Antihypertensive Effects in Vitro and in Vivo of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Bovine Bone Gelatin Hydrolysate

Abstract

In this study, we investigated the antihypertensive effects in vitro and in vivo of novel angiotensin-converting enzyme inhibitory (ACEI) peptides purified and identified from bovine bone gelatin hydrolysate (BGH). Thirteen ACEI peptides were identified from BGH, and among which, RGL-(Hyp)-GL and RGM-(Hyp)-GF exhibited high ACE inhibition with IC50 values of 1.44 and 10.23 μM. Molecular docking predicted that RGM-(Hyp)-GF and ACE residues of Glu384, His513, and Lys511 formed hydrogen-bonding interactions at distances of 2.57, 2.99, and 2.42 + 3.0 Å. RGL-(Hyp)-GL formed hydrogen bonds with Lys511 and Tyr523 and generated hydrogen-bonding interactions with His387 and Glu411 in the zinc­(II) complexation motif at distances of 2.74 and 3.03 + 1.93 Å. The maximal decrements in systolic blood pressure in spontaneously hypertensive rats induced by one-time gavage of RGL-(Hyp)-GL and RGM-(Hyp)-GF at 30 mg/kg were 31.3 and 38.6 mmHg. RGL-(Hyp)-GL had higher enzyme degradation resistance than that of RGM-(Hyp)-GF in vitro incubation in rat plasma, and they were sequentially degraded into pentapeptides and tetrapeptides within 2 h. Our results indicate that BGH can serve as a nutritional candidate to control blood pressure.

In vivo anti‐hypertensive effect of peptides from egg white and its molecular mechanism with ACE

“…Notably, in vivo the QIGLF reached its maximum effect faster than RVPSL, implying that QIGLF might be absorbed faster than RVPSL. And previous study has shown that the SBP maximum lowering of LSGYGP, β‐casein LHLPLP, CMP and RGM was occurred at 3, 4, 4 and 6 h after administration, respectively (Quiros et al ., 2007; Miguel et al ., 2007b; Zhao et al ., 2019; Cao et al ., 2020). The appearance may be due to the different absorption and metabolism, or the different transport rates at the location of the operation (Li et al ., 2012).…”

“…The anti‐hypertensive effects of QIGLF and RVPSL were evaluated by measuring the changes of SBP and DBP in the SHRs using the tail–cuff method after administration (Cao et al ., 2020). Before the measurement, SHRs were preheated in an insulation bucket at 37‐39°C for 5 min to undertake that the rat’s tail artery pulsations were measurable.…”

Developments for Collagen Hydrolysate in Biological, Biochemical, and Biomedical Domains: A Comprehensive Review

“…Depression and hypertension are important medical impairments that are extensively investigated with collagen hydrolysate [ 41 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ]. Recently, a couple of efforts by the same group were presented on diminution of hypertension using novel collagen hydrolysate [ 41 , 149 ].…”

ACE-inhibitory peptides from Laminaria japonica and their potential anti-hypertensive mechanism

“…Angiotensin I-converting enzyme (ACE), a zinc protease, plays a crucial role in regulating blood pressure for its ability of converting angiotensin I to the potent vasoconstrictor angiotensin II in the renin-angiotensin system and the deactivation of the vasodilator bradykinin in the kallikrein-kinin system (Cao et al, 2020;Ko et al, 2012). The application of ACE inhibitors has been accepted as one of the major therapeutic approaches to reducing hypertension (Wijesekara & Kim, 2010).…”

“…Currently, the detection and identification of ACE inhibitors from foods has attracted increasing attention for safety concerns (Admassu et al, 2018;Ko et al, 2012). Anti-hypertensive peptides with strong ACE inhibitory activity have been reported to be derived from animals (Kocak et al, 2020), fruits (Memarpoor-Yazdi et al, 2020), vegetables (Patten et al, 2016), eumycetes (Amorim et al, 2019) and other marine sources (Pujiastuti et al, 2019). Besides, there have been various studies conducted on their activities (García-Mora et al, 2017;Majumder & Wu, 2015;Raji et al, 2020).…”