十五種常用中藥之亞急性毒性(Ⅳ)

Subacute Toxicity of 15 Commonly Used Chinese Drugs(Ⅳ)

在衛生署出版之「中華民國中藥典範」中列有400種常用中藥，但對任何毒理作用均未述及；為評估中藥之亞急性毒性，以印證藥典記載之虛實並得以實驗澄清，並為將來有關藥效及毒理評估奠定實驗的基礎，而擬定此研究。於急性一半致死劑量 1/5 至 1/10 當亞急性毒性最大耐受量之參考劑量下； 本研究觀察連續口服十四天（每日一劑）敗醬草(1, 5 g/kg)，白茅根(1, 5 g/kg)，白芷(1, 5 g/kg)，川芎(1, 5 g/kg)，黨參 1, 5g/kg)，漢防己(1, 5 g/kg)，黃精(1, 5 g/kg)，金銀花(1, 5 g/kg)，蘆薈(1, 5g/kg)，忍冬(1, 5 g/kg)，升麻(1, 5 g/kg)，松節(1, 5 g/kg)，五加皮(1, 5 g/kg)，澤瀉(1, 5 g/kg)，知母(1, 5 g/kg)等十五種常用中藥材50%乙醇抽提液對大白鼠血液常規檢驗、臨床生化、自發性運動行為及整體之亞急性毒性。其整體觀察發現：漢防己、蘆薈、澤瀉等顯著抑制攝水量；蘆薈並可抑制排尿量；臨床血液檢驗結果顯示：黨參、蘆薈等影響總白血球數；臨床血液生化結果顯示：敗醬草、白茅根、黨參、金銀花、蘆薈、松節、及知母等影響全身營養標準之參考值如血漿總蛋白質、血清白蛋白；敗醬草、川芎、金銀花、忍冬、升麻、五加皮及澤瀉等均顯著增加肝功能 SGPT 值。黃精、蘆薈、松節等導致暫時性降低而五加皮則引起初期增加腎功能 Greatinine 值。於實驗結束解剖發現除了白茅根外，其餘被試之十四種常用中藥於被試之劑量下對心、肝、肺、或腎臟器之組織重或含水量等病理指標數據均有顯著之影響。於行為毒理評估發現敗醬草、升麻、松節及五加皮等導致抑制；而川芎則引起興奮自發性運動作用。被試之十五種常用中藥被試之劑量下均未發現任何對攝食量、及血紅素含量具有統計意義上之抑制作用。於此連續十五天亞急性毒性實驗中，這十五種常用中藥在此被試劑量下均未發現任何非可逆性、肉眼可視之病理及死亡毒性副作用。藉由此實驗計劃希望對近百種常用中藥之安全性評估及毒性資料，提供中醫健保的用藥基準。

As befitting the sabline designation of 'the art of healing', traditionally the development of professional acumen in the practice of traditional Chinese medicine relies heavily on years of accumulated clinical observations. The shortcomings are the relative lack of hard evidence, systemic documentation and uniformity in interpretation, which result in the unfortunate aura of mystique and reluctance in general acceptance. Relatively little is known about the toxicological profiles of the 400-commonly-used Chinese medicinal drugs listed in the 'Standard of Chinese Drugs, ROC'. The present project, entitled 'the evaluation of the subacute toxicity of commonly used Chinese medicinal drugs', of which the present report was a part, was initiated to provide experimental evidence to support or refute vague claims in traditional Chinese pharmacopoias and reference for future studies. The subacute toxicological and behavioral effects of 50% ethanol crude extracts of the following traditional Chinese medicinal drugs administered in single dosage (5, 10 g/kg, p.o., per day for 14 days) were quantitatively evaluated: 1.Baijiangcao, 2. Baimagen, 3. Baizhi, 4. Chuanxiong, 5. Dangshen, 6. Hanfangji, 7. Huangjing, 8. Jinyinhua, 9. Luhui, 10. Rendong, 11. Shengma, 12. Songjie, 13. Wujiapi, 14. Zexie, 15. Zhimu, respectively. The maximal tolerable doses ranging from 1/10 to 1/5 of LD50 were used as the reference dosages in this subacute experiment. In gross observations. it was found the water intake was decreased significantly after continuous oral administration of Hanfangji, Luhui or Zexie. The urinary output was decreased upon treatment with Luhui was also found. In hematological assessment, it was found that total WBC counts were temporary affected by Dangshen and Luhui. Clinical blood chemistry evaluation showed that the whole body nutrient standard reference values such as plasma total protein (T-P), or serum albumin content (ALB) were affected by Baijiangcao, Baimagen, Dangshen, Jinyinhua, Luhui, Songjie, & Zhimu. The standard liver functional test such as SGPT were significantly increased by Baijiangcao, Chuanxiong, Jinyinhua, Rendong, Shengma, Wujiapi and Zexie in all tested doses. The standard kidney functional test such as creatinine was transiently decreased by Huangjing, Luhui, & Songjie, while incresed by Whjiapi in initial treatment. In urinary analysis, the protein ureci is significantly increased after continuous treatment of Chuanxiong, Dangshen, Hanfangji, Jinyinhua, Rendong, Songjie, Wujiapi & Zexie. In behavioral toxicological evaluations, it was found Baijiangcao (both tested doses, in late phase), Shengma (5 g/kg, in initial phase), Songjie (5 g/kg, in initial phase), and Wujiapi (5 g/kg, al tested period) elicited marked inhibition on the locomotor activity; while Chuanxiong (1, 5 g/kg) caused a transient stimulation effect when compared with the control group. The tissue pathological reference standards such as the net tissue weight or water content of heart, liver, lung or kidney during postmortem examination were affected by all of the tested herbs, except Baimagen. No evidence of any irreversible visible pathological damage or mortality attributable to any of the test drugs occurred during the experimental period of 15 days. It is anticipated that these retrospective studies on subacute toxicity