To study the lignans from Parthenium hysterophorus Linn.Five lignans (1-5) were isolated from the 95% ethanol extract of the aerial parts of P. hysterophorus by silica gel,Sephadex LH-20,MCI,ODS,and preparative HPLC chromatographic techniques.Their structures were established on the basis of extensive spectroscopic analysis and comparison with the data in reported literatures.As a result,five compounds were identified as (7S,8S,7′E)-4,9,9′-trihydroxy-3,5,7,3′,5′-pentamethoxy-8,4′-oxyneolign-7′-ene (1),syringaresinol (2),medioresinol (3),pinoresinol (4),schisandrin (5).Compound 1 was a new compound,and compounds 3-5 were isolated from P. hysterophorus for the first time.All the compounds were screened for their in vitro anti-neuroinflammatory activities,and the results showed that compound 1 displayed significant activity with an IC₅₀ value of 21.10 ± 1.97 μmol/L.The other compounds were inactive,and all the compounds didn′t affect the cell survival under the test concentrations.