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 language | English (US) |
|---|---|
| Pages (from-to) | 1101-1110 |
| Number of pages | 10 |
| Journal | Free Radical Research |
| Volume | 43 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jan 1 2009 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Berberine chloride causes a caspase-independent, apoptotic-like death in Leishmania donovani promastigotes
AU - Saha, Piu
AU - Sen, Rupashree
AU - Hariharan, Chellaram
AU - Kumar, Deepak
AU - Das, Padma
AU - Chatterjee, Mitali
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
KW - Anti-leishmanial
KW - Apoptosis
KW - Berberine chloride
KW - Leishmaniasis
KW - Oxidative stress
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=70350525419&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350525419&partnerID=8YFLogxK
U2 - 10.1080/10715760903186124
DO - 10.1080/10715760903186124
M3 - Article
C2 - 19669998
AN - SCOPUS:70350525419
VL - 43
SP - 1101
EP - 1110
JO - Free Radical Research
JF - Free Radical Research
SN - 1071-5762
IS - 11
ER -