Effects of Plantago major Extracts and Its Chemical Compounds on Proliferation of Cancer Cells and Cytokines Production of Lipopolysaccharide-activated THP-1 Macrophages

BACKGROUND: Plantago major has been reported to have anticancer and anti-inflammatory properties. However, its antiproliferative and anti-inflammatory mechanisms have not been fully elucidated. Moreover, which plant parts are more suitable as starting materials has not been explored. OBJECTIVES: To investigate the antiproliferative activity of P. major extracts against MCF-7, MDA-MB-231, HeLaS3, A549, and KB cancer cell lines as well as their effects on inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, and interferon [IFN]-γ) production by lipopolysaccharide (LPS)-stimulated THP-1 macrophages. MATERIALS AND METHODS: The methanol and aqueous extracts of P. major from different plant parts and its chemical compounds, i.e., ursolic acid (UA), oleanolic acid (OA), and aucubin were tested in this experiment. RESULTS: Methanol and aqueous extracts of P. major seeds exhibited the greatest antiproliferative activity. The methanol extracts of seeds also demonstrated the highest inhibition of TNF-α, IL-1β, IL-6, and IFN-γ production. Interestingly, the roots, which were commonly discarded, exhibited comparable activities to those of leaves and petioles. Furthermore, UA exhibited stronger activities than OA and aucubin. CONCLUSIONS: The seeds are being proposed as the main source for further development of anticancer and anti-inflammatory products, whereas the roots could be included in the preparation of P. major derived products with respect to anti-inflammatory. SUMMARY: Amongst the parts of Plantago major, seeds exhibited the greatest antiproliferative activity against MCF-7, MDA-MB-231, HeLaS3, A549, and KB cell lines as well as the highest inhibition on TNF-α, IL-1β, IL-6, and IFN-γ production. The roots, which were commonly discarded, exhibited comparable antiproliferative and cytokines inhibition activities to those of leaves and petioles. Ursolic acid, a chemical compound of Plantago major, exhibited stronger activities than oleanolic acid and aucubin. The seeds are being proposed as the main source for further development of anticancer and anti inflammatory products, whereas the roots could be included in the preparation of Plantago major derived products with respect to anti inflammatory. Abbreviations used: TNF: Tumor Necrosis Factor; IL: Interleukin; IFN: Interferon; HPTLC: High Performance Thin Layer Chromatography; UA: Ursolic Acid; OA: Oleanolic Acid; AUC: Aucubin.