METHODS: Geraniin (95% purity) was extracted and purified from rambutan rind. Two groups of male Sprague-Dawley rats were fed with 60% high-fat diet and standard rat chow, respectively, for 12 weeks. High-fat diet-treated rats were then administered geraniin at different doses. Body weight, blood pressure and blood glucose readings were measured. At the end of treatment, blood was collected for analysis of glycated haemoglobin A1c (HbA1c), insulin, advanced glycation end-product (AGE) levels, renin, aldosterone and electrolytes.
RESULTS: Within the first week of treatment, even the lowest dose of geraniin caused a significant reduction in blood pressure, which was comparable to control diet-treated rats. There were no changes in serum electrolytes, renin or aldosterone. Similarly, there was a significant reduction in serum insulin, insulin resistance and AGE levels at the lowest dose. However, there was no significant decrease in fasting blood glucose or HbA1c. The effects of decreasing insulin, insulin resistance and AGEs were observed only at the lower doses, unlike the results observed for blood pressure reduction.
CONCLUSION: Geraniin at lower doses improved blood pressure and other metabolic parameters. Secondary metabolites of geraniin, associated with antihypertensive activity, are relatively different to those involved in inhibiting AGE formation and increasing insulin sensitivity. The secondary metabolites of geraniin may be individually responsible for the bioactivities demonstrated.
METHOD: Literature search was performed within the PubMed, ScienceDirect.com and Google Scholar.
RESULTS: The presence of proline at the C-terminal tripeptide of ACE inhibitor can competitively inhibit the ACE activity. The effects of other amino acids are less studied leading to difficulties in predicting potent peptide sequences. The broad specificity of the enzyme may be due to the dual active sites observed on the somatic ACE. The inhibitors may not necessarily competitively inhibit the enzyme which explains why some reported inhibitors do not have the common ACE inhibitor characteristics. Finally, the in vivo assay has to be carried out before the peptides as the antihypertensive agents can be claimed. The peptides must be absorbed into circulation without being degraded, which will affect their bioavailability and potency. Thus, peptides with strong in vitro IC50 values do not necessarily have the same effect in vivo and vice versa.
CONCLUSION: The relationship between peptide amino acid sequence and inhibitory activity, in vivo studies of the active peptides and bioavailability must be studied before the peptides as antihypertensive agents can be claimed.
METHODS: Sodium nitrite (50mg/L) was given to angiotensin II-infused hypertensive C57BL/6J (eight to ten weeks old) mice for two weeks in the drinking water. Arterial systolic blood pressure was measured using the tail-cuff method. Vascular responsiveness of isolated aortae and renal arteries was studied in wire myographs. The level of nitrite in the plasma and the cyclic guanosine monophosphate (cGMP) content in the arterial wall were determined using commercially available kits. The production of reactive oxygen species (ROS) and the presence of proteins (nitrotyrosine, NOx-2 and NOx-4) involved in ROS generation were evaluated with dihydroethidium (DHE) fluorescence and by Western blotting, respectively.
RESULTS: Chronic administration of sodium nitrite for two weeks to mice with angiotensin II-induced hypertension decreased systolic arterial blood pressure, reversed endothelial dysfunction, increased plasma nitrite level as well as vascular cGMP content. In addition, sodium nitrite treatment also decreased the elevated nitrotyrosine and NOx-4 protein level in angiotensin II-infused hypertensive mice.
CONCLUSIONS: The present study demonstrates that chronic treatment of hypertensive mice with sodium nitrite improves impaired endothelium function in conduit and resistance vessels in addition to its antihypertensive effect, partly through inhibition of ROS production.