Anti-SASP and anti-inflammatory activity of resveratrol, curcumin and β-caryophyllene association on human endothelial and monocytic cells

Abstract

A challenging and promising new branch of aging-related research fields is the identification of natural compounds able to modulate the senescence-associated secretory phenotype (SASP), which characterizes senescent cells and can contribute to fuel the inflammaging. We investigated both the anti-SASP and anti-inflammatory activities of a nutritional supplement, namely Fenoxidol™, composed of turmeric extract bioCurcumin (bCUR), Polydatin (the natural glycosylated precursor of Resveratrol-RSV), and liposomal β-caryophyllene (BCP), in two human cellular models, such as the primary endothelial cell line, HUVECs and the monocytic cell line, THP-1. Replicative and Doxorubicin-induced senescent HUVECs, both chosen as cellular models of SASP, and lipopolysaccharides (LPS)-stimulated THP-1, selected as a model of the inflammatory response, were treated with the three single natural compounds or with a combination of them (MIX). In both senescent HUVEC models, MIX treatment significantly reduced IL-1β and IL-6 expression levels and p16ink4a protein, and also increased SIRT1 protein level, as well as downregulated miR-146a and miR-21 expression, two of the so-called inflamma-miRNAs, more effectively than the single compounds. In THP-1 cells stimulated with LPS, the MIX showed a significant effect in decreasing IL-1β, IL-6, TNF-α, and miR-146a expression levels and Caspase-1 activation, in association with an up-regulation of SIRT1 protein, compared to the single compounds. Overall, our results suggest that the three analysed compounds can have a combined effect in restraining SASP in senescent HUVECs as well as the inflammatory response in LPS-stimulated THP-1 cells.

Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress

“…This experimental approach was applied to verify their potential synergistic effects. We previously reported that the combination of some natural compounds was able to improve their anti-inflammatory properties [ 37 ]. We firstly evaluated cell viability of yHUVEC ( Figure 2 A–D) and sHUVEC ( Figure 2 E–H) treated for 24 h and 72 h, respectively, with different concentrations of natural compounds alone.…”

“…Total RNA was isolated by using the Norgen Biotek Kit (Thorold, ON, Canada), according to the manufacturer’s instructions and stored at −80 °C until use. mRNA and miRNA expression was determined as previously described [ 37 ]. RT-qPCR analysis were standardized with RNU48 for miRNA expression and with GAPDH and β-actin for mRNA expression.…”

Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging

“…It has been demonstrated that targeted apoptosis of SC can attenuate age-related dysfunctions, therefore applying strategies that can selectively remove SC are of considerable interest in reducing SC burden with age [ 25 ]. Natural compounds, like resveratrol [ 26 ], EGCG [ 27 ] and probiotic bacterial metabolites [ 28 ], have been identified as “senolytics” or “senomorphics” which can specifically ablate SC by inhibiting anti-apoptotic pathways (i.e., Bcl-2) or alter their phenotype by interfering with inflammatory pathways controlling deleterious paracrine effects of cellular senescence [ 18 ]. Emerging early clinical trials are showing promising results of senolytics and senomporhics such as improvments in age-related morbidity and mortality [ 29 ].…”

Nutrition Interventions of Herbal Compounds on Cellular Senescence

“…Curcumin, a natural polyphenol compound, delays endothelial cell senescence induced by hydrogen peroxide through SIRT1 signaling [ 116 ]. Recent studies found that a combination of resveratrol, curcumin, and β -caryophyllene reduced the levels of SASP factors, such as IL-1 β and IL-6, in senescent HUVECs [ 117 ]. Wang and associates found that Ginseng-Sanqi-Chuanxiong extracts regulated mitosis through AMPK to prevent HG/palmitate-induced endothelial senescence and the production of mitochondrial ROS [ 118 ].…”