histology, clinical manifestations and site of onset, and the modeling method is simple. An acute or chronic colitis model can be established by adjusting the concentration of DSS and the time of administration. It is currently one of the most widely used animal models for studying IBD.

[0003] During the inflammatory response, nuclear receptors can inhibit the conduction of inflammatory signals. Studies have found that the expression of pregnane X receptor (PXR) is reduced in the intestines of IBD patients. PXR is a member of the nuclear receptor superfamily and is mainly expressed in structural tissues such as the kidney, liver, and intestine. It can be activated by a large number of ligands, such as artemisinin, an active ingredient in Chinese herbal medicine, and galangin in galangal, which can all act as ligands for PXR. Today, the anti-inflammatory effect of PXR in IBD has been widely recognized and is an effective drug intervention target for a variety of inflammatory diseases. After activation, PXR can inhibit the NF-κB pathway, thereby reducing the production of inflammatory factors and inhibiting intestinal inflammation. At the same time, the activation of PXR can promote cell proliferation and migration, which is a key factor in the healing process of epithelial cell damage. Pregnenolone Carbonitrile (PCN) is a specific agonist of rodent PXR and can be used as a positive control drug.

[0004] Chinese patent CN107007588A, published on August 4, 2017, discloses the use of furandienone in the preparation of drugs for treating colorectal cancer. Earlier studies have reported that furandienone has anti-inflammatory activity, but to date, there is no literature reporting the effect of furandienone on colitis and its molecular mechanism. Summary of the invention

[0005] The purpose of the first aspect of the present invention is to provide the use of furandienone or its derivatives in the preparation of products for treating inflammatory bowel disease.

[0006] The second aspect of the present invention aims to provide a medicine.

[0007] The second aspect of the present invention aims to provide a method.

[0008] In order to achieve the above-mentioned purpose of the present invention, the technical solution adopted by the present invention is:

[0009] The first aspect of the present invention provides the use of furandienone or its derivatives in the preparation of products for treating inflammatory bowel disease.

[0010] The English name of furandienone is (5E,9E)-3,6,10-trimethyl-8,11-dihydro-7H-cyclodeca[b]furan-4-one (FDN), and its structural formula is shown in Formula 1:

[0011]

[0012] Preferably, the furanadienone or its derivative comprises at least one of a pharmaceutically acceptable salt and a pharmaceutically acceptable modification.

[0013] Preferably, the pharmaceutically acceptable salt includes at least one of a metal salt, an ammonium salt, a salt formed with an inorganic acid, a salt formed with an organic base, a salt formed with an organic acid, a salt formed with a basic amino acid, and a salt formed with an acidic amino acid.

[0014] Preferably, the metal salt comprises an alkali metal salt or an alkaline earth metal salt.

[0015] Preferably, the alkali metal salt includes at least one of a sodium salt and a potassium salt.

[0016] Preferably, the alkaline earth metal salt includes at least one of calcium salt, magnesium salt, barium salt and aluminum salt.

[0017] Preferably, the salt formed with the organic base includes a salt formed with the following organic bases: at least one of trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine and N,N'-dibenzylethylenediamine.

[0018] Preferably, the salt formed with an inorganic acid includes a salt formed with the following inorganic acids: at least one of hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid.

[0019] Preferably, the salt formed with the organic acid includes a salt formed with the following organic acids: at least one of formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

[0020] Preferably, the salt formed with a basic amino acid includes a salt formed with the following basic amino acids: at least one of arginine, lysine and ornithine.

[0021] Preferably, the salt formed with the acidic amino acid includes a salt formed with the following acidic amino acids: at least one of aspartic acid and glutamic acid.

[0022] Preferably, the pharmaceutically acceptable modification comprises at least one of phosphorylation, sulfonation, acylation, glycosylation, ubiquitination, acetylation, methylation, sulfation, phospholipidation, and halogenation.

[0023] Preferably, the inflammatory bowel disease comprises at least one of undefined inflammatory bowel disease, ulcerative colitis, Crohn's disease, undifferentiated colitis, acute colitis, and chronic colitis.

[0024] Preferably, the inflammatory bowel disease is ulcerative colitis.

[0025] Preferably, the product comprises a medicine.

[0026] Preferably, the drug comprises pharmaceutically acceptable excipients, and / or any one or more other active ingredients.

[0027] Preferably, the pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrities, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, and carriers.

