Mulberry polyphenol extracts attenuated senescence through inhibition of Ras/ERK via promoting Ras degradation in VSMC

Abstract

Ageing is one of the major risk factors of human diseases, including cancer, diabetes, and cardiovascular disease. Mulberry exhibits a wide range of functions, such as anti-oxidant, anti-inflammation, and anti-diabetes. In this study, we investigated the role of mulberry polyphenol extract (MPE) in K-Ras-induced senescence of smooth muscle cells. Forced expression of K-Ras enhanced senescence of smooth muscle A7r5 cells as shown by the elevation of β-galactosidase activity. Treatment with MPE significantly repressed the Ras, phosphorylated ERK, and β−galactosidase level. MPE triggered the association of cyclins with their corresponding cyclin-dependent protein kinases and hyperphosphorylated retinoblastoma (RB). MPE also down-regulated the levels of K-Ras-induced CDK inhibitors. MPE enhanced the phosphorylated AMP-dependent protein kinase (AMPK) and inducible nitric oxide synthase (iNOS) level in the presence of K-Ras. Pretreatment with either L-NAME or AMPK inhibitor reversed the effects of MPE. In addition, L-NAME and AMPK inhibitor repressed the MPE-induced total and phosphorylated 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co A) level. MPE repressed K-Ras-induced G0/G1 arrest, whereas L-NAME and AMPK inhibitor blocked the effects of MPE. Our results indicated that MPE recovered the K-Ras-induced senescence of vascular smooth muscle cells through iNOS and AMPK-dependent pathway. Our findings suggested that MPE may prevent ageing-induced atherosclerosis.

Mulberry polyphenols ameliorate atherogenic migration and proliferation by degradation of K-Ras and downregulation of its signals in vascular smooth muscle cell

“…Treatment with MPE reversed the K-Ras-induced phenomenon. In contrast, MPE mitigates K-Ras-induced senescence and promoted proliferation of smooth muscle cells through the downregulation of K-Ras expression and its downstream signals 17 . The difference findings between this study and previous report 17 may result from distinct Ras expression pattern.…”

“…In contrast, MPE mitigates K-Ras-induced senescence and promoted proliferation of smooth muscle cells through the downregulation of K-Ras expression and its downstream signals 17 . The difference findings between this study and previous report 17 may result from distinct Ras expression pattern. Minamino et al demonstrated that transient overexpression of Ras stimulated proliferation of smooth muscle cells whereas senescence was observed after post-transfection for 72 h 27 .…”

“…These cells were incubated at 37 °C in a humidified atmosphere of 5% CO2. The K-Ras transfection procedures were performed as reported previously 17 .…”

PRDM16 Regulating Adipocyte Transformation and Thermogenesis: A Promising Therapeutic Target for Obesity and Diabetes

“…Pan et al (2019) found that resveratrol, as a natural stilbene with antiobesity effects, can enhance the expression of thermogenic-related proteins UCP1 and PRDM16 by activating SIRT1/PGC-1α (Pan et al, 2019). Mulberry leaves have been proven to have a variety of biological activities, such as antidiabetic and anti-inflammatory effects (Chen et al, 2022). Cheng et al (2022) showed that mulberry may induce the browning of iWAT by increasing the expression of brown marker genes and beige-specific genes (such as PRDM16) (Cheng et al, 2022).…”

Bioinformatic Study of the Active Compound of Morusin in Mulberry (Morus alba) against Breast Cancer

“…Mulberry (Morus alba) has traditionally been used to treat a wide range of conditions, including hypertension, diabetes, anemia, and malaria (Lallo, et al, 2020). Numerous studies have demonstrated the anticancer properties of mulberry extract, which can suppress the growth of breast cancer (Chen, et al, 2022;Wani, et al, 2023). Morus alba extract is reported to contain several active compounds including morusin (Panek-Krzyśko and Stompor-Gorący, 2021).…”