CN-122005515-A - Application of astaxanthin in preparation of medicine for preventing and treating pancreatitis related intestinal dysfunction and repairing intestinal mucosa barrier

Abstract

The invention provides application of astaxanthin in preparation of medicines for preventing and treating severe acute pancreatitis related intestinal dysfunction, intestinal flora imbalance or repairing intestinal mucosa barrier. In vivo experiments prove that astaxanthin can remarkably improve the damage of intestinal barrier induced by SAP, reduce the activity of serum diamine oxidase (DAO), repair jejunum villus structure and up-regulate the expression of tight junction protein (ZO-1, occludin, claudin), the mechanism relates to inhibiting local inflammatory reaction and oxidative stress, and specifically correct intestinal flora disorder, including restoring the proportion balance of the phylum of the thick-walled bacteria and the phylum of the bacteroides, improving the abundance of beneficial bacteria such as lactobacillus murinus, ruminococcus and the like, and the invention provides a new strategy for clinical treatment of SAP concurrent intestinal failure.

Inventors

• WU YAHUI
• FEI JIAN
• XU DAN
• XIAO GUOHUI
• XIE RONGLI
• GUO XIN
• CHEN CONG

Assignees

• 上海交通大学医学院附属瑞金医院

Dates

Publication Date

20260512

Application Date

20260213

Claims (8)

1. 1. Use of astaxanthin in the manufacture of a medicament for the prevention and treatment of severe acute pancreatitis-related intestinal dysfunction, dysbacteriosis of the intestinal tract or repair of the barrier of the intestinal mucosa.
2. 2. The use according to claim 1, wherein the prevention and treatment of intestinal dysfunction comprises decreasing serum diamine oxidase activity to decrease intestinal permeability.
3. 3. The use of claim 1, wherein the repair of the intestinal mucosal barrier comprises improving jejunum villus architecture and up-regulating expression of intestinal epithelial tight junction protein.
4. 4. The use according to claim 3, wherein the tight junction protein is selected from at least one of ZO-1, occludin and Claudin.
5. 5. The use according to claim 1, wherein the medicament is for the treatment of a disorder of intestinal flora characterized by a proportional imbalance of the phylum firmicutes and the phylum bacteroides.
6. 6. The use according to claim 5, wherein the medicament is for the treatment of intestinal microbiota micro-ecological disorders caused by reduced abundance of lactobacillus, ruminococcus or ileum.
7. 7. The use according to claim 1, wherein the medicament is for the treatment of intestinal tissue damage mediated by local inflammatory reactions and oxidative stress damage.
8. 8. A pharmaceutical composition for treating severe acute pancreatitis complicated with intestinal failure, characterized by comprising an effective amount of astaxanthin as an active ingredient, and being formulated as an enteric formulation for intestinal release.

Description

Application of astaxanthin in preparation of medicine for preventing and treating pancreatitis related intestinal dysfunction and repairing intestinal mucosa barrier Technical Field The invention relates to the technical field of biological medicines, in particular to application of astaxanthin in preparation of a medicine for preventing and treating severe acute pancreatitis related intestinal dysfunction, intestinal flora imbalance or repairing intestinal mucosa barrier. Background Severe acute pancreatitis (Severe Acute Pancreatitis, SAP) is a life threatening acute abdomen with pathological processes not limited to the pancreas locally, often accompanied by serious systemic complications. Intestinal dysfunction is one of the most common complications of SAP, and is manifested by damage to the intestinal mucosal barrier, increased intestinal permeability, dysbacteriosis and bacterial translocation, thereby exacerbating systemic inflammatory response and multiple organ failure, forming an "intestinal-pancreatic" vicious circle. Therefore, protecting the intestinal barrier function and maintaining the intestinal microecological stability are key links for treating SAP and improving prognosis. At present, the clinic treatment of SAP related intestinal dysfunction still lacks specific drugs, and mainly depends on symptomatic support treatment such as enteral nutrition support, intestinal rest, antibiotic prevention infection and the like. Although probiotics, prebiotics, etc. show some potential in regulating intestinal flora, their efficacy in critically ill patients is not yet stable and lacks direct evidence for intestinal barrier repair. Therefore, the development of a novel medicine which can effectively protect the intestinal mucosa barrier and systematically regulate the intestinal microenvironment has urgent clinical demands. Astaxanthin (Astaxanthin, AST) is a ketocarotenoid with very strong antioxidant and anti-inflammatory activity. Although there has been research focused on its role in the general inflammation model, there is no systematic report as to whether astaxanthin blocks the vicious circle of the "gut-pancreas" axis, in particular, whether it repairs the intestinal barrier by modulating specific gut flora and its metabolic characteristics, in the context of a specific high inflammatory storm of severe acute pancreatitis. Disclosure of Invention The invention aims to provide application of astaxanthin in preparation of medicines for preventing and treating severe acute pancreatitis related intestinal dysfunction, intestinal flora imbalance or repairing intestinal mucosa barrier. In a first aspect, the invention provides the use of astaxanthin in the manufacture of a medicament for the prevention of Severe Acute Pancreatitis (SAP) -related intestinal dysfunction, intestinal dysbacteriosis, or repair of the intestinal mucosal barrier. Preferably, the prevention and treatment of intestinal dysfunction is used to treat patients with severe acute pancreatitis with increased serum diamine oxidase (DAO) activity to reduce intestinal permeability. DAO is an enzyme present in the cytosol of intestinal mucosal epithelial cells, and elevated serum levels are a specific indicator of impaired intestinal barrier and increased permeability. Preferably, the repair of the intestinal mucosal barrier includes improving jejunal villus architecture (e.g., alleviating villus shedding, rupture, fusion), and up-regulating expression of intestinal epithelial tight junction proteins. The tight junction protein is selected from at least one of ZO-1, occludin and Claudin. Preferably, the medicament is for the treatment of a gut flora disorder characterized by a proportional imbalance of the phylum firmicutes (Bacillota) and the phylum bacteroides (Bacteroidota). Preferably, the medicament is for the treatment of intestinal microbiota micro-ecological disorders caused by reduced abundance of lactobacillus murine (Ligilactobacillus murinus), ruminococcus (Ruminococcus sp.) or ileum (Ileibacterium valens). The present inventors have found that astaxanthin, by enrichment of these key beneficial bacteria, is able to exert a barrier protective effect through the flora-host metabolic axis. Preferably, the medicament is for the treatment of intestinal tissue damage mediated by local inflammatory reactions and oxidative stress damage. The specific expression is that the IL-1 beta, IL-6 and TNF-alpha levels in intestinal tissues are reduced, the IL-10 level is improved, the ROS and MDA content is reduced, and the SOD and GSH-Px activities are improved. In a second aspect, the present invention provides a pharmaceutical composition for the treatment of severe acute pancreatitis complicated with intestinal failure, characterized in that it comprises an effective amount of astaxanthin as active ingredient and is formulated as an enteric formulation for intestinal release. Preferably, the enteric formulation is selected from ente