[Shenfu Injection regulates macrophage polarization via TLR4/NF-κB pathway to reduce inflammation in chronic heart failure].

This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF) and its effect on macrophage polarization. C57BL/6J mice were randomly assigned to the normal and model groups. The CHF model was established by intraperitoneal injection of isoproterenol(ISO, 7.5 mg·kg~(-1), 28 d). The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP). The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days. Cardiac function was evaluated using echocardiography. Hematoxylin-eosin(HE) staining was used to detect the pathomorphology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the values of serum NT-proBNP, interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), IL-10, and arginase 1(Arg-1). Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. Quantitative polymerase chain reaction(qPCR) and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway-related mRNA and protein expressions. Compared with the normal group, mice in the model group had lower values of left ventricular ejection fraction(LVEF) and left ventricular fractional shorte-ning(LVFS), higher values of left ventricular internal diastolic end-diastolic(LVIDd), left ventricular internal diastolic end-systolic(LVIDs), NT-proBNP, TNF-α, and IL-6(P<0.01); the number of macrophages increased in cardiac tissues(P<0.05), and the values of M1-F4/80~+CD86~+ were increased(P<0.01), while the values of M2-F4/80~+CD163~+ decreased(P<0.05); the mRNA and protein expressions of TLR4, myeloid differentiation factor 88(MyD88), IκB kinase α(IKKα), and NF-κB p65 in myocardial tissues were significantly elevated(P<0.05, P<0.01). Compared with the model group, mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF, LVFS, IL-10, and Arg-1 levels, and decreased LVIDd, LVIDs, NT-proBNP, TNF-α, and IL-6 levels(P<0.05, P<0.01); the cardiac F4/80~+CD11b~+(macrophage) and M1-F4/80~+ CD86~+ values were significantly down-regulated, while M2-F4/80~+CD163~+ values were increased(P<0.05, P<0.01); and the mRNA and protein expressions of TLR4, MyD88, IKKα, and NF-κB p65 in myocardial tissues were notably decreased(P<0.05, P<0.01). CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.

Effect of curcumin on glucose and lipid metabolism, FFAs and TNF-α in serum of type 2 diabetes mellitus rat models.

OBJECTIVE: To investigate how curcumin affects the glucose and lipid metabolism in type 2 diabetes mellitus (DM) rat models, and to explore its effect on the free fatty acid (FFA) and tumor necrosis factor α (TNF-α) in serum. METHODS: Successfully established type 2 DM rats were divided into three groups, i.e. the normal control group, model group and curcumin group, and received the medication for consecutive 8 weeks. Thereafter, we detected the level of fasting blood glucose (FBG), and the blood glucose at 30 min, 60 min and 120 min; besides, we also carried out the insulin tolerance tests to measure the levels of fasting serum insulin (FINS) and blood glucose at 40 min and 90 min; additionally, we also detected the levels of TC, TG, HDL-C, LDL-C, FFA and TNF-α in serum. The results were expected to discover the mechanism of curcumin in decreasing the blood glucose level in DM rats. RESULTS: Compared with the model group, AUCs of FBG, blood glucose at 30 min, 60 min and 120 min, and glucose were decreased in varying degrees in the curcumin group, and the differences had statistical significance (p < .05). After subcutaneous injection of insulin, we found that the blood glucose at 40 min and 90 min in the curcumin group was decreased, while AUC of glucose level was also decreased (p < .05 or .01). Eight weeks after medication, compared with the rats in the normal group, the levels of HDL-C, LDL-C, TC and TG in rats of the model group and the curcumin group were obviously increased (p < .05). In comparison with the model group, the level of LDL-C in rats of the curcumin group was also decreased significantly (p < .05). In comparison with the normal control group in the same period, we found that the content of FFAs and TNF-α in serum of rats of the model group were elevated significantly, and the differences had statistical significance (p < .05 or .01); the levels in the curcumin group were significantly decreased in comparison with the model group in the same period, and the difference had statistical significance (p < .05 or .01). CONCLUSION: Treatment with curcumin can significantly improve the metabolic disorder of glucose and lipid, enhance the sensitivity to the insulin, and ameliorate the resistance to insulin of the type II DM rats. Meanwhile, this treatment method can also significantly decrease the level of FFA and TNF-α in serum of type II DM rats. Thus, we inferred that the mechanism of curcumin to improve the insulin resistance might be correlated with the decreases of FFA and TNF-α in serum.