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The neurotoxicity of fumonisin B 1 (FB 1 ), a commonly detected mycotoxin in crops and the environment, has attracted considerable attention in recent years. However, no effective method for eliminating FB 1 completely exists due to the thermal stability and water solubility of this mycotoxin. Magnolol (MAG) is a neolignane with antioxidative and neuroprotective effects. It has been applied in neurotoxicity treatment. However, the application of MAG to attenuate FB 1 -induced toxicity has not been reported. This study explored the protective mechanism of MAG against FB 1 -induced damage in C6 cells through antioxidant and lipid metabolism modulation. Results showed that exposure to 15 μM FB 1 caused oxidative stress by changing the levels of malondialdehyde, reactive oxygen species, total superoxide dismutase, catalase, and total glutathione. These changes were reversed by MAG addition, especially at the concentration of 80 μM. The protective effects of MAG were further confirmed by the reduction in the phosphorylation levels of proteins in the MAPK signaling pathway. Lipidomics analysis identified 263 lipids, which belong to 24 lipid classes. Among all of the identified lipids, triglycerides (TGs), diglycerides (DGs), phosphatidylcholines (PCs), wax monoesters (WEs), Cers, and phosphatidylethanolamines (PEs) were major categories. Moreover, nine categories of lipids showed the opposite change trend in the FB 1 exposure and MAG 80 groups. A further investigation of the 34 co-occurring differential lipids with remarkable changes (P value < 0.05 and VIP value > 1) in the control, FB 1 exposure, and MAG 80 groups was performed. Therein, nine lipids (PCs, LPCs, and SM) were screened out as potential biomarkers to reveal the cytoprotective effects of MAG. This work is the first to investigate the rescue mechanism of MAG in FB 1 -induced cytotoxicity. The obtained results may expand the application of MAG to alleviate the toxicity of mycotoxins., 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 Ltd. All rights reserved.)

Inhibiting myocardial fibrosis can help prevent cardiovascular diseases, including heart failure. Magnolol (Mag), a natural component of Magnoliae officinalis, has been reported to inhibit fibrosis. However, the mechanism of Mag activity and its effects on myocardial fibrosis remain unclear. Here, we investigated the involvement of ALDH2, an endogenous protective agent against myocardial fibrosis, in the Mag-mediated inhibition of cardiac fibroblast proliferation and collagen synthesis. We found that Mag significantly inhibited cardiac fibroblast proliferation and collagen synthesis, based on the results of MTT, EdU and western blot assays. Moreover, molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) assays showed that Mag could bind directly and stably to ALDH2. Further analysis of the mechanism of these effects indicated that treatment with Mag dose-dependently enhanced ALDH2 activity without altering protein expression. Mag could enhance the activity of recombinant human ALDH2 proteins with a half-maximal effective concentration of 5.79 × 10 -5 M. In addition, ALDH2 activation via Alda-1 inhibited cardiac fibroblast proliferation and collagen synthesis, while ALDH2 inhibition via daidzin partially blocked the suppressive effects of Mag. In summary, Mag may act as a natural ALDH2 agonist and inhibit cardiac fibroblast proliferation and collagen synthesis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The effect of sesamin on intestinal flora was studied by in vitro animal fecal anaerobic fermentation system, and were analyzed by 16S rDNA sequencing. Results showed that sesamin modulated the composition of intestinal microorganisms and reshaped gut microbiome. The abundance of probiotics Lactobacillaceae and Bifidobacteriaceae increased, while the abundance of Enterobacteriaceae decreased. The properties of probiotics (Bifidobacterium bifidum and Lactophilus acidophilus) adhesion to epithelial colon cells (NCM460) were assessed by gram staining and plate counting methods. Results showed that sesamin increased the adhesive index of probiotics. Analysis of RT-qPCR, Western blot and immunofluorescence staining indicated that sesamin up-regulated the expression of the adhesive protein (β-cadherin and E-cadherin) of NCM460 cells. In conclusion, sesamin could promote the proliferation and adhesion of intestinal probiotics leading to modulating gut microbiota, which provided basis for sesamin as a food-borne functional factor for improving intestinal health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

One new sesquineolignan, piperneolignan A (1), four new neolignans, piperneolignans B-E (2-5), and eight known compounds were isolated from the leaves of Piper betle (Piperaceae) collected from Myanmar. These new structures were determined by analysis of MS and NMR data, and the absolute configuration of piperneolignan A was elucidated by electronic circular dichroism (ECD) calculations. Piperneolignan A (1), piperneolignan B (2), hydroxychavicol (6), p-hydroxycinnamaldehyde (10), and diallylcatechol (13) possessed anti-inflammatory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells with IC 50 values of 9.87, 45.94, 4.80, 26.40, and 40.45 μM, respectively, compared with the positive control NG-monomethyl-l-arginine (l-NMMA, IC 50  = 33.84 μM). The two hydroxy groups in the structure of hydroxychavicol are essential for activity, and dimerization or trimerization of hydroxychavicol decreases activity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Herein we report the preparation of 3,4-dibenzylfurans and some oxidized derivatives with lignan backbone. The compounds were prepared using the Friedel-Crafts reaction with BF 3 etherate as catalyst, demethylation with iodocyclohexane, acetylation and oxidation reactions. The antimicrobial activity was evaluated through their capacity to inhibit the growth of Gram positive and Gram negative bacteria, and of the yeast Candida albicans. Among ten products assayed four furans displayed a good antimicrobial activity against Staphylococcus aureus, S. epidermidis and C. albicans; on the contrary, none of the compounds were active against Pseudomonas aeruginosa. One of them inhibited the growth of S. aureus, S. epidermidis (biofilm producer strain) and C. albicans at 16 μg/mL, showing a bactericidal activity already after one hour of treatment. In summary, the results suggest a possible use of these derivatives for general disinfection practices or antimicrobial agents in cosmesis skin-care., 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 © 2020 Elsevier Ltd. All rights reserved.)

