Studies On The Active Constituents Of Ainsliaea Fulvioides

The genus Ainsliaea belongs to the Compositae family and consists of around 70 species. Among them, 44 species are distributed in the south regions of China, such as Sichuan, Guizhou and Yunan provinces. Most of them have been used as a folk medicine for the treatment of rhumatism, traumatic injuries, edema, stomachache.So far, several sesquiterpenes, triterpenes and flavonoids, have been isolated from this genus. Ainsliaea fulvioides is a medicinal herb growing mainly in south of China and no phytochemical studies on this plant have been reported. In this dissertation, we investigate the chemical constituents from A. fulvioides systematically, anti-inflammatory and anti-tumor activities. Thirty-two compounds were isolated from A. fulvioides by silica gel, Sephadex LH-20, preparative HPLC and preparative TLC and twenty-eight compounds were identified as follows by spectral analysis (1H-NMR, 13C-NMR, 2D NMR, EI-MS,ESI-MS,HRESI-MS, and IR) and the relative stereochemistry of two new compounds were determined by the X-ray diffraction: TE-1: daucosterol TE-2: 4-methylbenzoic acid TE-3: 1-heptadecanol TE-4: 1-dodecanol TE-5: n-dodecane TE-6:β-sitosterol TE-7: octadecanoic acid *TE-8: ainsliadimer B TE-9: gochnatiolide B TE-10: ainsliadimer A TE-11: umbelliferone *TE-12: ainsliatrimer A *TE-13: ainsliatrimer B TE-14: aescutin TE-15: gochnatiolide A TE-16: 4-hydroxy ethylbenzoate *TE-17: ainsliatone A TE-18: 1, 2-benzenediol TE-19: spinacetin TE-20: 4-hydroxylbenzaldehyde TE-21: 3,4-dihydroxy-benzaldehyde TE-22: luteolin TE-23: ayanin TE-24: apigenin TE-25: ameliaroside TE-26: piceol TE-27: quercetin-3-O-β-D-glucoside TE-28: syringinAmong them, TE-8, TE-12, TE-13, and TE-17 were new compounds. Up to now, TE-12 and TE-13 were the first two representatives of naturally occurring guaianolide-type sesquiterpene lactone trimers. TE-17 was a new nor-sesquiterpne lactone. Others were isolated from this plant for the first time. A proposed biogenesis for these trimers was illustrated by using natural Diels–Alder reaction in this thesis.Six sesquiterpenes from this plant were in vitro evaluated for their anti-tumor activities against four human cancer cell lines, A549, LOVO, CEM and MDA-MB-435 (MDA) using MTT assay with DOX (doxorubicin) as positive control. These compounds showed potent cytotoxicites against four human cancer cell lines, and TE-15 showed significant cytotoxicites with IC50 values of 3.24,0.17,0.01 and 0.13μg/ml respectively. Three sesquiterpenes from this plant were tested for the inhibitory activity against the production of NO in RAW264.7 macrophages stimulated by lipopolysaccharide (LPS) and against NF-κB activities in pNF-κB-luc-293 cells induced by LPS. The results showed that TE-12 had the 50% inhibitory rate against NF-κB activities at 1μg/ml.