摘要
論 文 摘 要 延胡索，又名元胡，為罌粟科(Papaveraceae)植物延胡索Corydalis yanhusuo W.T. Wang的乾燥塊莖，具有良好鎮痛作用，歷來用於治療頭痛、腹痛、月經痛，尤為婦科之要藥。本研究首先探討中藥典籍中記載具有鎮痛作用之中藥，如延胡索、芍藥、甘草、三七、香附子、苦參、山豆根、槐花等，其50%酒精萃取物，對醋酸誘導疼痛之抑制作用比較，結果顯示延胡索萃取物之抑制作用最強，且有劑量依存性的抑制疼痛作用，其IC50為129.3mg/kg，具有明顯且穩定鎮痛生理活性。 因此對延胡索進行活性成分之萃取及分離，大量延胡索以甲醇萃取，依生物鹼之分離法分離三級鹽基及四級鹽基，配合生物活性側定法之追蹤，結果三級鹽基具活性，再經部分分離及Aluminum Oxide column，得d-Corydaline及l-Tetrahydrocolumbamine兩種成分。 d-Corydaline及l-Tetrahydrocolumbamine以醋酸誘導疼痛為實驗模式進行鎮痛活性實驗，無論以皮下注射或口服方式給藥，均有劑量依存性的抑制疼痛作用，皮下注射給藥之IC50分別為39.7mg/kg及50.4mg/kg，d-Corydaline鎮痛作用較 l-Tetrahydrocolumbamine為強；口服給藥之IC50分別為19.8 mg/kg及62.9 mg/kg，d-Corydaline鎮痛作用強度為Morphine HCl之1/10，為l-Tetrahydrocolumbamine之三倍。另口服給藥時， d-Corydaline與嗎啡併用，可增強嗎啡鎮痛效果。若事先投予Naloxone (4 mg/kg,s.c.)，再投予延胡索50%酒精萃取物、 d-Corydaline及l-Tetrahydrocolumbamine之鎮痛結果，顯示鎮痛作用機轉與類阿片系統無關，應不具成癮性。 綜合以上之結果，延胡索之生物鹼成分d-Corydaline及 l-Tetrahydrocolumbamine具有明顯且穩定之生理活性，故可作為延胡索中藥材品質管制之兩個指標成分。另d-Corydaline無嗎啡之成癮性，與嗎啡合用可降低嗎啡之劑量，因而降低嗎啡之副作用，可應用作為中西藥整合良好輔助治療。 關鍵詞：延胡索，鎮痛，中藥材，機制，d-Corydaline， l-Tetrahydrocolumbamine
並列摘要
Abstract Corydalis tuber ( Yan-hu-suo in Chinese, The dry tuber of Corydalis yanhusuo W. T. Wang , Papaveraceae ) has been used for treatment of various pain : such as headache, abdominal pain, menstrual pain in traditional Chinese medicine. According to the Chinese herbal literatures, there are many Chinese herbs, such as Coicis semen, Corydalis tuber, Paeoniae radix rubra, Sophorae subprostratae radix, Aconiti sinensis tuber, Sophorae radix, Glycyrrhizae radix, Sophorae immaturi flos, Pseudoginseng radix, having analgesic effect. The first aim of this study was to investigate the antinociceptive effect of 50%ethanol extracts of those Chinese herbs mentioned above and the extract of Corydalis tuber showed more potent analgesic effect than others. The extract of Corydalis tuber has significant antinociceptive effect in a dose dependent manner on acetic acid-induced writhing assay in mice. Large amount of dry Corydalis tuber was extracted with methanol. The extract was separated to give tertiary and quaternary base of the alkaloids. The tertiary base of alkaloid has analgesic effect, when it was tested with biological assay. The crud alkaloid mixture was separated by partition and aluminum oxide column chromatography to give l-Tetrahydrocolumbamine and d-Corydaline. d-Corydaline or l-Tetrahydrocolumbamine administered by s.c., or p.o. produced significant and dose-related antinociception on acetic acid-induced writhing assay in mice. At the IC50 level, d-Corydaline (as a suspension in Tween 80 , p.o.) was about 10-times less potent than morphine HCl (p.o.), and was about 3-times more potent than l-Tetrahydrocolumbamine (as a suspension in Tween 80 , p.o.). 50% ethanol extract of Corydalis tuber, l-Tetrahydrocolumbamine or d-Corydaline were insensitive to naloxone, suggesting the lack of involvement with endogenous opioid. Consequently they do not have the side effect of addiction. In conclusion, l-Tetrahydrocolumbamine and d-Corydaline are shown to have prominent activity of analgesia and stable chemical property, and they can be chosen as the indicator components of the material of corydalis tuber, when it is taken for quality control. Having the pharmacological activity of analgesia, d-Corydaline can reduce the dose of morphine when it is used with morphine, so that the adverse effects of morphine can be reduced, d-Corydaline can be used in the complimentary therapy of pain control. Key words: Corydalis tuber, Herbs, Analgesic, mechanism, d-Corydaline, l-Tetrahydrocolumbamine.