Abstract
Testing and screening of plant-derived molecules on normal human cells in vitro is a widely used approach for discovering their eventual health beneficial effects for human ageing and longevity. As little is known about age-associated differential effects of such molecules, here we report that young (<25% replicative lifespan completed) and near-senescent (>90% replicative lifespan completed) human skin fibroblasts exposed for 1–15 days to a wide range of concentrations (0.1–100 μM) of the three selected phytochemicals, namely α-boswellic acid acetate (ABC), praeruptorin-A (PTA), and salvianolic acid-B (SAB) had age-related differential effects. The parameters studied were the metabolic activity (MTT assay), cellular morphological phenotype, one-step growth characteristics, expression of genes involved in the cell cycle regulation and cytokine network genes, protein levels of p53, cytosolic superoxide dismutase (SOD1) and microtubule-associated protein 1A/1B-light chain 3 (LC3), and the extent of protein carbonylation and protein aggregation as a sign of oxidative stress. All three compounds showed biphasic hormetic dose response by stimulating cell growth, survival and metabolic activity at low doses (up to 1 μM), while showing inhibitory effects at high doses (>10 μM). Furthermore, the response of early passage young cells was different from that of the late passage near-senescent cells, especially with respect to the expression of cell cycle-related and inflammation-related genes. Such studies have importance with respect to the use of low doses of such molecules as health-promoting and/or ageing-interventions through the phenomenon of hormesis.
Highlights
Testing and screening natural compounds, extracted from plants, for their potential benefits for human health is one of the topical areas in preventive and therapeutic biomedicine
We have utilized the above approach for screening phytochemicals by using the Hayflick model system of human cellular ageing in vitro [9], and have reported several ageing-modulatory effects of kinetin, zeatin, curcumin, rosmarinic acid (ROSM), ampelopsin (AMPEL), and amorfrutin-A
Our results show that the three compounds tested in this study have a typical biphasic hormetic dose response by stimulating cell growth, survival and metabolic activity at low doses, while showing inhibitory effects at high doses
Summary
Testing and screening natural compounds, extracted from plants, for their potential benefits for human health is one of the topical areas in preventive and therapeutic biomedicine. We have utilized the above approach for screening phytochemicals by using the Hayflick model system of human cellular ageing in vitro [9], and have reported several ageing-modulatory effects of kinetin, zeatin, curcumin, rosmarinic acid (ROSM), ampelopsin (AMPEL), and amorfrutin-A (AMOR) [10,11,12,13] Such a research and development strategy is supported by various governmental and private funding agencies, including the European Union (EU), through research and innovation actions (RIA). In continuation with the above RIA, we have tested three other compounds, namely α-boswellic acid acetate (ABC), praeruptorin-A (PTA), and salvianolic acid-B (SAB) on human skin fibroblasts undergoing serial passaging in vitro. Report the results of our investigations on comparing the effects of ABC, PTA, and
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