Polygala tenuifolia root extract attenuates ischemic stroke by inhibiting HMGB1 trigger neuroinflammation

Polygala tenuifolia Willd., a famous traditional Chinese medicine, has been widely applied to treat central nervous system diseases. In this study, P. tenuifolia root extract exhibited a moderate anti-ischemic effect on in-vitro oxygen-glucose deprivation/reperfusion (OGD/R) model. In transient middle cerebral artery occlusion (tMCAO) rats, P. tenuifolia root extract significantly attenuated brain infarction and neurological deficits in a dose-dependent manner. Compared with the sham group, the release of damage-associated molecular patterns (DAMPs)-HMGB1 in the ischemic brain was significantly higher, which was inhibited by P. tenuifolia root extract. To further explore such neuroprotective effects whether associated with aseptic inflammation, HMGB1-activated BV2 microglial cells model was established. The extract of P. tenuifolia was found to inhibit the downstream inflammatory response driven by HMGB1, with an IC₅₀ value of 49.46 μg/mL. In addition, the extract was also found to be able to directly interact with HMGB1 in the surface plasmon resonance (SPR) experiment. Phytochemical studies showed that the extract of P. tenuifolia root contains a large number of terpenoids, oligosaccharides and phenolic compounds, which likely contribute to the above observed biological activities. Our results not only provide some data support for the clinical application of P. tenuifolia against cerebral ischemia, but also clarify the potential target of P tenuifolia's anti-inflammatory properties.