Transepithelial transport across Caco-2 cell monolayers of angiotensin converting enzyme (ACE) inhibitory peptides derived from simulated in vitro gastrointestinal digestion of cooked chicken muscles

Sangsawad, Papungkorn; Roytrakul, Sittiruk; Choowongkomon, Kiattawee; Kitts, David D.; Chen, Xiumin; Meng, Guangtao; Li‐Chan, Eunice C.Y.; Yongsawatdigul, Jirawat

doi:10.1016/j.foodchem.2018.01.047

Cited by 48 publications

(23 citation statements)

References 36 publications

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“…Caco‐2 cells monolayers, which can simulate the structure and functions of human intestinal epithelium in vitro , are widely accepted as a potential model membrane in investigating and predicting the intestinal permeability and transport of various bioactive peptides . To exert their bioactivity in vivo , peptides must be absorbed and then reach target organs in an intact form.…”

Section: Resultsmentioning

confidence: 99%

“…In vitro gastrointestinal digestion was simulated and conducted according to the method described by Xie et al ., with a slight modification. The transepithelial transport of GP‐12 across Caco‐2 cell monolayers was conducted as described in previous studies . To determine which transport pathway was involved in the transepithelial transport of GP‐12 through the intestinal epithelium, Caco‐2 cell monolayers were preincubated for 0.5 h before transport experiment with a range of inhibitors (wortmannin, cytochalasin D and Gly‐Sar).…”

Section: Methodsmentioning

confidence: 99%

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Yak (Bos grunniens) bones collagen‐derived peptides stimulate osteoblastic proliferation and differentiation via the activation of Wnt/β‐catenin signaling pathway

Zhang

Zhu

et al. 2020

J Sci Food Agric

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BACKGROUND As the world's population is transitioning gradually to an ageing stage, the incidence of osteoporosis is increasing annually. Yak bone is one of the major components of Tibetan medicine and it has mainly been associated with an improvement in bone health, for example against osteoporosis. However, the functional bioactive ingredients and the underlying mechanisms are still unclear. RESULTS Sequential purification of yak‐bone hydrolysates was achieved by ultrafiltration, size exclusion chromatography, and semi‐preparative reverse‐phase high‐performance liquid chromatography. After this, 35 novel peptides were identified by mass spectrometry analysis, of which peptide GPAGPPGPIGNV (GP‐12) displayed the highest osteoblast proliferation‐promoting activity, with an increase of 42.7% in cell growth. An in vitro stability study demonstrated that GP‐12 was digested into smaller peptides (GP‐9, GV‐9, AV‐10 and GP‐11) after simulated gastrointestinal digestion and absorption (Caco‐2 cell monolayers) experiments. However, some of them still can be absorbed intact through the (Caco‐2 cell monolayers by a paracellular route (Papp: 5.36 ± 0.34 cm s−1). Flow cytometry results indicated that GP‐12 enhanced osteoblastic proliferation by inducing the alteration of the cell‐cycle progression both from the G0/G1 to the S phase and from the S to the G2/M phase. Quantitative real‐time polymerase chain reaction (PCR) and western blot results revealed that GP‐12 induced osteoblastic proliferation and differentiation in a dose–response manner through the activation of a Wnt/β‐catenin signaling pathway. CONCLUSION These findings highlighted that such peptides hold the promise of discovering candidates for functional and health‐promoting foods, which could be potentially used for the treatment of osteoporosis. © 2020 Society of Chemical Industry

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Yak (Bos grunniens) bones collagen‐derived peptides stimulate osteoblastic proliferation and differentiation via the activation of Wnt/β‐catenin signaling pathway

Zhang

Zhu

et al. 2020

J Sci Food Agric

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“…Furthermore, the number of patients suffering from hypertension continues to grow [2]. Angiotensin-converting enzyme (ACE) plays a critical role in blood pressure control systems (renin-angiotensin system) as it converts angiotensin I into angiotensin II, leading to the development of hypertension [3,4]. Therefore, it is quite essential to study the inhibition of ACE in order to prevent and manage hypertension.…”

