Hexane fraction of Globimetula braunii induces mitochondria-mediated apoptosis in Plasmodium berghei-infected mice

• Published in: Toxicology reports 2022-01, Vol.9, p.769-777
• Main Authors: Olanlokun, John Oludele, Ekundayo, Mercy Toluwase, Koorbanally, Neil Anthony, Olorunsogo, Olufunso Olabode
• Format: Article
• Language: English
• Subjects: adenosinetriphosphatase; antimalarials; antiplasmodial properties; Apoptosis; B-lymphocytes; caspase-3; Caspases; Cytochrome c; DNA; DNA fragmentation; drug therapy; enzyme-linked immunosorbent assay; erythrocytes; ethyl acetate; gas chromatography-mass spectrometry; Globimetula braunii; hexane; immunohistochemistry; intraperitoneal injection; lipid peroxidation; liver; Malaria; methanol; methylene chloride; mitochondria; parasitemia; permeability; phytochemicals; Plasmodium; Regular; Santalales; toxicology; triterpenoids
• ISSN: 2214-7500; 2214-7500
• DOI: 10.1016/j.toxrep.2022.04.002

Apoptosis is a common pathology in malaria and most antimalarial drugs induce apoptosis during chemotherapy. Globimetula braunii is an African mistletoe used for the treatment of malaria but its effect on mitochondria-mediated apoptosis is not known. Malarial infection was induced by the intraperitoneal injection of NK 65 strain Plasmodium berghei-infected erythrocytes into mice which were treated with graded doses (100–400 mg/kg) of methanol extract (ME), and fractions of n-hexane, dichloromethane, ethylacetate and methanol (HF, DF, EF and MF) for 9 days after the confirmation of parasitemia. Artequine (10 mg/kg) was used as control drug. The fraction with the highest antiplasmodial activity was used (same dose) to treat mice infected with chloroquine-resistant (ANKA) strain for 5 consecutive days after the confirmation of parasitemia. P-alaxin (10 mg/kg) was used as control drug. On the last day of the treatment, liver mitochondria were isolated and mitochondrial Permeability Transition (mPT) pore opening, mitochondrial F0F1 ATPase (mATPase) activity, lipid peroxidation (mLPO) and liver deoxyribonucleic acid (DNA) fragmentation were assessed spectrophotometrically. Caspases 3 and 9 were determined by Enzyme-Linked Immunosorbent Assay (ELISA) technique. Cytochrome c, P53, Bcl-2-associated X protein (Bax), and B-cell lymphoma-2 (Bcl2) were determined via immunohistochemistry. Phytochemical constituents of the crude methanol extract of Globimetula braunii were determined via the Gas Chromatography-Mass Spectrometry (GC-MS) analysis There was large amplitude mPT induction by malaria parasites, extract and fractions of Globimetula braunii. At 400 mg/kg, HF significantly (p