Bakkenolide‐IIIa Protects Against Cerebral Damage Via Inhibiting NF ‐ κ B Activation

Summary Aims This study was designed to examine the neuroprotective effects of bakkenolide‐IIIa, a major novel compound extracted from the rhizome of P. trichinous . Methods Transient focal cerebral damage model in rats and oxygen–glucose deprivation ( OGD ) in cultured hippocampal neurons were performed. The amount of apoptotic neurons was determined using TUNEL assay. The expressions of Bcl‐2, Bax, Akt, ERK 1/2, IKK β , I κ B α were measured using Western blot. The nuclear translocation and activation of NF ‐ κ B was measured using a fluorescence microscope and electrophoretic mobility shift assay ( EMSA ). Results Bakkenolide‐IIIa (4, 8, 16 mg/kg; i.g.) was administered immediately after reperfusion could reduce the brain infarct volume, and the neurological deficit, as well as a high dose of bakkenolide‐IIIa, increases the 72 h survival rate in cerebrally damaged rats. In vitro data demonstrated that bakkenolide‐IIIa could increase cell viability and decrease the amount of apoptotic cells in cultured primary hippocampal neurons exposed to OGD . Bakkenolide‐IIIa also dose‐dependently increased the ratio of Bcl‐2 to Bax. These results indicated that inhibition of apoptosis partly mediated the neuroprotection of bakkenolide‐IIIa. Furthermore, bakkenolide‐IIIa inhibited the phosphorylation of Akt, ERK 1/2, IKK β , I κ B α , and p65 in cultured hippocampal neurons exposed to OGD . Bakkenolide‐IIIa not only inhibited the nuclear translocation of NF ‐ κ B in cultured neurons exposed to OGD , but also inhibited the activation of NF ‐ κ B in peri‐infarct area in cerebrally damaged rats. Conclusion Collectively, our findings indicated that bakkenolide‐IIIa protects against cerebral damage by inhibiting AKT and ERK 1/2 activation and inactivated NF ‐ κ B signaling.