Four new steroidal glycosides from Lilium lancifolium Thunb. and their antitumor activity.

Four new steroidal glycosides (1-4), including two steroidal saponins named lililancifoloside B and C (1-2), one pregnane glycoside named lililancifoloside D (3), and one C22-steroidal lactone glycoside named lililancifoloside E (4), together with five known ones (5-9), were isolated from the bulbs of Lilium lancifolium Thunb. By using spectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS, the structures of 1-4 were elucidated. All isolates were tested for their cytotoxic potential against the MCF-7, MDA-MB-231, HepG2, and A549 cell lines. Compound 6 distinguished out among them, IC50 values of 3.31, 5.23, 1.78, and 1.49 µM against the four cell lines, respectively. Other compounds such as compound 3, 5, and 9 have also shown specific cytotoxic activity. Next, studies showed that compound 6 might cause HepG2 cells to undergo a cell cycle arrest during the G2/M phase and apoptosis.

Developments in the Antitumor Activity, Mechanisms of Action, Structural Modifications, and Structure-Activity Relationships of Steroidal Saponins.

Steroidal saponins, a class of natural products formed by the combination of spirosteranes with sugars, are widely distributed in plants and have various biological activities, such as antitumor, anti-inflammatory, anti-bacterial, anti-Alzheimer's, anti-oxidation, etc. Particularly, extensive research on the antitumor property of steroidal saponins has been conducted. Steroidal sapogenins, the aglycones of steroidal saponins, also have attracted much attention due to a vast range of pharmacological activities similar to steroidal saponins. In the past few years, structural modifications on the aglycones and sugar chains of steroidal saponins have been carried out and some achievements have been made. In this mini-review, the antitumor activity, action mechanisms, and structural modifications, along with the structure-activity relationships of steroidal saponins and their derivatives, are summarized.

Triterpenoid saponins and phenylpropanoid glycoside from the roots of Ardisia crenata and their cytotoxic activities.

Two new triterpenoid saponins, ardisicrenoside R and S (1 and 2), and one new phenylpropanoid glycoside, ardicrephenin (3), along with five known compounds (4-8), were isolated from roots of Ardisia crenata. Their structures were elucidated on the basis of NMR spectroscopic data and chemical methods. Compounds 2-7 were evaluated for their cytotoxic activities against A549, MCF-7, HepG2 and MDA-MB-231 cell lines by MTT assay. Ardicrenin (6) showed significant cytotoxicity, with IC50 values of 1.17 ± 0.01, 1.19 ± 0.06, 3.52 ± 0.23, and 16.61 ± 1.02 µmol·L-1, respectively.

Genus Lilium: A review on traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Lilium (family Liliaceae) is native to China and is mainly distributed in the temperate regions of the Northern Hemisphere such as Eastern Asia, Europe, and North America. There are about 109 species of this genus and 55 species in China. In America, the bulbs were used as food. In Europe, the petals and bulbs of Lilium candidum uesd as pectoral poultices, wound-healing remedy and a treatment for mastitis and shingles, the bulbs of L. martagon were used to treat every liver disease. In India, the bulbs are used medicinally as galactagogue, expectorant, aphrodisiac, diuretic, antipyretic and revitalizing tonic. In Asia, bulbs of this genus are often used to treat coughs, lung diseases, burns and swellings. AIM OF THE STUDY: The aim of this work was to summarize traditional uses, phytochemistry, pharmacology and toxicity, which provided a theoretical basis for the further study of Lilium plants and their applications in medicine, food and other industries. MATERIALS AND METHODS: Online scientific databases including Science Direct, American chemical society (ACS), Wiley Online Library, the Web of Science, China national knowledge internet (CNKI) and others were searched to identify eligible studies. More data were obtained from other Chinese medicine books. RESULTS: The literature survey revealed diverse traditional uses of the genus Lilium, mainly for the treatment of lung deficiency, hemostasis, anxiety, palpitations, asthma and vomiting. Over 180 compounds have been isolated and identified from the genus Lilium, including steroidal saponins, polysaccharides, phenolic glycerides, flavonoids and alkaloids. Different extracts and monomer compounds were so far evaluated for number of pharmacological activities including anti-tumor, anti-inflammatory, antioxidant, antibacterial, immunomodulatory, antidepressant and hepatoprotective activities. CONCLUSIONS: Lilium spp. are of much significance as ornamental flowers, but also have potential to treat various diseases, especially anti-inflammatory and antioxidant. However, most of the studies on pharmacological effects are still in in vitro, and further studies on mechanism-based pharmacological activities in vivo and in vitro are needed in the future. At present, there are limited researches on its safety and toxicological effects, which should be further explored.

Diosgenin Derivatives as Potential Antitumor Agents: Synthesis, Cytotoxicity, and Mechanism of Action.

Thirty-two new diosgenin derivatives were designed, synthesized, and evaluated for their cytotoxic activities in three human cancer cell lines (A549, MCF-7, and HepG2) and normal human liver cells (L02) using an MTT assay in vitro. Most compounds, especially 8, 18, 26, and 30, were more potent when compared with diosgenin. The structure-activity relationship results suggested that the presence of a succinic acid or glutaric acid linker, a piperazinyl amide terminus, and lipophilic cations are all beneficial for promoting cytotoxic activity. Notably, compound 8 displayed excellent cytotoxic activity against HepG2 cells (IC50 = 1.9 µM) and showed relatively low toxicity against L02 cells (IC50 = 18.6 µM), showing some selectivity between normal and tumor cells. Studies on its cellular mechanism of action showed that compound 8 induces G0/G1 cell cycle arrest and apoptosis in HepG2 cells. Predictive studies indicated that p38α mitogen-activated protein kinase (MAPK) is the optimum target of 8 based on its 3D molecular similarity, and docking studies showed that compound 8 fits well into the active site of p38α-MAPK and forms relatively strong interactions with the surrounding amino acid residues. Accordingly, compound 8 may be used as a promising lead compound for the development of new antitumor agents.