Search

Arctigenin is a bioactive dibenzylbutyrolactone-type lignan exhibiting various pharmacological activities. The neuroprotective effects of arctigenin were demonstrated to be mediated via inhibition of AMPA and KA type glutamate receptors in the somatosensory cortex of the rat brain. The aim of this study was to compare the effects of arctigenin with matairesinol and trachelogenin on synaptic activity in ex vivo rat brain slices. Arctigenin, matairesinol and trachelogenin were isolated from Arctium lappa, Centaurea scabiosa and Cirsium arvense , respectively, and applied on brain slices via perfusion medium at the concentration range of 0.5 - 40 µM. The effects of the lignans were examined in the CA1 hippocampus and the somatosensory cortex by recording electrically evoked field potentials. Arctigenin and trachelogenin caused a significant dose-dependent decrease in the amplitude of hippocampal population spikes (POPS) and the slope of excitatory postsynaptic potentials (EPSPs), whereas matairesinol (1 µM and 10 µM) decreased EPSP slope but had no effect on POPS amplitude. Trachelogenin effect (0.5 µM, 10 µM, 20 µM) was comparable to arctigenin (1 µM, 20 µM, 40 µM) (p > 0.05). In the neocortex, arctigenin (10 µM, 20 µM) and trachelogenin (10 µM) significantly decreased the amplitude of evoked potential early component, while matairesinol (1 µM and 10 µM) had no significant effect (p > 0.05). The results suggest that trachelogenin and arctigenin act via inhibition of AMPA and KA receptors in the brain and trachelogenin has a higher potency than arctigenin. Thus, trachelogenin and arctigenin could serve as lead compounds in the development of neuroprotective drugs., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Five new diarylbutyrolactones and sesquilignans (1A/1B:  - 4: ), including one pair of enantiomers (1A/1B: ), together with 10 known analogues (5:  - 14: ), were isolated from the whole plants of Saussurea medusa . Compound 1: was found to possess an unusual 7,8'-diarylbutyrolactone lignan structure. Separation by chiral HPLC analysis led to the isolation of one pair of enantiomers, (+)-1A: and (-)-1B: . The structures of the new compounds were elucidated by extensive spectroscopic data. All compounds, except compounds 5, 7: and 9: , were isolated from S. medusa for the first time. Moreover, compounds 1:  -  4, 8: and 10:  - 14: had never been obtained from the genus Saussurea previously. Compounds (+)- 1A, 2, 5, 7: , and 9:  - 11: were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC 50 values ranging from 10.1 ± 1.8 to 41.7 ± 2.1 µM. Molecular docking and iNOS expression experiments were performed to examine the interactions between the active compounds and the iNOS enzyme., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

To find inhibitors against skeletal muscle loss, we isolated a lignan compound ((-)-(2 R ,3 R -1,4-O-diferuloylsecoisolarciresinol, DFS) from the stem of Alnus japonica . C2C12 myoblasts were treated with DFS during differentiation. To induce an in vitro atrophic condition, differentiated myotubes were treated with dexamethasone (a synthetic glucocorticoid). DFS (10 nM) increased expression levels of myogenic factors and the number of multi-nucleated myotubes expressing myosin heavy chain (MHC). The myogenic potential of DFS could be attributed to p38 MAPK activation. DFS also protected against dexamethasone-induced damage, showing increased expression of MHC and mammalian target of rapamycin (mTOR), a major anabolic factor. Under atrophic condition, the anti-myopathy effect of DFS was associated with inactivation of NF- κ B signaling pathway and the subsequent suppression of muscle degradative E3 ligases and myostatin. DFS treatment also restored fast muscle fiber (type II a, II b, and II x), known to be susceptible to dexamethasone. These results indicate that DFS isolated from A. japonica can stimulate myogenesis via p38 MAPK activation and alleviate muscle atrophy by modulating the expression of genes associated with muscle protein anabolism/catabolism. Thus, we propose that DFS can be used as a pharmacological and nutraceutical agent for increasing muscle strength or protecting muscle loss., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Alcoholic liver disease is one of the leading causes of liver-related morbidity and mortality worldwide, but effective treatments are still lacking. Honokiol, a lignin-type natural compound isolated from the leaves and bark of Magnolia plants, has been widely studied for its beneficial effects on several chronic diseases. Accumulating studies have revealed that honokiol displays a potential therapeutic effect on alcoholic liver disease. In this study, the protective activity of honokiol on alcoholic liver disease was confirmed due to its significant inhibitory activity on the expression levels of inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1 β ) in EtOH-fed mice and in EtOH-induced AML-12 cells. Meanwhile, the expression of the lipid metabolic parameter sterol regulatory element-binding protein-1c was also reduced. However, peroxisome proliferator-activated receptor α was increased in animal and cell experiments, which indicates that the activity of honokiol was related to its regulated activity on lipid metabolism. The result showed that honokiol significantly inhibited the expression level of p38 α in vivo and in vitro . Blocking p38 α inhibited the expression levels of tumor necrosis factor-alpha, interleukin-6, interleukin-1 β , and sterol regulatory element-binding protein-1c but promoted the expression level of peroxisome proliferator-activated receptor α compared with the honokiol-treated group. Moreover, the forced expression level of p38 α further produced the opposite effect on inflammatory cytokines and lipid metabolism indicators. Furthermore, p38 α has been related to the activation of the nuclear factor kappa B signaling pathway. In our study, honokiol significantly inhibited the activation of the nuclear factor kappa B signaling pathway mediated by p38 α . In conclusion, the results suggest that honokiol might be an effective regulator of p38 α by downregulating the nuclear factor kappa B signaling pathway, thereby reducing the inflammatory response and lipid metabolism disorder in alcoholic liver disease., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Magnoliae Flos is a traditional herbal medicine used to treat nasal congestion associated with headache, empyema, and allergic rhinitis. In our preliminary screening of crude drugs used in Japanese Kampo formulas for melanin synthesis, the methanol extract of Magnoliae Flos was found to exhibit strong melanin synthesis activity. However, there have been no studies evaluating the effects of Magnoliae Flos or its constituents on melanogenesis. The present study aimed to isolate the active compounds from Magnoliae Flos that activate melanin synthesis in melanoma cells and three-dimensional human skin equivalent, and to investigate the molecular mechanism underlying melanin induction. The methanol extract of Magnoliae Flos induced an increase of melanin content in both B16-F1 and HMV-II cells. A comparison of melanin induction by three fractions prepared from the extract showed that the ethyl acetate fraction markedly induced melanin synthesis. Bioassay-guided separation of the ethyl acetate fraction resulted in the isolation of seven lignans (1:  - 7: ). Among them, (+)-magnolin (5: ) strongly induced melanin synthesis and intracellular tyrosinase activity. Furthermore, the ethyl acetate fraction and 5: clearly induced melanin content in a three-dimensional human skin equivalent. Molecular analysis revealed that 5: triggered the protein expression of tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Further analysis of transcriptional factors and signaling pathways demonstrated that 5: induces the protein expression of tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2 activated by the protein kinase A- and p38 mitogen-activated protein kinase-dependent pathways, leading to cAMP-responsive element-binding protein phosphorylation and microphthalmia-associated transcription factor expression. These findings demonstrate the potential of 5: as a potent therapeutic agent for hypopigmentation., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