Section: Introductionmentioning

confidence: 99%

“…ACE-inhibitory peptides, which are safer than synthetic ACE inhibitors, have been shown to be useful as antihypertensive drugs [10]. Furthermore, they are found in many food protein sources [4,11,12], including sea cucumber ( Acaudina molpadioidea ). The sea cucumber is a particularly good source of bioactive peptides and is rich in proteins that result in high yields of peptides [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…A number of structure–activity relationship studies have showed that peptides, such as APP [4], KPLL [20] and VYPFPGPIPNSLPQNIPP [21], exhibit high ACE-inhibitory activity, which suggests the importance of proline in controlling the ACE-inhibitory activity. ACE-inhibitory activity could be increased from 27.8% to 76.4% by adding proline to casein hydrolysates [11].…”

Section: Introductionmentioning

confidence: 99%

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Novel Natural Angiotensin Converting Enzyme (ACE)-Inhibitory Peptides Derived from Sea Cucumber-Modified Hydrolysates by Adding Exogenous Proline and a Study of Their Structure–Activity Relationship

Liu

Zhao

et al. 2018

Marine Drugs

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Natural angiotensin converting enzyme (ACE)-inhibitory peptides, which are derived from marine products, are useful as antihypertensive drugs. Nevertheless, the activities of these natural peptides are relatively low, which limits their applications. The aim of this study was to prepare efficient ACE-inhibitory peptides from sea cucumber-modified hydrolysates by adding exogenous proline according to a facile plastein reaction. When 40% proline (w/w, proline/free amino groups) was added, the modified hydrolysates exhibited higher ACE-inhibitory activity than the original hydrolysates. Among the modified hydrolysates, two novel efficient ACE-inhibitory peptides, which are namely PNVA and PNLG, were purified and identified by a sequential approach combining a sephadex G-15 gel column, reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), before we conducted confirmatory studies with synthetic peptides. The ACE-inhibitory activity assay showed that PNVA and PNLG exhibited lower IC50 values of 8.18 ± 0.24 and 13.16 ± 0.39 μM than their corresponding truncated analogs (NVA and NLG), respectively. Molecular docking showed that PNVA and PNLG formed a larger number of hydrogen bonds with ACE than NVA and NLG, while the proline at the N-terminal of peptides can affect the orientation of the binding site of ACE. The method developed in this study may potentially be applied to prepare efficient ACE-inhibitory peptides, which may play a key role in hypertension management.

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Current genetic engineering strategies for the production of antihypertensive ACEI peptides

Gomes

Ferreira

Carvalho

et al. 2020

Biotech & Bioengineering

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Hypertension is a major and highly prevalent risk factor for various diseases. Among the most frequently prescribed antihypertensive first‐line drugs are synthetic angiotensin I‐converting enzyme inhibitors (ACEI). However, since their use in hypertension therapy has been linked to various side effects, interest in the application of food‐derived ACEI peptides (ACEIp) as antihypertensive agents is rapidly growing. Although promising, the industrial production of ACEIp through conventional methods such as chemical synthesis or enzymatic hydrolysis of food proteins has been proven troublesome. We here provide an overview of current antihypertensive therapeutics, focusing on ACEI, and illustrate how biotechnology and bioengineering can overcome the limitations of ACEIp large‐scale production. Latest advances in ACEIp research and current genetic engineering‐based strategies for heterologous production of ACEIp (and precursors) are also presented. Cloning approaches include tandem repeats of single ACEIp, ACEIp fusion to proteins/polypeptides, joining multivariate ACEIp into bioactive polypeptides, and producing ACEIp‐containing modified plant storage proteins. Although bacteria have been privileged ACEIp heterologous hosts, particularly when testing for new genetic engineering strategies, plants and microalgae‐based platforms are now emerging. Besides being generally safer, cost‐effective and scalable, these “pharming” platforms can perform therelevant posttranslational modifications and produce (and eventually deliver) biologically active protein/peptide‐based antihypertensive medicines.

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Transepithelial transport across Caco-2 cell monolayers of angiotensin converting enzyme (ACE) inhibitory peptides derived from simulated in vitro gastrointestinal digestion of cooked chicken muscles

Cited by 48 publications

References 36 publications

Yak (Bos grunniens) bones collagen‐derived peptides stimulate osteoblastic proliferation and differentiation via the activation of Wnt/β‐catenin signaling pathway

Yak (Bos grunniens) bones collagen‐derived peptides stimulate osteoblastic proliferation and differentiation via the activation of Wnt/β‐catenin signaling pathway

Novel Natural Angiotensin Converting Enzyme (ACE)-Inhibitory Peptides Derived from Sea Cucumber-Modified Hydrolysates by Adding Exogenous Proline and a Study of Their Structure–Activity Relationship

Current genetic engineering strategies for the production of antihypertensive ACEI peptides

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