Qi-Huang decoction ameliorates renal injury in candidaemia via Dectin-1/NF-κB/IκBζ signaling pathway regulated by miR-32-5p.

Qi-Huang Decoction (QHD), a combined prescription of Buzhong Yiqi decoction and Dachengqi decoction, is used for gastrointestinal protection post-operation at present. Previously, we found that QHD could ameliorate Candida colitis through Dectin-1 associated pathway, but was rather weak against Candida albicans in vitro. This study explores the protection mechanism of QHD by which miR-32-5p mediated Dectin-1/NF-κB/IκBζ signaling pathway in candidaemia associated renal injury caused by C. albicans. Signaling pathways were screened by network pharmacology. A murine systemic candidiasis model was established to investigate the therapeutic effect of QHD at 10, 20 and 40 g/kg on candidaemia. The antifungal and anti-inflammatory activity of QHD drug-containing serum (QHD-DS) at 5 and 20 g/kg was monitored in RAW264.7 and MPC5 cells. Dectin-1 inhibitor laminarin (LAM), miR-32-5p mimic and inhibitor, NF-κB antagonist TPCA, and silenced NFKBIZ were employed to analyze the activation of Dectin-1/NF-κB/IκBζ signaling pathway in the protection of QHD against colonization of and inflammation caused by C. albicans. In addition, the antifungal potential of NFKBIZ in combination with miR-32-5p, Dectin-1 and NF-κB was also examined. The NF-κB pathway is most likely to participate in the treatment of QHD against candidaemia. QHD at 40 g/kg significantly prolonged survival rate, ameliorated severity of kidney injury, reduced tissue fungal burden, and neutralized renal inflammation in mice with candidaemia. Similarly, QHD-DS at 5 and 20 g/kg was effective to inhibit C. albicans growth and increased inflammation induced by fungal β-glucan in RAW264.7 and MPC5 cells. QHD deactivated Dectin-1/NF-κB signaling, but LAM abolished this protection. In contrast to downregulated miR-32-5p, overexpressed miR-32-5p assisted QHD-DS at 5 and 20 g/kg to improve candidaemia. NFKBIZ, miR-32-5p target gene, was positively correlated with Dectin-1 and NF-κB. Silenced NFKBIZ abandoned the antifungal and anti-inflammatory potentials of QHD by downregulating TNF-α and IL-1β. Furthermore, si-NFKBIZ could be synergistic with miR-32-5p inhibitor, LAM and TPCA to weaken the QHD-DS's anti-colonization of C. albicans. NFKBIZ, not NF-κB, might be the principle governor in renal inflammation and fungal propagation during candidaemia. QHD can ameliorate candidaemia associated renal inflammation via miR-32-5p mediated Dectin-1/NF-κB/IκBζ signaling pathway. QHD presents promising potential for clinical therapy of candidaemia.