Anti-proliferative activity of leaves of Launaea capitata Asteraceae: Phytochemical, cytotoxicity and in silico studies

Abstract

Purpose: To investigate the phytochemical contents of Launaea capitata (L. capitate) and its potential cytotoxic activity. Also, to examine its molecular modeling by docking of the isolated compounds.Methods: L. capitata was methanol-extracted and successively fractionated followed by determination of the total phenolic and flavonoid contents. Major constituents were isolated and purified. 3-(4, 5- Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity assays were conducted for all fractions. In silico studies were conducted using four anticancer target kinases, namely, protein kinase B (PKB/AKT), phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), and rapidly accelerated fibrosarcoma kinases (RAFK).Results: The results showed that total phenolic constituents ranged from 0.150 ± 0.004 to 60.229 ± 0.822 mg Gallic Acid Equivalent/g of dry extract, while the total flavonoid content varied from 0.004 ± 0.002 to 18.129 ± 1.599 mg quercetin equivalent/g of dry extract. Furthermore, the ethyl acetate fraction contained the highest amount of phenolic and flavonoid contents, which seemed to constitute the most effective anti-proliferative fraction. The plant’s major constituent was apigenin-7-O-glycoside and was isolated from the ethyl acetate fraction. The MTT cytotoxicity assay revealed the anti-proliferative activity of ethyl acetate and butanol fractions, and apigenin-7-O-glycoside with half-maximal concentration (IC50) comparable to that of doxorubicin. In silico studies revealed that apigenin-7-Oglycoside showed a better binding score and ligand efficiency when compared with standard ligands/inhibitors for AKT/PKB and PI3K, suggesting potential multiple targets for its anti-cancer activities.Conclusion: L. capitata contains considerable amounts of phenolic and flavonoid components. Its major constituent, apigenin-7-O-glycoside is a potential lead compound for developing new anticancer compounds. Keywords: Launaea capitata, Total phenolics, Total flavonoids, Docking, Cytotoxicity