Ajugol attenuates renal injury in multiple myeloma by blocking LILRB4 signaling pathway to reduce PFKFB3 expression

Abstract

Motherwort exhibits a curative effect on kidney damage and its component, ajugol, also might improve kidney damage. Therefore, this study assesses the mechanism whereby ajugol alleviates renal injury in multiple myeloma. After establishment of animal model of multiple myeloma (n = 30), mice received treatment with low-dose and high-dose ajugol (n = 10, each group). And 10 healthy mice were taken as control group and 10 modeled mice were untreated (model group). Following treatment, the serum and spinal cord samples of the mice were collected, in which the levels of Cys-C, RBP, Cr, UN, CD4+, CD8+, and CD25+ were examined and the expression of LILRB4 and PFKFB3 proteins in myeloma tissue were detected. Compared with model group, the levels of serum Cys-c, RBP, Cr and UN in low-dose and high-dose groups decreased, but were still higher than those in control group (P <0.05). Of ajugol groups, the levels in high-dose group were lower (P <0.05). Importantly, the treatment of ajugol greatly alleviated lesions of myeloma tissue and reduced infiltration of inflammatory cells via lowering the levels of serum CD4+, CD8+, and CD25+. Besides, ajugol dose-dependently decreased LILRB4 and PFKFB3 expression in myeloma tissue samples. Ajugol, a bioactive component of motherwort, blocked the LILRB4 signaling and reduced PFKFB3 expression to inhibit the activity of immune cells and thereby alleviating renal injury in multiple myeloma. This is related to significant inhibition of multiple myeloma cell glycolysis and reduction of intracellular energy metabolism, indicating the anti-cancer potential of ajugol.