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Four newly identified benzophenone analogs [nigrophenone A-D (1-4)] and a pyrrolidinone analog [nigropyrrolidinone (5)], alongside thirteen known congeners (6-18), were isolated from Nigrospora sphaerica. Transcriptome analysis revealed that 6 might have the potential to modulate T-cell immunity. Quantitative measurements of the binding affinities between eighteen natural molecules and the immunological checkpoint receptors PD-1 and PD-L1 were performed using Surface Plasmon Resonance (SPR). The results of SPR analysis showed that 1-18 have K D values ranging from 1.8 to 99.5 μM for PD-1 and from 10.6 to 99.5 μM for PD-L1. Competitive inhibition studies, employing SPR and ELISA assays, have indicated that compounds 6, 10, 15, and 18 are capable of inhibiting the PD-1/PD-L1 interaction. Additionally, compound 6 exhibited notable in vitro anticancer potency through the augmentation of activating signals and the upregulation of PD-1 expression on CD8 + T cells, concurrently elevating the secretion of IFN-γ and IL-2, thereby inhibiting the proliferation of LLC and MC38 cells and promoting MC38 apoptosis. Moreover, compound 6 modulates the PI3K/Akt pathway, which is a key downstream effector of the PD-1/PD-L1 axis. These compounds are considered promising candidates for more in-depth exploration because they could significantly inhibit PD-1/PD-L1 interactions in tumor immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Three previously undescribed coumarins ( 1 - 3 ) were obtained from the roots of Notopterygium incisum . Their chemical structures were elucidated using a variety of spectroscopic techniques and chemical calculations. The inhibitory effects of these new compounds on NO production and pro-inflammatory factors ( IL-1β , IL-6 , and TNF-α ) in LPS-stimulated RAW 264.7 cells were investigated. Further studies revealed that compound 1 suppressed the expression of COX-2 and iNOS while also reduced ROS accumulation. Western blot analysis demonstrated that compound 1 could inhibit the PI3K/AKT pathway by decreasing the levels of p-PI3K and p-AKT. Collectively, these findings suggest that compounds 1 - 3 exhibit promising anti-inflammatory properties.

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Eleven new highly oxygenated eremophilane-type sesquiterpenoids were isolated from the whole plant of Synotis solidaginea, including two pairs of C-8 S/R epimers. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configurations of 1 and 9 were confirmed by single-crystal X-ray crystallography using Cu Kα radiation. All the isolates were tested for the inhibition of LPS-stimulated NO production in macrophage-like mouse monocytic leukemia RAW264.7 cells. Compound 1 exhibited weak inhibitory effects with an IC 50 of 71.2 μM., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interest in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC 50 value of 8.39 ± 0.09 μM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An undescribed trichodenone derivative (1), two new diketopiperazines (3 and 4) along with a bisabolane analog (2) were isolated from Trichoderma hamatum b-3. The structures of the new findings were established through comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR, Marfey's analysis as well as comparisons of ECD. The absolute configuration of 2 was unambiguously confirmed by NMR, ECD calculation and Mo 2 (AcO) 4 induced circular dichroism. Compounds 1-4 were tested for their fungicidal effects against eight crop pathogenic fungi, among which 1 showed 51% inhibition against Sclerotinia sclerotiorum at a concentration of 50 μg/mL., Competing Interests: Declaration of competing interest The authors did not report any potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model., Competing Interests: Declaration of Competing Interest The authors did not report any potential conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo., Objective: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents., Materials and Methods: A C 18 column (3 × 100 mm, 2.6 μm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified., Results: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues., Conclusion: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo., (© 2023 John Wiley & Sons Ltd.)

