Rosa centifolia petal extract induces endothelium-dependent and endothelium-independent vasorelaxation in rat aorta and prevents accumulation of inflammatory factors in human umbilical vein endothelial cells.

This study aims to investigate the vasorelaxation effects of a Rosa centifolia petal extract (ROSE CRYSTA®-70: ROSE-70) on the isolated aorta and the protective effect of ROSE-70 on human umbilical vein endothelial cells (HUVECs) dysfunction. ROSE-70 inhibited phenylephrine (PE) -induced contraction in an endothelium-dependent and endothelium-independent manner; however, this relaxation was lower in the endothelium-denuded aorta. ROSE-70-induced relaxation was attenuated by L-NG -nitroarginine methyl ester (L-NAME), a nitric oxide synthase inhibitor in the endothelium-intact aorta. Moreover, the relaxation in the endothelium-denuded aorta in response to increases in cAMP was inhibited by SQ22536, an adenylate cyclase inhibitor, and this relaxation was also attenuated by 4-aminopyridine, a voltage-activated K+ channel inhibitor. ROSE-70 contains high concentrations of quercetin, rutin, and other compounds. Pure quercetin and rutin also inhibited PE-induced contraction in an endothelium-dependent manner, although rutin-induced relaxation was milder in the endothelium-denuded aorta. ROSE-70 significantly increased the phosphorylation (at Ser1177) of eNOS in HUVECs. Moreover, ROSE-70 potently suppressed high glucose- and H2 O2 -induced accumulation of tumor necrosis factor-α (TNF-α) and nuclear factor-kappa B (NF-κB) were investigated in human umbilical vein endothelial cells (HUVECs). In this study, we defined the mechanism of ROSE-70-induced vasorelaxation in rat aorta and demonstrated that ROSE-70 has anti-inflammatory effects in endothelial cells. PRACTICAL APPLICATIONS: Endothelial cells play a role in vascular homeostasis. Endothelial dysfunction is caused by a variety of risk factors such as hypertension, arteriosclerosis, hyperglycemia, and oxidative stress. ROSE-70 is a food ingredient and the powdered form of an extract from the rose petal with >70% of the content corresponding to rose petal polyphenols such as rutin, quercetin, and protocatechuic acid. This study revealed that vasorelaxation effects of ROSE-70 and the protective role of ROSE-70 on the dysfunction of endothelial cells by high glucose and superoxides were investigated for the first time. We showed the mechanisms of ROSE-70- induced endothelium-dependent vasorelaxation and the protective effects of endothelial cells from high glucose and superoxide. ROSE-70 has been shown to have antiaging, skin elasticity-enhancing, skin-lightening, anti-allergic, sugar-absorbing, and lipolytic effects (URL: https://www.toyohakko-healthcare. com/en/rose_crysta70/). Therefore, the authors believe that ROSE-70 is an excellent food ingredient that has preventive and antiaging effects on lifestyle-related diseases.

Proximity Proteomics Has Potential for Extracellular Vesicle Identification.

Extracellular vesicles (EVs) are biomarkers and mediators of intercellular communication. In biological samples, EVs are secreted by various types of cells. The proteomic identification of proteins expressed in EVs has potential to contribute to research and clinical applications, particularly for cancer. In this study, the proximity-labeling method-based proteomic approach was used for EV identification, labeling membrane components proximal to a given molecule on the EV membrane surface. Due to the small labeling range, proteins on the surface of the same EVs are likely to be labeled by selecting a given EV surface antigen. The protein group of cancer cell-secreted EV (cEV), which abundantly expresses a close homologue of L1 (CHL1), was examined using a model mouse for lung cancer (LC). cEV-expressed proteins were identified by proteomic analysis of enzyme-mediated activation of radical sources by comparing serum EVs from wild-type and LC mice. SLC4A1 was found to be co-expressed in CHL1-expressing EVs, highlighting EVs expressing both CHL1 and SLC4A1 as candidates for cEVs. Serum EVs expressing both CHL1 and caspase 14 were significantly elevated in LC patients compared with healthy individuals. Thus, the combination of proximity labeling and proteomic analysis allows for effective EV identification.

Endothelium-independent vasodilator effects of nobiletin in rat aorta.

Nobiletin is a one of the polymethoxyflavones contained in the peel of citrus fruits, such as Citrus depressa. In this study, the effect of nobiletin-induced relaxation on phenylephrine (PE)-induced contraction of endothelium-denuded rat aorta was investigated. Nobiletin inhibited PE- or KCl-induced contractions in a concentration-dependent manner in endothelium-intact and -denuded aortas. However, this relaxation was stronger in PE-induced contractions than in KCl-induced contractions; moreover, the nobiletin-induced relaxation was significantly increased on PE-induced contraction in endothelium-intact aorta. ODQ significantly inhibited the nobiletin-induced relaxation in endothelium-denuded aorta; however, SQ22536 did not affect the relaxation. In addition, IBMX synergistically enhanced the nobiletin-induced relaxation. Nobiletin increased cGMP levels in aorta. Also, IBMX significantly increased cGMP content in aorta, and ODQ significantly reduced cGMP levels. Nobiletin-induced relaxation was significantly inhibited by the Ca2+-activated K+ (BK) channel inhibitor iberiotoxin (IbTX) and the ATP-sensitive K+ (KATP) channel inhibitor glybenclamide. Sodium nitroprusside-induced relaxation was suppressed by IbTX, but not by glybenclamide. These results suggest that nobiletin inhibits PE-induced contractions of endothelium-denuded rat aorta by increasing cGMP levels via GC activation. Moreover, the present findings indicate the possibility that nobiletin opened BK channels by a cGMP-related signal, but KATP channels were opened by a cGMP-nonrelated signal in rat aorta.