Anthelmintic activity and non-cytotoxicity of phaeophorbide-a isolated from the leaf of Spondias mombin L

• Published in: Journal of ethnopharmacology 2021-11, Vol.280, p.114392, Article 114392
• Main Authors: Ogedengbe-Olowofoyeku, Abosede N., Ademola, Isaiah O., Wright, Colin W., Idowu, Sunday O., Fatokun, Amos A.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Anacardiaceae - chemistry; Animals; Anthelmintics; Anthelmintics - chemistry; Anthelmintics - isolation & purification; Anthelmintics - pharmacology; Caco-2 Cells; Cell Line; Cytotoxicity; Haemonchus - drug effects; Humans; Lethal Dose 50; Medicinal plants; Mice; Phaeophorbide a; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - toxicity; Plant Leaves; Spondias mombin
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2021.114392

Helminthosis (worm infection) is a disease of grazing livestock, with significant economic implications. Increasing resistance to existing synthetic anthelmintics used to control helminthosis and the unwanted presence of residues of the anthelmintics reported in meat and dairy products present a serious global health challenge. These challenges have necessitated the development of novel anthelmintics that could combat drug resistance and exhibit better safety profiles. Spondias mombin L. (Anacardiaceae) is a plant that has been used traditionally as a worm expeller. The aim of the work reported herein was to isolate and characterise anthelmintic compound(s) from S. mombin leaf, establishing their bioactivity and safety profile. Adult Haemonchus placei motility assay was used to assess anthelmintic bioactivity. Bioassay-guided chromatographic fractionation of acetone extract of S. mombin leaf was carried out on a silica gel stationary phase. The structure of the compound was elucidated using spectroscopy (1H and 13C NMR) and Liquid Chromatography-Mass Spectrometry (LC-ESI-MS). Screening to exclude potential cytotoxicity against mammalian cells (H460, Caco-2, MC3T3-E1) was done using alamar blue (AB) and CellTitreGlo (CTG) viability reagents. The acetone extract yielded an active fraction 8 (Ethyl acetate: methanol 90:10; anthelmintic LC50: 3.97 mg/mL), which yielded an active sub-fraction (Ethyl acetate: Methanol 95:5; anthelmintic LC50: 53.8 μg/mL), from which active compound 1 was isolated and identified as phaeophorbide-a (LC50: 23.0 μg/mL or 38.8 μM). The compound was not toxic below 200 μM but weakly cytotoxic at 200 μM. Phaeophorbide-a (1) isolated from S. mombin leaf extract and reported in the plant for the first time in this species demonstrated anthelmintic activity. No significant toxicity to mammalian cells was observed. It therefore represents a novel anthelmintic pharmacophore as a potential lead for the development of novel anthelmintics. [Display omitted] •Phaeophorbide-a was isolated from acetone extract of Spondias mombin leaf.•The compound exhibited anthelmintic activity, with an LC50 of 23.0 μg/mL (38.8 μM).•It was not toxic to cultured HeLa, Caco-2 and MC3T3-E1 cells at concentrations below 200 μM.•Its chemical structure could serve as a pharmacophore for anthelmintic drug development.