Antioxidant, Anti-Inflammatory, and Cytotoxic Activities Against Drug-Sensitive and Drug-Resistant Cancer Cells of the Extracts of Clausena excavata, Millettia pachycarpa, and Uvaria grandiflora

Objective: This study aimed to analyze the chemical profiles of bioactive compounds in extracts from different parts of Clausena excavata (C. excavata), Millettia pachycarpa (M. pachycarpa), and Uvaria grandiflora (U. grandiflora), and to examine their antioxidant, anti-inflammatory, and cytotoxic effects on drug-sensitive and -resistant cancer and normal cells.Material and Methods: Ethyl acetate extracts from C. excavata fruits (FCE), M. pachycarpa roots and leaves (RMP and LMP), and U. grandiflora twigs and leaves (TUG and LUG) were analyzed for total phenolic and flavonoid content and the chemical profiles of bioactive compounds. Antioxidant activities were determined using various methods. Anti-inflammatory properties were investigated in lipopolysaccharide-stimulated RAW264.7 cells, and cytotoxicity was evaluated in doxorubicin-sensitive and -resistant leukemic cells (K562 and K562/adr), breast cancer cells (MCF-7 and MCF-7/adr), and normal cells (peripheral blood mononuclear cells; PBMCs). Results: The extracts contained bioactive compounds, including carbazole alkaloids, xanthones, and coumarins in FCE; isoflavonoids, coumarins, and rotenoids in RMP and LMP; and alkaloids, cyclohexenes, and flavonoids in TUG and LUG. TUG, RMP, and LMP exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, whereas RMP demonstrated the most potent 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide radical scavenging activities. LUG showed strong MCA, and LMP showed superior FRAP. FCE exhibited notable anti-inflammatory activity, whereas RMP showed significant cytotoxicity against MCF-7 and MCF-7/adr cells, with minimal toxicity to PBMCs. TUG also proved effective against drug-resistant leukemia cells.Conclusion: These findings highlight the potential of these plants for use in dietary supplements and cancer treatments, especially for drug-resistant cancers.