Inhibitory Effects of Roseoside and Icariside E4 Isolated from a Natural Product Mixture (No-ap) on the Expression of Angiotensin II Receptor 1 and Oxidative Stress in Angiotensin II-Stimulated H9C2 Cells

Abstract

Hypertension is a major risk factor for the development of cardiovascular diseases. This study aimed to elucidate whether the natural product mixture No-ap (NA) containing Pine densiflora, Annona muricate, and Monordica charantia, or its single components have inhibitory effects on hypertension-related molecules in Angiotensin II (Ang II)-stimulated H9C2 cells. Individual functional components were isolated and purified from NA using various columns and solvents, and then their structures were analyzed using ESI–MS, 1H-NMR, and 13H-NMR spectra. H9C2 cells were stimulated with 300 nM Ang II for 7 h. NA, telmisartan, ginsenoside, roseoside (Roseo), icariside E4 (IE4), or a combination of two components (Roseo and IE4) were administered to the cells 1 h before Ang II stimulation. The expression and activity of hypertension-related molecules or oxidative molecules were determined using RT-PCR, western blot, and ELISA. Ang II stimulation increased the expression of Ang II receptor 1 (AT1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), tumor growth factor-β (TGF-β) mRNA, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and the levels of hydrogen peroxide (H2O2) and superoxide anion (•O2−) and reduced anti-oxidant enzyme activity. NA significantly improved the expression or activities of all hypertension-related molecules altered in Ang II-stimulated cells. Roseo or IE4 pretreatment either decreased or increased the expression or activities of all hypertension-related molecules similar to NA, but to a lesser extent. The pretreatment with a combination of Roseo and IE4 (1:1) either decreased or increased the expression of all hypertension-related molecules, compared to each single component, revealing a synergistic action of the two compounds. Thus, the combination of single components could exert promising anti-hypertensive effects similar to NA, which should be examined in future animal and clinical studies.

Rutin Modulates MAPK Pathway Differently from Quercetin in Angiotensin II-Induced H9c2 Cardiomyocyte Hypertrophy

“…Extracellular signal-related kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2), and p38 kinase (p38) are three MAPKs that have been reported to be involved in cardiac hypertrophy [ 3 ]. Activation of AT1R by Ang II also activates NADPH oxidase that increases the generation of reactive oxygen species (ROS), particularly superoxide anion [ 4 ]. Superoxide dismutase (SOD) converts the anion to less reactive molecules.…”

Pinus thunbergii Parl. Extracts Reduce Acute Inflammation by Targeting Oxidative Stress

“…According to our LC-MS analyses, PTP contained large amounts of quinic acid, which has been reported to possess potent antioxidant properties and antineuroinflammatory activity [ 33 ]. Furthermore, PTP contains roseoside and icariside E4, which are known to alleviate oxidative stress [ 34 ], as well as pinocembrin, which also possesses anti-inflammatory effects [ 35 ]. Therefore, our study is the first to identify PTP as a novel potential natural anti-inflammatory agent.…”

Icariside II regulates TLR4/NF-κB signaling pathway to improve septic lung injury

“…ICA II could alleviate LPS-induced neuroinflammation by inhibiting the TLR4 / MyD88 /NF-κB pathway, and also alleviate eosinophilic airway inflammation and remodeling by inhibiting the NF-κB and STAT3 pathways in an asthma mouse model [11]. Notably, many studies showed the effects of ICA II on inflammatory response and oxidative stress [19]. ICA II overcome BRAF inhibitor resistance in melanoma via the induction of ROS production [20].…”