Antioxidant, anti-inflammatory, analgesic, and in vitro-in vivo cytotoxicity effects of Spondias venulosa (Engl.) Engl. leaf extracts on MCF-7/S0.5 and OV7 cancer cell lines

Abstract Ethnopharmacological relevance Spondias Venulosa is a plant whose ethnobotanical uses were neither scientifically investigated nor documented despite the overwhelming use of the leaf extract as antioxidant, pain relief, anti-inflammatory, and anticancer agent in traditional medicine in Nigeria. Aim of the study To evaluate the antioxidant, anti-inflammatory, analgesic and cytotoxic activity of S. venulosa leaf extracts on MCF-7/S0.5 and OV7 cancer cell lines and isolate the phyto-constituent responsible for its possible bioactivity. Materials and methods The antioxidant activity was determined by DPPH and H2O2 radical scavenging activities, anti-inflammatory was evaluated by carrageenan induced paw edema in mice, analgesic activity was carried out by acetic acid induced writhing in mice while cytotoxicity activity of the extract was investigated in vitro and in vivo by MTT assay and tumor induction model by trypan blue dye exclusion assay respectively. Identification and characterization of the bioactive compound present in S. Venulosa were done using the GC-MS, FTIR, 1D and 2D NMR spectroscopy. Results The 1H-NMR showed six protons signals while 13C-NMR showed twenty-six carbons consisting of methyl, methylene and quaternary groups characteristic of lactones. Ethyl acetate (EF) fraction showed highest biological activities in terms of antioxidant, anti-inflammatory, analgesic and cytotoxic activities on MCF-7/S0.5 and OV7 cancer cells because of higher amount of phenolic and flavonoid contents. The EF showed an IC50 values of 12.18 ± 0.20 (SI = 1.97) and 4.12 ± 0.001 (SI = 77.67) on MCF-7/S0.5 and OV7 cell lines respectively. Most of the biological activities of the extracts were dose-dependent. The isolated compound showed the highest selective index on cancer cells especially against OV7 with IC50 value of 2.01 ± 0.01; SI > 100 when compared with the control drug doxorubicin with IC50 value of 2.20.80 ± 0.01; SI = 25.57. Extracts of S. venulosa showed strong MST and %ILS on tumor-treated mice in dose-dependent fashion. The extract showed significant reductions in TCV and VCC at higher concentration, and low levels of liver biomarker (AST, ALP and ALT) which is an indication of the tolerance of S. Venulosa in the animals. In addition, a lactone flavonoid compound 6-hydroxy-4,4.7a-tetrahydrobenzofuran-2(4H)-one (i.e. 6-OH-THBF) was identified as one of the bioactive compounds largely responsible for some of the observed pharmacological activities. Conclusion The 6-OH-THBF isolated from EF fraction was the most potent on the two cancer cell lines, and it showed the highest selective against cancerous and normal Vero E6 cell line. Our study showed that S. Venulosa extract possessed the acclaimed pharmacological action in traditional medicine.