Protective Effects of Naringenin on the Inflammatory Damage and Blood Hypercoagulability Induced in Mice with TNBS-Induced Ulcerative Colitis
Objective:To investigate the protective effects of Naringenin,an active ingredient of Fructus Aurantii Immaturus,on the inflammatory damage and blood hypercoagulability of ulcerative colitis(UC)induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS)in mice.Methods:Sixty male Kunming mice were randomly divided into normal control group,model control group,naringenin groups at doses of 60,40,and 20 mg/kg,and salazine sulfasopyridine group(500 mg/kg).All groups were pre-administered for 7 days,and on the 7th day of the experiment,mice were subjected to fasting without water deprivation for 24 h.Except for the normal control group,the other 5 groups were given TNBS(100 mg/kg)mixed with 50％ethanol in equal volume for colonic instillation to induce colitis.After modeling,the mice were given TNBS for 3 days.At the end of the experiment,blood samples were collected from the orbital sinus of mice to detect the bleeding time(BT),clotting time(CT),and hemorheology.HE staining was conducted to observe the pathological changes in colon tissue.ELISA was performed to deter-mine the contents of tissue factor(TF)and interleukin-6(IL-6)in the serum as well as the levels of nuclear factor kappa-B(NF-κB)and inhibitor of kappa B protein kinase(IKKα)in mouse colon tissue.The expressions of vascular endothelial growth factor endothelial growth factor A(VEGFA)and hypoxia-inducible factors α(HIF-1α)in the colon were detected by immunofluorescence and Western Blot.Results:Compared with the normal control group,mice in the UC model control group exhibited serious pathological damage in colon tissue,as well as significantly increased(P＜0.001)BT,CT and the whole blood viscosity,plasma viscosity,and hematocrit at high shear(200/s),medium shear(50/s),and low shear(10/s)rates.Moreover,the levels of TF and IL-6 in serum,the contents of NF-κB and IKKα in colon tissue and the expressions of VEGFA and HIF-1α were significantly increased in UC mice(P＜0.01).Compared with model control group,mice of the naringenin groups at various doses showed a significant improvement.The BT and CT of mice were significantly shortened(P＜0.05),and whole blood viscosity,plasma viscosity and hematocrit were significantly decreased(P＜0.01).The serum contents of TF and IL-6 and NF-κB and IKKα in colon tissue and the expressions of VEGFA and HIF-1α were significantly decreased(P＜0.05).Conclusion:Naringenin has a good therapeutic effect on UC mice,and its mechanism may be related to the alleviation of inflammatory reaction and improvement of hyperco-agulability.
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