The Panxi area in Sichuan Province is the main area for the production of truffles in China, and several species of truffle are known to exist in this region. Nevertheless, it is unclear what the differences in chemical composition between the truffles are. Using an ultra-high-performance liquid chromatography quadrupole/orbitrap high-resolution mass spectrometry coupled with Compound Discoverer 3.0, we identified chemical components in three mainly known truffles from the Panxi region. Further analysis of chemical composition differences was conducted using principal component analysis, and orthogonal partial least squares discriminant analysis. Note that, 78.9% of the variance was uncovered by the principal component analysis model. As a result of the orthogonal partial least squares discriminant analysis model, the three species of truffles (Tuber pesudohimalayense, Tuber indicum, and Tuber sinense) from Panxi were better discriminated, with R 2 X, R 2 Y, and Q 2 being 0.821, 0.993, and 0.947, respectively. In this study, 87 components were identified. T. pesudohimalayense contained significantly higher levels of nine different compounds than the other two species. Hence, it was possible to identify similarities and differences between three species of truffles from Panxi in terms of chemical composition. This can be used as a basis for quality control., (© 2023 Wiley-VCH GmbH.)

Amestolkins A ( 1 ) and B ( 2 ), two previously undescribed phthalides sharing the same planar structure of (1, 5-dihydroxyhexyl)-7-hydroxyisobenzofuran-1(3 H )-one were isolated from Talaromyces amestolkiae . Their absolute configurations were elucidated by comprehensive analyses of spectroscopic evidences in high-resolution electrospray mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) combined with electronic circular dichroism (ECD) and NMR calculations. 1 and 2 showed anti-neuroinflammatory activity by inhibiting the gene expressions of proinflammatory factors including C-C motif chemokine ligand 2 (CCL-2), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), as well as attenuating the excretion of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells at the concentration of 30 μM.

Cichorium intybus L. (Asteraceae), belonging to the tribe Cichorieae of the family Asteraceae, has a long history as an edible and medicinal food. Sesquiterpene lactones are commonly considered as its major active constituents. In the current study, five unreported sesquiterpene lactones, including one 12,8-guaianolide and four 12,6-guaianolides were isolated from C. intybus roots, as well as 16 known analogues. The planar structures and relative configurations of these compounds were elucidated by extensive spectroscopic analysis. The absolute configurations were determined by the time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculation method. Bioassay results showed that seven of the isolates exhibited remarkable NO production inhibitory activity in LPS-stimulated RAW264.7 macrophages, with IC 50 values ranging from 1.83 to 38.81 μM. Some of them can significantly decrease the secretion of inflammatory cytokines (TNF-α and IL-6). Cytotoxicity assays demonstrated that intybusins B, as well as four known compounds, displayed obvious inhibitory activities against four human tumor cells, with IC 50 values ranging from 9.01 to 27.07 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum , trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huo, Lei, Guo, Hu, Kuang, Liu, Peng, Dai, Wang, Gu, Guo and Deng.)

Three previously undescribed polyketides [proliferatin A-C (1-3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1-3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1-3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Transcriptome analysis is shown to be an effective strategy to understand the potential function of natural products. Here, it is reported that 11 previously undescribed hydroanthraquinones [nigroquinones A-K ( 1 - 11 )], along with eight known congeners, were isolated from Nigrospora sphaerica . Their structures were elucidated by interpreting spectroscopic and spectrometric data including high-resolution mass spectra and nuclear magnetic resonance. The absolute configurations of 1 - 11 were confirmed by electronic circular dichroism calculations. Transcriptome analysis revealed that 3 (isolated in the largest amount) might be anti-inflammatory. Assays based on LPS-induced RAW264.7 macrophages and zebrafish embryos confirmed that some of the isolated hydroanthraquinones attenuated the secretion of pro-inflammatory mediators in vitro and in vivo . Further Western blotting and immunofluorescence experiments indicated that 4 (which showed the most obvious nitric oxide inhibition) could suppress the expression of nuclear factor-kappa-B (NF-κB), phosphorylation of the inhibitor of NF-κB kinase and inhibit the transportation of NF-κB to the nucleus. Hence, the suppression of the NF-κB signaling pathway may be responsible for the anti-inflammatory effect. These results show that bioactivity evaluation on the basis of transcriptome analysis may be effective in the functional exploration of natural products.

Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated. Methods: For the estimation of the anti-inflammatory activity of fusaproliferin ( 1 ) and its analogs ( 2 - 4) in vitro and in vivo , lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1 - 4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways. Results: 1 - 4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1 - 4 exhibited affinity for the TLR4 protein with KD values of 23.5-29.3 μM. Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kuang, Lei, Li, Peng, Wang, Dai, Wang, Gu, Deng and Guo.)

Ulcerative Colitis (UC) is a major form of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. There is still a substantial need of small molecules with greater efficacy and safety for UC treatment. Here, we report a N-acetyldopamine dimer (NADD) elucidated (2R,3S)-2-(3',4'-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2″-aminoethyl)-1,4-benzodioxane, which is derived from traditional Chinese medicine Isaria cicadae , exhibits significant therapeutic efficacy against dextran sulfate sodium (DSS)-induced UC. Functionally, NADD treatment effectively relieves UC symptoms, including weight loss, colon length shortening, colonic tissue damage and expression of pro-inflammatory factors in pre-clinical models. Mechanistically, NADD treatment significantly inhibits the expression of genes in inflammation related NF-κB and MAPK signaling pathways by transcriptome analysis and western blot, which indicates that NADD inhibits the inflammation in UC might through these two pathways. Overall, this study identifies an effective small molecule for UC therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wang, Gong, Hu, Gui, Zhang, Tan, Yu, Liao, Luo, Tang, Dai, Deng, Wang and Guo.)

Two new phenolic glycosides 7 R ,8 R -threo-4,7,9,9'-tetrahydroxy-3-methoxy-8- O -4'-neolignan-3'- O -(3''-α-L-arabinofuranosyl)- β -D-glucopyranoside. ( 1 ), 4-(4'-hydroxyphenyl)-2-butanone-4''- O -(6- β -D-xylosyl)-β- D -glucopyranoside ( 2 ), along with two known related analogues 7 R ,8 R -threo-4,7,9,9'-tetrahydroxy-3-methoxy-8- O -4'-neolignan-3'- O -β- D -glucopyranoside ( 3 ), 4-(4'-hydroxyphenyl)-2-butanone-4'- O -β- D -glucopyranoside ( 4 ) were obtained from the roots of Sanguisorba o ffi cinalis . Combined with acid hydrolysis derivatization, the absolute configurations of these new compounds were elucidated by comprehensive analyses of spectroscopic data including nuclear magnetic resonance (NMR), electrospray ionization high resolution mass (HRESIMS) as well as circular dichroism (CD). Compounds 1 - 4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol ( 1 ) and seven analogues, including six previously undescribed [elatumenol A-F ( 2 - 4 , 6 - 8 , respectively)], along with two new orsellinic acid esters [elatumone A and B ( 9 and 10 )], were isolated from Chaetomium elatum . The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3 , 4 , 7 , and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1β, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

As part of our search for compounds with cytotoxicity from endophytes of traditional Chinese medicines, two novel nor-sesquiterpenoids ( 1 - 2 ) with a new skeleton containing a tetrahydrofuran moiety were isolated form a rice medium of Fusarium tricinctum , an endophytic fungus isolated from the root of Ligusticum chuanxiong . The structures of these two previously undescribed compounds were elucidated by interpretation of the spectroscopic evidences including NMR correlations as well as MS data. The absolute configurations of these two compounds were confirmed by TD-DFT-ECD calculations. An MTT assay indicated that compound 1 exhibited moderate cytotoxic activity against MV4-11 with an IC 50 value of 22.29 μM.

