title: Glabridin induces oxidative stress mediated apoptosis like cell death of malaria parasite Plasmodium falciparum.
abstract: Plants are known as the source of novel agents for developing new antimalarial drugs. Glabridin is a polyphenolic flavonoid, a main constituent in the roots of Glycyrrhiza glabra possesses various biological activities. However, its anti-plasmodial activity is unexplored. In the present work, it is for the first time demonstrated that glabridin inhibits Plasmodium falciparum growth in vitro with an IC50 23.9±0.43μM. Glabridin showed poor cytotoxicity in vitro with an IC50 246.6±0.88μM against Vero cell line and good selectivity index (9.6). In erythrocytic cycle, trophozoite stage was found to be most sensitive to glabridin. In silico study showed that glabridin inhibits Pf LDH enzyme activity by acting on NADH binding site. Glabridin induced oxidative stress by the generation of reactive oxygen and nitrogen species. Glabridin could induce apoptosis in parasite as evidenced by the depolarization of mitochondrial membrane potential (Δψm), activation of caspase like proteases and DNA fragmentation. These results indicate that glabridin exhibits antiplasmodial activity and is suitable for developing antimalarial agent from a cheap and sustainable source.
authors.affiliation: Molecular Bioprospection Department, CSIR- Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow-226 015, India.
authors.forename: Harveer Singh
authors.initials: HS
authors.lastname: Cheema
authors.affiliation: Metabolic and Structural Biology Department, CSIR- Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow-226 015, India.
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.affiliation: Molecular Bioprospection Department, CSIR- Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow-226 015, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Pal
authors.affiliation: Metabolic and Structural Biology Department, CSIR- Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow-226 015, India.
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.affiliation: Molecular Bioprospection Department, CSIR- Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow-226 015, India.
authors.forename: Dnyneshwar U
authors.initials: DU
authors.lastname: Bawankule
authors.affiliation: Molecular Bioprospection Department, CSIR- Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow-226 015, India. Electronic address: mpdarokar@yahoo.com.
authors.forename: Mahendra P
authors.initials: MP
authors.lastname: Darokar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020134:Catalytic Domain; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008958:Models, Molecular; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species; D014709:Vero Cells
chemical_list: D007529:Isoflavones; D010636:Phenols; D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; C107601:glabridin
keywords: Apoptosis; Glabridin; Oxidative stress; P. falciparum; Pf LDH; Reactive oxygen species