Steroidal saponins from rhizome of Paris polyphylla var. chinensis and their anti-inflammatory, cytotoxic effects.

Five undescribed compounds, including two cholestane glycosides parispolyosides A and E, and three spirostanol glycosides parispolyosides B-D, were isolated from rhizome of Paris polyphylla var. chinensis (Franch.) Hara, together with twenty-one known steroidal saponins. Their chemical structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. Two of these compounds demonstrated potent inhibitory effect on NO production stimulated by lipopolysaccharide in raw 264.7 cells with IC50 values of 61.35 µM and 37.23 µM. Four compounds exhibited moderate inhibitory activity against HepG2 cells with IC50 values ranging from 9.43 to 24.54 µM. Molecular docking analysis revealed that the potential mechanism of NO inhibition by the active compounds was associated with the interactions with iNOS protein.

Gigantol exerts anti-lung cancer activity by inducing ferroptosis via SLC7A11-GPX4 axis.

Gigantol, a naturally occurring dibenzyl compound derived from various orchid species within the Dendrobium genus, exhibits notable pharmacological activity. We found that gigantol has significant anti-lung cancer properties, both in vitro and in vivo, which it exerts through the induction of ferroptosis. Furthermore, we found gigantol's specific interaction with the subunit solute carrier family 7 member 11 (SLC7A11) within the cystine/glutamate antiporter system (system Xc-), leading to the inhibition of glutathione (GSH) synthesis. This, in turn, disrupts redox homeostasis. Additionally, gigantol hinders the uptake of extracellular cystine via lung cancer cells, resulting in reduced cellular levels of cysteine, a vital precursor in GSH synthesis. This reduction, in turn, leads to an increase in the levels of glutamate. Simultaneously, our study reveals that the decrease in GSH significantly inhibits the activity of glutathione peroxidase 4 (GPX4), a key enzyme within the antioxidant system. Remarkably, N-acetylcysteine, a cystine precursor, effectively reverses gigantol-induced ferroptosis in lung cancer cells. This provides further confirmation that the anti-lung cancer mechanism of gigantol is to induce ferroptosis of lung cancer cells by targeting the SLC7A11-GPX4 signaling axis. In conclusion, our study underscores gigantol's potential as a promising candidate drug for the treatment of patients with lung cancer in clinical practice.

[New steroidal saponins from aerial parts of Paris polyphylla var. chinensis].

The shortage of Paridis Rhizoma promotes comprehensive utilization and development research of waste aerial parts of the original plant. The chemical compositions of the aerial parts of Paris polyphylla var. chinensis were clarified based on the ultrahigh performance liquid chromatography tandem quadrupoles time of flight mass spectrometry(UPLC-QTOF-MS/MS) in the previous investigation, and a series of flavonoids and steroidal saponins were isolated. The present study continued the isolation and structure identification of the new potential compounds discovered based on UPLC-QTOF-MS/MS. By using silica gel, ODS, flash rapid preparation, and other column chromatography techniques, combined with prepared high performance liquid chromatography, five compounds were isolated from the 75% ethanol extract of the aerial parts of P. polyphylla var. chinensis, and their structures were identified by spectral data combined with chemical transformations, respectively, as(23S,25R)-23,27-dihydroxy-diosgenin-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(1),(25R)-26-O-ß-D-glucopyranosyl-furost-5-en-3ß,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(2),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(3),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(4), and aculeatiside A(5). Among them, compounds 1-4 were new ones, and compound 5 was isolated from P. polyphylla var. chinensis for the first time.

[Separation and structural elucidation of C25 epimers of furostanol saponin from aerial parts of Paris polyphylla var. chinensis].

Paris polyphylla var. chinensis(PPC) is used as one of the origin plants of Paridis Rhizoma described in the Chinese Pharmacopoeia(2020 edition). Its resources shortage makes the planting scale gradually expand, and plenty of aerial parts are abandoned because of not being effectively used. On the basis of previous research, this study separated steroidal saponins to further clarify the chemical composition of the aerial parts of PPC. As a result, three pairs of 25R or 25S epimers of furostanol saponins were obtained by various column chromatography techniques. Their structures were identified as neosolanigroside Y6(1), solanigroside Y6(2), neoprotogracillin(3), protogracillin(4), neoprotodioscin(5) and protodioscin(6) by spectral data combining with chemical transformation. Compound 1 is a new compound, and compounds 2, 3 and 5 are isolated from Paris plants for the first time. Compounds 4 and 6 are isolated from this plant for the first time. Previously, only several spirostanol glycosides with 25S configuration were isolated from Paris plants. Guided by mass spectrometry, the present study isolated the furostanol saponins with 25S configuration from this genus for the first time, which further enriches the chemical information of Paris genus and provides a reference for the isolation of similar compounds.