Abstract Title:

Berberine chloride causes a caspase-independent, apoptotic-like death in Leishmania donovani promastigotes.

Abstract Source:

Free Radic Res. 2009 Aug 7:1-10. Epub 2009 Aug 7. PMID: 19669998

Abstract Author(s):

Piu Saha, Rupashree Sen, Chellaram Hariharan, Deepak Kumar, Padma Das, Mitali Chatterjee

Article Affiliation:

Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, India.


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.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Apoptotic : CK(5217) : AC(3846)

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