Four Pairs of Neuroprotective Aryldihydronaphthalene-Type Lignanamide Enantiomers from the Herbs of Solanum lyratum.

Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40 µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.

Four pairs of neolignan enantiomers with distinctive isochroman moiety from the fruits of Crataegus pinnatifida and their protective activities against H2O2-induced SH-SY5Y cells.

Four pairs of neolignan enantiomers (±)-1- (±)-4 with a distinctive isochroman moiety, including seven undescribed compounds, were isolated and identified from the fruits of Crataegus pinnatifida. Structural characterization of these compounds was established through comprehensive spectroscopic analyses, as well as quantum chemical calculations of ECD and NMR data. The preliminary bioassay displayed that compounds (+)-2 and (±)-3 exerted protective activities against H2O2-induced human neuroblastoma SH-SY5Y cells compared with the positive control. These bioactive compounds could be potential candidates for further pharmaceutical applications.

Neuroprotective and acetylcholinesterase inhibitory activities of alkaloids from Solanum lyratum Thunb.: An in vitro and in silico analyses.

The n-BuOH extract from the herb of Solanum lyratum Thunb. (Solanaceae) was purified by various chromatographic methods, which led to the isolation of seven undescribed alkaloids ((-)-(7'S)-N-feruloyltyramine A, (+)-(7'R)-N-feruloyltyramine A, (+)-(7'S)-N-solanamide A, (-)-(7'R)-N-solanamide A, 7'S-perillascens, solanpyrrole A, and (Z)-asmurratetra A) and 13 known alkaloids, including four pairs of enantiomers. Extensive spectroscopic data and electronic circular dichroism (ECD) calculations were applied to determine the structures of the undescribed compounds. In in vitro biological activity assays, (-)-(7'S)-N-feruloyltyramine A and (+)-(7'R)-N-feruloyltyramine A exhibited pronounced neuroprotective effects against SH-SY5Y cell damage with survival rates of 75.98% and 76.61%, respectively, at 50 µM. Additionally, (-)-(7'S)-N-feruloyltyramine A and N-cis-feruloyl-3'-methoxy-tyramine displayed acetylcholinesterase (AChE) inhibitory effects with IC50 values of 7.41 ± 1.76 µM and 9.21 ± 0.89 µM, respectively. Molecular docking simulations revealed that (-)-(7'S)-N-feruloyltyramine A had a binding site for AChE. These findings reveal the structural diversity of the bioactive compounds in S. lyratum and provides insights into the use of this information for the production of functional components in the pharmaceutical industry.

Vibsane-type diterpenoids from Viburnum odoratissimum inhibit hepatocellular carcinoma cells via the PI3K/AKT pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with an elevated danger of metastasis and a short survival rate. Vibsane-type diterpenoids with novel structures possess marked antitumor activities against multiple cancer cells. However, the exact mechanism is poorly unclear. PURPOSE: To assess the antitumor mechanism of vibsane-type diterpenoids derived from Viburnum odoratissimum (V. odoratissimum) against HCC cells in vitro and in vivo. METHODS: The main constituents in the ethyl acetate extract of V. odoratissimum (EAVO) were identified by LC-MS/MS. The antiproliferative activity of EAVO in vitro was evaluated by MTT assays. Annexin V-FITC/PI, AO/EB, and Hoechst 33,258 staining were employed to detect apoptosis. JC-1 fluorescence dye was used to detect the mitochondrial membrane potential (MMP). The levels of intracellular ROS and mitochondrial superoxides were assessed by H2DCF-DA and MitoSox staining, respectively. The levels of oxidative stress were determined by ROS Green™ H2O2 probe, hydroxyphenyl fluorescein (HPF), and the C11 BODIPY 581/591 fluorescent probe. Transcriptomics was performed to investigate the antitumor mechanism of EAVO in HCC. The molecular mechanism by which EAVO suppressed HCC cells was verified by Western blot, RT-PCR, and HTRF® KinEASE™-STK S3 kits. The efficacy and safety of EAVO in vivo were evaluated using Hep3B xenograft models. RESULTS: Vibsane-type diterpenoids were the main constituents of EAVO by LC-MS/MS. EAVO suppressed proliferation, aggravated oxidative stress, and promoted apoptosis in HCC cells. Moreover, EAVO dramatically inhibited tumor growth in Hep3B xenograft models. Transcriptomics results indicated that EAVO inhibited HCC cell proliferation by regulating the PI3K/AKT pathway. Vibsanin B, vibsanol I, and vibsanin S isolated from EAVO was used to further verify the antitumor activity of vibsane-type diterpenoids subsequently. Interestingly, the kinase results showed that vibsanin B and vibsanol I exhibited vital AKT kinase inhibitory activities. CONCLUSIONS: Collectively, this study provided a comprehensive mechanism overview of vibsane-type diterpenoids against HCC cells in vitro and in vivo. It also laid a foundation for further antitumor investigation of vibsane-type diterpenoids in V. odoratissimum.