A series of oxime ester-derivatives were prepared by utilizing the schizandrin (1), a major compound isolated from Schisandra grandiflora, which is deployed in different traditional system of medicine. The in vitro antiproliferative activities of the synthesized compounds were assessed against a selected panel of human cancer cell lines (A549, RKO P3, DU145 and Hela) and normal cell (HEK293). Several of these derivatives were found more potent in comparison to parent compound, schizandrin (1). Particularly, 4a and 4b demonstrated potent activity against DU-145 and RKOP3 cell lines with IC 50 values of 3.42 µM and 3.35 µM respectively. To characterize the molecular mechanisms involved in antitumoral activity, these two compounds, 4a and 4b were selected for further studies. Cell cycle analysis revealed that both the compounds were able to induce apoptosis and cell cycle arrest at G 0 /G 1 phase. To know the extent of apoptosis in DU145 and RKOP3 cell lines, Annexin V-FITC were performed. Moreover, the tubulin polymerization assay indicated that 4a and 4b exhibits potent inhibitory effect on the tubulin assembly. Molecular docking studies and competitive binding assay also indicated that 4a and 4b effectively bind at the colchicine binding site of the tubulin., 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 © 2020 Elsevier Ltd. All rights reserved.)

Dehydrodieugenol B and five related natural neolignans were isolated from the Brazilian plant species Nectandra leucantha. Three of these compounds were shown to be active against murine (B16F10) and human (A2058) melanoma cells but non-toxic to human fibroblasts (T75). These results stimulated the preparation of a series of 23 semi-synthetic derivatives in order to explore structure-activity relationships and study the biological potential of these derivatives against B16F10 and A2058 cell lines. These structurally-related neolignan derivatives were analyzed by multivariate statistics and machine learning, which indicated that the most important characteristics were related to their three-dimensional structure and, mainly, to the substituents on the neolignan skeleton. The results suggested that the presence of hydroxyl or alkoxyl groups at positions 3, 4 and 5 (with appropriate sidechains) promoted an increase in electropological and charge density, which seem to be important for biological activity against murine (B16F10) and human (A2058) melanoma cells., 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 © 2020 Elsevier Ltd. All rights reserved.)

One of the arctigenin stereoisomers, (8R,8'R)-trans-form 1, showed stereospecific cytotoxicity against insect cells, Sf9 and NIAS-AeAl-2 cells. By the comparison with other stereoisomers, the most importance of the 8'R stereochemistry for the higher activities was clarified. On the other hand, the wider range of activity level among stereoisomers against cancer cells, HL-60, was not observed. The structure-activity relationship research using derivatives bearing (8R,8'R)-trans-form was performed to show the same level of activities of 3-iodo, 4-iodo, and 3,4-methylenedioxy derivatives 28, 29, and 36 as (8R,8'R)-trans-arctigenin 1. In the examination of thiono derivatives, 4-iodo thiono and 3,4-methylenedioxy thiono derivatives 66, 67 showed similar level of activities to that of (8R,8'R)-trans-arctigenin 1. The expression of ribosomal 28S rRNA gene of Sf9 cells was increased by (8R,8'R)-trans-arctigenin 1, whereas a degradation of DNA was not observed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The neuroprotective effects and potential mechanisms of (-)-Syringaresinol-4-O-β-D-glucopyranoside (SRG), a natural lignan glycoside extracted from Cortex Albizziae, were investigated using corticosterone (CORT)-induced PC12 cells as an in vitro anxiety model. PC12 cells were treated with 100 μM CORT and 5, 10, or 20 μM SRG for 48 h. Cell viability and lactate dehydrogenase (LDH) leakage were measured. Apoptosis were detected using FITC-coupled Annexin V (AV) and propidium iodide (PI) staining flow cytometric analyses and TUNEL assays. Rhodamine 123 and Fluo-3-AM staining flow cytometric analyses were used to detect mitochondrial membrane potential (ΔΨm) and intracellular calcium concentration ([Ca 2+ ] i ), respectively. Western blot was used to detect brain-derived neurotrophic factor (BDNF), Bax, Bcl-2, cAMP-response element binding protein (CREB), cytosolic cytochrome c (Cyt c), caspase-3, and cleaved caspase-3. Experimental data showed that SRG promoted cell proliferation, reduced LDH release, inhibited apoptosis, improved ΔΨm values, decreased [Ca 2+ ] i , up-regulated CREB, BDNF, and Bcl-2, down-regulated Bax and Cyt c protein expression levels, and reduced caspase-3 activity. This suggests that SRG has neuroprotective and antiapoptotic effects in the pathogenesis of anxiety disorders, and its mechanisms are partly connecte to inhibition of the mitochondrial apoptotic pathway and activation of pathways involving CREB and BDNF., 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 © 2020 Elsevier Ltd. All rights reserved.)

