Paeoniflorin Attenuates Radiation-Induced Brain Injury Associated with Modulation of Microglial Polarization and ERK/MAPK Signaling.

Background

Radiation-induced brain injury (RIBI) is a common side effect of cranial radiotherapy that severely impairs patients' neurological function and quality of life. Currently, effective and safe remedies for RIBI remain limited. Paeoniflorin (PF), a key component of total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora, is a traditional Chinese herbal compound with well-documented anti-inflammatory, antioxidant, and neuroprotective benefits. Our prior research demonstrated that TGP alleviates RIBI; however, its deeper protective mechanisms are still unknown. Purpose: The purpose of this study was to investigate the protective mechanisms of TGP against RIBI, focusing on the effects of PF on microglial polarization.

Methods

In vivo, we assessed the effects of TGP on microglial polarization using immunofluorescence colocalization analysis. In vitro, we evaluated the effects of PF on microglial polarization through CCK-8, qRT-PCR, flow cytometry, Western blot, and ELISA. Additionally, we utilized network pharmacology, molecular docking, and molecular dynamics simulations, together with qRT-PCR and Western blotting, to investigate the key pathway molecules involved in PF's modulation of microglial polarization.

Results

In vivo, TGP attenuated radiation-induced alterations in microglial polarization by decreasing the expression of M1-associated markers and increasing the expression of M2-associated markers. Consistently, PF modulated radiation-induced BV2 cell polarization by decreasing the level of M1-associated marker expression and increasing the level of M2-associated marker expression. Mechanistic analyses suggest that ERK signaling may be involved in the regulation of microglial polarization induced by the PF.

Conclusion

TGP and its major bioactive component, PF, may attenuate RIBI by modulating microglial polarization, with the ERK signaling pathway potentially involved in this process, supporting the potential of PF as a candidate strategy for RIBI.