| In recent years,high-fat diet has become an increasingly popular diet.It affects the function of the intestinal barrier,changes the permeability of the intestine,and allows endotoxins to enter the blood circulation,thereby increasing the risk of intestinal inflammation,and easily causing obesity.Related metabolic diseases seriously threaten people's health,and the use of drugs to treat inflammation often accompanies many side effects and causes body damage.Therefore,it is of great significance to find a natural way to reduce inflammation damage.As a plant that people are familiar with,pomegranate has a long history of development in our country,and it is widely planted and rich in yield.It is not only edible but also of high medicinal value.Pomegranate peel polyphenols are extremely abundant compounds in the pomegranate peel.Its anti-inflammatory properties have received widespread attention in recent years,but the effect of pomegranate peel polyphenols on intestinal tissues to alleviate metabolic inflammation caused by high-fat diets has not been studied.Therefore,this study first conducted in vivo experiments to establish a model of obese rats induced by high-fat diet.The pomegranate peel polyphenols extracted from this laboratory was used as a test substance to intervene.Determination of IL-6,TNF-?,IL-1? and Endotoxin levels,histological analysis of rat colon and expression of inflammatory related molecules p-p65/p65,p-JNK/JNK,and Bax in colon tissues,explored the amelioration effect of pomegranate peel polyphenols on the colon inflammatory injury caused by high-fat diet.Next,in order to further verify the effect of pomegranate peel polyphenols and analyze the components that play a key role in this study,in vitro cell experiments were performed to establish a model of Caco-2 cell inflammation induced by LPS.Pomegranate peel polyphenols,punicalagin and urolithin A pre-protected the cells.Through cell activity detection,the levels of cell tight junction proteins ZO-1 and Claudin-1 were determined.The inflammatory factor IL-6 secreted by the cells and the inflammatory mediators NO,PGE2 and inflammation in the cells were measured.The detection of inflammatory related molecules p65,Bax,pJNK/JNK,and the determination of ROS production in the cells,explored the molecular mechanism of pomegranate peel polyphenols to improve the inflammatory response and cell permeability of Caco-2 cells induced by LPS.The findings are as follows:(1)Pomegranate peel polyphenols have a certain reversal effect on the increase of inflammatory factor expression in serum caused by high-fat diet.Compared with the control group,the levels of IL-6 and TNF-? in the serum of rats fed a high-fat diet were significantly increased,and high-dose pomegranate peel polyphenols(300 mg/kg)could reverse the expression of IL-6.Low-dose pomegranate peel polyphenols(150 mg/kg)and high-dose pomegranate peel polyphenols can reverse the expression of TNF-?.In addition,the serum endotoxin concentration in rats fed in high-fat diet was almost twice that of rats fed in normal diet,and low-dose pomegranate peel polyphenols significantly inhibited its expression.Low-dose pomegranate peel polyphenols treatment also reduced the increase in EL-1? levels caused by high-fat diet.In addition,pomegranate peel polyphenols can improve chronic inflammation of colon tissues caused by high-fat diet.Compared with the high-fat group,the administration of pomegranate peel polyphenols effectively reduced the mRNA expression levels of IL-6,TNF-?,and IL-1?in colon tissues.Compared with the control group,the levels of p-p65/p65,p-JNK/JNK,and Bax in the high-fat group were significantly increased,and were inhibited by the treatment with pomegranate peel polyphenols.(2)Pomegranate peel polyphenols have a certain repair effect on colon tissue damage caused by high-fat diet in rats.H&E staining results showed that the colon tissue of the control group rats showed normal tissue structure,while that of the high-fat group rats showed obvious inflammatory cell infiltration,disordered arrangement of intestinal glands,thinning of muscle layers and appearance Tissue edema.After treatment with low-dose and high-dose pomegranate peel polyphenols,it showed less infiltration of inflammatory cells,regular arrangement of glands in the tissue,normal thickness of the colon muscle layer,and histological damage was improved to a certain extent.(3)Pomegranate peel polyphenols and its metabolically active substances can improve Caco-2 cell permeability enhancement caused by LPS.Compared with the control,LPS significantly reduced the protein expression of ZO-1.After treatment with pomegranate peel polyphenols,punicalagin and urolithin A,the protein expression level of ZO-1 was successfully increased.There was no significant difference in Claudin-1 protein expression.(4)Pomegranate peel polyphenols can reverse the inflammatory response of Caco-2 cells caused by LPS,and urolithin A has the most significant effect.Pomegranate peel polyphenols extract,punicalagin,and urolithin A all reduced the expression of IL-6,NO,and PGE2 caused by LPS,and also inhibited intracellular ROS production.In addition,treatment with 100 ?g/mL pomegranate peel polyphenols extract and urolithin A reduced LPS-induced enhanced expression of NF-?B protein p65.Urolithin A treatment also reduced Bax protein expression levels induced by LPS.And compared with the LPS group,the treatment with 100 pM punicalagin and urolithin A significantly reduced the pJNK/JNK protein expression level.In summary,pomegranate peel polyphenols can improve the inflammatory damage of the colon caused by high-fat diet to a certain extent,reduce the inflammation response and cell permeability of Caco-2 cells induced by LPS,and its metabolite urolithin A may be a key component of pomegranate peel polyphenols to exert intestinal physiological effects.This has laid a certain foundation for the development of pomegranate-related products and future research on the physiological effects of pomegranate extract. |
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