Stereochemical insights into structurally diverse lignanamides from the herbs of Solanum lyratum Thunb.

A chemical investigation of Solanum lyratum Thunb. (Solanaceae) afforded six pairs of enantiomeric lignanamides consisting of twelve undescribed compounds, along with two undescribed racemic mixtures, and the separations of the enantiomers were accomplished by chiral-phase HPLC. The structures of these undescribed compounds were elucidated by the analysis of spectroscopic data, NMR and electronic circular dichroism calculations. All isolated compounds were assessed for neuroprotective activities in H2O2-induced human neuroblastoma SH-SY5Y cells, and acetylcholinesterase (AChE) inhibitory activities. Among tested isolates, some enantiomeric lignanamides exhibited conspicuous neuroprotective effects and AChE inhibitory effect.

Solanoids F - I: Terpenoids from Solanum lyratum with neuroprotective effects against H2O2-induced SH-SY5Y cell injuries.

Four new terpenoids, solanoids F - I (1-4), together with eleven known compounds (5-15), were isolated from the whole herb of Solanum lyratum. The chemical structures were characterized by spectroscopic techniques, and electronic circular dichroism (ECD) data analysis was adopted to confirm the absolute configurations of 1-4. Compounds 1-6, 8 and 12-15 exhibited neuroprotective effects against H2O2-induced oxidative damage of human SH-SY5Y cells. Additionally, this study also combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore the potential targets and signaling pathways of active terpenoids components in intervening Alzheimer's disease (AD).

Targeted isolation of diterpenoids and sesquiterpenoids from Daphne gemmata E. Pritz. ex Diels using molecular networking together with network annotation propagation and MS2LDA.

Investigation of the whole plant of Daphne gemmata E. Pritz. ex Diels (Thymelaeaceae) using molecular networking coupled to Network Annotation Propagation (NAP) and unsupervised substructure annotation (MS2LDA) led to the discovery of five tigliane diterpenoids, 14 guaiane sesquiterpenoids, one rhamnofolane diterpenoid and three carotene sesquiterpenoids. The structures of the eight undescribed compounds, daphnorbol A and daphnegemmatoids A-G, were characterized by detailed spectroscopic analyses, NMR and ECD calculations, application of Snatzke's method and single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their cytotoxic activities against HepG2, A549, and MCF-7 cells by MTT assay. Daphnorbol A exhibited significant cytotoxic activity against HepG2 and A549 cells with IC50 values of 4.06 µM and 6.35 µM, respectively. Prostratin showed potent cytotoxic activity against HepG2 and A549 cells with IC50 values of 6.06 µM and 5.45 µM, respectively. Further Hoechst 33,258 and AO-EB staining assays indicated that daphnorbol A and prostratin could induce apoptosis in HepG2 and A549 cells.