Plant-Derived Molecules α-Boswellic Acid Acetate, Praeruptorin-A, and Salvianolic Acid-B Have Age-Related Differential Effects in Young and Senescent Human Fibroblasts In Vitro

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.

Effect of Thymbra capitata (L.) Cav. on Inflammation, Senescence and Cell Migration

“…Indeed, rosmarinic acid increases lifespan in C. elegans [99] and in an animal model of familial amyotrophic lateral sclerosis [179] and protects cells from UV radiation-induced aging [180,181] as well as in other models of cell senescence [102,[182][183][184]. Salvianolic acid B [185][186][187] and apigenin [188][189][190][191][192][193][194] also exert strong anti-aging effects. Considering the results of the isolated compounds, it would be expected that the HRW would prevent cell senescence; however, our results show that the HRW alone induces cell senescence, thus suggesting that these compounds can have antagonistic effects when in a complex mixture.…”

Salvianolic Acid B: A Review of Pharmacological Effects, Safety, Combination Therapy, New Dosage Forms, and Novel Drug Delivery Routes

“…Salvianolic acid B exerts excellent protective effects not only on damaged organs and tissues, but also on different types of tumors, inflammation, depression, and spinal cord injury by improving the corresponding indices. Studies have demonstrated that salvianolic acid B can protect against coronavirus disease 2019 [ 224 , 225 ], exerts anti-aging effects [ 226 , 227 ], and can be used in the treatment of uremic syndrome [ 228 ]. Recently, commercially available dosage forms based on salvianolic acid B mainly include injections containing Salvia miltiorrhiza polyphenol acid for injection and salvianolic acids for injection.…”