Chemical Constituents Of The Rhizome Of Ligusticum Chuanxiong Hort.and Their Biological Activities

The chemical constituents of the rhizome of Ligusticum chuanxiong Hort.were isolated and identified,and the anti-inflammatory and antioxidant activities of the isolated compounds were evaluated.It was found that some compounds had dual inhibitory effects against inflammatory response and oxidative stress.The rhizome of L.chuanxiong Hort.was extracted with 75%ethanol to obtain the extract,and then the petroleum ether part was obtained by petroleum ether extraction.Chemical constituents of petroleum ether extraction part of the rhizome of L.chuanxiong Hort.were separated and purified by silica gel,C18 reversed-phase silica gel,Sephadex LH-20,MCI and semi-preparative high performance liquid chromatography.Their structures were identified by means of NMR,MS and X-Ray Diffraction.The anti-inflammatory and antioxidant effects of the compounds were evaluated by NAD(P)H:quinone reductase(QR)induction assay and nitric oxide production inhibition test(NO).Twenty-nine compounds were isolated from the petroleum ether extract of the rhizome of L.chuanxiong Hort.,including two new compounds and twenty-seven known compounds.Two new phthalides are 3-butylidene-6-hydroxy-7-ethoxy-phthalide(1),1",3’-seco-1’-ethoxy-3,3a’,8,6’-diligustilide(2);twelve known phthalides are(Z)-3-butylidene-7-methoxy-phthalide(3),(Z)-butylidene phthalide(4),senkyunolide A(5),senkyunolide H(6),senkyunolide I(7),senkyunolide R(8),senkyunolide S(9),6-hydroxy-butylphthalide(10),(Z)-6-hydroxyl-7-methoxyligustilide(11),riligustilide(12),senkyunolide P(13),and levistolide A(LA,14);four aromatic compounds are vanillin(15),(E)-ferulic acid(16),ferulaldehyde(17),and(E)-coniferyl ethyl ether(18);eleven other compounds:8-O-acetylfalcarindiol(19),pregnenolone(20),β-sitosterol(21),daucosterol(22),palmitic acid(23),hexacosane(24),monononadecanoin(25),(11Z,14Z)-11,14-heptadecadienoic-1-ol(26),5,5’-dimethoxybiphenyl-2,2’-diol(27),5,5’-dibutoxy-2,2’-bifuran(28)and hexadecane(29).The anti-inflammatory and antioxidant activities of the isolated compounds were evaluated.The results showed that phthalide compounds 2,5,6,10,11,12,13,14 and compounds 17,18,20,28 showed QR-induced activity.Phthalides 3,5,’6,8,13,14,and compounds 17,18,19,20,27,28 showed NO production inhibitory activity.Compound 14 was able to induce Nrf2 transcription,and at the same time,it dose-dependen tly upregulated the protein levels of Nrf2 and its downstream genes NQO1 and γ-GCS,which indicated that 14 is an activator of Nrf2 signaling pathway.Collectively,twenty-nine compounds were isolated from the rhizome of L.chuanxiong Hort.,including two new compounds.Phthalides 5,6,13,14 and compounds 17,18,20,28 have potential anti-inflammatory and anti-oxidation activities.Among them,14(LA)is a potential agonist of Nrf2 signaling pathway.The results enrich the chemical and biological diversity of the rhizome of L.chuanxiong Hort.,suggesting that phthalides and organic phenolic acids may be the active substances of the rhizome of L.chuanxiong Hort.in intervening inflammation and oxidative stress-related diseases,which laid a foundation for the biological mechanism of the rhizome of L.chuanxiong Hort.in treating diseases in the future.