[0028] Furthermore, in order to facilitate medication, the active ingredient furandienone or its derivatives can be processed into a specific dosage form with any one or more pharmaceutically acceptable excipients. These excipients can be diluents (such as starch, pregelatinized starch, dextrin, sucrose, lactose, mannitol and microcrystalline cellulose, etc.), absorbents (such as calcium sulfate, calcium hydrogen phosphate, light magnesium oxide and calcium carbonate, etc.), wetting agents (such as water and ethanol, etc.), binders (such as hydroxypropyl methylcellulose, povidone, starch slurry and syrup, etc.), disintegrants (such as dry starch, sodium hydroxymethyl starch, low-substituted hydroxypropyl cellulose, effervescent disintegrants and cross-linked polyvinylpyrrolidone, etc.), lubricants (magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol and micropowder, etc.), and other ingredients. silica gel, etc.), colorants (such as titanium dioxide, sunset yellow, methylene blue and medicinal iron oxide, etc.), coating materials (such as acrylic resin, hydroxypropyl methylcellulose and povidone, etc.), solvents (such as water for injection, ethanol, propylene glycol and glycerol, etc.), acid-base regulators (such as hydrochloric acid, lactic acid, sodium hydroxide, tartaric acid and sodium tartrate, etc.), antioxidants (such as sodium sulfite, sodium pyrosulfite and sodium thiosulfate, etc.), antibacterial agents (such as phenol, benzyl alcohol and thimerosal, etc.), and isotonic regulators (such as sodium chloride and glucose, etc.).

[0029] Preferably, the dosage form of the product includes a dosage form for enteral administration or a dosage form for parenteral administration.

[0030] Preferably, the dosage form for administration via the gastrointestinal tract includes at least one of powders, tablets, granules, capsules, sustained-release agents, solutions, dry suspensions, effervescent tablets, emulsions, suspensions, syrups, drops, and chewable tablets.

[0031] Furthermore, the dosage forms for administration through the gastrointestinal tract include but are not limited to enteric-coated tablets, coated tablets, film-coated tablets, sugar-coated tablets, dispersible tablets, sucking tablets, chewable tablets, effervescent tablets, scratched tablets, sustained-release and controlled-release dosage forms such as sustained-release tablets, sustained-release coated tablets, controlled-release tablets, orally disintegrating tablets, lozenges, oral patches, etc.

[0032] Preferably, the non-intestinal administration dosage form includes at least one of an injection dosage form, a respiratory tract administration dosage form, a skin administration dosage form, a mucosal administration dosage form, and a cavity administration dosage form.

[0033] Furthermore, the injectable dosage forms include but are not limited to injection solutions, injection solutions, intravenous injection solutions, injection suspensions, sterile powders for injection, intravenous injections, water injections, injection emulsions, powder injections, injections, sterile powder injections, freeze-dried powder injections, etc.

[0034] Preferably, the product is administered to a mammal.

[0035] Preferably, the mammal comprises a human.

[0036] In the first aspect of the present invention, the present invention finds that furanadienone can be used as a natural PXR agonist, which can bind to the PXR ligand binding domain and effectively inhibit the pathological manifestations of DSS-induced colitis in C57BL / 6J mice. - / - There was no therapeutic effect in mice.

[0037] The second aspect of the present invention provides a medicine comprising a therapeutically effective amount of furandienone or a derivative thereof.

[0038] In some embodiments of the present invention, the therapeutically effective amount in mice is 1 to 30 mg / kg; preferably, 5 to 20 mg / kg; more preferably, 8 to 12 mg / kg.

[0039] The third aspect of the present invention provides any one of the methods 1) to 2), comprising the following steps: treating cells with furandienone or a derivative thereof.

[0040] 1) A method for activating the pregnane X receptor in vitro for non-therapeutic purposes;

[0041] 2) A method for inhibiting inflammation in vitro for non-therapeutic purposes.

[0042] The beneficial effects of the present invention are:

[0043] 1. Use mass spectrometry technology to screen out effective natural product furanodienones that can bind to PXR.

[0044] 2. The present invention found through in vivo animal experiments that furandienones can effectively inhibit the disease severity of the DSS-induced C57BL / 6J mouse colitis model, alleviate the phenomenon of colon shortening, bloody stools in mice, weight loss, etc.

[0045] 3. The present invention found through in vivo animal experiments that furandienone can effectively inhibit the activation of the NF-κB pathway in the colon of mice and the levels of its downstream inflammatory factors.

[0046] 4. The present invention found through in vivo animal experiments that furandienone can alleviate the intestinal mucosal barrier damage caused by DSS.

[0047] 5. The present invention verifies that furandienone is a PXR-specific agonist through in vivo animal experiments. - / - In mice, it was unable to inhibit the disease progression of colitis in mice.

