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Five new secoiridoid glycosides, cornusphenosides E-I (

Searching for PD-1/PD-L1 inhibitor from medicinal plants has become a potential method to discover small molecular cancer immunotherapy drugs. Using PD-1/PD-L1 inhibitory activity assay

Guided by TNF-α secretion inhibitory activity assay, four taraxastane-type triterpenoids, including two new ones, 22-oxo-20-taraxasten-3β, 30-diol (1) and 22α-hydroxy-20-taraxasten-30β, 30-triol (2), have been obtained from an active fraction of the petroleum ether-soluble extract of the the medicinal and edible plant Cirsium setosum. Their structures were elucidated by spectroscopic data and CD data analysis. In the TNF-α secretion inhibitory activity assay, compounds 1 and 2 were active with the IC50 of 2.6 and 3.8 μmol·L-1, respectively. In addition, compounds 1 and 2 showed moderately selective cytotoxicity against the human ovarian cancer (A2780) and colon cancer (HCT-8) cell lines.

Gymnadenia conopsea R. Br. is a traditional Tibetan medicinal plant that grows at altitudes above 3000 m, which is used to treat neurasthenia, asthma, coughs, and chronic hepatitis. However, a comprehensive configuration of the chemical profile of this plant has not been reported because of the complexity of its chemical constituents. In this study, a rapid and precise method based on ultra-high performance liquid chromatography (UPLC) combined with an Orbitrap mass spectrometer (UPLC&ndash, Orbitrap&ndash, MS/MS) was established in both positive- and negative-ion modes to rapidly identify various chemical components in the tubers of G. conopsea for the first time. Finally, a total of 91 compounds, including 17 succinic acid ester glycosides, 9 stilbenes, 6 phenanthrenes, 19 alkaloids, 11 terpenoids and steroids, 20 phenolic acid derivatives, and 9 others, were identified in the tubers of G. conopsea based on the accurate mass within 3 ppm error. Furthermore, many alkaloids, phenolic acid derivates, and terpenes were reported from G. conopsea for the first time. This rapid method provides an important scientific basis for further study on the cultivation, clinical application, and functional food of G. conopsea.

Five new secoiridoid glycosides, cornusphenosides E-I (1–5), were isolated and characterized from an active fraction of ethanol extract of the fruits of Cornus officinalis. Their structures were determined by extensive spectroscopic data analysis, including 2 D NMR and HRESIMS experiments. In the preliminary assay, compound 5 (when evaluated at 10 μM) showed the neuroprotective effect against H2O2-induced SH-SY5Y cell damage.

Searching for PD-1/PD-L1 inhibitor from medicinal plants has become a potential method to discover small molecular cancer immunotherapy drugs. Using PD-1/PD-L1 inhibitory activity assay in vitro, a bioactive fraction was obtained from the ethanol extract of Gymnadenia conopsea. A sensitive UPLC-HRMS/MS method was established for the rapid screening and identification of compositions from bioactive fraction. Based on the characteristic fragmentation patterns of standards analysis and extracted ion chromatogram (EIC) method, 46 compounds were rapidly screened and identified (including 35 succinic acid ester glycosides and 11 other compounds), among which 17 compounds were tentatively identified as new compounds.

Sparassis crispa is a kind of edible fungus widely grows in the north temperate zone, which shows various medicinal properties. Due to the complexity of chemical constitutes of this species, few investigations have acquired a comprehensive configuration for the chemical profile of it. In this study, a strategy based on ultra-high performance liquid chromatography (UPLC) combined with Orbitrap mass spectrometer (MS) was established for rapidly characterizing various chemical components in S. crispa. Through the summarized MS/MS fragmentation patterns of reference compounds and systematic identification strategy, a total of 110 components attributed to six categories were identified for the first time. Moreover, allergic rhinitis (AR) is a worldwide inflammatory disease seriously affecting human health, and the development of drugs to treat AR has been a topic of interest. It has been reported that the extracts of S. crispa showed obvious inhibitory effects on degranulation of mast cell- and allergen-induced IgE and proinflammatory mediators, but the active components and specific mechanism were still not clear. Src family kinases (SFKs) participate in the initial stage of allergy occurrence, which are considered the targets of AR treatment. Herein, on the basis of that self-built chemical database, virtual screening was applied to predict the potential SFKs inhibitors in S. crispa, using known crystal structures of Hck, Lyn, Fyn, and Syk as receptors, followed by the anti-inflammatory activity evaluation for screened hits by intracellular calcium mobilization assay. As results, sparoside A was directly confirmed to have strong anti-inflammatory activity with an IC50 value of 5.06 &plusmn, 0.60 &mu, M. This study provides a useful elucidation for the chemical composition of S. crispa, and demonstrated its potential inhibitory effects on AR, which could promote the research and development of effective agents from natural resources.