Cupressus macrocarpa is a windbreak tree and is reported to have various cytotoxic effects. A natural product study on the leaves of C. macrocarpa has yielded ten secondary metabolites, including three new diterpenoids (1-3), four known diterpenoids (4-7), and three known lignans (8-10). The structures of all isolated compounds were elucidated via the interpretation of spectroscopic methods, especially 2D NMR and mass analyses. In the cytotoxic assays, compounds 1-3 and 7-10 showed inhibition effect against HepG2, MDA-MB-231, and A549 cells with IC 50 values ranging from 0.004 to 19.9 μg/mL. Moreover, the anti-inflammatory assays revealed that (-)-matairesinol (8) had significant inhibitory activities on superoxide anion generation (IC 50  = 2.7 ± 0.3 μM) and elastase release (IC 50  = 6.6 ± 0.7 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 © 2020 Elsevier Ltd. All rights reserved.)

Stilbenes and benzofuran neolignans are important groups of plant phenolics therefore they play a significant role in plants and human health. The objective of this study was to investigate the structure-activity relationships of naturally occurring stilbene and benzofuran neolignan derivatives as acetylcholinesterase inhibitors. A series of these compounds were prepared and assessed for their inhibition on acetylcholinesterase activity. δ-Viniferin, pterostilbene trans-dehydrodimer, pallidol, grossamide, and boehmenan exerted acetylcholinesterase inhibitory potential. The several oligomeric compounds protected against cell damage resulting from t-BHP exposure and inhibited lipopolysaccharide/interferon-gamma (LPS/IFNγ)-induced NO production in vitro. Our findings highlight the great potential of pterostilbene trans-dehydrodimer, pallidol, and boehmenan as multifunctional nutraceuticals for management of neurodegenerative diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Recently, our research team reported the anti-amnesic potential of desalted-hydroethanolic extracts of Salicornia europaea L. (SE-EE). In this study, we performed bioactivity-guided isolation and identification of Acanthoside B (Aca.B), from SE-EE, as the potential bioactive candidate and examined anti-amnesic activity with its potential mechanism of action using an in vivo model. S7-L3-3 purified from SE-EE showed enhanced in vitro acetylcholinesterase (AChE) inhibitory activity. The isolated S7-L3-3 was identified and characterized as Aca.B using varied spectral analyses, i.e., Nuclear magnetic resonance (NMR), Ultraviolet-visible (UV-Vis), and Electrospray ionization-mass spectrometry (ESI-MS). In the in vitro studies, Aca.B exhibited negligible toxicity and showed a dose-dependent nitric oxide inhibitory potential in Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. In the in vivo studies, the oral administration of Aca.B to mice showed enhanced bioavailability and dose-dependent repression of the behavioral/cognitive impairment by regulating the cholinergic function, restoring the antioxidant status, attenuating the inflammatory cytokines/mediators and actively enriching neurotropic proteins in the hippocampal regions of the scopolamine-administered mice., (Copyright © 2019. Published by Elsevier Ltd.)

