中草藥之止血與血小板活性探討

Hemostatic and Anti-Platelet Aggregation Activities of Natural Sources

李銘坤(Ming-Kun Lee)

指導教授 ： 楊玲玲 ； 顏焜熒

臺北醫學大學/藥學院/生藥學研究所/碩士(1999年)

摘要

出血性疾病及血栓症為歷年常見之血液功能不全疾病,而臨床上所使用之凝血藥與抗凝血藥,常有出血,過敏,身體不適等副作用,因此本論文將以具止血作用之中藥材及天然物中之香豆素成分分二部分進行活性探討. 第一部分止血中藥之活性評估,以Tajima's Method評估白芨(Bletilla striata Reichenbach fil)5%,2.5%及1.25%及花生皮(Arachis hypogaea)皮萃取物15.2mg/ml,7.6mg/ml及3.8mg/ml三種濃度水溶液,對正常鼷鼠,評估?凝血時間(coagulation time)?出血時間(bleeding time)?血小板數目變化,及?以Heparin誘導之病理性出血時間(pathological bleeding time);由各萃取物於體外對膠原(collagen)，及腺?酸二磷酸(ADP)所誘導人體富含血小板血漿(Platelet Rich plasma)之凝集活性,其結果如下: (1)白芨: 5%, 2.5%及1.25%白芨水溶液對正常動物之凝血時間，出血時間,及對於肝素(Heparin)誘導之病理性出血時間均有明顯之縮短效果,同時發現對正常動物之血小板數亦有增加趨勢。另,比較白芨分別以水,50%甲醇,及70%丙酮各種萃取物之血小板凝集活性,結果以水萃取物於1000mg/ml及100mg/ml下,顯示對膠原(collagen)及腺?酸二磷酸(ADP)誘導之血小板凝集具有促進作用.由以上結果,除證實傳統白芨水抽取物具有止血作用,乃因其能增加血小板數目及凝集之促進外,我國傳統以水做為中藥煎煮之溶液仍是較佳之方式. (2)落花生: 落花生96%酒精萃取物15.2mg/ml,7.6mg/ml及3.8mg/ml對正常動物之凝血時間,出血時間,與肝素(Heparin)誘導之病理性出血時間皆有明顯之縮短外,亦增加正常動物之血小板數目。且100mg/ml下對膠原(collagen)及腺?酸二磷酸(ADP)所誘導血小板凝集作用有促進作用。以上結果證實落花生具有止血之作用,其作用方式與白芨相似。 綜合以上結果,白芨與落花生的確具有止血之活性,且白芨止血有效成分,以水抽取之傳統中藥水煎煮方式仍為較安全之溶液。 第二部分抗血栓天然物之開發研究,以14種?喃香豆素(Furanocoumarin),其中包括2種Angelicin type 及12種Psoralen type ,依濁度測定法(the turbidimetric method)評估以膠原(collagen)、腺?酸二磷酸(ADP) 、花生四烯酸(arachidonic acid) 、 凝血?(Thrombin)及血小板活化物質(Platelet activinr factor)為誘導劑,進行人體富含血小板血漿凝集試驗與對照組Aspirin比較，結果顯示Angelicin type 中，Sphondin具顯著抑制血小板凝集活性。而Psoralen type 中，則以Bergapten對於collagen，Phellopterin對於ADP ，Bergapten對於Thrombin及Sphondin對於PAF所

關鍵字

白芨 ； 落花生 ； 止血活性 ； 天然香豆素 ； 抗血小板凝集

並列摘要

Hemostatic Abnormalities including the hemorrhage and thrombosis are the common diseases in human.There are still many sede effects in therapy drugs up to the present day. So this research uses the traditionalchinese hemostatic herbs and natural occurring furocoumarins and evaluates the hemostatic and anti-platelet activities of them.And the paper is divided into two parts. Part one. Bletillae tuber is the dried stem of the Orchidaceae plant Bletilla striata Thunb. It is used in traditional Chinese medicine with clinical application for lung, nose, and stomach hemorrhageing as well as for ameliorating post-operative bleeding, burns, and dermal splitting caused by aridity. At present research of the Bletillae tuber is limited to antibiotic applications and none has yet been conducted into hemostasis. The Dictionary of Traditional Chinese Medicine records that oral intake of the entire peanut (minus the shell) is effective in slowing bleeding in hemophiliacs. According to the dictionary, the potency of the skin is 50 times that of the nut . We still do not understand the principles behind this. This research project employs the delivery method of traditional chinese method and mixes powered Bletilla tuber into a 1.25%, 2.5%, and 5% gel solutions and peanut skinof Arachis hypogaea into 15.2mg/ml, 7.6mg/ml and 3.8mg/ml. Oral administration is given to both normal mice and heparin-induced pathological bleeding animal model of ICR mice to determine coagulation time, bleeding time, and changes in platelet count to assess the hemostatic activity of the bletillae tuber and arachis hypogaea. The resul The platelet aggregation of water extract, 50% methanol extract and 70% acetone extract of bletillae tuber and 96% Alcohol extract of peanut skinof Arachis hypogaea to collagen and ADP induced platelet aggregation in platelet rich plasma (PRP) from healthy blood donors. The results exhibited that the water extract of bletilla striata and 96% alcohol extract of Arachis hypogaea promoted the induced platelet aggregation . Part two.The anti-platelet aggregation of 14 furocoumarins including 2 angelicin type and 12 psoralen type to Collagen, ADP, arachidonic acid, Thrombin and PAF induced platelet aggregation in platelet rich plasma (PRP) from the healthy blood donors (without taking any medicine 2 week before) by the turbidimetric method. Aspirin is used as the positive control group. The results exhibited that Bergapten to the collagen, Phellopterin to the ADP, Psoralen to the Arachidonic acid, and Sphondin to the Thrombin a Psoralen (C5-H and C8-H ) is the most potency compound to the A.A induced platelet aggregation. If the side chain of C5 and C8 position are replaced with others , the anti-platelet activities will be decreased. Angelicin type show more potency than psoralen type in Thrombin and PAF induced platelet aggregation.The Sphondin (C5-H and C8-OCH3) shows the best anti-platelet activities to the thrombin and PAF induced platelet aggregation. When the side chain of C5 and C8 positions are exchanged ,it shows almost

並列關鍵字

Bletilla striata ； Arachis hypogaea ； Hemostasis ； Furocoumarin ； Anti-platelet aggregation

參考文獻

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