Abstract: | 本研究利用 GC/MS 對具有鎮咳和祛痰效果之款冬花製品和抗神經毒性之藤紫丹進行吡咯里西啶生物鹼 (pyrrolizidine alkaloids, PAs) 之定性和定量,更進一步利用高效能液相層析儀將藤紫丹之主要 PAs 化合物 9-angeloylretronecine分離純化,並以NMR鑑定其結構後作為標準品。款冬花的部分,本研究蒐集藥局販售含款冬花之複方成藥及科學中藥,在這些樣品中發現至少有 11 個 PAs 化合物,分別為: 7-angeloylretronecine、9-angeloylretronecine、7-tigloylplatynecine、9-angelyl- platynecine、sencecionine、bulgarsenine、integerrimine、platyphylline、neoplatyphylline、senkirkine、neosenkirkine,其中有七個 PAs 化合物在款冬花中首次發現,PAs 化合物為 otonecine 型態的 senkirkine 含量比其餘 PAs 化合物多出數倍,在科學中藥之 PAs 化合物總含量為 24.93±9.04~55.54±14.21 μg/g,複方成藥則為 0.24~8.72 μg/g。藤紫丹的部分則從青草店購得,經 GC/MS 分析後發現藤紫丹至少有 17 個 PAs 化合物,分別為: 9-angeloyltrachelamthamidine、9-senecioyltrachelamthamidine、9-tigloyltrachelam- thamidine、unknown、7-angeloylretronecine、9-angeloylretronecine、macrophylline、7-senecioylretronecine/7-tigloylretronecine、9-senecioyletronecine、macrophylline isomer、9-tigloylretronecine、viridiflorine、supinine、amabiline/ coromandalinine、lycopsamine、rinderine、3'-acetylechinatine/3'-acetyllycopsamine。這 17 個 PAs 化合物皆為 monoester,藤紫丹中主要含量之 PAs 化合物為 retronecine 型態之monoester 的 9-angeloylretronecine。11 批之藤紫丹的 PAs 化合物總含量為 25±3.8~69.51±2.57 μg/g。款冬花及藤紫丹之定量結果依 EFSA 所訂定之標準,並按照適當的方法服用,短期內不會有中毒的可能,但仍需注意在長期服用下造成的肝毒性及致腫瘤的發生。本研究提供款冬花製品與藤紫丹之定性和定量結果,作為中草藥和藥品使用上之評估。
Alkaloid extracts were analysed to detect and quantify the pyrrolizidine alkaloids in Tussilage farara L. and Tournefortia sarmentosa Lam. using gas-chromatography mass spectrometry (GC/MS), and further utilize HPLC and NMR to purified and identified the major PAs 9-angeloylretronecine of T. sarmentosa. In T. farara part, the samples include dry plants, scientific Chinese medicine and Chinese medicine are collected from pharmacy stores. We have investigated eleven PAs: 7-angeloylretronecine, 9-angeloylretronecine, 7-tigloylplatynecine, 9-angelylplaty- necine, sencecionine, bulgarsenine, integerrimine, platyphylline, neoplatyphylline, senkirkine, neosenkirkine. Among them, seven PAs are detected for the first time. The main cause of the toxicity PAs as otonecine type of macrocyclic diester of senkirkine, although it’s toxicity in this 11 PAs are not the strongest, it’s content than the rest of PAs extra times. The total content of PAs in scientific Chinese medicine was 24.93±9.04~55.54±14.21 μg/g, while that of Chinese medicine was 0.24~8.72 μg/g. In the T. sarmentosa part, all samples purchased from traditional Chinese medicine stores from Taiwan. After analysis by GC/MS, We have investigated 17 PAs: 9-angeloyltrachelamthamidine, 9-senecioyltrachelamthamidine, 9-tigloyltrachelam- thamidine, unknown, 7-angeloylretronecine, 9-angeloylretronecine, macrophylline, 7-senecioylretronecine/7-tigloylretronecine, 9-senecioyletronecine, macrophylline isomer, 9-tigloylretronecine, viridiflorine, supinine, amabiline/coromandalinine, lycopsamine, rinderine, 3'-acetylechinatine/3'-acetyllycopsamine, which only supinine been reported in previous report, and the remaining PAs are detected for the first time. These 17 PAs are all monoester. The major PAs is 9-angeloylretronecine, a retronecine type, it’s toxicity is weaker than senkirkine. The average total PA concentration varied from 25±3.8~69.51±2.57 μg/g in T. sarmentosa. The quantitative results are based on recommended dietary allowance by EFSA and taken according to appropriate method, there will be no possibility of poisoning in the short term, but it’s still necessary to pay attention to the hepatotoxicity and tumorigenesis in the long term. This study will provide the qualitative and quantitative as an assessment of the use of Chinese medicines, thereby reducing the toxicity caused by the treatment. |