Defatted-sesame meal (DSM), a byproduct of sesame oil, has attracted considerable interest in the food industry because of its strong antioxidant activity. The aim of this study was to measure the content and distribution of lignans in DSM and evaluate their antioxidant activity after thermal processing and in vitro digestion. The results showed that the sesame lignans (SL) content and antioxidant activity were significantly influenced by the temperature and time during thermal preparation, and the maximum antioxidant potency composite index (ACI) was obtained after roasting the samples at 240 °C for 20 min. As sesame seed was processed with longer time and higher temperature, more pinoresinol diglucoside (PD) and sesamol were measured in DSM. According to the correlation matrix under thermal preparation, a significant contribution to the antioxidant potency of DSM was discovered. After in vitro digestion, the release amount of lignans increased by 19.6%, and the values of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and ACI gradually declined after digestion, with a 40% decrease in both the DPPH radical scavenging activity and the ACI from oral to intestinal phase. These results could be used to help improve the bioavailability of SL and obtaining high quality sesame byproducts., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To control the fish fungal pathogen Saprolegnia, the effects of the petroleum ether extracts of Magnolia officinalis were evaluated by a rapeseed (Brassicanapus) microplate method in vitro. By loading on an open silica gel column and eluting with petroleum ether-ethyl acetate-methanol, honokiol (C 18 H 18 O 2 ) and magnolol (C 18 H 18 O 2 ) were isolated from Magnolia officinalis. Saprolegnia parasitica growth was inhibited significantly when honokiol concentration was >8.0 mg/L, and magnolol concentration was >9.0 mg/L, with EC 50 values of 4.38 and 4.92 mg/L, respectively. Six honokiol and magnolol derivatives were designed, synthesized and evaluated for their anti-Saprolegnia activity. According to the results, double bond and hydroxyl played an important role in inhibiting Saprolegnia. Mechanistically, through the scanning electron microscope observation, honokiol and magnolol could cause the Saprolegnia parasitica mycelium tegumental damage including intensive wrinkles and nodular structures. Moreover, compared to traditional drugs kresoxim-methyl (LC 50  = 0.66 mg/L) and azoxystrobin (LC 50  = 2.71 mg/L), honokiol and magnolol showed a lower detrimental effect on zebrafish, with the LC 50 values of 6.00 and 7.28 mg/L at 48 h, respectively. Overall, honokiol and magnolol were promising lead compounds for the development of commercial drugs anti-Saprolegnia., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Novel isoxazole and pyrazole analogs based on natural biphenyl-neolignan honokiol were synthesized and evaluated for their inhibitory activities against nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells. The isoxazole skeleton was constructed via nitrile oxide cycloaddition from oxime 3 and pyrazole was generated by condensation of 4-chromone and alkylhydrazine. Among the analogs, 13b and 14a showed stronger inhibitory activities with IC 50 values of 8.9 and 1.2 µM, respectively, than honokiol., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Three pairs of enantiomeric neolignans 1a/1b-3a/3b were isolated from the stems of Picrasma quassioides, and separated successfully by chiral-phase HPLC. Their structures were established by comprehensive spectroscopic analyses as well as ECD spectroscopy. The in vitro cytotoxicity of the isolates was evaluated against human hepatocellular carcinoma HepG2 and Hep3B cells. Among them, 1 and its enantiomers 1a/1b, 3 and 3a/3b displayed similar cytotoxicity in pair-wise comparison against HepG2 and Hep3B cells, and the similar effects of 2 and 2a/2b were found in Hep3B cells. Interestingly, 2a and 2b had different cytotoxic activities on HepG2 cells with IC 50 values of 35.6 μM and 104.4 μM, respectively. In addition, 2 exerted middle cytotoxicity against HepG2 cells with an IC 50 value of 78.6 μM. The different cytotoxicity between enantiomers 2a and 2b attracted our interest. To investigate the underlying mechanisms responsible for the distinct cytotoxicity, we further assessed the effects of 2a and 2b on cell cycle distribution, cell apoptosis and reactive oxygen species (ROS) generation. The results indicated that 2a had more significant effect than 2b on apoptosis induction and ROS generation, but both had no obvious effect on cell cycle of HepG2 cells. It is concluded that the different configurations of 2a/2b determined the enantioselective cytotoxicity on HepG2 cells through apoptosis induction and ROS generation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Staphylococcus aureus is a major and dangerous human pathogen that causes a range of clinical manifestations of varying severity, and is the most commonly isolated pathogen in the setting of skin and soft tissue infections, pneumonia, suppurative arthritis, endovascular infections, foreign-body associated infections, septicemia, osteomyelitis, and toxic shocksyndrome. Honokiol, a pharmacologically active natural compound derived from the bark of Magnolia officinalis, has antibacterial activity against Staphylococcus aureus which provides a great inspiration for the discovery of potential antibacterial agents. Herein, honokiol derivatives were designed, synthesized and evaluated for their antibacterial activity by determining the minimum inhibitory concentration (MIC) against S. aureus ATCC25923 and Escherichia coli ATCC25922 in vitro. 7c exhibited better antibacterial activity than other derivatives and honokiol. The structure-activity relationships indicated piperidine ring with amino group is helpful to improve antibacterial activity. Further more, 7c showed broad spectrum antibacterial efficiency against various bacterial strains including eleven gram-positive and seven gram-negative species. Time-kill kinetics against S. aureus ATCC25923 in vitro revealed that 7c displayed a concentration-dependent effect and more rapid bactericidal kinetics better than linezolid and vancomycin with the same concentration. Gram staining assays of S. aureus ATCC25923 suggested that 7c could destroy the cell walls of bacteria at 1×MIC and 4×MIC., (Copyright © 2017. Published by Elsevier Ltd.)

The new lignano-9,9'-lactones (α,β-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC 50 =12μM), however, it was inactive against HeLa cells (EC 50 >100μM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC 50 values of 10μM and 9.4μM against HL-60 cells, respectively. Against HeLa cells, the EC 50 value of the derivative 66 was 27μM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference., (Copyright © 2017. Published by Elsevier Ltd.)

