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Cichorium endivia L. (Asteraceae) is a wide edible plant that grows in the Mediterranean region. In this study, a phytochemical investigation of C. endivia L. ethanolic extract led to the isolation of stigmasterol (1), ursolic acid (2), β-amyrin (3), azelaic acid (4), vanillic acid (5), (6S, 7E)-6-hydroxy-4,7-megastigmadien-3,9-dione (S(+)-dehydrovomifoliol) (6), 4-hydroxy phenyl acetic acid (7), vomifoliol (8), ferulic acid (9), protocatechuic acid (10), kaempferol (11), p. coumaric acid (12), and luteolin (13). In addition, the total phenolic content as well as the in vitro antioxidant activity of C. endivia L. extract were estimated. Moreover, we inspected the potential gonado-protective effect of C. endivia crude extract, its phenolic fraction, and the isolated coumaric, vanillic, and ferulic acids against methotrexate (MTX)-induced testicular injury in mice. There were seven groups: normal control, MTX control, MTX + C. endivia crude extract, MTX + C. endivia phenolic fraction, MTX + isolated coumaric acid, MTX + isolated vanillic acid, and MTX + isolated ferulic acid. MTX was given by i.p. injection of a 20 mg/kg single dose. The crude extract and phenolic fraction were given with a dose of 100 mg/kg/day, whereas the compounds were given at a dose of 10 mg/kg/day. A histopathological examination was done. The testosterone level was detected in serum together with the testicular content of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), interleukin 1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated x protein (Bax), p53, and miR-29a. C. endivia crude extract, the phenolic fraction, and the isolated compounds showed significant elevation in their levels of testosterone, CAT, SOD, Bcl-2 with a significant decrease in their levels of MDA, TNF-α, IL-1β, IL-6, NF-κB, Bax, P53, and miR-29a compared to those of the MTX control group. In conclusion, C. endivia mitigated MTX-induced germ cell toxicity via anti-inflammatory, antioxidant, and antiapoptotic effects.

Cichorium endivia. L, consumed either cooked or eaten raw in salads, is a popular kind of vegetable cultivated all around the World. Its components have been widely used in folk medicine in anti-inflammatory therapy. However, the anti-cancer activity of the components has never been reported. In this study, (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (1), an amino acid isolated from C. endivia. L, was found for the first time to show cytotoxic activity in colorectal cancer cell line HCT-8. Compound 1 at concentrations of 0.5–4 μM induced apoptosis of HCT-8 cells in a dose-dependent manner. The compound 1-induced apoptosis in HCT-8 cells was accompanied by the loss of mitochondrial membrane potential, the activation of caspase-3, caspase-8 and caspase-9, the up-regulation of Bax and the down-regulation of Bcl-2. In addition, compound 1 suppressed the activation of NF-κB, which acts as an inhibitor of apoptosis. Taken together, these results suggested that compound 1 could significantly induce apoptosis of HCT-8 cells through the suppression of NF-κB signaling pathway, and thus can be considered as a potential candidate for developing chemotherapeutic drugs against cancer.