[0048] 6. The present invention separates and identifies PXR agonists from natural products. Not only are the raw materials abundant and readily available, they are cheap and easy to prepare, but they also have few side effects and are suitable for clinical promotion and use. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0050] Figure 1 Binding analysis of FDN and PXR protein, including: (A) Binding level of FDN and fusion protein (hPXR-LBD-SRC1); (B) Close-up view of the ligand binding pocket of PXR bound to FDN; (C) Superposition of the structures of FDN and dabrafenib (DAB) bound to PXR (orange, PDB code 6HJ2).

[0051] Figure 2 The effect of FDN in alleviating DSS-induced colitis in C57BL / 6J mice, including: (A) body weight change; (B) DAI index; (C) colon length; n=6, compared with the DSS group, ***p<0.001.

[0052] Figure 3 This is the effect of FDN on the expression of NF-κB pathway proteins p-p65 and p-IκB.

[0053] Figure 4 The results of FDN's inhibition of colon inflammatory factors (A) IL-1β, (B) IL-6, and (C) TNF-α in C57BL / 6J mice; compared with the DSS group, ***p<0.001, *p<0.05.

[0054] Figure 5 The effect of FDN on the pathological changes of colon tissue in C57BL / 6J mice (hematoxylin-eosin staining).

[0055] Figure 6 The effect of FDN on the intestinal mucosal proteins Occludin and ZO-1 in C57BL / 6J mice (immunofluorescence).

[0056] Figure 7 The effect of FDN on DSS-induced colitis in PXR- / - mice, including: (A) body weight change; (B) DAI index; (C) colon length. n = 6, compared with the DSS group, ***p < 0.001; ns: no significant difference, no significant difference.

[0057] Figure 8The results of FDN's inhibition of colon inflammatory factors (A) IL-1β, (B) IL-6, and (C) TNF-α in PXR- / - mice; compared with the DSS group, **p<0.01, *p<0.05, ns: no significant difference.

[0058] Fig. 9 The effect of FDN on the pathological changes of colon tissue in PXR- / - mice (hematoxylin-eosin staining). DETAILED DESCRIPTION

[0059] The following will be combined with the embodiments to clearly and completely describe the concept of the present invention and the technical effects produced, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0060] In the following examples, the materials, reagents, etc. used were obtained from commercial sources unless otherwise specified.

[0061] The sources of the main reagents and materials are as follows:

[0062] Reagents: methylcellulose (M112869, Aladdin); furanodienones (HF029913, Herbest); PCN (P911021, Macklin); dimethyl sulfoxide (DMSO, Sigma); DSS (MP Biomedical); ZO-1 (CY3) and occludin (488) fluorescent antibodies (Thermo Fisher Scientific); p-p65 and p-IκB antibodies (Proteintech); HRP-labeled anti-rabbit IgG (Abcam); mouse IL-6, IL-1β and TNF-a ELISA kits (BioLegend); HE staining solution (Wuhan Bolfu Biotechnology Co., Ltd.); DAB color development kit (K3468, DAKO); DAPI (Wuhan Bolfu Biotechnology Co., Ltd.).

[0063] Mice: C57BL / 6J male mice were obtained from SeBiona Bio-Tech. - / - Male mice (Nr1i2-ko) were obtained from Saiye (Suzhou) Biotechnology Co., Ltd. All mice were SPF grade and maintained under a strict 12-h light cycle.

[0064] Instruments and equipment: microplate reader (SpectraMax M2); microscope (Nikon Eclipse CI, Nikon, Japan); fluorescence microscope (80i, Nikon, Japan); MicroCal Auto-iTC200 isothermal titration calorimeter.

[0065] Example 1 Analysis of the binding of natural compound FDN to PXR protein

[0066] 1. Experimental methods

[0067] (1) Isothermal titration calorimetry (ITC)

[0068] The binding effect of FDN on PXR was investigated using the human PXR receptor ligand binding domain (hPXR-LBD, residues 130-434). In order to enhance the stability of the PXR protein, it was co-expressed with a fragment of steroid receptor coactivator-1 (SRC-1, 623-710). Specifically, the PXR-LBD gene was cloned into the pRSET-A vector (with a His6 tag at the N-terminus), and the SRC-1 fragment gene was inserted into the pACYC184 vector, and then the hPXR-LBD-SRC1 protein was expressed using Escherichia coli BL21 (DE3) cells. The purified hPXR-LBD-SRC1 protein (25 μM) was dissolved in 400 μL PBS containing 0.5% (v / v) DMSO, and FDN was used at a concentration of 200 μM. Titration of the FDN solution with the his-tagged hPXR-LBD-SRC1 fusion protein resulted in an exothermic binding event. Microcal Origin 7 software analyzes integrated thermal effects.