To control the parasitic disease of Dactylogyrus intermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10mg/L. Compared to traditional drug praziquantel (EC 50 =2.69mg/L), ether derivatives 2g and 2h exhibited slightly higher anti-parasitic activity, with the EC 50 values of 2.48 and 1.52mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids 4a and 4b also removed D. intermedius effectively, with the EC 50 values of 2.13 and 2.07mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds 4a and 4b caused the D. intermedius tegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that 4a and 4b can be used for preventing and controlling Dactylogyrus infections and considered as promising lead compounds for the development of commercial drugs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Sialidases are key virulence factors that remove sialic acid from host cell surface glycans, thus unmasking receptors to facilitate bacterial adherence and colonization. In this study, we report the isolation and characterization of novel inhibitors of the Streptococcus pneumoniae sialidases NanA, NanB, and NanC from Myristica fragrans seeds. Of the isolated compounds (1-12), malabaricone C showed the most pneumococcal sialidases inhibition (IC 50 of 0.3μM for NanA, 3.6μM for NanB, and 2.9μM for NanC). These results suggested that malabaricone C and neolignans could be potential agents for combating S. pneumoniae infection agents., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A new lignan, 9'-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4-12) have been isolated from the active fractions, CHCl 3 (IC 50 , 0.32μgmL -1 ) and EtOAc (IC 50 , 0.55μgmL -1 ) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC 50 values of 3.7 and 3.3μM, respectively. 9'-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The chemical characterization of Selaginella tamariscina leaves resulted in the isolation of five lignanoside derivatives (1-4 and 6) and one neolignan (5). These compounds include three new lignanosides, tamariscinosides D-F (1-3), and one liriodendrin (4) that were isolated for the first time from this plant, together with two known compounds, (2R,3S)-dihydro-2-(3,5-dimethoxy-4-hydroxyphenyl)-7-methoxy-5-acetyl-benzofuran (5) and moellenoside B (6). The chemical structures of these isolated compounds were determined using 1D and 2D NMR, MS, and CD spectroscopic data, and the results were compared to data previously reported in the literatures. These compounds were also evaluated in terms of their inhibition of NO production in lipopolysaccharide (LPS)-stimulated activity in the macrophage cell line RAW 264.7. Among them, compounds 1, 2, 5, and 6 exhibited a significant inhibition with IC 50 values ranging from 32.3 to 55.8μM., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Seven new neolignans (1-2, 7-11) and five known compounds (3-6, 12) were isolated from the 70% EtOH extract of hawthorn seeds. Their structures were determined by spectroscopic analyses. The antioxidant and anti-inflammatory activities of all the isolates were investigated. Most of the isolates showed moderate radical scavenging activity in the DPPH assay and significant activities in the ABTS and FRAP assays. Furthermore, compounds 7-12 exhibited marked nitric oxide (NO) inhibition and compounds 1-4 had a potent necrosis factor-α (TNF-α) inhibitory effect. The results we obtained showed that hawthorn seeds can be regarded as a potential new and cheap source of antioxidants and inflammation inhibitors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Dioxins and dioxin-like compounds (DLCs) enter the body mainly through diet and cause various toxicological effects through activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. Some plant extracts and phytochemicals are reported to suppress this transformation. However, most of these reports have been from in vitro experiments and few reports have been from in vivo experiments. In addition, there has been no report of foodstuffs that effectively prevent AhR-associated morphological abnormalities such as deformities caused by dioxins and DLCs in vivo. In this study, we show that secoisolariciresinol (SECO), a natural lignan-type polyphenolic phytochemical found mainly in flaxseed, has a rescuing effect, actually suppressing morphological abnormalities (pericardial edema) in zebrafish embryos exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126), a dioxin-like PCB congener. Importantly, the rescuing effect of SECO was still evident when it was applied 16 h after the beginning of exposure to PCB126. This study suggests that SECO may be useful as a natural suppressive agent for morphological abnormalities caused by dioxins and DLCs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Five new flavonoids, griffinones A-E (1-5), a new biphenylneolignan, griffilignan A (6) and ten known compounds were isolated from the n-hexane and EtOAc extracts of Millettia griffithii. The structures of the new compounds were determined by 1D and 2D NMR, and by HRMS. The anti-inflammatory activity of the isolated compounds was evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. Among the isolated compounds, compounds 1, 2 and 14 showed significant anti-inflammatory activity with IC50 values of 20.4, 2.1 and 35.7μM, respectively and no obvious toxicities were observed at 100μM. Western blot and PCR assay further showed that inhibition of nitric oxide production by compound 2 was associated with suppression of iNOS expression. Modeling studies suggested that the amino group, phenyl ring as well as the isopentenyl tails of compound 2 could help bind to iNOs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Activation of peroxisome proliferator-activated receptors (PPARs) plays a crucial role in cellular energy metabolism that directly impacts mitochondrial biogenesis. In this study, we demonstrate that syringaresinol, a pharmacological lignan extracted from Panax ginseng berry, moderately binds to and activates PPARβ with KD and EC50 values of 27.62±15.76μM and 18.11±4.77μM, respectively. Subsequently, the expression of peroxisome proliferator-activated receptor γ coactivator-1α together with PPARβ transcriptional targets, mitochondrial carnitine palmitoyltransferase 1 and uncoupling protein 2, was also enhanced in terms of both mRNA and protein levels. The activation of these proteins induced mitochondrial biogenesis by enrichment of mitochondrial replication and density within C2C12 myotubes. Importantly, knockdown of PPARβ reduced the syringaresinol-induced protein expression followed by the significant reduction of mitochondrial biogenesis. Taken together, our results indicate that syringaresinol induces mitochondrial biogenesis by activating PPARβ pathway., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Ethyl 2-(4-methoxyphenyl)-3-(thiophene-2-carbonyl)cyclopropanecarboxylates 2(a-f) and ethyl 4-aryl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-5-carboxylates 4(a-f) were synthesized by simple procedure. The synthesized new compounds were screened in vitro for their antimicrobial and antioxidant activities. The compounds 2b and 4f showed excellent antibacterial activity; while 2b and 4f showed remarkable antifungal properties. The results of antioxidant activity studies revealed that compounds 4b and 4f manifested profound antioxidant potential. The docking studies were done for the final compounds. The ADME result indicates that all these molecules possess pharmaceutical properties in the range of 95% of drugs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

To estimate the effect of methyl group of dihydroguaiaretic acid, which shows many kinds of biological activities, on biological activity, both enantiomers of 9'-dehydroxyimperanene (5, 6) and 7,8-dihydro-9'-dehydroxyimperanene (7, 8) lacking one of the methyl groups of dihydroguaiaretic acid were synthesized. (S)-7,8-Dihydro-9'-dehydroxyimperanene (7) showed 4-6-fold higher cytotoxic activity than all stereoisomers of dihydroguaiaretic acid (2-4). The IC50 values of (S)-7,8-dihydro-9'-dehydroxyimperanene (7) against HL-60 and HeLa cells were 6.1μM and 5.6μM, respectively. Though only one of three stereoisomers of dihydroguaiaretic acid showed antibacterial activity against a gram negative bacterium, both enantiomers of 5-8 showed antibacterial activity against a gram negative bacterium. This is a Letter on biological activity of 9-norlignan, in which one of methyl groups of lignan is absent., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A series of arctigenin-4-yl carbamate derivatives were synthesized and evaluated for potency in reducing β-amyloid (Aβ) content in HEK293-APPswe cells. Most of the arctigenin-4-yl aralkyl or aryl carbamate derivatives showed improved potency in reducing Aβ content. Among the synthesized compounds, arctigenin-4-yl (3-chlorophenyl)carbamate (20) exhibited the strongest potency with 78.7% Aβ content reduction at 20μM. Furthermore, the effect of arctigenin-4-yl (4-chlorophenyl)carbamate (19) and arctigenin-4-yl (3-chlorophenyl)carbamate (20) on lowing Aβ content was better than arctigenin under the concentrations of 1, 10 and 20μM., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

