In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction
Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases. In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by P...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2025.1528184/full |
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| author | Shuzhi Zhang Jingjing Guo Shikun Suo Li Ju Zhaoqiang Jiang Pingshuan Dong Yanli Wang Yali Dang Laijing Du |
| author_facet | Shuzhi Zhang Jingjing Guo Shikun Suo Li Ju Zhaoqiang Jiang Pingshuan Dong Yanli Wang Yali Dang Laijing Du |
| author_sort | Shuzhi Zhang |
| collection | DOAJ |
| description | Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases. In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by Peptideomics and molecular docking. Subsequently, the mechanisms were verified using a high glucose-induced vascular smooth muscle cells (VSMCs) dysfunction model. Results showed that ACEI activity of broccoli crude peptide increased by 70.73 ± 1.42% after digestion. The enzymatic hydrolysates of crude broccoli peptides before and after digestion were detected by HPLC. The digested crude peptides were highly stable (with a stability level > 90%) in the intestine and possessed a strong absorptive potential. Five peptides with high stability and strong permeability were first identified, including HLEVR, LTEVR, LEHGF, HLVNK, and LLDGR, which exhibited high activity with IC50 values of 3.19 ± 0.23 mM, 17.07 ± 1.37 mM, 0.64 ± 0.02 mM, 0.06 ± 0.01 mM, and 2.81 ± 0.12 mM, respectively. When the VSMCs model was exposed to Ang II, the expressions of PCNA, MMP2, and Bcl2 were increased, while the expression of BAX was inhibited. When the VSMCs was exposed to high glucose (HG), the Ang II concentration significantly increased. This indicates that HG elevated Ang II levels. Finally, five peptides significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK and p38 MAPK phosphorylation. Notably, in exploring VSMCs dysfunction on a high glucose-induced model, ACEI peptides resulted in down-regulation of ACE and up-regulation of ACE2 expression. Therefore, it can be further referenced for the functional food against hypertension and cardiovascular diseases. |
| format | Article |
| id | doaj-art-2fc586e97cef41148f44c24844b624bb |
| institution | Kabale University |
| issn | 2296-861X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Nutrition |
| spelling | doaj-art-2fc586e97cef41148f44c24844b624bb2025-01-27T05:14:40ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-01-011210.3389/fnut.2025.15281841528184In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunctionShuzhi Zhang0Jingjing Guo1Shikun Suo2Li Ju3Zhaoqiang Jiang4Pingshuan Dong5Yanli Wang6Yali Dang7Laijing Du8School of Phamacy, Hangzhou Medical College, Hangzhou, ChinaLuoyang Key Laboratory of Cardiovascular Science, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, ChinaCollege of Food Science and Engineering, Ningbo University, Ningbo, ChinaSchool of Phamacy, Hangzhou Medical College, Hangzhou, ChinaSchool of Phamacy, Hangzhou Medical College, Hangzhou, ChinaHenan Provincial Key Laboratory of Cardiovascular Disease Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, ChinaCollege of Food Science and Engineering, Ningbo University, Ningbo, ChinaCollege of Food Science and Engineering, Ningbo University, Ningbo, ChinaLuoyang Key Laboratory of Cardiovascular Science, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, ChinaMany natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases. In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by Peptideomics and molecular docking. Subsequently, the mechanisms were verified using a high glucose-induced vascular smooth muscle cells (VSMCs) dysfunction model. Results showed that ACEI activity of broccoli crude peptide increased by 70.73 ± 1.42% after digestion. The enzymatic hydrolysates of crude broccoli peptides before and after digestion were detected by HPLC. The digested crude peptides were highly stable (with a stability level > 90%) in the intestine and possessed a strong absorptive potential. Five peptides with high stability and strong permeability were first identified, including HLEVR, LTEVR, LEHGF, HLVNK, and LLDGR, which exhibited high activity with IC50 values of 3.19 ± 0.23 mM, 17.07 ± 1.37 mM, 0.64 ± 0.02 mM, 0.06 ± 0.01 mM, and 2.81 ± 0.12 mM, respectively. When the VSMCs model was exposed to Ang II, the expressions of PCNA, MMP2, and Bcl2 were increased, while the expression of BAX was inhibited. When the VSMCs was exposed to high glucose (HG), the Ang II concentration significantly increased. This indicates that HG elevated Ang II levels. Finally, five peptides significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK and p38 MAPK phosphorylation. Notably, in exploring VSMCs dysfunction on a high glucose-induced model, ACEI peptides resulted in down-regulation of ACE and up-regulation of ACE2 expression. Therefore, it can be further referenced for the functional food against hypertension and cardiovascular diseases.https://www.frontiersin.org/articles/10.3389/fnut.2025.1528184/fullgastrointestinal digestion simulationACEI peptidesbroccoliVSMCsAng IIACE2 |
| spellingShingle | Shuzhi Zhang Jingjing Guo Shikun Suo Li Ju Zhaoqiang Jiang Pingshuan Dong Yanli Wang Yali Dang Laijing Du In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction Frontiers in Nutrition gastrointestinal digestion simulation ACEI peptides broccoli VSMCs Ang II ACE2 |
| title | In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction |
| title_full | In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction |
| title_fullStr | In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction |
| title_full_unstemmed | In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction |
| title_short | In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction |
| title_sort | in vitro gastrointestinal digestion simulation screening of novel acei peptides from broccoli mechanism in high glucose induced vsmcs dysfunction |
| topic | gastrointestinal digestion simulation ACEI peptides broccoli VSMCs Ang II ACE2 |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2025.1528184/full |
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