Effects of Isorhamnetin in Human Amniotic Epithelial Stem Cells in vitro and Its Cardioprotective Effects in vivo

Abstract

Cardiac hypertrophy and fibrosis are major pathophysiologic disorders that lead to serious cardiovascular diseases (CVDs), such as heart failure and arrhythmia. It is well known that transforming growth factor β (TGFβ) signaling pathways play a major role in the proliferation of cardiac hypertrophy and fibrosis, which is mainly stimulated by angiotensin II (AgII). This study aimed to investigate the cardioprotective potential of isorhamnetin (ISO) in human amniotic epithelial stem cells (hAESCs) through global gene expression analysis and to confirm its beneficial effects on cardiac hypertrophy and fibrosis in the AgII-induced in vivo model. In vitro, biological processes including TGFβ, collagen-related functions, and inflammatory processes were significantly suppressed in ISO pretreated hAESCs. In vivo, continuous AgII infusion using an osmotic pump induced significant pathological fibrosis and myocardial hypertrophy, which were remarkably suppressed by ISO pretreatment. ISO was found to reverse the enhanced TGFβ and Collagen type I alpha 1 mRNA expression induced by AgII exposure, which causes cardiovascular remodeling in ventricular tissue. These findings indicate that ISO could be a potential agent against cardiac hypertrophy and fibrosis.

Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3-O-Glucoside on Cell Differentiation

“…In the present study, we have used hAECs that were preserved at the Tsukuba Human Tissue Biobank Center (THB). THB was established at the University of Tsukuba in November 2013 with an aim to reserve human biospecimens to promote medical research [ 56 , 57 ]. The protocol for isolation, collection, and use of hAECs and other biospecimens was approved by the Ethical Review Committee of the University of Tsukuba Hospital (approval code: H27-58, approval date: 10 July, 2015).…”

Pharmacological Mechanisms of Tinglizi against Chronic Heart Failure Determined by Network Pharmacology and Molecular Docking

“…Isorhamnetin has a protective effect on ischemia–reperfusion injury of isolated rat hearts [ 26 ]. ISO was found to reverse the enhanced TGF- β and collagen type I alpha 1 mRNA expression induced by AgII exposure, which causes cardiovascular remodeling in ventricular tissue [ 27 ]. Isorhamnetin treated myocardial-related diseases by regulating PI3K, Akt, and NF- κ B signaling pathway [ 28 ].…”

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

“…Li and colleagues revealed that isorhamnetin could also inhibit the growth of the gefitinib resistant PC9 cells (PC9-IR) by downregulating BCL-2 gene expression and PCNA protein expression, inhibiting DNA synthesis and upregulating P53 , BAX and CASP3 gene expression [ 22 ]. Along with this, Aonuma et al [ 71 ] demonstrated that isorhamnetin might efficiently suppress hypertrophy and fibrosis induced by angiotensin II in cardiac tissue by regulating transforming growth factor (TGF-β) pathways. Furthermore, it might have appreciated properties on potential clinical consequences of cardiovascular diseases by the renin-angiotensin system regulation.…”

“…We have established a stem cell-based tool using a perinatal stem cell, human amniotic epithelial cells (hAECs), to evaluate the bioactivities of natural compounds employing whole-genome microarray analysis [ 71 , 140 , 141 , 142 , 143 , 144 ]. In recent years, an increasingly large number of bioactive compounds of medicinal plants have been screened for their potential therapeutic and preventive effects.…”

“…However, because of its stem cell-like properties, it can be used for the initial screening of target compounds. We have previously explored antifibrotic [ 71 ] and hepatic differentiation-inducing [ 170 ] potential of isorhamnetin in hAECs. In the present study, we have performed a targeted secondary analysis of our previously published data [ 71 ] to explore the potential functionalities of isorhamnetin in diabetes ( Figure 4 ).…”