CN-121987617-A - Application of hesperetin in preparation of medicine for activating aromatic hydrocarbon receptor pathway

Abstract

The application relates to the technical field of biological medicines, in particular to application of hesperetin in preparation of a medicine for activating an aromatic hydrocarbon receptor pathway. The application provides application of hesperetin in preparation of a medicament for activating an aromatic hydrocarbon receptor pathway. In particular, hesperetin is effective in activating the arene receptor pathway by promoting nuclear translocation of the arene receptor and/or up-regulating expression of downstream target genes. The activated arene receptor pathway further up-regulates the expression of the tight junction protein and/or inhibits the expression of the pro-inflammatory factor, thereby achieving the efficacy of improving intestinal barrier damage and/or regulating intestinal flora disorders. Therefore, hesperetin can be used as a medicament for preventing or treating diseases, disorders or conditions related to the activity of aromatic hydrocarbon receptors, and has important application value in improving intestinal barrier damage and/or regulating intestinal flora disorder.

Inventors

• SONG MINGYUE
• YANG JIAN
• MA ZEYUAN

Assignees

• 华南农业大学

Dates

Publication Date

20260508

Application Date

20260320

Claims (10)

1. 1. The application of hesperetin in preparing a medicament for activating an aromatic hydrocarbon receptor pathway is characterized in that the structure of the hesperetin is as follows: 。
2. 2. The use according to claim 1, wherein the activation of the arene receptor pathway is effected by promoting nuclear translocation of the arene receptor and/or up-regulating expression of a downstream target gene.
3. 3. The use according to claim 2, wherein the target gene comprises one or both of cytochrome P450 family 1 subfamily a member 1, cytochrome P450 family 1 subfamily B member 1.
4. 4. The use according to claim 1, wherein activation of the arene receptor pathway upregulates expression of the claudin and/or inhibits expression of the pro-inflammatory factor.
5. 5. The use according to claim 4, wherein the tight junction proteins comprise a closure protein and/or a scaffold protein.
6. 6. The use of claim 4, wherein the pro-inflammatory factor comprises one or more of IL-6, IL-1 β, TNF- α.
7. 7. The use according to claim 1, wherein the mass fraction of hesperetin in the medicament is 0.01% -0.1%.
8. 8. Use of hesperetin for the preparation of a product for improving intestinal barrier damage and/or for modulating intestinal flora disorders; the intestinal barrier injury or intestinal flora disorder is caused by cephalosporin antibiotics and/or quinolone antibiotics; The improvement of intestinal barrier damage or the regulation of intestinal flora disorder is that hesperetin acts by regulating intestinal flora-mediated tryptophan metabolism and then activating an arene receptor pathway.
9. 9. The use according to claim 8, wherein the modulation of gut flora mediated tryptophan metabolism promotes proliferation of beneficial bacteria, thereby up-regulating tryptophan metabolites in the gut.
10. 10. The use according to claim 9, wherein the beneficial bacteria include one or more of bacteroides, lactobacilli, bifidobacteria, faecalis.

Description

Application of hesperetin in preparation of medicine for activating aromatic hydrocarbon receptor pathway Technical Field The application relates to the technical field of biological medicines, in particular to application of hesperetin in preparation of a medicine for activating an aromatic hydrocarbon receptor pathway. Background Aromatic hydrocarbon receptor (AhR) is a highly evolutionarily conserved ligand-activated transcription factor, widely distributed in various tissues and cells in the human body, and plays a key regulatory role in various physiological and pathological processes. In recent years, ahR has been increasingly studied as a drug action target, for example, ahR can be activated by endogenous and exogenous compounds, wherein exogenous ligands comprise Polycyclic Aromatic Hydrocarbons (PAHs), dioxins (TCDD), polychlorinated biphenyls (PCBs) and the like, endogenous ligands comprise Kynurenines (KYN) and 6-formylindole [3,2-b ] carbazole (FICZ) which are tryptophan metabolites, and indole derivatives generated by intestinal flora metabolism are also important endogenous activating ligands for AhR. After the ligand activates AhR, the ligand can be involved in regulating and controlling various biological processes such as cell proliferation, tissue repair, immune response, oxidative stress and the like. Research shows that AhR knockout or dysfunction aggravates tissue injury and fibrosis process, and AhR is proved to be a very valuable drug and functional product acting target. In particular, ahR is closely related to a variety of diseases. AhR was found to be involved in chemical defense and metabolic regulation of endogenous substances in the liver, while regulating oxidative stress and apoptosis in the kidney. Kyn plays an important role in the central nervous system and peripheral tissues by activating AhR, including suppressing immune responses and participating in processes such as carcinogenesis. The intestinal flora metabolite can improve intestinal mucosa injury and regulate intestinal flora disorder by activating AhR, thereby maintaining intestinal homeostasis. In addition, ahR abnormalities are also closely associated with kidney fibrosis, inflammatory response, and various lesions of liver and kidney tissue. Although AhR activation plays an important role in maintaining organism homeostasis, improving intestinal mucosa injury, regulating intestinal flora disorder and the like, ahR pathway activation drugs with safety and high efficiency are still relatively deficient at present. Therefore, development of a novel AhR pathway activating drug with natural sources and high safety is needed to meet the actual demands of intestinal health maintenance and related functional product development. Disclosure of Invention The invention aims to overcome the defect and the defect that medicines for activating an AhR pathway are still deficient in the prior art, and provides application of hesperetin in preparation of medicines for activating an aromatic hydrocarbon receptor pathway. It is a further object of the present invention to provide the use of hesperetin for the preparation of a product for improving damages of the intestinal barrier and/or for modulating disturbances of the intestinal flora. The above object of the present invention is achieved by the following technical scheme: the invention discloses application of protecting hesperetin in preparing a medicament for activating an aromatic hydrocarbon receptor pathway, wherein the structure of the hesperetin is as follows: 。 The application provides application of hesperetin in preparation of a medicament for activating an aromatic hydrocarbon receptor pathway. In particular, hesperetin can realize the effects of improving intestinal barrier injury and/or regulating intestinal flora disorder by promoting nuclear translocation of an aromatic hydrocarbon receptor and/or up-regulating the expression of a downstream target gene of the hesperetin to activate an aromatic hydrocarbon receptor pathway, and further up-regulating the expression of a tight junction protein and/or inhibiting the expression of a proinflammatory factor. Further, the activation of the arene receptor pathway is operative to promote nuclear translocation of the arene receptor and/or up-regulate expression of a downstream target gene. Still further, the target gene includes one or two of cytochrome P450 family 1 subfamily a member 1 (CYP 1 A1), and cytochrome P450 family 1 subfamily B member 1 (CYP 1B 1). Further, activation of the arene receptor pathway can up-regulate expression of the claudin and/or inhibit expression of the pro-inflammatory factor. Still further, the tight junction proteins include a occluding protein (Occludin) and/or a scaffolding protein (ZO-1). Still further, the pro-inflammatory factors include one or more of IL-6, IL-1. Beta. And TNF-alpha. Further, the mass fraction of the hesperetin in the medicine is 0.01% -0.1%. Furthermore, the mass f