Cytotoxicity and synergistic anticancer activity of Kigelia africana (Lam.) Benth. and Spathodea campanulata P. Beauv. polyherbal extracts

The global oncology landscape is increasingly challenged by systemic toxicity and the evolution of multidrug resistance (MDR) in conventional chemotherapeutics. In response, ethnopharmacological research has shifted toward investigating the synergistic logic of traditional African medicine and rational multi-target drug design. This study evaluated the cytotoxicity and anticancer potential of Kigelia africana and Spathodea campanulata , two Bignoniaceae species traditionally used for malignant and inflammatory conditions. These species were specifically investigated to understand whether their polyherbal extracts enhance their selectivity index (SI) against distinct human cancer lineages. Bioactive constituents were extracted from the leaves and fruits of both species using a polarity gradient (aqueous, ethanolic, methanolic, and acetone solvents) to produce nine distinct single and polyherbal extracts. Antiproliferative efficacy was determined via MTT assays against four human cancer cell lines (HepG2, MCF-7, Caco-2, and A549) and a non-malignant Vero cell control. Selectivity was quantified using the Selectivity Index (SI) and half-maximal inhibitory concentrations (IC 50 ), with doxorubicin as a reference standard. While organic extracts exhibited higher cytotoxicity toward normal Vero cells, the K. africana hot water leaf macerate (A02) was the safest, thereby supporting traditional preparation methods. Extracts A03 ( K. africana hot water fruit macerate), A08 (a 1:1 methanolic polyherbal leaf extract), and A09 ( K. africana acetone fruit extract) showed exceptional anticancer potency (IC 50 < 0.7 µg/mL) and high selectivity. The methanolic polyherbal extract (A08) achieved a peak SI of 492, demonstrating that the alcohol matrix optimizes multi-component phytochemical synergy. Notably, extract A09 effectively reduced HepG2 cell viability, suggesting potential in overcoming standard chemotherapeutic resistance via the modulation of baseline multidrug resistance phenotypes. The exceptional anticancer selectivity of this polyherbal extract provides evidence for the synergistic logic found in traditional African medicine. The high selectivity indices (up to 492) and the ability of extract A09 to target resistant HepG2 cells suggest that these plant species are potent sources of selective, multi-target anticancer agents. This study supports the traditional use of K. africana and S. campanulata and highlights their potential as highly effective plant species for future oncological therapies. Nonetheless, the observed cytotoxicity on Vero cells suggests a limited therapeutic window in their current crude form. Therefore, future studies should focus on bioassay-guided fractionation to isolate specific bioactive compounds with higher selectivity.