A fluorometric imaging plate reader (FLIPR) assay utilizing Chinese hamster ovary (CHO) cells stably transfected with GABA A receptors of α 1 β 2 γ 2 subunit composition was evaluated and validated for rapid screening of plant extract libraries and efficient localization of active compounds in extracts. Validation was performed with pure compounds and extracts known to contain allosteric GABA A receptor modulators. Plants extracts that had been previously reported as active in an assay using Xenopus laevis oocytes transiently expressing GABA A receptors of α 1 β 2 γ 2 subunit composition were also active in the FLIPR assay. A protocol for HPLC-based activity profiling was developed, whereby separations of 0.4 - 1.2 mg of extracts on an analytical HPLC column were found to be sufficient for the sensitivity of the bioassay. The protocol successfully localized the activity of known GABAergic natural products, such as magnolol in Magnolia officinalis , valerenic acid in Valeriana officinalis , and piperine in Piper nigrum extract. EC 50 values of compounds (magnolol: 4.81 ± 1.0 µM, valerenic acid: 12.56 ± 1.2 µM, and piperine: 5.76 ± 0.7 µM) were found to be comparable or lower than those reported using Xenopus oocyte assays., Competing Interests: The authors declare no conflicts of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

This is a comparative study on the intraspecific chemical variability of Aristolochia cordigera species, collected in two different regions of Brazil, Biome Cerrado (semiarid) and Biome Amazônia (coastal). The use of GC-MS and statistical methods led to the identification of 56 compounds. A higher percentage of palmitone and germacrene-D in the hexanes extracts of the leaves of plants from these respective biomes was observed. Phytochemical studies on the extracts led to the isolation and identification of 19 known compounds, including lignans, neolignans, aristolochic acids, indole- β -carboline, and indole alkaloids. In addition, two new indole alkaloids, 3,4-dihydro-hyrtiosulawesine and 6- O -( β -glucopyranosyl)hyrtiosulawesine, were isolated and a new neolignan, cis -eupomatenoid-7, was obtained in a mixture with its known isomer eupomatenoid-7. Their structures were determined by spectroscopic methods, mainly by 1D- and 2D-NMR. The occurrence of indole alkaloids is being described for the first time in the Aristolochiaceae family. Moreover, the in vitro susceptibility of intracellular amastigote and promastigote forms of Leishmania amazonensis to the alkaloids and eupomatenoid-7 were evaluated. This neolignan exhibited low activity against promastigotes (IC 50  = 46 µM), while the alkaloids did not show inhibitory activity. The new alkaloid 6- O -( β -glucopyranosyl)hyrtiosulawesine exhibited activity in the low micromolar range against Plasmodium falciparum , with an IC 50 value of 5 µM and a selectivity index higher than 50., Competing Interests: Conflict of Interest: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Grandisin, a lignan isolated from many species of plants, such as Virola surinamensis , is a potential drug candidate due to its biological properties, highlighted by its antitumor and trypanocidal activities. In this study, the inhibitory effects of grandisin on the activities of human cytochrome P450 enzymes were investigated by using human liver microsomes. Results showed that grandisin is a competitive inhibitor of CYP2C9 and a competitive and mechanism-based inhibitor of CYP3A4/5. The apparent K i value for CYP2C9 was 50.60 µM and those for CYP3A4/5 were 48.71 µM and 31.25 µM using two different probe substrates, nifedipine and midazolam, respectively. The apparent K I , k inact , and k inact /K I ratio for the mechanism-based inhibition of CYP3A4/5 were 6.40 µM, 0.037 min -1 , and 5.78 mL · min -1  µmol -1 , respectively, by examining nifedipine oxidation, and 31.53 µM, 0.049 min -1 , and 1.55 mL · min -1  µmol -1 , respectively, by examining midazolam 1'-hydroxylation. These apparent k inact /K I values were comparable to or even higher than those for several therapeutic drugs that act as mechanism-based inhibitors of CYP3A4/5. CYP1A2 and CYP2D6 activities, in turn, were not substantially inhibited by grandisin (IC 50 > 200 µM and 100 µM, respectively). In contrast, from a concentration of 4 µM, grandisin significantly stimulated CYP2E1 activity. These results improve the prediction of grandisin-drug interactions, suggesting that the risk of interactions with drugs metabolized by CYP3A4/5 and CYP2E1 cannot be overlooked., (Georg Thieme Verlag KG Stuttgart · New York.)

