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    題名: 常用烏頭屬藥材及相關製劑之藥理與毒理活性評估
    Evaluation of the Toxicity and the Pharmacology of Aconitum Herbs
    作者: 賴美州
    貢獻者: 中國藥學暨中藥資源學系博士班
    關鍵詞: 烏頭屬;川烏;草烏 Aconitum;Chuan Wu;Cao Wu
    日期: 2011-07-27
    上傳時間: 2011-10-17 16:00:07 (UTC+8)
    出版者: 中國醫藥大學
    摘要: 烏頭屬植物屬於毛茛科多年生草本植物,屬於有毒植物,需經炮製,降低毒性增進療效,使藥物在臨床上使用更加安全。烏頭屬植物中的川烏、草烏、天雄及附子為常用中藥。在中國及日本許多傳統中藥中,使用Aconitum屬植物,廣泛應用在鎮痛、抗發炎、降血糖和治療神經系統方面的疾病。烏頭屬植物均可減少由醋酸所引起疼痛之扭體次數。川烏、草烏、天雄及附子,能減少福馬林引起之前後期舔足反應時間。對中樞及周邊具有止痛作用。其鎮痛效果與抑制花生四烯酸代謝,減少前列腺素合成有關。抗發炎試驗中川烏、草烏、天雄及附子粗萃物可明顯抑制λ-carrageenan誘導的急性足蹠腫脹。抗發炎作用機轉可能藉由提升肝臟中抗氧化酵素,而利於清除自由基;此外亦能抑制發炎足蹠組織中MAD含量,而減少脂質過氧化;抑制TNF-α的活性,進而減少前列腺素的生成,而達到抗發炎的作用。草烏在清除DPPH自由基能力、Trolox當量總抗氧化能力、還原力等實驗評估上均具有最好的抗氧化能力;川烏次之,天雄、附子則較無抗氧化之活性。總酚類、類黃酮類和黃酮醇類含量之測定結果,亦顯示總酚類、類黃酮類和黃酮醇類含量以草烏最高,繼而為川烏、天雄和附子。在降血糖表現上,毛茛科烏頭屬植物皆可降低血糖,STZ(streptozotocin)及DIO(diet-induced obesity)所誘導的第1及第2型糖尿病的大鼠,分別以附子及天雄為最佳。在急性毒性試驗上,經炮製後的烏頭屬植物,其毒性均降低。在慢性毒性試驗,烏頭屬藥材於中劑量(600 mg
    /kg/day)或是高劑量(3000 mg/kg/day)連續使用3個月後,大鼠即會出現腎損傷;尤其是以高劑量草烏(3000 mg/kg/day)處理的大鼠腎損傷的情況最為嚴重且其腎球體間質細胞明顯的擴大,同時腎臟中轉化生長因子(TGF-β1)有過度表現的現象,天雄引至腎臟傷害的能力最輕微。在成分分析方面以aconitine、mesaconitine及hypaconitine為指標成分,以草烏的生物鹼含量最高,其次為川烏、天雄及附子。
    將上述所得的結果,將毒性較低藥效較佳的天雄,應用在含有烏頭屬成分常用方劑-八味地黃丸、六味地黃丸、天雄及肉桂對DIO所誘導的第2型糖尿病的大鼠進行比較。六味地黃丸及八味地黃丸對第2型糖尿病大鼠的血糖、血脂及腎功能上有很好的改善效果。但單獨或合併使用天雄或肉桂,對第2型糖尿病的大鼠腎功能反而有害。此外,將烏頭屬植物製成軟膏,以川烏軟膏對傷口癒合度最佳。綜合本研究結果,烏頭屬植物在鎮痛、抗炎、抗氧化及降血糖之作用,具有一定之效果,未來應可開發作為臨床上的輔助治療藥物使用。
    In the anti-inflammation experiments, Chuan Wu, Cao Wu, Tian Syong, and Fu Zih can also significantly inhibit the λ-carrageenan-induced paw edema. Mechanism of anti-inflammation may increase significantly antioxidant activities and can be conducive to the elimination of free radicals. In addition, the mechanism can reduce the MDA level in paw content and subsequently the lipid peroxidaton. TNF-α activities are accordingly suppressed and the prostaglandin production reduced; however, the anti-inflammation can be achieved. By means of promoting the anti-oxidation enzyme in livers, In terms of the scavenging of free radicals and Trolox equivalent capacity (TEAC), Cao Wu has the best anti-oxidation effects in experiment; Chuan Wu comes in second. However, Tian Syong and Fu Zih have the least anti-oxidation effects. In terms of total polyphenols, flavonoids and flavonols tests, Cao Wu ranges the highest in containing the three elements tested, followed by Chuan Wu, Tian Syong and Fu Zih.In terms of reducing blood sugar, the commonly used Aconitum herbs (Chuan Wu, Cao Wu, Tian Syong and Fu Zih) are all very effective. Type 1 and Type 2 rats with STZ-induced diabetic and DIO-induced diabetic Fu Zih and Tian Syong are most effective in this respect.In acute toxicity tests, the toxicity of the Aconitum herbs is reduced after preparation. In chronic toxicity tests, rats who have received repeated oral treatment at medium dose (600 mg/kg/day) and high dose (3000 mg/kg/day) for three months is tested with serious renal damage. Those rats having received the highest dose (3000 mg/kg/day) suffer from the most renal damage and the most enhanced degree of mesangial expansion and higher expression of TGF-
    顯示於類別:[中國藥學暨中藥資源學系暨碩博班] 博碩士論文

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