Seven undescribed terpenoids, including three pairs of enantiomers, named (±)-rugulolides A-C, and one cyclopentenone derivative, named rugulolide D, together with twenty-six known compounds, were isolated from the aerial parts of Elsholtzia rugulosa. The chiral separation of rugulolides A-C was achieved by high-performance liquid chromatography using the chiral column. Their structures were elucidated unambiguously based on comprehensive spectroscopic analysis in conjunction with electronic circular dichroism (ECD) and single-crystal X-ray diffraction experiments. Rugulolides A-D are rare naturally occurring terpenoid derivatives featuring a methylated α,β-unsaturated-γ-lactone or a cyclopent-2-en-1-one nucleus. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cell, among them, four compounds showed moderate inhibition with IC 50 values ranging from 12.46 to 23.10 μM., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Two new dihydrophenanthrofurans (1 and 2) and two new bisbibenzyl derivatives (3 and 4) were isolated from the traditional Chinese medicinal plant Dendrobium nobile, along with four known compounds (5-8). The absolute configurations of compounds 1 and 4 were elucidated through extensive NMR and ECD spectroscopic analyses. New compounds showed no antimicrobial activity against four gram-positive bacterial strains and four gram-negative bacteria at the concentration of 1 mg/mL, but displayed significant cytotoxic activity against HepG2 human hepatic cell line with the IC 50 values ranging from 1.25 μM to 19.47 μM., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Five previously undescribed compounds, including two dendrobine-type alkaloids (1 and 2), three bibenzyl derivatives (3-5), along with six known compounds were isolated from orchids Dendrobium findlayanum. The structures and absolute configurations of the undescribed compounds were elucidated on the basis of HR-ESIMS, NMR spectroscopy, optical rotation value, as well as electronic circular dichroism (ECD) calculations. The cytotoxic effects of the isolated compounds on three human tumour cell lines (A172, SHSY5Y, and Hela) were evaluated by the MTT assay. Compound 6 showed excellent inhibitory activities against three human tumour cell lines with IC 50 ranging from 1.65 μM to 3.77 μM. All these compounds were assessed for their activity of promoting the gastrointestinal motility of zebrafish treated with Nile red. Compound 6 have excellent activity to promote the gastrointestinal motility of zebrafish at the concentration of 0.3 μM., Competing Interests: Declaration of Competing Interest The authors have declared that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chemical epigenetic manipulation was applied to explore secondary metabolite of an endophytic fungus Penicillium herquei , which was obtained from the fruiting body of Cordyceps sinensis , and three previously undescribed polyketides with pyran-2-one scaffold were isolated from its fermentation broth containing 10 mg/L 5-aza-2-deoxycytidine (a frequently-used DNA methyltransferase inhibitor). The structures of these new compounds were identified by extensive spectroscopic analyses, and their absolute configurations were elucidated by quantum chemical ECD calculations.

Two previously undescribed sesquiterpenes along with nine known compounds were isolated from the fermentation broth of Aspergillus fumigatus , an endophyte of Ligusticum wallichii . Their structures were elucidated through extensive spectroscopic analysis combined with quantum chemical ECD calculations. Two new compounds exhibited moderate growth inhibition against MV4-11 and MDA-MB-231 cell lines.

Phytopathogenic fungi have been considered as being an enormous threat in the agricultural system. In our search of new antifungal natural products, nine new halogenated cyclopentenones, bicolorins A-I ( 1-3 , and 5-10 ), along with three known cyclopentenones ( 4 , 11 , and 12 ) were isolated from the endophytic fungus Saccharicola bicolor of Bergenia purpurascens by the one strain-many compounds strategy. Their structures and absolute configurations were elucidated based on extensive spectroscopic analysis, X-ray crystallographic analysis, and time-dependent density functional theory-equivalent circulating density calculations. Compounds 1-12 showed antifungal activities against five phytopathogenic fungi ( Uromyces viciae-fabae , Pythium dissimile , Gibberella zeae , Aspergillus niger, and Sclerotinia sclerotiorum ). Especially, bicolorins B and D ( 2 and 5 ) exhibited strong antifungal activities against P. dissimile with the MIC values of 6.2 and 8.5 μg/mL, respectively, compared with the positive control cycloheximide (MIC of 8.6 μg/mL). Additionally, bicolorin D was proven to be potently antifungal against S. sclerotiorum in vitro and in vivo. This work provides an effective strategy for searching antifungal candidate agents.

