Mechanism Analysis of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide from Isochrysis zhanjiangensis Microalgae for Suppressing Vascular Injury in Human Umbilical Vein Endothelial Cells

Abstract

Microalgae are primary producers with multiple nutrients in aquatic environments and mostly have applications in biological feed and fuel industry. There are few studies assessing the angiotensin-I-converting enzyme (ACE) inhibition potential of Isochrysis zhanjiangensis, other than its antioxidant potential. In this study, we evaluated a peptide from I. zhanjiangensis (PIZ, FEIHCC) and its vascular endothelial factors and mechanism in human umbilical vein endothelial cells (HUVEC). The results reveal that PIZ (IC 50 = 61.38 μM) acts against ACE in a non-competitive binding mode. In addition, PIZ inhibits angiotensin II (Ang II)-induced vascular factor secretion and expression by blocking inflammation and apoptosis through nuclear factor κB (NF-κB), nuclear erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), and the serine/threonine kinase (Akt) signal pathways. This study reveals that PIZ has potential to be developed as a therapeutic agent for hypertension and provides a new method of high-value utilization of I. zhanjiangensis.

Heptapeptide Isolated from Isochrysis zhanjiangensis Exhibited Anti-Photoaging Potential via MAPK/AP-1/MMP Pathway and Anti-Apoptosis in UVB-Irradiated HaCaT Cells

“…Cells grown to a suitable density were treated with different concentrations of DAPTMGY (20,50, and 100 μM) for 2 h, washed with phosphate-buffered saline (PBS), and exposed to UVB light using a Philips PL-S 9W/01 source (peak emission at 311 nm; Royal Dutch Philips Electronics Ltd., Holland). In this study, 40 mJ/cm 2 was selected as the radiation dose.…”

“…For example, peptides isolated from I. zhanjiangensis exhibited antioxidant effect [19]. Chen et al found that I. zhanjiangensis can inhibit angiotensin converting enzyme activity, thus exhibiting antihypertensive properties [20]. Howev this research is neither extensive nor comprehensive; thus, there is a lack of accumula results.…”

Bioprospecting of microalgae metabolites against cytokine storm syndrome during COVID-19

“…In a study conducted by Chen et al [ 25 ], a novel peptide (amino acid sequence: Phe-Glu-Ile-His-Cys-Cys; molecular weight 750.28 Da) recovered from Isochrysis zhanjiangenesis was shown to possess the ability to block angiotensin-I-converting enzyme (ACE) via a mixed non-competitive mode [ 25 ]. The RAS signalling system maintains homeostasis of the vascular functions and is primarily involved in regulation of blood pressure, vascular tone and blood volume control [ 26 ].…”

“…The resultant endothelial dysfunction and ARDS is a direct result of the infection and aberrant RAS signalling which contributes to amplified IL-6 production [ 2 ]. Due to the ability of SARS-CoV-2 to use ACE2 as sites of cellular entry, there have been calls to repurpose ACE inhibitor drugs to mediate cytokine storms in COVID-19 patients [ 2 , 26 ] and sits on the same page as the purified peptide by Chen et al [ 25 ]. Pro-inflammatory responses elicited by Ang-II include recruitment of inflammatory leukocytes and adhesion molecules that have been shown to increase expression of cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways [ 25 ] (Fig.…”

“…Due to difficulty in targeting PLA 2 enzymes [ 40 ], COX-2, a key enzyme in mediating pro-inflammatory PGE 2 has been a preferred target to counter AA products [ 40 ]. Metabolites from microalgae with COX-2 inhibiting ability include oxylipins [ 32 ], peptides [ 25 ], sterols [ 41 ], carotenoids [ 31 ] and lipids [ 42 ] from several groups of microalgae. Due to the fact that PGE2 and leukotriene B4 (LTB4) promotes “leaky” vascular endothelium, the AA pathway has been suggested to be a possible therapeutic target in SARS-CoV-2-induced inflammation by reducing inflammation caused by the endothelium compromise thus reducing migration of leukocytes to site of infection [ 43 ].…”