As part of our ongoing search for bioactive constituents of natural Korean medicinal plants, three new lignan derivatives, sambucasinol A-C (1-3), together with 7 known compounds (4-10) were isolated from the twigs of Sambucus williamsii. The structures of these new compounds were determined by a combination of 1D and 2D NMR spectroscopic data analysis, as well as circular dichroism (CD) spectroscopy studies. Here, we evaluated the anti-inflammatory effects of 1-10 in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cells. Compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in LPS-activated BV-2 cells, with IC50 values of 6.82, 7.04, and 14.70 μM, respectively. Additionally, we evaluated the effects of compounds 1-10 on NGF induction in a C6 rat glioma cell line. Compounds 1-3 upregulated NGF secretion to 183.95 ± 2.63%, 153.99 ± 5.15%, and 155.96 ± 5.15%, respectively, without any significant cell toxicity. Moreover, all isolates were evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and XF498 cell lines. Compounds 1-3 showed consistent cytotoxicity against the four human cell lines, with IC50 values in the range of 11.07-19.62 μM., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

(-)-Cubebin, isolated from the seeds of Piper cubeba, and its five different types of derivatives (a total of 17), with varying functionalities, were tested for their in vitro anticancer activity against six human cancer cell lines (A549, K562, SiHa, KB, HCT116 and HT29) using MTT assay. Cubebin as well as its derivatives containing lactone and amide groups showed significant anticancer activity. In some of the tested cell lines, the amide derivatives showed higher activity. Morphological analysis indicated that these compounds act through apoptosis mediated pathway of cell death and we expect that these results will pave new paths in the development of novel anticancer agents by the derivatization of (-)-cubebin., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The CHCl3 soluble fraction of the 80% MeOH extract of the stems of Firmiana simplex strongly inhibited nitric oxide production in lipopolysaccharide-activated BV-2 cells. A bioactivity-guided column chromatographic separation yielded two new lignans, firmianols A and B (1-2) together with seventeen known lignans (3-19). The structural elucidation of the new compounds was determined by spectroscopic methods, including 1D, 2D NMR and HR-FAB-MS. All isolated lignans were evaluated for their antineuroinflammatory effects on nitric oxide (NO) production in lipopolysaccharides (LPS)-activated murine microglia BV2 cells. Among the isolated, compounds 14 and 15 showed potent inhibitory activity against NO production (IC50 1.05 and 0.929 μM, respectively) without cell toxicity in murine microglia BV-2 cells. Compounds 11-13 and 17 also exhibited strong inhibitory effects on NO production, with IC50 values ranging from 7.07 to 15.28 μM., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In this study, we evaluated the in vitro cytotoxicity of fractions and isolated constituents from Cinnamomum parthenoxylon woods against human leukemia HL-60 and U937 cells. The n-Hex, EtOAc, and MeOH-H2O fractions of the woods inhibited cell proliferation in both cell lines. Our phytochemical investigation of the n-Hex and EtOAc fractions led to the isolation of lignans and phenylpropanoids, whose chemical structures were confirmed by spectroscopic analyses. All isolated compounds were evaluated for their in vitro antileukemic activity; especially, hinokinin and cubebin exhibited strong inhibition toward U937 cell proliferation. Morphological observation indicated that these cytotoxic actions were mediated by apoptosis. Our findings suggested that an oxygenated functional group at the C-9 position in dibenzylfuran skeleton contributed their potency. In addition, these results enhanced the ethnopharmacological value of C. parthenoxylon., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

