Berberine chloride causes a caspase-independent, apoptotic-like death in Leishmania donovani promastigotes. 2009

Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
Department of Pharmacology, Institute of Post Graduate Medical Education and Research, 244 B, Acharya JC Bose Road, Kolkata, 700 020, 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.

UI MeSH Term Description Entries
D007893 Leishmania donovani A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals and causes visceral leishmaniasis (LEISHMANIASIS, VISCERAL). The sandfly genera Phlebotomus and Lutzomyia are the vectors. Leishmania (Leishmania) donovani,Leishmania leishmania donovani,Leishmania donovanus,Leishmania leishmania donovanus,donovani, Leishmania leishmania,donovanus, Leishmania,donovanus, Leishmania leishmania,leishmania donovanus, Leishmania
D007898 Leishmaniasis, Visceral A chronic disease caused by LEISHMANIA DONOVANI and transmitted by the bite of several sandflies of the genera Phlebotomus and Lutzomyia. It is commonly characterized by fever, chills, vomiting, anemia, hepatosplenomegaly, leukopenia, hypergammaglobulinemia, emaciation, and an earth-gray color of the skin. The disease is classified into three main types according to geographic distribution: Indian, Mediterranean (or infantile), and African. Black Fever,Kala-Azar,Fever, Black,Kala Azar,Visceral Leishmaniasis
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000981 Antiprotozoal Agents Substances that are destructive to protozoans. Schizonticides,Agents, Antiprotozoal
D001599 Berberine An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. Umbellatine
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

Related Publications

Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
December 2013, Experimental parasitology,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
May 2007, Journal of medical microbiology,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
June 2013, Parasitology international,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
March 2004, Antimicrobial agents and chemotherapy,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
July 2001, Journal of cell science,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
September 1983, The Indian journal of medical research,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
December 2009, International journal of antimicrobial agents,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
May 2024, Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
January 2021, Annals of parasitology,
Piu Saha, and Rupashree Sen, and Chellaram Hariharan, and Deepak Kumar, and Padma Das, and Mitali Chatterjee
January 2014, Journal of medical microbiology,
Copied contents to your clipboard!