Banxia Xiexin decoction combined with 5‐ASA protects against CPT‐11‐induced intestinal dysfunction in rats via inhibiting TLR4/NF‐κB signaling pathway

Abstract

Abstract Background Banxia Xiexin decoction (BXD) can control irinotecan (CPT‐11)‐caused delayed diarrhea, but the corresponding mechanism remains undefined. Aims This paper aimed to uncover the mechanism of BXD in regulating CPT‐11‐caused delayed diarrhea. Materials & Methods Sprague‐Dawley (SD) rats were assigned into the control, model, BXD low‐dose (BXD‐L, 5 g/kg), BXD medium‐dose (BXD‐M, 10 g/kg), BXD high‐dose (BXD‐H, 15 g/kg), 5‐aminosalicylic acid (5‐ASA, 10 mL/kg), and BXD‐M + 5‐ASA groups. Rats were injected intraperitoneally with 150 mg/kg CPT‐11 at Day 4 and Day 5 to induce delayed diarrhea, and later treated with various doses (low, medium, and high) of BXD and 5‐ASA for 9 days, except for rats in control group. The body weight of rats was measured. The rat colon tissue injury, inflammatory cytokine levels, and the activation of toll‐like receptor 4/nuclear factor‐κB (TLR4/NF‐κB) signaling pathway were detected. Results BXD (5, 10, or 15 g/kg) or 5‐ASA (10 mL/kg) alleviated body weight loss and colon tissue injury, decreased levels of inflammatory cytokines, and inactivated TLR4/NF‐κB signaling pathway in CPT‐11‐induced model rats. BXD at 10 g/kg (the optimal concentration) could better treat CPT‐11‐induced intestinal dysfunction, as evidenced by the resulting approximately 50% reduction on injury score of model rats. Moreover, BXD‐M (10 g/kg) synergistic with 5‐ASA (10 mL/kg) further strengthened the inhibition on rat body weight loss, colon tissue injury, inflammatory cytokine levels, and TLR4/NF‐κB signaling pathway. Conclusion To sum up, BXD has a protective effect against CPT‐11‐induced intestinal dysfunction by inhibiting inflammation through inactivation TLR4/NF‐κB signaling pathway. In particular, the combined use of BXD and 5‐ASA holds great promise for treating CPT‐11‐induced delayed diarrhea.

Keywords

• Banxia Xiexin decoction
• colon tissue injury
• delayed diarrhea
• inflammation
• Irinotecan
• TLR4/NF‐κB signaling pathway