Revealing the anti-senescence effects and related mechanisms of flavonoid extracts from the buds of Wikstroemia chamaedaphne Meisn on D-galactose-induced PC12 cells based on network pharmacology and transcriptomics

Abstract

Background

Natural products are an important source of drugs or lead compounds for the treatment of senescence. The buds of Wikstroemia chamaedaphne Meisn are a traditional Chinese medicine to cure edema, schizophrenia and epilepsy. A flavonoid extract of W. chamaedaphne (FEW) was prepared from the methanolic extract of W. chamaedaphne by our group previously, which was including eight flavonoids with a content of (55.19 ± 0.32) %. In this study, the anti-senescence effects and related mechanisms of FEW on D-galactose-induced PC12 cells were investigated for the first time.

Results

High doses of D-galactose could induce PC12 cell senescence, whereas FEW could delay PC12 cell senescence by decreasing SA-β-gal positivity, increasing SOD activity, reducing MDA levels, improving cell morphology, inhibiting cell cycle arrest and down-regulating the expression of senescence-related proteins P16, P21 and P53. Subsequently, potential mechanisms underlying anti-senescence effects of FEW were elucidated through integration of network pharmacology and transcriptomics. The main signaling pathways involved by FEW were found to be cancer signaling pathway, FOXO signaling pathway, PI3k–Akt signaling pathway, AGE–RAGE signaling pathway, protein digestion and uptake, etc. The anti-senescence effects of FEW may be related to the PI3k–Akt signaling pathway as revealed by western blot experiments.

Conclusion

Our study revealed that FEW has anti-senescence effects. This may suggest that FEW acts as an anti-senescence agent for age-related neurological diseases.