RESUMO
Lobetyolin (LBT) is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codonopsis pilosula, known as Radix Codonopsis or Dangshen. Twelve traditional Chinese medicinal preparations containing Radix Codonopsis were identified; they are generally used to tonify spleen and lung Qi and occasionally to treat cancer. Here we have reviewed the anticancer properties of Codonopsis extracts, LBT and structural analogs. Lobetyolin and lobetyolinin are the mono- and bis-glucosylated forms of the polyacetylenic compound lobetyol. Lobetyol and LBT have shown activities against several types of cancer (notably gastric cancer) and we examined the molecular basis of their activity. A down-regulation of glutamine metabolism by LBT has been evidenced, contributing to drug-induced apoptosis and tumor growth inhibition. LBT markedly reduces both mRNA and protein expression of the amino acid transporter Alanine-Serine-Cysteine Transporter 2 (ASCT2). Other potential targets are proposed here, based on the structural analogy with other anticancer compounds. LBT and related polyacetylene glycosides should be further considered as potential anticancer agents, but more work is needed to evaluate their efficacy, toxicity, and risk-benefit ratio.
RESUMO
A new polyacetylene glycoside, (5R)-6E-tetradecene-8,10,12-triyne-1-ol-5-O-ß-glucoside (1), was isolated from the flower of Coreopsis lanceolata (Compositae), together with two known compounds, bidenoside C (10) and (3S,4S)-5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-ß-glucopyranoside (11), which were found in Coreopsis species for the first time. The other known compounds, lanceoletin (2), 3,2'-dihydroxy-4-3'-dimethoxychalcone-4'-glucoside (3), 4-methoxylanceoletin (4), lanceolin (5), leptosidin (6), (2R)-8-methoxybutin (7), luteolin (8) and quercetin (9), were isolated in this study and reported previously from this plant. The structure of 1 was elucidated by analyzing one-dimensional and two-dimensional nuclear magnetic resonance and high resolution-electrospray ionization-mass spectrometry data. All compounds were tested for their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and compounds 2-4, 6 and 7 inhibited DPP-IV activity in a concentration-dependent manner, with IC50 values from 9.6 to 64.9 µM. These results suggest that C. lanceolata flower and its active constituents show potential as therapeutic agents for diseases associated with type 2 diabetes mellitus.
Assuntos
Coreopsis/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Flores/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Concentração Inibidora 50RESUMO
An ongoing phytochemical investigation of the rhizomes of Atractylodes lancea resulted in the isolation of four new C10-type polyacetylene glycosides (1-4). Their structures were elucidated on the basis of extensive spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of compounds 2-4 were determined by comparing the specific rotations of their aglycones. Notably, compounds 2 and 3 exhibited significant hepatoprotective activities against APAP-induced HepG2 cell injury at a concentration of 10 µM. Compounds 2 and 3 showed weak anti-inflammatory effects on LPS-induced NO production in microglia BV2 cells at a concentration of 10 µM.
Assuntos
Atractylodes/química , Glicosídeos/isolamento & purificação , Poli-Inos/isolamento & purificação , Rizoma/química , Animais , Glicosídeos/química , Células Hep G2 , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Poli-Inos/farmacologiaRESUMO
Objective: To study the chemical constituents in the capitulum of Coreopsis tinctoria. Methods: The constituents were separated and purified by AB-8 macroporous resin, silica gel, Sephadex LH-20, ODS column chromatography, and preparative HPLC. The structures were elucidated on the basis of chemical evidences, spectroscopic methods, and optical rotation data. The new compound was evaluated for its inhibitory activity against LPS-activated NO production in BV-2 microglial cells using the Griess assay. Results: Five polyacetylenes were obtained from the fraction of 50% ethanol extract of C. tinctoria identified as (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1-ol-3-O-β-D-glucopyranoside (1),(2S)-(3Z,11E)-decadiene-5,7,9-triyne-1,2-diol (2),(2R)-(3E,5E,11E)-triene-7,9-diyne-1,2-diol (3),(E)-7-phenyl-2-heptene-4,6-diyn-1-ol (4), and (Z)-7-phenyl-2-heptene-4,6-diyn-1-ol (5). Conclusion: Compound 1 is a new polyacetylene glycoside named coreoside E and shows weak anti-inflammatory activity. Compounds 3 and 5 are isolated from the plants of C. tinctoria for the first time.