Combination of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos improves cardiac function of diabetic cardiomyopathy mice by regulating the unfolded protein response signaling pathway

Diabetic cardiomyopathy (DCM) is a unique clinical entity elicited by diabetes independent of other cardiovascular risk factors, of which the pathological mechanisms and treatment strategies remain largely undefined. This study aimed to clarify the role of unfolded protein response (UPR) signaling pathway in the pathogenesis of DCM, and to explore the effect of aqueous extract of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos (DH) on DCM mice. Cardiac function of DCM mice was evaluated by echocardiography, and lipid profile of left ventricular was analyzed by untargeted lipidomics. The results showed that DH significantly improved the diabetic symptoms, cardiac dyslipidemia, and systolic dysfunction of DCM mice. UPR signaling pathway was significantly down-regulated in the left ventricular of DCM mice. DH significantly up-regulated the transcriptions of key transducers in UPR signaling pathway. Conditional knockout of Xbp1 in cardiomyocyte (a key regulator in UPR signaling pathway) eliminated the protective effect of DH on cardiac systolic function of DCM mice, which suggested that UPR signaling pathway, especially the Xbp1, was required for DH protection against DCM. In conclusion, DH improved cardiac function of DCM mice, and this effect was dependent on its regulation of UPR signaling pathway.