Study Of The Protective Effect And Mechanism Of Naringin On Inflammatory Bowel Disease In Mice

Peroxisome proliferator-activated receptor γ(PPARγ)is a very important member in the nuclear receptor superfamily.Previously studies have shown that anti-inflammatory role of PPARγ in experimental colitis models mainly through regulating several transcription factors such as nuclear factor-κB(NF-κB).Therefore,regulating PPARγ and PPARγ-related pathways for the treatment of IBD has a great prospect.IBD(Inflammatory bowel disease,IBD)is a kind of inflammatory bowel disease,chronic and easy recurrence.Human and animal infected are mainly manifested as abdominal pain,diarrhea,blood stool and so on.The disease not only poses a threat to the lives of humans or animals,but also affects people’s daily life and quality of life,and is likely to develop into colon cancer.Although we already have a certain understanding of IBD,its specific pathogenesis is not yet clear,and there is a lack of effective prevention and treatment drugs.With the in-depth research of IBD by scientists from various countries,there are currently a large number of drugs for the treatment of IBD,but these drugs can only be treated symptomatically,difficult to cure,and have toxic and side effects and are prone to drug resistance.This has a great negative impact on IBD patients.Therefore,exploring and screening natural candidate drugs with little side effects for the prevention and treatment of IBD is the hotspot and difficulty of current research.Naringin is a kind of food additives that extracted from the most abundant flavonoid content of grapefruit and citrus seeds.In addition,it has a lot of biological and pharmacological activities,such as anti-inflammatory and antioxidants.Therefore,this study intends to explore the effect of Naringin on the IBD mouse model and its potential underlying mechanism through the IBD mouse model induced by dextran sulfate sodium(DSS),to provide human and animal colitis prevention and treatment experimental basis.These results showed that Naringin can reduce the weight loss,disease activity index(DAI)and colon length shorten of mice.The pathological histology data showed a large number of inflammatory cells infiltrates the mucosa and submucosa.Goblet cells were lost,mucous membrane and connective tissue were injured;however,Naringin significantly reduced the colon tissue pathology change.These results suggest that Naringin can protect mice from DSS-induced IBD.Therefore,on this basis,we further studied the possible mechanism of Naringin on DSS-induced IBD in mice.The results showed that Naringin can play an anti-IBD role through up-regulating the expression of PPARγ,inhibiting the activation of NLRP3 inflammasome and down-regulating the activation of its downstream signaling pathway,thereby inhibiting the secretion of inflammatory cytokines TNF-α,IL-1β and IL-6.Naringin can also regulate the expression of intestinal tight junction protein(zo-1),and alleviate a series of pathological changes such as colon mucosal injury,goblet cell disappearance and connective tissue hyperplasia caused by DSS In order to further study whether the anti-inflammatory effect of Naringin is achieved by regulating PPARγ pathway,we conducted some experiments in vitro.We used PPARγ inhibitor GW9662 to treat RAW264.7 cells that stimulated by LPS.The results showed that,compared with the Naringin group,the secretion of TNF-α and the phosphorylation level of each protein in NF-κB pathway were significantly increased,and the expression of PPARγ was decreased after GW9662 treatment.These results suggested that,although GW9662 treatment can inhibit the effect of Naringin that up-regulated the expression of PPARγ.However,Naringin lost its function of activating PPARγ after GW9662 treament.Therefore,we believe that Naringin may exert its anti-inflammatory effect by regulating and activating the expression of PPARγ,and its specific regulatory mechanism needs to be further studied.The above results indicate that Naringin is likely to be a potential natural drug for the prevention of inflammatory bowel disease,and it may play an anti-inflammatory role by activating the expression of PPARγ,which provides a theoretical and experimental basis for the development of drugs for the prevention and treatment of colitis in humans and animals.