Phenylpropanoid-conjugated pentacyclic triterpenoids from the whole plants of Leptopus lolonum induced cell apoptosis via MAPK and Akt pathways in human hepatocellular carcinoma cells.

Our present and previous phytochemical investigations on Leptopus lolonum have resulted in the isolation of almost 30 phenylpropanoid-conjugated pentacyclic triterpenoids (PCPTs). During the continuous study on PCPTs, this kind of triterpenoid ester is considered as a natural product with low toxicity because of it's widely distribution in natural plants and edible fruits including kiwi fruit, durian, jujube, pawpaw, apple and pear. In the present work, we report the isolation, structural elucidation and cytotoxic evaluation of four new PCPTs (1-4) which obtained from L. lolonum. In addition, the possible biosynthesis pathway for 28-norlupane triterpenoid and potent effect of phenylpropanoid moiety for increasing the cytotxic effect of triterpenoids were also discussed. Among these compounds, compound 1 exhibited the highest cytotoxic effect on HepG2 cells with IC50 value of 11.87 µM. Further flow cytometry and western blot analysis demonstrated that 1 caused G1 cell cycle arrest by up-regulated the expression of phosphorylated p53 protein in HepG2 cells and induced cell apoptosis via MAPK and Akt pathways. These results emphasized the potential of PCPTs as lead compounds for developing anti-cancer drugs.

New phenylpropanoid-conjugated pentacyclic triterpenoids from the whole plants of Leptopus lolonum with their antiproliferative activities on cancer cells.

Most of Euphorbiaceae plants are considered as folk medicinal plants because of their various pharmacological effects. However, there are eight Leptopus genus plants which belong to Euphorbiaceae have never be investigated. Thus, four Leptopus genus plants were collected to study their chemical constituents and pharmacological activities. In the present work, the cytotoxicities of the extracts of four Leptopus genus plants were evaluated before phytochemical experiments. And nine new phenylpropanoid-conjugated pentacyclic triterpenoids, along with twenty-two known compounds were isolated from the whole plants of Leptopus lolonum. The structures of these new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. All triterpenoids were screened for their cytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Among these isolates, the triterpenoid with a phenylpropanoid unit showed increasing cytotoxicity on cancer cells, which suggested the importance of the phenylpropanoid moiety.