摘要
Background:Baicalein has been shown to have anti-inflammatory and anti-tumor activities.However,the mechanisms underlying its anti-inflammatory effect on colitis remain unclear.Methods:A dextran sodium sulfate(DSS)-induced model of acute colitis was established in BALB/c mice(6-8 weeks old,weighing 18-22 g).Six groups of mice received:(1)water for 10 days(control),n=6;(2)DSS 4%solution in the drinking water for 7 days,followed by normal water for 3 days,n=7;(3),(4),and(5)as for group 2 plus baicalein(10,20,40 mg/kg)administered once daily starting on day 1,n=6;and(6)as for(2)plus 5-aminosalicylic acid(50 mg/kg)administered once daily starting on day 1,n=6.Body weights,stool consistency,and hematochezia were recorded,and the severity of colitis was evaluated using a disease activity index.On day 11,the mice were euthanized,and organs and blood were collected for analysis.Serum inflammatory factors were detected by enzyme-linked immunosorbent assay;CD11b-positive cells were analyzed by immunofluorescence microscopy;expression of retinoic-acid-receptor-related orphan nuclear receptor gamma,sphingosine kinase 1(SPHK1),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)was detected by immunohistochemistry;and expression of nucleotide-binding oligomerization domain 2(NOD2),SPHK1,sphingosine 1-phosphate receptor 1(S1PR1),total STAT3,and p-STAT3 were detected by western blotting analysis.Inter-group differences were compared using Student’s t test.Results:Baicalein treatment dose-dependently reduced DSS-induced weight loss(P<0.01 or P<0.05),splenomegaly(P<0.01),and colonic damage,as reflected by amelioration of diarrhea,rectal bleeding,and colonic ulceration,congestion,edema(shown as colon length,P<0.05 or P<0.01),and inflammatory cell infiltration.Baicalein also significantly decreased the levels of inflammatory mediators in the serum(P<0.01)and colon,and significantly inhibited expression of NOD2 SPHK1,S1PR1,and p-STAT3 in the colon(P<0.05).Conclusions:Baicalein treatment ameliorated coliti
基金
This work was supported by the grants from the National Natural Science Foundation of China(Nos.81603143,21807041)
Shandong Medical and Health Science and Technology Development Project(Nos.2017WS646,2017WS653)
Teachers'Research Support Fund of Jining Medical University(No.JYFC2018KJ037)
National Natural Science Foundation Breeding Programs of Jining Medical University(No.JYP201708).
