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

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 hydro‐alcoholic extract of Scabiosa flavida prevents the SA‐ß‐GAL activity in NIH3T3 cells induced by H 2O 2. Scabiosa flavida affects lipid peroxidation and reactive oxygen species generation in H 2O 2‐induced senescence NIH3T3 fibroblasts. Scabiosa flavida reduced G0/G1 arrest in senescent fibroblasts. S. flavida changed the messenger RNA expression of senescence‐associated inflammatory cytokines interleukine‐1ß IL‐1ß, IL‐6, and NF‐κB, as well as p38, p53, and p16INK4aINK4a. Scabiosa flavida exhibited a significant role to impede senescence process, in part via antioxidant function.