Lespedeza bicolor Turcz. Honey Prevents Inflammation Response and Inhibits Ferroptosis by Nrf2/HO-1 Pathway in DSS-Induced Human Caco-2 Cells

Abstract

Lespedeza bicolor Turcz. (L. bicolor) honey, a monofloral honey, has garnered increased attention due to its origin in the L. bicolor plant. A previous study has shown that L. bicolor honey can ameliorate inflammation. In this study, we aimed to investigate the effects of L. bicolor honey extract and its biomarker (Trifolin) on DSS-induced ulcerative colitis (UC). Our results demonstrated that L. bicolor honey extract and Trifolin significantly increased the expression levels of the tight junction cytokines Claudin-1 and ZO-1. Additionally, they decreased the pro-inflammatory factors TNF-α and IL-6 and enhanced the antioxidant factors NQO1 and GSTA1. Based on metabolomic analyses, L. bicolor honey extract and Trifolin regulated the progression of UC by inhibiting ferroptosis. Mechanistically, they improved the levels of SOD and iron load, increased the GSH/GSSG ratio, reduced MDA content and ROS release, and upregulated the Nrf2/HO-1 pathway, thereby inhibiting DSS-induced UC. Moreover, the expression levels of ferroptosis-related genes indicated that they decreased FTL, ACSL4, and PTGS2 while increasing SLC7A11 expression to resist ferroptosis. In conclusion, our study found that L. bicolor honey improves DSS-induced UC by inhibiting ferroptosis by activating the Nrf2/HO-1 pathway. These findings further elucidate the understanding of anti-inflammatory and antioxidant activities of L. bicolor honey.