Department of Pharmacology, Institute of Post Graduate Medical Education and Research, 244 B, Acharya JC Bose Road, Kolkata, 700 020, India.
Free Radic Res. 2009;43(11):1101-10. doi: 10.1080/10715760903186124.
Berberine chloride, a quarternary isoquinoline alkaloid, is a promising anti-leishmanial compound, IC(50) being 7.1 microM in L. donovani promastigotes. This leishmanicidal activity was initiated by its pro-oxidant effect, evidenced by enhanced generation of reactive oxygen intermediates that was accompanied by depletion of thiols; pre-incubation in N-acetyl cysteine, attenuated its cell viability, corroborating that generation of free radicals triggered its parasiticidal activity. Externalization of phosphatidylserine and elevation of intracellular calcium preceded depolarization of the mitochondrial membrane potential, which translated into an increase in the sub G(0)/G(1) population and was accompanied by DNA laddering, hallmarks of apoptosis. Berberine chloride failed to induce caspase activity and anti-leishmanial activity in the presence of a pan caspase inhibitor, Z-Val-Ala-DL-Asp (methoxy)-fluoromethylketone remained unchanged, which indicated that the apoptosis was caspase independent. Collectively, the data indicates that Berberine chloride triggers an apoptosis-like death following enhanced generation of reactive oxygen species, thus meriting further pharmacological investigations.
盐酸小檗碱，一种季铵异喹啉生物碱，是一种很有前途的抗利什曼原虫化合物，在 L. donovani 前鞭毛体中的 IC(50)为 7.1 μM。这种杀利什曼原虫活性是由其促氧化剂作用引发的，这一点可以通过增强活性氧中间体的产生来证明，同时伴随着硫醇的耗竭；用 N-乙酰半胱氨酸预先孵育会减弱其细胞活力，这证实了自由基的产生触发了其杀寄生虫活性。磷脂酰丝氨酸的外化和细胞内钙离子的升高先于线粒体膜电位的去极化，这转化为 G0/G1 亚群的增加，并伴随着 DNA 梯状条带，这是细胞凋亡的标志。盐酸小檗碱在存在泛半胱天冬酶抑制剂 Z-Val-Ala-DL-Asp（甲氧基）-氟甲基酮的情况下未能诱导半胱天冬酶活性和抗利什曼原虫活性，其活性保持不变，这表明凋亡是半胱天冬酶非依赖性的。总的来说，这些数据表明盐酸小檗碱在增强活性氧生成后引发类似细胞凋亡的死亡，因此值得进一步进行药理学研究。
