sapogenins and 25-hydroxyprotopanaxadiol

25-Hydroxyprotopanaxadiol (25-OH-PPD) and 25-methoxylprotopanaxadiol (25-OCH3-PPD), two ginseng sapogenins, have potent antitumor activity and their effects on gastric cancer (BGC-823, SGC-7901, MKN-28) cells and a gastric mucosa (GES-1) cell line are reported.. Both compounds significantly inhibited the growth of gastric cancer cells, while having lesser inhibitory effects on GES-1 cells by MTT assay. A mechanistic study revealed that the two ginseng sapogenins could induce apoptosis in BGC-823 cells by morphological observation, DNA fragmentation, flow cytometry and western blot analysis. Besides, the apoptosis was inhibited by Ac-DEVD-CHO, a caspase 3 inhibitor, which was confirmed by cell viability analysis.. These results indicate that 25-OH-PPD and 25-OCH3-PPD have potential to be promising agents for the treatment of gastric cancer.

Topics: Antineoplastic Agents; Caspases; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA Damage; Ginsenosides; Humans; Panax; Sapogenins; Signal Transduction; Stomach Neoplasms

The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3β;12β;20-triol (25-OCH3-PPD). Optimized SMEDDS formulations for 25-OCH3-PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH3-PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH3-PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route.

Topics: Administration, Oral; Animals; Biological Availability; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Stability; Emulsions; Female; Ginsenosides; Male; Nanomedicine; Rats; Rats, Wistar; Sapogenins; Solubility; Surface-Active Agents