[0069] (2) Molecular docking

[0070] The structure of the FDN ligand was downloaded from PubChem and then used The LigPrep utility in the suite was used to prepare the ligand structure. The Prime Macrocycle conformational search tool was used in conjunction with the OPLS3e force field to optimize the ligand structure in implicit water. The PXR structure grid was set up using default parameters and the binding box was centered on the center of mass of the FDN crystal ligand. Re-docking of FDN within its crystal structure resulted in a good binding pose (from the crystal structure XP score = -8.962 kcal mol-1), confirming the ability of this method to predict interactions within the binding site for this ligand.

[0071] 2. Experimental results

[0072] like Figure 1 As shown in Figure A, analysis of the total heat shift at increasing concentrations of PXR-LBD-SRC1 protein indicated that the binding stoichiometry was approximately 2:1. The dissociation constant (Kd) derived from curve fitting analysis was 4.5 μM. Figure 1 As shown in Figure 2B, FDN is a relatively small compound that interacts with a small set of eight PXR LBP residues ( In contrast, the potent PXR agonist and anticancer drug Dabrafenib (DAB) occupies a larger volume and makes more contacts with LBP residues ( Figure 1 C), which is consistent with its higher affinity for the receptor (EC50 = 87 nM). The two main anchoring points of FDN include (1) multiple contacts between its ten-membered ring and the so-called PXRπ-trap composed of amino acids F288, W299 and Y306, and (2) hydrogen bonding between the carbonyl part of FDN and Q285. In addition, the FDN furanyl ring is in close contact with M243, M246, S247 and F288.

[0073] Example 2 Study on the efficacy of natural compounds in improving DSS-induced colitis in C57BL / 6J mice

[0074] 1. Experimental methods

[0075] (1) Construction of DSS-induced acute colitis model in C57BL / 6J mice and pharmacodynamic evaluation

[0076] Forty SPF-grade 6-8-week-old male C57BL / 6J mice were adaptively raised for 7 days and randomly divided into 4 groups (6 mice in each group): control group (Control), model group (DSS), positive control group PCN (10 mg / kg), and FDN group (10 mg / kg). The DSS group was given 2.8% DSS (w / v) aqueous solution orally for 7 days (days 4-10). FDN and PCN were gavaged on days 1-10 (dissolved in 3% DMSO and 1% methylcellulose). The weight of mice was recorded every day, and the disease activity index (DAI) was scored based on weight loss, stool viscosity and fecal bleeding. The score for each indicator ranged from 0 to 4. The mice were killed on day 11 and colon tissues were collected for analysis.

[0077] (2) Histopathological analysis

[0078] Colon tissue was stained with hematoxylin and eosin (H&E) for histological analysis. The fixed colon was embedded in paraffin and sliced ​​for use. After hematoxylin-eosin staining, the sections were dehydrated and dried, mounted with neutral gum, and then observed under a microscope. For immunohistochemistry, tissue sections were incubated with p-p65 and p-IκB antibodies (Proteintech) and HRP-labeled anti-rabbit IgG (abcam), stained with hematoxylin and DAB, mounted with neutral gum, and the final stained sections were observed under a microscope system (Nikon Eclipse CI, Nikon). For immunofluorescence, tissue sections were incubated with ZO-1 (CY3) and occludin (488) fluorescent antibodies (Thermo Fisher Scientific), and mounted with anti-fluorescence quencher after DAPI staining, stored at 4°C in the dark, and observed under a fluorescence microscope.

[0079] (3) Determination of inflammatory factors in colon tissue

[0080] After grinding, the colon tissue was centrifuged and the supernatant was taken for ELISA and BCA protein quantification. According to the instructions of the ELISA kit (Biolegend; IL-6 (#431315), IL-1β (#432615) and TNF-α (#430915)), the inflammatory factors TNF-α, IL-6, and IL-1β were detected and analyzed.

