Acute Toxicity and Bioactivity Evaluation of Commonly Used Chinese Drugs: Analgesic Chinese Drugs

常用中藥急性毒性及生物活性之評估：止痛用中藥

楊行義(Hsing-Yi Yang) ； 陳介甫(Chieh-Fu Chen)

《中醫藥雜誌》 3卷2期 (1992/10) Pp. 41-59

https://doi.org/10.6940/JCM.199210_3(2).05

摘要

行政院衛生署所編之「中華民國中藥典範」中列有四百種常用中藥，雖然此「典範」中述及八十餘種中藥之藥理作用；但對毒理作用均未述及。本實驗測定23種東郭先生（1.Badou巴豆，2.Baijili白蒺黎，3.Chuanwu川鳥，4.Danggui當歸，5.Danshen丹參，6.Duzhong杜仲，7.Fangfeng防風，8.Fuzi附子，9.Gancao甘草，10.Goube藳本，11.Hangfangji漢防己，12.Jixueteng鷄血藤，13.Mudanpi牡冉皮，14.Mutong木通，15.Niuxi牛膝，16.Paichi白芷，17.Qinghao青蒿，18.Shengma升麻，19.Songjie松節，20.Tiannanxing天南星，21.Wuzhuyu吳茱萸，22.Xianhecao仙鶴草，23.Yanhusuo延胡索）等常用中藥材之50%乙醇粗提取物在實驗動物之一半致死量、自發性運動、踏車行爲及對止痛作用之影響。結果發現：
（一）腹腔注射後三天內之一半致死劑量1.白蒺黎，2.當歸，3.杜仲，4.藳本，5牛膝，6白芷，7.升麻，8松節，9.仙鶴草等九種中藥材大於40g/kg（原生藥重量爲單位）外，其餘十四種均有相當之毒性。
（二）腹腔注射預處理一小時，除了白蒺黎(5, 10g/kg)、川烏(1g/kg)木通(1, 2.5g/kg)及松節(5, 10g/kg)外，其餘所有被測十九種藥材均有中度至深度的抑制醋酸導致區是鼠腹部攀縮之反應。
（三）腹腔注射巴豆(2.5, 5, 10, 25mg/kg)，丹參(10g/kg)，附子(1, 2.5g/kg)，防風(5g/kg)，藳本(10g/kg)，漢防己(2.5, 5g/kg)，升麻(1g/kg)，延胡索(1, 2.5/kg)等八種中藥材具有中度生深度的延長熱板導致路鼠後肢回縮之時間。防風(5g/kg)，漢防己(5g/kg)，升麻(1g/kg)等三種中樞性抗傷害（止痛）作用可被預先30min腹腔注射atropine(1mg/kg)或naloxone(3mg/kg)明顯但非完全的阻斷。
（四）毒性作用發現巴豆產生腹瀉、黏膜發炎、呼吸困難、川鳥、附了產生心衰竭、甘草酸產生痙學、吳茱萸產生類似毒蕈素作用，臨床使用時須謹慎考慮其副作用。
（五）自發性行爲除附子(0.5, 1g/kg)，甘草酸(0.5, 1g/kg)，白芷(5g/kg)，青蒿(1g/kg)，延胡索(0.2, 1g/kg)外，其餘十八種被試中藥均有相當的抑制作用。
願此資料能充實再版「典範」中常用中藥之生物活性及毒性評估。

