Objective: To investigate the effect of total alkaloids of Sophora alopecuroides (TASA) on dextran sulfate sodium (DSS)-induced colitis in mice.
Methods: Chronic experimental colitis was induced by administration of 4 cycles of 4% DSS. Fifty mice were randomly distributed into 4 groups (normal, DSS, DSS/high-dose TASA, and DSS/low-dose TASA groups) by a random number table with body weight stratification. Mice in the normal group (n=11) and DSS-induced colitis control group (n=15) received control treatment of 20 mL/kg distilled water; DSS plus TASA high- and low-dose groups (n=12 each) were treated with TASA solution (20 mL/kg) at the doses of 60 mg/kg and 30 mg/kg, respectively. The severity of colitis was assessed on the basis of clinical signs, colon length, and histology scores. Moreover, secretory immunoglobulin A (sIgA) and haptoglobin (HP) were analyzed by enzyme linked immunosorbent assay; intercellular adhesion molecule 1 (ICAM-1) and macrophage-migration inhibitory factor (MIF) gene expressions were analyzed by quantitative reverse transcriptase realtime polymerase chain reaction (qRT-PCR) using SYBA green I; and nuclear factor κ B (NF-κ B) expression and activation and p65 interaction with the promoter of ICAM-1 gene were assessed by Western blotting and chromatin immunoprecipitation assay.
Results: TASA administration significantly attenuated the damage and substantially reduced HP elevation and maintained the level of cecum sIgA. TASA inhibited the ICAM-1 gene expression and had no effect on MIF gene expression. Also, TASA was able to reduce phospho-I κ B α (p-I κ B α) protein expression; however, it had no effect on the activation of I κ B kinase α (IKK α) and inhibitor of NF-κ B α (I κ B α). Moreover, TASA inhibited the p65 recruitment to the ICAM-1 gene promoter.
Conclusions: TASA had a protective effect on DSS-induced colitis. Such effect may be associated with its inhibition of NF-κ B activation and blockade of NF-κ B-regulated transcription activation of proinflammatory mediator gene.