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

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

Research output: Contribution to journalArticle

Abstract

Berberine chloride, a quarternary isoquinoline alkaloid, is a promising anti-leishmanial compound, IC50 being 7.1 M 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 G0/G1 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.

Original languageEnglish (US)
Pages (from-to)1101-1110
Number of pages10
JournalFree Radical Research
Volume43
Issue number11
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Berberine
Leishmania donovani
Caspases
Chlorides
Apoptosis
Reactive Oxygen Species
Acetylcysteine
Caspase Inhibitors
Mitochondrial Membrane Potential
Phosphatidylserines
Depolarization
Alkaloids
Sulfhydryl Compounds
Inhibitory Concentration 50
Free Radicals
Cysteine
Cell Survival
Cells
Pharmacology
Oxygen

Keywords

  • Anti-leishmanial
  • Apoptosis
  • Berberine chloride
  • Leishmaniasis
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry

Cite this

Berberine chloride causes a caspase-independent, apoptotic-like death in Leishmania donovani promastigotes. / Saha, Piu; Sen, Rupashree; Hariharan, Chellaram; Kumar, Deepak; Das, Padma; Chatterjee, Mitali.

In: Free Radical Research, Vol. 43, No. 11, 01.01.2009, p. 1101-1110.

Research output: Contribution to journalArticle

Saha, Piu ; Sen, Rupashree ; Hariharan, Chellaram ; Kumar, Deepak ; Das, Padma ; Chatterjee, Mitali. / Berberine chloride causes a caspase-independent, apoptotic-like death in Leishmania donovani promastigotes. In: Free Radical Research. 2009 ; Vol. 43, No. 11. pp. 1101-1110.
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