血根鹼被認為與造成人類流行病水腫有很大之關係。流行病水腫主要
是因為食用了污染的芥子油中毒而導致之結果，其臨床症狀包括了水腫﹑
心衰竭﹑呼吸困難﹑巨肝等。血根鹼也已知會對脊椎動物產生毒性導致呼
吸麻痺而死亡，同時亦有報導指出血根鹼具細胞及肝毒性。除了毒性之外，
有許多報導證實血根鹼具多種藥理活性，且被用在許多產品，如漱口水﹑
牙膏以及咳嗽和感冒成藥中。雖然有關血根鹼的毒性已有許多報導，但其
致毒機制仍不十分清楚。因此，我們將於本計畫中針對血根鹼之致毒機制
作一深入的研究。
在去年度的實驗中，我們以分離之橫膈膜、胸主動脈以及心肌來探討
血根鹼之毒性與藥性。我們證實了血根鹼確實會透過不同的機制造成橫膈
膜之巒縮而導至肌肉的麻痺，抑制血管之收縮作用，並觀察到血根鹼會誘
發心臟肌肉之巒縮。本年度，我們證實了將進一步探討血根鹼造成心臟肌
肉之巒縮主要是透過鈣離子內流的作用所引起的。同時，我們亦證實了血
根鹼確實會對肝細胞造成傷害，主要是透過對粒線體的傷害而來。Sanguinarine, a benzophenanthridine alkaloid, has been implicated in outbreaks of
human poisoning known as epidemic dropsy which is characterized by edema of the legs,
congestive heart failure, hepatomegaly, ataxia and glaucoma. Sanguinarine is toxic to
vertebrates when administered orally or intraperitoneally with death resulting mainly from
respiratory paralysis. Sanguinarine is shown to be cytotoxic and a possible liver toxin.
Besides its toxicity, sanguinarine has been used in many over-the counter products including
toothpaste, mouthwash, cough and cold remedies, and homeopathic preparations. Although
much more with respect to the toxic effects of sanguinarine has been carried out, the
mechanism of action of this compound is still unclear. The goal for current project is to
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elucidate the toxic effect of sanguinarine on respiratory and cardiovascular system and liver
and the possible underline mechanism of action.
In previous year, by using the isolated diaphragm, thoracic aorta and cardiac muscle
strips, we have found that sanguinarine could directly induce contracture of diaphragm and
leading to the paralysis of the muscle, inhibit the agonist-induced vasocontraction of the aorta,
and induce contracture of the cardiac muscle through different mechanisms. In this year, we
have proof that the contracture induced by sanguinarine in the cardiac muscle is mainly due to
the induction of calcium influx. We have also found that sanguinarine is cytotoxic to the
hepatocyte possibly due to the inhibition of mitochondria
