Effects of Cudrania tricuspidata on anti‐senescence in high glucose‐treated endothelial cells via the Akt/p53/p21 pathway

Abstract

Vascular complications significantly contribute to the incidence of diabetes mellitus and the associated mortality (Brownlee, 2005). The major causes of vascular complications in diabetes are endothelial dysfunction and hyperglycemia related to damaged neovascularization (Sheetz & King, 2002). Endothelial dysfunction is a major cause of atherosclerosis development; therefore, it is important that the vessels are healthy to lower the risk of cardiovascular complications associated with diabetes mellitus (Kinlay, Libby, & Ganz, 2001). Endothelial cell (EC) senescence is involved in vascular aging (Yin & Pickering, 2016), and senescence is an independent risk factor for vascular diseases. Thus, EC senescence promotes vascular dysfunction (Bachschmid et al., 2013). Cellular senescence is regulated by various molecular signaling pathways. The known biomarkers of cellular senescence include the p53 (tumor suppressor), p21 (cell cycle kinase-dependent inhibitor), and retinoblastoma (Rb; cell cycle regulator) proteins. Moreover, the p53/p21/Rb pathway is activated in response to senescence (Muller, 2009). The tumor suppressor gene, p53, is involved in several aspects of cell biology, including cell proliferation, senescence, and death. p53 responds to signals by initiating the first step of irreversible cell cycle arrest. Recently, the Akt/p53/p21/Rb pathway was shown to play an important role in the regulation of cellular senescence (Feng et al., 2016). Additionally, senescence-associated beta-galactosidase (SA-β-gal) is a representative biomarker of senescence (Sikora, Bielak-Zmijewska, & Mosieniak, 2014). Cudrania tricuspidata (CT) is used in Korean traditional medicine to treat inflammation, gastritis, tumors, and hepatocellular damage (Chang et al., 2008). The use of its leaves, fruits, and roots is described in the study of traditional medicine in Donguibogam, a classic Eastern medicine book used in various countries, including Korea, China, and Japan. The roots and leaves of this perennial herb contain bioactive substances that exhibit anti-cancer, anti-oxidant, and hypoglycemic effects. The root bark of CT is reported to have anti-platelet (

Cudrania tricuspidata Root Extract Prevents Methylglyoxal‐Induced Inflammation and Oxidative Stress via Regulation of the PKC‐NOX4 Pathway in Human Kidney Cells

“…Previous studies have shown that the fruit, leaves, and roots of CT also have various biological activities, including antioxidant [ 50 , 51 ], anti-inflammatory [ 52 ], antiobesity [ 53 ], hepatoprotective [ 54 ], and neuroprotective [ 16 , 55 ] effects. It has recently been reported that CT displays antisenescence effects on endothelial cells exposed to high glucose, a major diabetic factor [ 56 ]. In addition, renal protective effects have been reported for cudratricusxanthone A, an active component of CT, in cecal ligation and puncture-induced septic mice [ 17 ]; however, the effects of CT on DN have not been studied.…”

Characterization and phylogenetic analysis of the complete plastome of Maclura tricuspidata (Moraceae)

“…2017 ; Choi et al. 2020 ; Kim and Park 2020 ; Lee and Choi 2020 ). However, the complete plastomes of Maclura have not been reported.…”