Effect of liraglutide on blood pressure: a meta-analysis of liraglutide randomized controlled trials.

BACKGROUND: Several clinical trials have studied the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycometabolism and cardiovascular risk factors since they were identified. Because of their cardiovascular benefits and efficacy in lowering glucose, GLP-1RAs are becoming increasingly important in clinical therapy for patients with or without pathoglycaemia. The aim of this study was to assess the effect of the GLP-1RA liraglutide on blood pressure based on randomised controlled trials (RCTs). METHODS: We searched PubMed for RCTs published from 2009 to 2018 comparing the effect of liraglutide on blood pressure with that of placebo in individuals with or without pathoglycaemia. RCTs in humans that included data describing blood pressure changes from baseline to the end of the trial were selected for inclusion in the meta-analysis. RESULTS: A total of 18 RCTs that enrolled 7616 individuals in the liraglutide group and 6046 individuals in the control group were included in this meta-analysis. Compared with placebo, liraglutide reduced systolic blood pressure (SBP) by 3.18 mmHg (95% CI -4.32, - 2.05), P < 0.00001, but had no significant effect on diastolic blood pressure (DBP). Subgroup analysis showed that the degree of reduction in SBP was associated with the dose of liraglutide but that significance disappeared when the intervention lasted over 1 year. Liraglutide 3.0 mg/d significantly reduced DBP by 1.46 mmHg (95% CI -2.61, 0.32), P = 0.01, but liraglutide 1.8 mg/d slightly increased DBP by 0.47 mmHg (95% CI 0.11, 0.83), P = 0.01, compared with placebo. CONCLUSIONS: This meta-analysis demonstrated that liraglutide significantly reduced SBP in individuals with or without pathoglycaemia compared with placebo, but the difference was no longer significant when the intervention lasted over 1 year. Moreover, the effect of liraglutide on blood pressure is associated with the dose. This finding may provide additional evidence for cardiovascular protection.

Anthraquinone G503 induces apoptosis in gastric cancer cells through the mitochondrial pathway.

G503 is an anthraquinone compound isolated from the secondary metabolites of a mangrove endophytic fungus from the South China Sea. The present study elucidates the anti-tumor activity and the underlying mechanism of G503. Cell viability assay performed in nine cancer cell lines and two normal cell lines demonstrated that the gastric cancer cell line SGC7901 is the most G503-sensitive cancer cells. G503 induced SGC7901 cell death via apoptosis. G503 exposure activated caspases-3, -8 and -9. Pretreatment with the pan-caspase inhibitor Z-VAD-FMK and caspase-9 inhibitor Z-LEHD-FMK, but not caspase-8 inbibitor Z-IETD-FMK, attenuated the effect of G503. These results suggested that the intrinsic mitochondrial apoptosis pathway, rather than the extrinsic pathway, was involved in G503-induced apoptosis. Furthermore, G503 increased the ratio of Bax to Bcl-2 in the mitochondria and decreased the ratio in the cytosol. G503 treatment resulted in mitochondrial depolarization, cytochrome c release and the subsequent cleavage of caspase -9 and -3. Moreover, it is reported that the endoplasmic reticulum apoptosis pathway may also be activated by G503 by inducing capase-4 cleavage. In consideration of the lower 50% inhibitory concentration for gastric cancer cells, G503 may serve as a promising candidate for gastric cancer chemotherapy.