Platycoside A

A platycoside-rich fraction from the root of Platycodon grandiflorum enhances cell death in A549 human lung carcinoma cells via mainly AMPK/mTOR/AKT signal-mediated autophagy induction.[Pubmed:27989873]

J Ethnopharmacol. 2016 Dec 24;194:1060-1068.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Platycodon grandiflorum (PG), commonly known as Kilkyong in Korea, Jiegeng in China, and Kikyo in Japan, has been extensively used as a traditional anti-inflammatory medicine in Asia for the treatment of respiratory conditions, such as bronchitis, asthma, and tonsillitis. Platycosides isolated from PG are especially well-known for their anti-cancer effects. AIM OF THE STUDY: We investigated the involvement of autophagic cell death and other potential molecular mechanisms induced by the platycoside-containing butanol fraction of PG (PGB) in human lung carcinoma cells. MATERIALS AND METHODS: PGB-induced growth inhibition and cell death were measured using a 5-diphenyl-tetrazolium bromide (MTT) assay. The effects of PGB on autophagy were determined by observing microtubule-associated protein 1 light chain 3 (LC3) redistribution with confocal microscopy. The PGB-mediated regulation of autophagy-associated proteins was investigated using Western blotting analysis. Furthermore, the anti-cancer mechanism of PGB was confirmed using chemical inhibitors. A high-performance liquid chromatography (HPLC)-DAD system was used to analyze the platycosides in PGB. RESULTS: In A549 cells, PGB induced significant autophagic cell death. Specifically, PGB upregulated LC3-II in a time- and dose-dependent manner, and it redistributed LC3 via autophagosome formation in the cytoplasm. PGB treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and subsequently suppressed the AKT/mammalian target of the rapamycin (mTOR) pathway. Furthermore, PGB inhibited cell proliferation by regulating the mitogen-activated protein kinase (MAPK) pathways. In this study, six types of platycosides were identified in the PGB using HPLC. CONCLUSIONS: PGB efficiently induced cancer cell death via autophagy and the modulation of the AMPK/mTOR/AKT and MAPK signaling pathways in A549 cells. Therefore, PGB may be an efficacious herbal anti-cancer therapy.

Platycoside N: a new oleanane-type triterpenoid saponin from the roots of Platycodon grandiflorum.[Pubmed:21119565]

Molecules. 2010 Nov 30;15(12):8702-8.

A new oleanane-type triterpenoid saponin, named platycoside N (1), together with six known saponins, was isolated from the roots of Platycodon grandiflorum. On the basis of acid hydrolysis, comprehensive spectroscopic data analyses and comparison with the spectral data of the known compounds, its structure was elucidated as 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-2beta,3beta,16alpha,23-te trahydroxyolean-12-en-28-oic acid 28-O-beta-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside. The six known compounds were platycodin D (2), deapioplatycodin D (3), platycodin D3 (4), deapioplatycodin D3 (5), platycoside E (6) and deapioplatycoside E (7).

Liquid chromatography/mass spectrometry-based structural analysis of new platycoside metabolites transformed by human intestinal bacteria.[Pubmed:19726152]

J Pharm Biomed Anal. 2010 Jan 5;51(1):202-9.

Platycosides, the main active constituents of Platycodi Radix, have been thoroughly studied for the characterization of their potent biological activities. However, metabolism of platycosides has not yet been characterized. A HPLC electrospray ionization-tandem mass spectrometry (LC/ESI-MS(n)) approach was applied to new complex platycoside metabolites transformed by human intestinal bacteria to identify their structures and determine metabolic pathway. The molecular weights of metabolites were identified by LC/ESI-MS analysis in both positive and negative modes. Structures for the platycoside metabolites were proposed by the molecular weights and the expected enzymatic activity of intestinal microbes on platycoside. In the second step, successive LC-MS(n) analysis was used to demonstrate the proposed structures. Under ESI tandem mass conditions, the sequential fragmentation patterns of [M+Na](+) ions exclusively showed signals, consistent with the cleavage of glycoside bonds, rearrangement and some cross-ring cleavage, thus allowing the rapid identification of platycoside metabolites. The metabolites identified in the time-dependent metabolism experiments enable us to propose several microbial pathways for platycosides. Even though the metabolites of some platycosides may have unknown structures and low levels, the analytical tools presented in this study made it possible to obtain a rapid and complete characterization of new metabolites and their metabolism pathway in human intestinal bacteria.

Platycoside O, a new triterpenoid saponin from the roots of Platycodon grandiflorum.[Pubmed:21617591]

Molecules. 2011 May 26;16(6):4371-8.

A new unusual minor triterpenoid saponin, platycoside O (1), was isolated from the 75% EtOH extract obtained from the roots of Platycodon grandiflorum, together with four known saponins: platycoside M-3 (2), platycoside J (3), platycoside F (4) and platycoside B (5). The structure of 1 was determined as 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-2beta,3beta,16alpha,23-te trahydroxyolean-12-en-24-methoxyl, 24-oxo-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabino pyranoside on the basis of spectral analysis and chemical evidence.