(+)- and (-)-liriodenol, a pair of unprecedented enantiomeric lignans bearing a 1,1-disubstituted olefinic group, were isolated from the barks of Liriodendron hybrid. The structure and relative configurations were determined by comprehensive analysis of MS and NMR spectroscopy. The cytotoxicity of these three lignans ((±)-, (+)-, and (-)-liriodenol) was evaluated in vitro against four selected human tumor cell lines, where (+)-liriodenol showed more significant cytotoxic effects than the (±)- and (-)-liriodenol enantiomers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Coumarinlignan (1), possessing a unique coumarin-containing lignan skeleton, was isolated from the stems of Kadsura heteroclita. Its structure and absolute configuration were determined by spectroscopic techniques, especially 2D NMR and X-ray crystallographic data analyses. The proposed biosynthetic pathway is discussed. This new compound showed good anti-HBV activity against HBeAg and HBsAg, and moderate anti-fibrotic and neuroprotective activities., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We present the synthesis of new derivatives of natural products magnolol (1) and honokiol (2) and their evaluation as allosteric ligands for modulation of GABAA receptor activity. New derivatives were prepared via metal assisted cross-coupling reactions in two consecutive steps. Compounds were tested by means of two-electrode voltage clamp electrophysiology at the α1β2γ2 receptor subtype at low GABA concentrations. We have identified several compounds enhancing GABA induced current (IGABA) in the range similar or even higher than the lead structures. At 3μM, compound 8g enhanced IGABA by factor of 443, compared to 162 and 338 of honokiol and magnolol, respectively. Furthermore, 8g at EC10-20 features a much bigger window of separation between the α1β2γ2 and the α1β1γ2 subtypes compared to honokiol, and thus improved subtype selectivity., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Syringaresinol exists either exclusively as one enantiomer or enantiomeric mixtures in plant foods. We found that (+)-syringaresinol, but not (-)-syringaresinol, upregulates silent information regulator two ortholog 1 (SIRT1) gene expression, and thus, Panax ginseng berry with predominantly high contents of (+)-syringaresinol exhibits higher activity in inducing SIRT1 gene expression than Acanthopanax senticosus Harms stem with almost equal proportion of the two enantiomers. These findings highlight the importance of the absolute configuration of syringaresinol for the biological activity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Excessive NO (nitric oxide) has been associated with the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). In our screening system using LPS-activated BV2 microglial cells, the methanolic extract of Disporum viridescens leaves was found to have significant NO inhibitory activity. Bioactivity-guided isolation yielded a new phenylpropanoid characterized as 4-ally-2,6-dimethoxyphenyl 1-O-β-D-apiofuranosyl (1→6)-β-D-glucopyranoside (12) with 21 known compounds from the leaves of D. viridescens. Among them, compounds 2 and 4 significantly inhibited NO production. Thus, we further elucidated the anti-inflammatory mechanism of these lignans. Especially, compound 4 inhibited the expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) through the suppression of the MAPK signaling pathway. Taken together, the anti-inflammatory activities of the active constituents isolated from D. viridescens leaves could have therapeutic potential against neurodegenerative diseases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The synthesized 7-aryl derivatives of (7R,7'S,8S,8'S)-(+)-verrucosin were applied to growth inhibitory activity test against ryegrass at 1mM. 7-(3-Ethoxy-4-hydroxyphenyl) derivative 12 and 7-(2-hydroxyphenyl) derivative 4 showed comparable activity to those of (+)-verrucosin against the root (-95%) and the shoot (-60%), respectively. The growth inhibitory activity test against lettuce using synthesized 7-aryl derivatives of (7S,7'R,8R,8'R)-(-)-verrucosin at 1mM showed that the activities of 7-(3-hydroxyphenyl) derivative 20 and 7-(3-ethoxy-4-hydroxyphenyl) derivative 28 are similar to that of (-)-verrucosin against the root (-95%). Against the shoot, 7-(3-hydroxyphenyl) derivative 20 showed higher activity (-80%) than that of (-)-verrucosin (-60%). As the next step, (7S,7'R,8R,8'R)-7-(3-hydroxyphenyl)-7'-aryl-(-)-verrucosin derivatives, in which the most effective 3-hydroxyphenyl group is employed as 7-aromatic ring, were synthesized for the assay against lettuce. In this experiment, 7'-(2-hydroxyphenyl) derivative 37 and 7'-(3-hydroxyphenyl) derivative 38 showed similar activity to that of derivative 20. The effect of 7- and 7'-aryl structures of 7,7'-epoxylignanes on the plant growth inhibitory activity was clarified. The 7- and 7'-aryl structures were simplified to show comparable activity to or higher activity than that of (-)-verrucosin. The plant growth inhibitory activity of a nutmeg component, (+)-fragransin C3b, was estimated as -80% inhibition at 1mM against ryegrass roots., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Investigation of the bark of Zanthoxylum simulans afforded six new dimeric lignans zanthpodocarpins C-H (1-6) bearing an unusual α,β-unsaturated ketone group. The new structures of 1-6 were determined by using detailed spectroscopic analysis. All of the isolated compounds were examined for their inhibitory effects against rat joint synovial cell and splenocyte proliferation. Compounds 1-6 showed potent anti-inflammatory activities with IC50 values ranging from 18.6 to 36.1μM, and 13.8 to 74.3μM., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We have previously shown that nectandrin B, a potent natural activator of AMP-activated protein kinase (AMPK) results in endothelium-dependent relaxation via endothelial nitric oxide synthase phosphorylation. This study examined the effects of nectandrin B on monocyte adhesion and on the expression of adhesion molecules in endothelial cells, an initial event in atherogenesis. Nectandrin B inhibited tumor necrosis factor-α (TNFα)-induced monocytoid THP-1 cell adhesion to ECV 304 human endothelial cells. This lignan also suppressed TNFα-induced protein and mRNA expression of two cell adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). In addition, expression of cyclooxygenase-2 and inducible nitric oxide synthase were diminished by nectandrin B treatment. Reporter gene and immunoblot analyses revealed that transcription factor activities of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and cyclic AMP response element binding protein (CREB) were inhibited by nectandrin B. Moreover, nectandrin B activated AMP-activated protein kinase (AMPK) in ECV 304 cells. Transfection of a dominant-negative mutant form of AMPK (DN-AMPK) partially reversed inhibitory effects of nectandrin B on the expression of VCAM-1 and ICAM-1, and on the transcriptional activity of CREB., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

