Ursolic acid alleviates early brain injury after experimental subarachnoid hemorrhage by suppressing TLR4-mediated inflammatory pathway.

Our previous studies proved that ursolic acid (UA) protected against early brain injury (EBI) by modulating oxidative stress after experimental subarachnoid hemorrhage (SAH), but it has not been evaluated yet about its effects on an inflammatory pathway in a SAH model. This study was undertaken to evaluate the influence of UA on the toll-like receptor 4 (TLR4) signaling pathway after SAH. Adult male SD rats were divided into vehicle-treated sham, vehicle-treated SAH, and UA-treated SAH groups. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 48 h after SAH. UA administration markedly decreased the expressions of TLR4 pathway-related agents, such as intercellular adhesion molecule-1 (ICAM-1), TLR4, nuclear factor-κB (NF-κB) P65, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9. Apoptosis detected by TUNEL indicated that fewer positive cells appeared in UA administration SAH groups than the control group. In conclusion, UA may attenuate EBI after SAH in rats by suppressing the TLR4-mediated inflammatory pathway.