<b>Phytochemistry and Cytotoxicity of <i>Asphodelus aestivus</i> Brot., Growing in Libya</b>

Background: Aesphodelus aestivus Brot. (Family: Asphodelaceae) is a Libyan medicinal plant that has been used in traditional medicine for treating various human ailments, especially inflammatory conditions, burns and wounds. The cytotoxic activities of the n-hexane, dichloromethane (DCM), and methanol (MeOH) extracts from the leaves and tubers of this species were tested against five human cancer cell lines. Methods: The MTT assay was used to test cytotoxicity. Extracts from leaves and tubers were evaluated for their effects on cancer cell viability. The selectivity index (SI) was calculated using human normal prostate cells (PNT2). Seven compounds, including flavonoids and anthraquinones, were isolated and structurally characterized using different chromatographic (vacuum liquid chromatography (VLC) and preparative HPLC) and spectroscopic (UV, NMR and MS) techniques. The isolated compounds 2, 4, 5, and 7 were tested for cytotoxicity against the prostate cancer (PC3) cell line. Results: Tubers exhibited higher cytotoxicity than leaves. The DCM tuber extract showed potent activity against A549 and PC3 cell lines with IC50 values of 16 and 19 µg/mL, respectively. The MeOH and n-hexane extracts demonstrated no cytotoxicity in the tested cell lines. Leaves exhibited moderate cytotoxicity against HepG2 and A549, with IC50 values of 70 and 90 µg/mL, respectively. The tuber extract showed a high selectivity index (SI = 26) for PC3 cells over normal prostate cells. Seven compounds were isolated from the various fractions of A. aestivus, two flavonoids, quercetin 7-O-rhamnoside (1) and luteolin (2), a ferulate derivative, p-hydroxy-phenethyl trans-ferulate (3), and four anthraquinones, chrysophanol anthrone (4), chrysophanol-10,10’-bianthrone (5), aloe-emodin (6) and C-α-rhamnopyranosyl bianthracene-9, 9’, 10 (10’H)-trione glycoside (7). Compounds 1, 3, 4, 5 and 7 were isolated for the first time from A. aestivus. Among isolated compounds, the bianthracene-trione (compound 7) displayed significant cytotoxicity against PC3 (IC50 = 62.0 µM), comparable to the reference drug paclitaxel (IC50 = 57.9 µM). Conclusion: The DCM extract of A. aestivus tubers demonstrated potent and selective cytotoxic activity, particularly against lung and prostate cancer cell lines. Compound 7, a bianthracene-trione, exhibited promising activity comparable to paclitaxel. These findings highlight the therapeutic potential of A. aestivus for cancer treatment.