Six new ellagitannins, brevipetins B-G ( 5 and 7 - 11 ), and a new phenolic glucoside, brevipetin A ( 4 ), along with six known compounds were isolated from the traditional Chinese medicinal plant Cleidion brevipetiolatum . Their structures and absolute configurations were determined by spectroscopic analyses, chemical methods, and TD-DFT-ECD calculations. Compounds 5 - 11 exhibited NO inhibitory effects with IC 50 values of 1.9-8.2 μM, and 9 showed the most potent inhibitory effect (IC 50 : 1.9 μM). An in vivo anti-inflammatory assessment of 9 showed that it exerts therapeutic effects in both the carrageenan-induced rat paw edema and collagen-induced arthritis (CIA) models at 50 mg/kg oral administration. The enhanced protein and mRNA expression levels of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in LPS-stimulated RAW 264.7 cells were dose-dependently suppressed by 9 . An anti-inflammatory mechanistic study revealed that 9 suppressed NF-κB activity by inhibiting IκBα phosphorylation and blocking translocation of p65 from the cytosol to the nucleus. Therefore, 9 might have the potential to be developed as a lead compound for relieving rheumatoid arthritis.

Two new terpene glycosides ( 1 - 2 ) along with two known analogs ( 3 - 4 ) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1 - 4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

Four previously undescribed isochromanes were isolated from the fermentation broth of an endophytic fungus Aspergillus fumigatus , which was obtained from the fruiting body of Cordyceps sinensis . Their structures were elucidated through extensive spectroscopic analyses. One racemic isochromane was further purified by chiral HPLC to yield a pair of enantiomers and their absolute configurations were determined by quantum chemical ECD calculations. These isolated compounds were evaluated for cytotoxicity against two cell lines (MV4-11 and MDA-ME-231) and the result showed that compounds 1a and 2 exhibited moderate growth inhibition against MV4-11 cell line.

Three new thiodiketopiperazines ( 1 ⁻ 3 ), along with two known analogues ( 4 and 5 ), were isolated from the fermentation broth of Penicillium crustosum . Their structures were elucidated through extensive spectroscopic analysis and the absolute configurations of new compounds were determined by Mosher ester analysis and calculated ECD spectra. Compound 4 and 5 have the activity to promote the gastrointestinal motility of zebrafish via acting on the cholinergic nervous system.

Five new polyketides, including two pairs of enantiomers and a racemate, were isolated from the fermentation broth of Aspergillus fumigatus , an endophytic fungus isolated from Cordyceps sinensis . Their structures were identified using one-dimensional (1D) and two-dimensional (2D) NMR experiments, and the absolute configurations of the enantiomers were confirmed using electronic circular dichroism (ECD) calculations. Compounds 1a and 2a exhibited inhibitory activity against the MV4-11 cell line in vitro, with IC 50 values of 23.95 µM and 32.70 µM, respectively.

A novel isoquinoline alkaloid, mahimbrine A, possessing a rare benzotropolone framing scaffold, was isolated from the endemic plant of Mahonia imbricata . Its structure was established on the basis of extensive spectroscopic analysis. A plausible biosynthetic route of mahimbrine A was proposed. Mahimbrine A showed no antimicrobial activity at the concentration of 1 mg/mL.