關鍵字

中藥 ； 急性毒性 ； 運動活動性 ； 止痛

並列摘要

Of the 400 commonly-used Chinese drugs listed in the ”Standards of Chinese Drugs, ROC”. (edited and published by the Deparment of Health, Executive Yuan, ROC), approximately 80 entries carry descriptions of their pharmacological properities, but no mention of their toxicological characteristics. Toxic profiles LD50 (medium lethal dose) and antinociceptive effects of 50% ethanol crude extracts of the following 23 traditional Chinese medicinal drugs which are prescribed as analgesic agents were evaluated quantitatively: 1. Tiglii Semen (Badou), 2. Tribuli Fructus (Baijili), 3. Aconiti Carmichaeli Radix (Chuanwu), 4. Angelicae Sinensis (Danggui), 5. Salivae Miltiorrhizae Radix (Danshen), 6. Eucommiae Cortex (Duzhong), 7. Saposhinkoviae Radix (Fangfeng), 8. Aconiti Coreani Tuber (Fuzi), 9. Glycyrrhizae Radix (Gancao), 10. Ligusticum Sinensis Rhizoma et Radix (Gouben), 11. Hanfangchi Radix (Hanfangji), 12. Millettiae Caulis (Jixueteng), 13. Moutan Radicis Cortex (Mudanpi), 14. Akebiae Caulis (Mutong), 15. Achyranthis Radix (Niuxi), 16. Angelicae Dahuriae Radix (Paichi), 17. Artemisiae Apiaceae Herba (Qinghao), 18. Cimicifugae Rhizoma (Shengma), 19. Pini Nodi Lignum (Songjie), 20. Arisaematis Rhizoma (Tiannanxing), 21. Evodiae Fructus (Wuchuyu), 22. Agrimoniae Herba (Xianhecao), and 23. Corydalidis Tuber (Yanhusuo), respectively. In the LD50 test, it was found that the LD50 of Baijili, Danshen, Danggui, Gouben, Niuxi, Paichi, Shengma, Songjie and Xianhecao were greater than 40 g/kg after oral administration of a single dose during a 3-day observation period. Adverse reactions such as diarrhea, mucous inflammation, respiratory depression for Badou; heart failure for Chuanwu & Fuzi; tremor for glycyrrhzic acid, and muscarinic effects for Wuchuyu were observed following intraperitoneal administration at higher dose in mice. In the locomotor activity test, it was found that Fuzi (0.5 g/kg), glycyrrhzic acid (0.5, 1 g/ kg), Paichi (5 g/kg), Qinghao (1 g/kg), Yanhusuo (0.2, 1 g/kg) caused no significant changes compared with control group, while all the others 18 herb extracts tested elicited a moderate to marked degree of inhibition. In the treadmill performance test, it was found that only Jisueteng( 1.25, 2.5, & 5 g/kg i.p) caused a dose-dependent and significant inhibitory effect in mice. At therapeutic dose range (less than 1/5 LD50 i. p.), the following antinociceptive results were obtained in our laboratory: (1) Intraperitoneal pretreatment with Baijili (5, 10 g/kg), Chuanwu (1g/kg), Mutong (1, 2.5 g/kg), and Songjie (5, 10 g/kg) caused no significant antinociceptive effects in mice, as determined either by the hot-plate method or acetic acid-induced abdominal constrictive response. (2) Intraperitoneal pretreatment one hour in advance, Badou, Danggui, Danshen, Duzhong, Fangfeng, Chuanwu, Gancao, Gouben, Hanfangji, Jixueteng, Mudanpi, Niuxi, Paichi, Qinghao, Shengma, Tiannanxing, Wuchuyu, Xianhecao, Yanhusuo elicited moderate to marked antinociceptive effects as dertermined by acetic acid-induced abdominal constrictive response. (3) Intraperitoneal pretreatment with Badou (2.5, 5, 10, 25 mg/kg), Danshen (10 g/kg), Fugi (1, 2.5 g/kg), Fangfeng (5 g/kg), Gouben (10 g/kg), Hanfangji (2.5, 5 g/kg), Shengma (1 g/kg). Yanhusuo (1, 2.5 g/kg) elicited moderate to marked antinociceptive effects as determined by the hot plate method. The centrally-mediated antinociceptive effects of Fangfeng (5 g/kg), Hanfangji (5 g/kg), and Shengma (1 g/kg) could be effectively and significantly blocked by atropine (1 mg/kg i.p. at -30 min) or naloxone (3 mg/kg i.p. at -30 min). It is anticipated that the results from this study will provide a reliable standard for the toxicity and bioactivity of those Chinese drugs which are commonly prescribed in ROC.

並列關鍵字

Chinese medicine ； Acute toxicity ； Locomotor activity ； Analgesic effect