【作者】 杨炳友；

【导师】 匡海学；

【作者基本信息】 黑龙江中医药大学 ， 中药学， 2005， 博士

【摘要】 洋金花为茄科植物白曼陀罗Datura metel L.的干燥花,又名曼陀罗花、风茄花、山茄子、大颠茄和白花曼陀罗等。洋金花生理活性较强,药用历史悠久,应用十分广泛。《中国药典》2005版记载其性味辛、温,有小毒;具平喘止咳、镇痛解痉、麻醉之功效。近年来临床应用洋金花制剂治疗银屑病取得了显著的治疗效果,但对洋金花中治疗银屑病活性成分及其药理作用的研究鲜有报道。为了确定洋金花中治疗银屑病的有效部位,并深入阐明有效部位中的活性成分,对洋金花50%EtOH提取组分进行了药理学实验和化学成分研究。 本文首次从病理环节入手,进行了抗炎、抗瘙痒、抗增殖及对免疫功能的影响等方面的药理学研究,结果表明洋金花50%EtOH提取组分制成的洋金花胶囊具有抗炎、抗皮肤瘙痒、促进皮肤鳞片角化、抗过敏、对抗有丝分裂数等药理作用,其对体液免疫有一定的抑制作用,但对细胞免疫无明显影响。首次确定了洋金花50%EtOH提取组分是治疗银屑病的有效部位。 本文对洋金花治疗银屑病的有效部位进行了系统的提取分离和结构鉴定研究。通过硅胶、ODS、Sephadex LH-20等柱色谱和HPLC等手段,分离出58个化合物,采用¹H-NMR、¹³C-NMR、¹H-¹HCOSY、¹H-¹³CCOSY、HMBC和NOESY等1D及2D-NMR波谱学测试技术,并结合ESI-MS、FAB-MS等质谱,鉴定了40个化合物的结构,其中有25个醉茄内酯类化合物、2个酰胺类化合物、3个木脂素类化合物、3个倍半萜类化合物,7个芳香族类化合物。在这40个化合物中,确定有17个醉茄内酯类化合物和2个酰胺类化合物为新化合物,另有15个化合物在该植物中首次发现。19个新化合物分别被命名为洋金花素A（5α,12β,15β-trihydroxy-6α,7α-epoxy-（20R,22R）-1-oxo-witha-2,24-dienolide）、洋金花素B（5α,6β,15β,21-tetrahydroxy-（20R,22R）-1-oxo-witha-24-enolide）、洋金花素C（5α,6β,12β,21-tetrahydroxy-27-O-methyl-（20R,22R）-1-oxo-witha-2,24-dienolide）、洋金花素D（5α,6β,12β,21-tetrahydroxy-（20R,22R）-1-oxo-witha-24-enolide）、洋金花素E（5α,6β,12β,21-tetrahydroxy-（20R,22R）-1-oxo-witha-2,24-dienolide）、洋金花素F（5α,6β,12β-trihydroxy-27-methoxy-21,24-epoxy-（20S,22R,25S）-1-oxo-witha-2-enolide）、洋金花素G（5α,6β,12β,27-tetrahydroxy-21,24-epoxy-（20S,22R,25S）-1-oxo-witha-2-enolide）、洋金花素H[E-1,10-seco-6β,12β,27-trihydroxy-（20R,22R）-witha-3,5,24-trieno-lide-1-acid]。洋金花苷B（5α,27-dihydroxy-6α,7α-epoxy-（20R,22R）-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside）、洋金花苷C（5α,12β,27-trihydroxy-6α,7α-epoxy-（20R,22R）-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside）、洋金花苷D（5α,6α,7β,27-tetrahydroxy-（20R,22R）-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside）、洋金花苷E（5α,6β,7α,27-tetrahydroxy-（20R,22R）-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside）、洋金花苷F（5α,6β,7α,12β,27-pentahydroxy-（20R,22R）-1-oxowitha-2,24-dienolide-27-O-β—glucopyranoside）、更多还原

【Abstract】 Flos Datura is the dry flower of Datura metel L which belongs to the family of Solananeae. It was recorded originally in 《Compendium of Materia Medica 》 and has been recorded in every edition of 《Chinese Pharmacopoeia》 including the newest edition in 2005. It has the long history to be used as traditional Chinese medicine and utilized widely to cure many diseases such as cough, asthma, convulsion, etc. due to its strong and wide biological activities. It has been reported that clinical use of Flos Datura showed significant effect on the treatment of psoriasis .However.few of works on its active constituents and pharmacological effects related to the treatment of psoriasis are reported .Chemical and pharmaceutical research have been conducted on the part extracted with 50% ethanol from Flos Datura for the aims of searching the effective section and further determining the active compounds for psoriasis. The experiment results confirmed that the capsules made from the extracted with 50% ethanol from Flos Datura had the effects of antiinflammation, inhibiting skin itch, improving the cutinization of skin scales , antiallergic and inhibiting mitosis. This suggested that the capsules of Flos Datura could inhibit the immunity of body fluid, but not the cell immunity. It is the first time that the chemical constituents extracted with 50% ethanol from Flos Datura was confirmed to be the effective part for the treatment of psoriasis .In the course of our studies on chemical constituents in effective parts of treating psoriasis, 58 compounds were isolated with silica, gel, reversed-phase (ODS) , Sephadex LH-20 column chromatography and HPLC, of which the structures of 40 compounds were fully determined according to the chemical and physicochemical evidence (1D and 2D-NMR). 19 novel compounds were firstly reported and 15 compounds were firstly found in Datara metel L .Among them there are 25 withanolide compounds, 3 lignans compounds, 3 sesquiterpenoids compounds, 2 amide compounds and 7 others.The withanolides comprise a group of complex sterodial lactones which occur in the Solanaceae family. They are of considerable phytochemical, chemotaxonomic and biological interest.The structures of the nine hovel withanolide glycosides were identified as Daturameteloside B (5α, 27-dihydroxy-6α, 7α- epoxy-(20R, 22R)-1-oxo-witha-2, 24-dienolide -27-O-β-D-glucopyranoside), Daturameteloside C (5α, 12β, 27-trihydro-xy-6α, 7α-epoxy- (20R, 22R) -1- oxo-witha-2,24-dienolide- 27-O-β-D-glucopyranosi-de), Daturameteloside D (5α,6α,7β,27-tetrahydroxy - (20R, 22R) -1-oxo-witha-2, 24-dienolide -27-O-β-D-Glucopyranoside), DaturametelosideE (5α, 6β, 7a, 27-tetrahydroxy - (20R, 22R) -1-oxo-witha-2, 24-dienolide -27-O-β-D-glucopyranoside),更多还原