Guided by the UPLC-ESIMS profile, seven previously undescribed halogenated dihydroisocoumarins, palmaerones A-G, along with eleven known dihydroisocoumarins, were isolated from Lachnum palmae, an endophytic fungus from Przewalskia tangutica by exposure to a histone deacetylase inhibitor SAHA. Structures of the isolates were elucidated by analysis of their NMR, MS and optical rotation values. The antimicrobial, anti-inflammatory and cytotoxic activities of palmaerones A-G were evaluated. Palmaerones A-G showed antimicrobial activities against the strains (C. neoformans, Penicillium sp., C. albicans, B. subtilis and S. aureus), and palmaerone E exhibited potential antimicrobial activities against all the test strains with the MIC value in the range of 10-55 μg/mL. Palmaerones A and E exhibited moderate inhibitory effects on NO production in LPS-induced RAW 264.7 cells, with the IC 50 values of 26.3 and 38.7 μM, respectively and no obvious toxicities were observed at 50 μM. Palmaerone E showed weak cytotoxicity against HepG2 with the IC 50 value of 42.8 μM. This work provides an effective strategy for expanding natural product resource., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Eight previously undescribed oleanane-type triterpenoid saponins, clematangoticosides A-H, together with eight known saponins, were isolated from the whole plants of Clematis tangutica (Maxim.) Korsh. Their structures were elucidated by extensive spectroscopic analysis, in combination with chemical methods (acid hydrolysis and mild alkaline hydrolysis). Clematangoticosides D-G were found to be unusual 23, 28-bidesmosidic glycosides. The cytotoxic activities of all of the isolated saponins were evaluated against the four human cancer cell lines SGC-7901, HepG2, HL-60 and U251MG. Clematoside S, sapindoside B, kalopanax saponin A, and koelreuteria saponin A exhibited cytotoxicity against all of the test cancer cell lines with IC50 values in the range of 1.88-27.20 μM, while clematangoticoside D and F showed selective cytotoxicity against SGC-7901 with IC50 values of 24.22 and 21.35 μM, respectively., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To study the Chemical constituents from Przewalskia tangutica., Methods: The compounds were isolated and identified from n-butanol extract of Przewalskia tangutica by various chromatographic and spectral techniques., Results: Twelve polar compounds were isolated and identified as scopolin( 1),fabiatrin( 2),rutin( 3),queroetin-3-O-rutinoside-7-O-β-D-glucopyranoside( 4),protocatechuate( 5),vanillic acid( 6),thymine( 7),uracil( 8),cytosine( 9),adenine( 10),uridine( 11) and adenosine( 12)., Conclusion: Compounds 3 ~ 5,8 ~ 12 are obtained from Przewalskia tangutica for the first time.

Three novel oxazoline alkaloids, 1-oxa-3-azaspiro [4.5] dec-2-ene-8-one (1), 1-oxa-3-azaspiro [4.5] dec-2, 6-diene-8-one (2), and 1-oxa-3-azaspiro [4.5] dec-10-methoxy-2, 6-diene-8-one (3) were isolated from the methanol extract of the whole plant of Gymnotheca chinensis. The chemical structures were established by means of spectroscopic analysis including one- and two-dimensional NMR spectroscopy.

Four rare polycyclic spiro lignans (1-4) and four new biphenyl tetrahydrofuranone lignans (5-8) were isolated from the whole plant of Gymnotheca involucrata. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configuration of 1 was confirmed by single crystal X-ray diffraction. Bioassay results showed that compounds 2 and 6 exhibited weak antifungal activity against Uromyces viciae-fabae at 100 ppm in leaf-disc assays, while compound 3 demonstrated moderate insecticidal activity against Diabrotica balteata at 500 ppm in an artificial diet assay., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To study the chemical constituents of n-butanol extract in the broth of Myrothecium verrucaria., Methods: The chemical constituents were isolated,purified and identified by various chromatographic and spectral techniques., Results: 14 compounds were isolated and identified from n-butanol extracts of Myrothecium verrucaria broth. They were identified as cyclo-( Pro-Phe)( 1),cyclo-( 4-OH-Pro-Phe)( 2),cyclo-( 4-OH-Pro-Leu)( 3),cyclo-( Ala-Pro)( 4),cyclo-( 4-methyl-Pro-9-propyl-Gly)( 5),cyclo-( Pro-Gly)( 6),cyclo-( Phe-Gly)( 7),cyclo-( Leu-Leu)( 8),N-acetyl tryptamine( 9),N-( 2-phenylethyl) acetamide( 10),N-( 2-hydroxyphenethyl) acetamide( 11),N-( 4-hydroxyphenethyl) acetamide( 12),uracil( 13) and thymine( 14)., Conclusion: Compounds 1 ~ 14 are obtained from the strain Myrothecium verrucaria for the first time.