[0081] 2. Experimental results

[0082] The results showed that compared with the mice in the Control group, the body weight of the mice in the modeling group and the treatment group gradually decreased after DSS-induced ulcerative colitis ( Figure 2 A), and the disease activity index DAI score increased ( Figure 2 Middle B), the colon length was significantly shortened ( Figure 2 Middle C), Figure 2 D is a representative colon diagram. The administration of natural PXR agonists FDN and PCN can increase the colon length of DSS mice and reduce the DAI score; the results of IHC staining, such as Figure 3 As shown in the results, FDN can significantly inhibit the expression levels of p-p65 and p-IκB proteins in colon tissue induced by DSS, and can inhibit the activation of inflammatory factors related to the downstream of NF-κB signaling pathway, such as IL-6, IL-1β, and TNF-α ( Figure 4 ); H&E colon pathology analysis Figure 5As shown in the figure, the overall structure of the intestinal tissue of mice with DSS-induced colitis was abnormal, local mucosal necrosis was obvious, the normal structure of the intestinal tissue basically disappeared, a large number of inflammatory cells were present in the whole layer of tissue, and there were dense areas of inflammatory cell aggregation. The histological microstructure of the drug-treated group was improved, the infiltration of inflammatory cells was reduced, and there was no area of ​​inflammatory cell aggregation. It could alleviate the changes in the colonic crypt morphology of mice in the DSS group and protect goblet cells. The immunofluorescence results showed that compared with the model group, FDN effectively maintained the tight distribution of occludin and ZO-1 in the inflamed colon, reduced the reduction of tight junction proteins, and protected the integrity of the intestinal barrier ( Figure 6 ). Thus, it can be seen that the natural PXR agonist of the present invention can effectively improve the colon pathological damage of mice.

[0083] Example 3 Study on the efficacy of natural compounds on DSS-induced colitis in PXR- / - mice

[0084] 1. Experimental methods

[0085] The animal experiment modeling, inflammatory factor determination, and H&E staining methods were all the same as those in Example 2.

[0086] 2. Experimental results

[0087] like Figure 7 As shown, the natural PXR agonist FDN of the present invention has no therapeutic effect on the weight loss, colon shortening and increased DAI index of DSS-induced PXR- / - mice with colitis, and has no inhibitory effect on the increased levels of colon inflammatory factors IL-6, IL-1β, and TNF-α ( Figure 8 ), nor could it improve the pathological damage in the colon group ( Fig. 9 ).

[0088] The above are some experimental results from a large number of research results by the applicant, but they can already illustrate that the natural PXR agonist of the present invention binds to the PXR target, activates the PXR signal, inhibits its downstream NF-κB signaling pathway and the release of inflammatory factors, thereby alleviating the weight loss, colon shortening and DAI index increase in mice caused by DSS, and can reduce the infiltration of inflammatory cells in the colon and the secretion of IL-6, IL-1β, TNF-α inflammatory factors, increase the expression of occludin and ZO-1 proteins, maintain the intestinal barrier, and has good anti-inflammatory activity, which provides a scientific basis for its use in the preparation of drugs for the treatment of colitis.

Claims

1. Use of furandienone or its derivatives in the preparation of drugs for treating inflammatory bowel disease.

2. The use according to claim 1, characterized in that: The furandienone or its derivative includes at least one of a pharmaceutically acceptable salt and a pharmaceutically acceptable modification.

3. The use according to claim 2, characterized in that: The pharmaceutically acceptable salt includes at least one of a metal salt, an ammonium salt, a salt formed with an inorganic acid, a salt formed with an organic base, a salt formed with an organic acid, a salt formed with a basic amino acid, and a salt formed with an acidic amino acid; and / or The pharmaceutically acceptable modification includes at least one of phosphorylation, sulfonation, acylation, glycosylation, ubiquitination, acetylation, methylation, sulfation, phospholipidation, and halogenation.

4. The use according to claim 1, characterized in that: The inflammatory bowel disease includes at least one of undefined inflammatory bowel disease, ulcerative colitis, Crohn's disease, undifferentiated colitis, acute colitis, and chronic colitis.

5. The use according to claim 1, characterized in that: The products include pharmaceuticals.

6. The use according to claim 5, characterized in that: The drug includes pharmaceutically acceptable excipients, and / or any one or more other active ingredients.

7. The use according to claim 6, characterized in that: The pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrities, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, and carriers.

8. The use according to claim 5, characterized in that: The dosage form of the product includes a dosage form for gastrointestinal administration or a dosage form for parenteral administration; Preferably, the dosage form for administration via the gastrointestinal tract includes at least one of powder, tablet, granule, capsule, sustained-release agent, solution, dry suspension, effervescent tablet, emulsion, suspension, syrup, drops, and chewable tablet; Preferably, the non-intestinal administration dosage form includes at least one of an injection dosage form, a respiratory tract administration dosage form, a skin administration dosage form, a mucosal administration dosage form, and a cavity administration dosage form.

9. A drug, characterized in that: The medicament comprises a therapeutically effective amount of furandienone or a derivative thereof.

10. Any of the methods 1) to 2) comprises the following steps: treating cells with furanadienone or its derivatives; 1) A method for activating the pregnane X receptor in vitro for non-therapeutic purposes; 2) A method for inhibiting inflammation in vitro for non-therapeutic purposes.

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