Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress.

Nrf2 / HO - 1 信号的激活 ： 中药通过保护血管内皮细胞免受氧化应激来治疗动脉粥样硬化的重要分子机制。

• 影响指数: 12.822
• 发表时间: 12 2021
• 来源期刊: J Adv Res
• DOI: 10.1016/j.jare.2021.06.023
• PMID: 35024180
• 文章类型: Journal Article
• 作者列表: Zhang Q,Liu J,Duan H,Li R,Peng W,Wu C

关键词: 7-HMR, (−)-7(S)-hydroxymatairesinol; ADH, andrographolide; AGE, advanced glycation end product; AMP, Athyrium Multidentatum; APV, aqueous extracts of Prunella Vulgaris; ARE, antioxidant reaction elements; AS, atherosclerosis; ASD-IV, Astragaloside IV; ASP, Angelica sinensis polysaccharide; ASTP, Astragalus polysacharin; Akt, protein kinase B; Ang, Angiotensin; ApoE, apolipoprotein E; Atherosclerosis; BAECs, bovine artery endothelial cells; BBR, Berberine; BITC, benzyl isothiocyanate; C3G, Cyanidin-3-O-glucoside; CINM, Cinnamaldehyde; CNC, Cap'n'collar; CREB, cAMP-response element binding protein; CVDs, cardiovascular diseases; CVRF, cardiovascular risk factors; DMY, Dihydromyricetin; ECC, (−)-Epicatechin; ECs, endothelial cells; EGCG, epigallocatechin-3-O-gallate; ERK, extracellular regulated protein kinases; ET, endothelin; EXS, Xanthoceras sorbifolia; FFA, Fatty Acids; GPx, Glutathione peroxidase; GSD Rg1, Ginsenoside Rg1; GTE, Ganoderma tsugae extracts; Gau A, Glaucocalyxin A; HAMS, human anthocyanin medicated serum; HG, high glucose; HIF-1, Hypoxia-inducible factor 1; HO-1, heme oxygenase; HUVECs, human umbilical vein endothelial cells; HXC, Huoxue capsule; Hcy, Homocysteine; Herbal medicine; ICAM, intercellular adhesion molecule; IL, interleukin; KGRE, extracts of KGR; KRG, Korean red ginseng; Keap1, kelch-like epichlorohydrin-related proteins; LWDH, Liuwei-Dihuang pill; MA, maslinic acid; MAPKK, mitogen-activated protein kinase kinase; MAPKs, mitogen-activated protein kinases; MCGA3, 3-O-caffeoyl-1-methylquinic acid; MCP-1, monocyte chemotactic protein 1; MMPs, matrix metalloproteinases; Molecular mechanism; NAF, Nepeta Angustifolia; NF-κB, nuclear factor kappa-B; NG, naringenin; NQO1, NAD(P)H: quinone oxidoreductase; Nrf2, nuclear factor erythroid-2 related factor 2; Nrf2/HO-1 signaling; OA, Oleanolic acid; OMT, Oxymatrine; OX-LDL, oxidized low density lipoprotein; Oxidative stress; PA, Palmitate; PAA, Pachymic acid; PAI-1, plasminogen activator Inhibitor-1; PEITC, phenethyl isocyanate; PI3K, phosphatidylinositol 3 kinase; PKC, protein kinase C; PT, Pterostilbene; RBPC, phenolic extracts derived from rice bran; ROS, reactive oxygen species; SAL, Salidroside; SFN, sulforaphane; SMT, Samul-Tang Tang; SOD, superoxide dismutase; Sal B, salvianolic acid B; SchB, Schisandrin B; TCM, traditional Chinese medicine; TNF, tumor necrosis factor; TXA2, Thromboxane A2; TrxR1, thioredoxin reductase-1; US, uraemic serum; VA, Vanillic acid; VCAM, vascular cell adhesion molecule; VEC, vascular endothelial cells; VEI, vascular endothelial injury; Vascular endothelial cells; XAG, xanthoangelol; XXT, Xueshuan Xinmaining Tablet; Z-Lig, Z-ligustilide; eNOS, endothelial NO synthase

Mesh: Atherosclerosis / drug therapy; Endothelial Cells / metabolism; Heme Oxygenase-1 / metabolism; Herbal Medicine; Humans; NF-E2-Related Factor 2 / metabolism; Oxidative Stress; Pharmaceutical Preparations

Abstract

Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury.
This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs.
A literature search was carried out regarding our topic with the keywords of \"atherosclerosis\" or \"Nrf2/HO-1\" or \"vascular endothelial cells\" or \"oxidative stress\" or \"Herbal medicine\" or \"natural products\" or \"natural extracts\" or \"natural compounds\" or \"traditional Chinese medicines\" based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed.
These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies.
Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

摘要

最近,Nrf2/HO-1作为细胞内防御氧化应激的主要调控途径受到广泛关注,被认为是减轻内皮细胞损伤的理想靶点。
本文旨在总结在ECs中潜在发挥抗氧化应激保护作用的天然单体/提取物。
对我们的主题进行了文献检索，关键词为“动脉粥样硬化”或“Nrf2/HO-1”或“血管内皮细胞”或“氧化应激”或“草药”或“天然产物”或“天然提取物”或“天然化合物”或“中药”，基于草药经典书籍和科学数据库，包括Pubmed，SciFinder,Scopus,WebofScience,GoogleScholar,BaiduScholar,和其他人。然后，我们分析了不同类型的天然化合物通过保护血管内皮细胞免受氧化应激来治疗动脉粥样硬化的可能分子机制。此外,讨论了未来可能的研究前景。
这些在ECs中对氧化应激具有保护作用的药物主要包括苯丙素类化合物，黄酮类化合物，萜类化合物,和生物碱。这些药物中的大多数缓解了由于氧化应激导致的ECs细胞凋亡，并且该机制与Nrf2/HO-1信令激活有关。然而,尽管通过激活Nrf2/HO-1信号发挥针对EC损伤的保护作用的天然药物的各个方面的研究不断取得进展，基于这些药物开发治疗动脉粥样硬化(AS)和其他心血管疾病的新药需要更详细的临床前和临床研究.
我们的本文提供了通过激活Nrf2/HO-1对ECs抵抗氧化应激具有保护活性的天然试剂的最新信息。我们希望这篇综述将为进一步开发用于治疗AS和其他CVD的天然药物的新型候选药物提供一些方向。