A new monoterpenoid indole alkaloid compound (1) and six known monoterpenoid indole alkaloids compounds (2-7) were isolated from the barks of Voacanga africana Staph. The structures were established by spectral analysis as ibogamine-16-carboxylic acid,17,20-didehydro-5,6-dioxo-10-methoxy-methyl ester (1), voacamine (2), vobasine (3), voacangine (4), voacristine (5), 19-epi-voacristine (6) and 19-epi-heyneanine (7). Compound 1 was confirmed by X-ray crystallographic analysis. All of the isolated compounds were evaluated for cytotoxicity against five cell lines (HEPG-2, A375, MDA-MB-231, SH-SY5Y, CT26). Among them, compounds 2 and 6 displayed significant inhibitory activities, compounds 3, 4 and 5 showed moderate inhibitory activities, while compounds 1 and 7 showed no inhibitory activities against the five cell lines.

Two new resorcylic acid lactones, 13-hydroxyhidroresorcylide (1) and 12-hydroxyhidroresorcylide (2), along with four known congeners (3-6) were isolated from Saccharicola bicolor, an endophytic fungus from Bergenia purpurascens. Their structures were elucidated by interpretation of the spectroscopic evidence.

Seven cyclic lipopeptide biosurfactants (1-7) were isolated for the first time from the fermentation broth of endophytic Bacillus clausii DTM1 and were identified as anteisoC13[Val7] surfactin-(L-Glu)-O-methyl-ester (1), anteisoC12[Val7] surfactin (2), anteisoC15[Val7] surfactin (3), isoC14[Leu7] surfactin (4), anteisoC12[Leu7] surfactin (5), nC13[Leu7] surfactin (6), and anteisoC14[Leu7] surfactin-(L-Glu)-O-methyl-ester (7); 1 has not been isolated before as a natural product from any source. Plate-based herbicide and insecticide bioassays showed that all compounds exhibited interesting insecticidal and herbicidal activities.

Objective: To study the alkaloids of Voacanga africana., Methods: The alkaloids were isolated by normal phase silica gel and Sephadex LH-20 column chromatography. Their structures were elucidated by analysis of spectroscopic data., Results: Eight alkaloids were isolated and their structures were elucidated as voacangine(1), voacangine hydroxyindolenine(2), 19R-epi-voacristine(3), epi-ibogaine(4), vobasine(5), 19-epi-heyneanine(6), vobtusine(7) and voacamine(8)., Conclusion: Compounds 2-4 and 6 are isolated from this plant for the first time.

Objective: To investigate the chemical constituents of Ardisia tenera Mez., Methods: Compounds were isolated by normal phase silica gel, MCI GEL and Sephadex LH-20 gel column chromatography. Their structures were elucidated by analyses of spectroscopic data., Results: Eight compounds were isolated, and their structures were elucidated as bauerenol (I), myristic acid (II), 11-phenyl-1-(2',6'-dihydroxy-4'-methoxy-phenyl)-undecan-1 -one (III), ardisinone A( IV), ardisinone B( V ), ardisinone C( VI), ardisinone F (VI), beta-sitosterol (VIII)., Conclusion: All of these compounds are obtained from this plant for the first time.