Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Abstract

Nectandrin B (NecB) is a bioactive lignan compound isolated from Myristica fragrans (nutmeg), which functions as an activator of AMP-activated protein kinase (AMPK). Because we recently found that treatment with NecB increased the cell viability of old human diploid fibroblasts (HDFs), the underlying molecular mechanism was investigated. NecB treatment in old HDFs reduced the activity staining of senescence-associated β-galactosidase and the levels of senescence markers, such as the Ser 15 phosphorylated p53, caveolin-1, p21 waf1 , p16 ink4a , p27 kip1 , and cyclin D1. NecB treatment increased that in S phase, indicating a enhancement of cell cycle entry. Interestingly, NecB treatment ameliorated age-dependent activation of AMPK in old HDFs. Moreover, NecB reversed the age-dependent expression and/or activity changes of certain sirtuins (SIRT1−5), and cell survival/death-related proteins. The transcriptional activity of Yin-Yang 1 and the expression of downstream proteins were elevated in NecB-treated old HDFs. In addition, NecB treatment exerted a radical scavenging effect in vitro , reduced cellular ROS levels, and increased antioxidant enzymes in old HDFs. Moreover, NecB-mediated activation of the AMPK pathway reduced intracellular ROS levels. These results suggest that NecB-induced protection against cellular senescence is mediated by ROS-scavenging through activation of AMPK. NecB might be useful in ameliorating age-related diseases and extending human lifespan.

Metabolite Profiling of Rambutan (Nephelium lappaceum L.) Seeds Using UPLC-qTOF-MS/MS and Senomorphic Effects in Aged Human Dermal Fibroblasts

“…The main chemical components in the three different N. lappaceum extracts were identified by comparing the references with the MS fragmentation pattern of each peak (Figure S44 in Supplementary Material). Specifically, the DAD chromatogram and the MS/MS fragmentation profiles showed that the pulp of N. lappaceum mainly contained disaccharides, while the major components of the N. lappaceum peels were identified as gallic acid, corilagin, and geraniin, which was consistent with previous reports [9]. The extract of the N. lappaceum seed was found to be dominated by flavonoids based on molecular networking.…”

“…Recent data have demonstrated that the activation or enforced expression of sirtuins (SIRTs) increases lifespan in animal models, making sirtuins a potential target for healthy aging. Silent mating type information regulation 2 homolog (SIRT1), also known as NAD-dependent deacetylase-1, also mediates the beneficial antiaging effects of caloric restriction and natural products, such as resveratrol, which can extend the human lifespan [9].…”

Rosmarinic acid improves boar sperm quality, antioxidant capacity and energy metabolism at 17°C via AMPK activation

“…Jang et al. (2019) showed that nectandrin B‐mediated activation of the AMPK pathway prevents cellular senescence by reducing intracellular ROS levels. In terms of sperm, AMPK is an important connection between metabolism energy and sperm fertility, which helps to regulate sperm motility, mitochondrial activity, membranes and acrosome reaction (Martin‐Hidalgo et al., 2018).…”

Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells

“…Transcription factor expression analysis was performed as described previously. 30 MIA PaCa-2 and BxPC-3 cells were seeded on a black 96-well plate and grown for 24 hours. The cells were transduced using the lentiviral supernatant for 24 hours.…”