With the goal of developing soluble epoxide hydrolase (sEH) inhibitors with novel chemical structures, the sEH inhibitory activities of 30 natural compounds were evaluated using both a fluorescent substrate, 3-phenyl-cyano(6-methoxy-2-naphthalenyl)methyl ester- 2-oxiraneacetic acid, and a physiological substrate, 14,15-epoxyeicosatrienoic acid. To evaluate the selectivity of sEH inhibition, the inhibition of microsomal epoxide hydrolase (mEH), which plays a critical role in detoxification of toxic epoxides, was determined using human liver microsomes. Honokiol and β-amyrin acetate, isolated from Magnolia officinalis and Acer mandshuricum, respectively, displayed strong inhibition of sEH activity, with respective IC50 values of 0.57 μM and 3.4 μM determined using the fluorescent substrate, and 1.7 μM and 6.1 μM determined using 14,15-epoxyeicosatrienoic acid. mEH activity was decreased to 49% or 61% of control activity by 25 μM honokiol or β-amyrin acetate, respectively. These results suggest that β-amyrin acetate and honokiol exhibit sEH inhibitory activity, although their sEH selectivity should be improved., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Sesamin (Ses), one of the major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced injury in liver have not been clarified. The aim of the present study was to investigate the hepatoprotective effects of sesamin on oxidative stress and apoptosis in mice exposed to CCl4. Our data showed that sesamin significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) in liver, were suppressed by treatment with sesamin. Furthermore, TUNEL assay showed that CCl4-induced apoptosis in mouse liver was significantly inhibited by sesamin. In exploring the underlying mechanisms of sesamin action, we found that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of CCl4 treated mice. Sesamin increased expression levels of phosphorylated Jun N-terminal kinases (JNK) in liver, which in turn inactivated pro-apoptotic signaling events restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 proteins and decreasing the release of mitochondrial cytochrome c in liver of CCl4 treated mice. JNK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against CCl4 induced liver injury by regulating the expression levels of phosphorylated c-Jun proteins, necrosis factor-alpha (TNF-α) and Bak. In conclusion, these results suggested that the inhibition of CCl4-induced apoptosis by sesamin is due at least in part to its anti-oxidant activity and its ability to modulate the JNK signaling pathway., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Three new lignans (3, 4, and 6) along with eight known lignans and phenyl propanoids were isolated from the dried roots of Pulsatilla koreana, an oriental folk medicine. Based upon the results of combined spectroscopic and chemical methods, the structures of new compounds were determined to be lignan glycosides. Included among the known compounds are three compounds (5, 7, and 8) isolated first time from this plant as well as two compounds (2 and 11) previously reported only as synthetic derivatives. These compounds significantly inhibited the action of Sortase A from Streptococcus mutans OMZ65, an isolate from human oral cavity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Gomisin A, one of the major dibenzocyclooctadiene lignans isolated from Schisandra chinensis Baill., has proved to possess a variety of pharmacological effects. The aim of the present study was to investigate the anti-inflammatory and neuroprotective effects of gomisin A as well as its potential molecular mechanisms. It was found that gomisin A not only inhibited the production of NO and PGE2 in a concentration-dependent manner but also suppressed the expressions of iNOS and COX-2 in LPS-stimulated N9 microglia without observable cytotoxicity. Gomisin A was also able to attenuate the mRNA expression and the production of pro-inflammatory factors TNF-α, IL-1β and IL-6. Moreover, LPS induced reactive oxygen species (ROS) production, NADPH oxidase activation, and gp91phox expression, which were markedly inhibited by gomisin A in microglia. Furthermore, the data showed that gomisin A significantly down-regulated the TLR4 protein expression, and inhibited nuclear transcription factor (NF)-κB and mitogen-activated protein kinases (MAPKs) signaling pathways. Additionally, gomisin A alleviated the cell death of SH-SY5Y neuroblastoma, rat primary cortical and hippocampal neurons induced by the conditioned-media from activated microglia. In summary, gomisin A may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Six dihydrobenzofuran type neolignans were isolated from the dried ripe seeds of Myristica fragrans Houtt. (family: Myristicaceae) and their chemical structures were identified as licarin B (1), 3'-methoxylicarin B (2), myrisfrageal A (3), isodihydrocainatidin (4), dehydrodiisoeugenol (5), and myrisfrageal B (6), respectively, on the basis of spectroscopic data analyses. Among them, compounds 3 and 6 are new compounds. Compounds 1-6 showed inhibition of nitric oxide production in lipopolysaccharide-activated murine monocyte-macrophage RAW264.7 with IC50 values of 53.6, 48.7, 76.0, 36.0, 33.6, and 45.0 μM, respectively. These values were compared to those of the positive controls, indomethacin and L-N(6)-(1-iminoethyl)-lysine, which have IC50 values of 65.3 and 27.1 μM, respectively. Further compounds 3, 5 and 6 suppressed LPS-induced iNOS mRNA expression in a does-dependent manner in RAW 264.7 cells assayed by real-time RT-PCR. Compounds 3, 5 and 6 may inhibit NO overproduction via inhibition of iNOS mRNA expression. The results provided valuable information for further investigation of compounds 1-6 as anti-inflammatory and chemopreventive agents., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Three new diterpenes (7, 15 and 17) and two new neolignans (19 and 20) along with nineteen known compounds have been isolated from the fruits of Vitex rotundifolia. Their structures were elucidated by a combination of 1D and 2D NMR, HRESI-MS, and CD data. All isolates were tested for their inhibitory activities on LPS-induced nitric oxide production in RAW264.7 cells. Of these, compounds 3, 4, 7, 13, 15, 19, and 24 found to inhibit nitric oxide production with the IC50 values ranging from 11.3 to 24.5μM., (Copyright © 2013 Elsevier Ltd. All rights reserved.)