Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells

Abstract

Aging contributes to an increased risk of developing a number of neurodegenerative and chronic disorders, predominantly related to oxidative stress (OS) and defects in the antioxidant balance. This study focused on the antisenescence effect of four plant species (Falcaria vulgaris, Ixiolirion tataricum, Ajuga chamaecistus, and Scabiosa flavida) on H2O2‐induced premature senescence in rat NIH3T3 fibroblasts, which were found to be rich in effective phytochemicals with traditional ethnobotanical backgrounds. Plant materials were collected, identified, and extracted. To determine the viability of NIH3T3 cells, an MTT assay was conducted. The levels of OS markers and the senescence‐associated ß‐galactosidase (SA‐ß‐GAL) activity were analyzed by the Elisa reader. The cell cycle pattern was evaluated by flow cytometry. The expression of senescence‐related inflammatory cytokines and the molecules involved in aging signaling pathways were investigated using the real‐time reverse transcription polymerase chain reaction (RT‐PCR). H2O2 treatment decreased cell viability and increased lipid peroxidation (LPO) and the reactive oxygen species (ROS) in NIH3T3s. However, S. flavida exhibited low cytotoxicity, reduced OS and SA‐ß‐GAL activities in NIH3T3 cells compared with the H2O2‐treated group. I. tataricum was the second best plant, although it was more toxic to NIHT3T cells. S. flavida decreased G0/G1 arrest and facilitated the G2/M transition of NIH3T3s, also downregulated the expression of p38, p53, p16, and the related inflammatory mediators. S. flavida potentially modulated senescence‐associated hallmarks in fibroblasts exposed to H2O2, thus it may inhibit the aging process via controlling the OS. Therefore it is a promising candidate for future antiaging explorations.

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum

“…LF is mainly composed of fibroblasts. Previous studies show that P16 is related to fibroblast senescence [6], and the inhibition of S100A8 protein may lead to the decrease of fibroblast growth and apoptosis [7]. We speculate that P16 and S100 may be related to the hypertrophy of LF.…”

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum

“…LF is mainly composed of broblasts. Previous studies show that P16 is related to broblast senescence [6], and the inhibition of S100A8 protein may lead to the decrease of broblast growth and apoptosis [7]. We speculate that P16 and S100 may be related to the hypertrophy of LF.…”

A Systematic Review of the Potential Chemoprotective Effects of Resveratrol on Doxorubicin-Induced Cardiotoxicity: Focus on the Antioxidant, Antiapoptotic, and Anti-Inflammatory Activities

“…On the other hand, the free radicals are commonly generated in the cells, but they are neutralized by several defense mechanisms [ 78 ]. In oxidative stress conditions, such as chemotherapy, the amount of free radicals increases and an imbalance is created between the generated free radicals and the antioxidant defense system [ 79 , 80 ]. It has been reported that the use of doxorubicin increases the ROS level of cardiac cells, and subsequently, they are able to attack the cell macromolecules, leading to malfunction of the heart tissue [ 35 , 38 , 50 , 59 ].…”