Using a cell-based cytotoxicity assay, two new polyhydroxylated sterols, 16(S),22(S)-epoxy-3β,5α,6β,20(R),23(R),25-hexahydroxy-7-ergostene and 3β,7β,8α,25-tetrahydroxy-5,22E-ergostadiene were isolated from the ethyl acetate portion of the ethanolic extract of Monascus purpureus. Their structures were elucidated by spectroscopic analysis and in comparison with those reported in the literature. Both compounds showed cytotoxic activity against the lung adenocarcinoma (A549) with IC50 values of 12.6 and 18.5 μM, exhibited moderate activities against human ovarian cancer (A2780), with IC50 values of 8.8 and 9.4 μM.

Five norursane-type triterpenoids, including three novel of 3β-28-norursa-12,17,19,21-tetraene-3-ol (1), 3β-28-norursa-12,20(30)-dien-3-ol (2) and 3β-28-norursa-12,16,20(30)-triene-3-ol (3), as well as two known 3β-28-norursa-17,19,21-trien-3-ol (4) and 3β-28-norursa-12-ene-3-ol (5) were isolated from the ethyl acetate dissolved fraction of the ethanol extract from Rosmarinus officinalis. Their structures were elucidated by HR-ESI-MS, IR, 1D- and 2D-NMR spectroscopic methods. Compounds 1–5 exhibited significant inhibitory effect on NO production in LPS-activated RAW264.7 cells, and compounds 2, 3 and 5 shown better anti-inflammatory activity.

Three previously undescribed iridoids, cornusfurals A&ndash, C, were isolated from the ethanolic extracts of fruits of Cornus officinalis. Their structures were elucidated by spectroscopic methods, including one-dimensional and two-dimensional nuclear magnetic resonance, ultraviolet spectroscopy, infrared spectroscopy, and mass spectrometry. The neuroprotective activity was evaluated by measuring corticosterone-induced damage in PC12 cells. The results showed that cornusfural B decreased corticosterone-induced PC12 cell damage compared with that in model cells.

Cirsium setosum (C. setosum) has a potential antihyperglycemic effect, but it is unclear what bioactive components play a key role. According to the &alpha, glucosidase inhibition activity, three new taraxastane-type triterpenoids of 3&beta, hydroxy-30-hydroperoxy-20-taraxastene (1), 3&beta, hydroxy-22&alpha, methoxy-20-taraxastene (2), and 30-nor-3&beta, 22&alpha, dihydroxy-20-taraxastene (3), as well as five known taraxastane triterpenoids of 3&beta, 22-dihydroxy-20-taraxastene (4), 20-taraxastene-3,22-dione (5), 3&beta, acetoxy-20-taraxasten-22-one (6), 3&beta, hydroxy-20-taraxasten-22-one (7), and 30-nor-3&beta, hydroxy-20-taraxastene (8) were obtained from the petroleum ether-soluble portion of the ethanol extract from C. setosum. All chemical structures of the compounds were elucidated by spectroscopic data analysis and compared with literature data. Compounds 4&ndash, 8 were identified for the first time from this plant, and compounds 1, 2, 4, and 7 exhibited more potent &alpha, glucosidase inhibitory activity&mdash, with IC50 values of 18.34 &plusmn, 1.27, 26.98 &plusmn, 0.89, 17.49 &plusmn, 1.42, and 22.67 &plusmn, 0.25 &mu, M, respectively&mdash, than acarbose did (positive control, IC50 42.52 &plusmn, 0.32 &mu, M).

Four new sesquiterpenoids (1&ndash, 4) and six known sesquiterpenoids (5&ndash, 10), were isolated from the EtOAc phase of the ethanolic extract of Ainsliaea yunnanensis. Their structures were established by spectroscopic methods, including 1-D, 2-D NMR and HPLC-MS. All compounds were tested for their anti-inflammatory effect by the inhibition of the activity of NLRP3 inflammasome by blocking the self-slicing of pro-caspase-1, which is induced by nigericin, then the secretion of mature IL-1&beta, mediated by caspase-1, was suppressed. Unfortunately none of the compounds showed an anti-inflammatory effect.

The experiments were performed on 97 albino rabbits. GABA administered through injection into the fourth ventricle caused inhibition on respiratory movement or decrease in phrenic nerve discharge activity. Diazepam produced similar effects as GABA. GABA receptor antagonists, bicuculline and picrotoxin, could reverse the respiratory depressant effect of GABA. Either bicuculline or picrotoxin given alone caused an increase in respiration. These results suggest that endogeneous GABA might be an inhibitory neurotransmitter involved in the central regulation of respiration.

Experiments were carried out on 48 unanesthetized, vogotomized, gallamine triethiodide immobilized and artificially ventilated rabbits. Injection of thyrotropin releasing hormone (TRH) into lateral ventricle resulted in a marked increase in respiratory rate and phrenic nerve discharge frequency and a significant elevation of arterial blood pressure. However, no change in respiratory activity and blood pressure was observed when an equal dose of TRH was injected intravenously. On the contrary, morphine administered intravenously produced a decrease in respiratory activity and blood pressure, which could be reversed by TRH applied intralateral-ventricularly. These findings indicate that TRH can stimulate respiratory activity, elevate blood pressure centrally and antagonize morphine-induced depression in respiration and blood pressure.