Banca de DEFESA: GABRIELLY HILÁRIO DA SILVA

ANTIHYPERTENSIVE PEPTIDES EXTRACTED FROM CYANOBACTERIA Arthrospira platensis

cyanobacteria, enzymatic hydrolysis, inhibition kinetics, ACE inhibitors,
hypertension, meta-analysis, kidney diseases.

Hypertension is a silent disease with etiology related to genetic, lifestyle, and environmental
factors; and it can lead to the development of cardiovascular diseases. Some pharmacological
treatments are commonly used in clinical practice, including the use of ACE inhibitors.
Although they exhibit positive blood pressure lowering responses, chronic patients have
several side effects. Natural alternatives that mitigate side effects and improve the quality of
life of patients with chronic use of antihypertensive drugs are the target of this investigation.
The cyanobacterium Arthrospira (Spirulina) platensis has been highlighted for producing
different bioactives of biotechnological importance applied to health, such as peptides with
antihypertensive activity. The objective of this study was to produce, extract and evaluate the
angiotensin-I converting enzyme (ACE) inhibitory activity of peptides obtained from A.
platensis biomass after gastrointestinal digestion (DGI) process in vitro. The cyanobacterium
was grown in autotrophic condition and the cell biomass subjected to DGI in vitro under
simulated physiological conditions with the enzymes pepsin and pancreatin sequentially. The
supernatant was then ultrafiltered with 3 and 10 KDa cut-off membranes, and the fractions
were: AP-I: >10KDa, AP-II: 3-10KDa and AP-III < 3KDa. The fraction with the highest
iECA activity was purified by FPLC-Superdex G-75 and SOURCE™ RPC, respectively, and
the peaks obtained were determined for peptide concentration and iECA activity. All
ultrafiltered fractions exhibited high ACE inhibitory activity, in which AP-III obtained the
highest degree of inhibition of 90.43±0.89% and IC50 = 0.001 mg/mL, The AP-III fraction
was subjected to purification by AKTA Superdex-G75 system obtaining four peaks (FS-I, II,
III and IV). These were reapplied on a reverse phase FPLC column generating six peaks (Fr-I,
II. III. IV, V). In addition, we performed a systematic review and meta-analysis to verify the
nephroprotective response of using Spirulina (Arthrospira) or C-phycocyanin in the context
of renal diseases in preclinical models. Treatment with Spiriluna (Arhrospira) or C-ficocyanin
presented an improvement in serum concentrations (mg/dL) of the four biomarkers of renal
function analyzed: creatinine, uric acid, urea, and proteinuria. There was also a decrease in
systolic blood pressure levels in the context of hypertension. These results corroborate the
potential use of these peptides in the formulation of antihypertensive drugs or nutraceutical
foods, as well as suggest further investigations on the use of Spirulina for the treatment of
renal diseases.