To observe the protective effect and mechanism of low-dose Ligusticum chuanxiong for long-term administration on delaying aging brain by constructing an aging rat model with blood stasis，to provide a basis for clinical medication of L.chuanxiong.Methods:A total of 66 SD rats were divided into blank group，model group，vitamin E group，2 g L.chuanxiong group，4 g L.chuanxiong group and 2 g L.chuanxiong+Panax ginseng group，with 11 in each group.All groups，except the blank group，were given D-galactose(300 mg/kg，ip) for 42 consecutive days，during which drugs were administered for 14 days.On the 15th day，the rats were given ice water bath for 20 minutes for 14 consecutive days，and 0.1% of 0.8 mg/kg adrenaline was injected on the last day.Serum superoxide dismutase(SOD) was detected by WST-1 assay，and the glutathione peroxidase(GSH-Px) activity and total antioxidant capacity(T-AOC) was detected by colorimetry.Malondialdehyde(MDA)，a product of lipid peroxidation，was detected by thiobarbituric acid(TBA) method.Enzyme-linked immunosorbent assay was performed to determine the content of protein carbonyl compounds(PC) and the contents of nitric oxide(NO)，endothelial nitric oxide synthase(eNOS)，thromboxane B2(TXB2) and endothelin-1(ET-1) in brain tissue.Western blot was used to detect the expressions of phosphatidylinositol 3-kinase(PI3K)，protein kinase B(AKT) and hypoxia-inducible factor 1α(HIF-1α) in brain tissue.Results:Compared with the blank group，the model group had decreased body weight(P<0.001)，lowered SOD，GSH-Px and T-AOC(P<0.001，P<0.01，P<0.01)，eNOS(P<0.01) and HIF-1α(P<0.05) and increased MDA and PC(P<0.001) and NO，TXB2 and ET-1(P<0.001，P<0.05，P<0.001).Compared with the model group，2 g and 4 g L.chuanxiong up-regulated GSH-Px，enhanced T-AOC，reduced NO，TXB2 and ET-1，and elevated eNOS(P<0.01).In addition，4 g L.chuanxiong increased HIF-1α(P<0.01).After combination of 1 g L.chuanxiong and 1 g P.ginseng，SOD and GSH-Px were elevated，while MDA and PC were lowered; there was a decrease in NO，TXB2 and ET-1(P<0.001，P<0.05，P<0.001) while an increase in eNOS(P<0.001); HIF-1α was increased(P<0.01).Conclusion:For the aging rat model with blood stasis，low-dose L.chuanxiong can improve endothelial function and inhibit oxidative stress，exerting an antioxidant effect.L.chuanxiong at a reduced dose plays a synergistic role with P.ginseng，which may protect the brain through HIF-1α pathway.