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橙皮苷通过靶向 VEGFR2 介导的 PI3K/AKT/mTOR 信号通路抑制血管生成。

Eriocitrin Inhibits Angiogenesis by Targeting VEGFR2-Mediated PI3K/AKT/mTOR Signaling Pathways.

机构信息

Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea.

Department of Food Science and Nutrition, College of Health Sciences, Dong-A University, Busan 49315, Republic of Korea.

出版信息

Nutrients. 2024 Apr 8;16(7):1091. doi: 10.3390/nu16071091.

DOI:10.3390/nu16071091
PMID:38613124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11013780/
Abstract

Eriocitrin, a flavanone found in peppermint and citrus fruits, is known to possess many physiological activities. However, the anti-angiogenic effects of eriocitrin are yet to be fully elucidated. Therefore, the objective of this research was to explore the anti-angiogenic effects of eriocitrin both in vitro and in vivo as well as its underlying mechanism. Anti-angiogenic effects of eriocitrin were evaluated utilizing in vitro models of angiogenesis, including inhibition of tube formation, and induction of apoptosis in human umbilical vein endothelial cells (HUVECs). A chorioallantoic membrane (CAM) assay in chick embryos was also performed to evaluate the in vivo effects of eriocitrin on angiogenesis. Results showed significant eriocitrin effects on proliferation, tube formation, migration, and apoptosis in HUVECs. Furthermore, in vivo analysis revealed that eriocitrin significantly suppressed the formation of new blood vessels. In particular, it regulated MAPK/ERK signaling pathway and VEGFR2, inhibited the downstream PI3K/AKT/mTOR signaling pathway, and activated apoptosis signals such as caspase cascades. In HUVECs, the expression of matrix metalloproteinases (MMP-2 and MMP-9) exhibited an inhibitory effect on angiogenesis through the suppression of the signaling pathway. Therefore, eriocitrin presents potential for development into an antiangiogenic therapeutic agent.

摘要

橙皮苷，一种存在于薄荷和柑橘类水果中的黄烷酮，已知具有许多生理活性。然而，橙皮苷的抗血管生成作用尚未完全阐明。因此，本研究旨在探讨橙皮苷在体内和体外的抗血管生成作用及其潜在机制。利用体外血管生成模型，包括抑制人脐静脉内皮细胞（HUVEC）管形成和诱导细胞凋亡，评估橙皮苷的抗血管生成作用。还在鸡胚绒毛尿囊膜（CAM）实验中评估了橙皮苷对血管生成的体内作用。结果表明，橙皮苷对 HUVEC 的增殖、管形成、迁移和凋亡有显著影响。此外，体内分析表明橙皮苷显著抑制了新血管的形成。特别是，它调节了 MAPK/ERK 信号通路和 VEGFR2，抑制了下游的 PI3K/AKT/mTOR 信号通路，并激活了细胞凋亡信号，如 caspase 级联。在 HUVEC 中，基质金属蛋白酶（MMP-2 和 MMP-9）的表达通过抑制信号通路对血管生成表现出抑制作用。因此，橙皮苷具有开发为抗血管生成治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cae/11013780/39d0130b5754/nutrients-16-01091-g011.jpg
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