Podophyllotoxin, a lignan still extracted from the rhizomes of Podophyllum hexandrum (Berberidaceae), is the starting molecule for the semisynthesis of widely used anticancer drugs such as etoposide. However, this source is threatened by the over-collection of P. hexandrum . Plants belonging to the Linaceae and Cupressaceae families could be attractive alternative sources with species that contain the lignan podophyllotoxin or its precursors and derivatives. Wild flax species, such as Linum flavum , as well as some Juniperus and Callitris species were investigated for their lignan content, and the in vitro antiproliferative capacity of their extracts was assayed on four tumor cell lines. Some of the lignans were detected by LC-HRMS for the first time in these extracts.In addition, lignans purified from these plants and compounds semisynthesized from commercially available podophyllotoxin were tested in terms of their in vitro antiproliferative activity. The genus Juniperus was the most promising given its in vitro antiproliferative effects, which were also observed with extracts from L. flavum and Callitris species.The in vitro antiproliferative effect of the plant extracts studied here appears to correlate well with the contents of the aryltetralin lignan podophyllotoxin and its glycoside as well as with deoxypodophyllotoxin and 6-methoxypodophyllotoxin. The strongest correlation between the lignan content of the extracts and the antiproliferative activity was observed for 6-methoxypodophyllotoxin. Regarding the possibility of producing large renewable amounts of 6-methoxypodophyllotoxin, this molecule could be of interest to produce new anticancer drugs and to bypass the resistance mechanisms against podophyllotoxin-derived drugs., (Georg Thieme Verlag KG Stuttgart · New York.)

Nortrachelogenin is a pharmacologically active lignan found in knot extracts of Pinus sylvestris . In previous studies, some lignans have been shown to have anti-inflammatory properties, which made nortrachelogenin an interesting candidate for our study. In inflammation, bacterial products and cytokines induce the expression of inducible nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E synthase-1. These enzymes synthesize factors, which, together with proinflammatory cytokines, are important mediators and drug targets in inflammatory diseases.The effects of nortrachelogenin on the expression of inducible nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E synthase-1 as well as on the production of nitric oxide, prostaglandin E 2 , and cytokines interleukin-6 and monocyte chemotactic protein-1 were investigated in the murine J774 macrophage cell line. In addition, we examined the effect of nortrachelogenin on carrageenan-induced paw inflammation in mice.Interestingly, nortrachelogenin reduced carrageenan-induced paw inflammation in mice and inhibited the production of inflammatory factors nitric oxide, prostaglandin E 2 , interleukin-6, and monocyte chemotactic protein-1 in J774 macrophages in vitro . Nortrachelogenin inhibited microsomal prostaglandin E synthase-1 protein expression but had no effect on cyclooxygenase-2 protein levels. Nortrachelogenin also had a clear inhibitory effect on inducible nitric oxide synthase protein expression but none on its mRNA levels, and the proteasome inhibitor lactacystin reversed the effect of nortrachelogenin on inducible nitric oxide synthase expression, suggesting a post-transcriptional mechanism of action.The results revealed hitherto unknown anti-inflammatory properties of nortrachelogenin, which could be utilized in the development of anti-inflammatory treatments., (Georg Thieme Verlag KG Stuttgart · New York.)

Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Our previous study demonstrated that arctigenin exerts neuroprotective effects both in vitro and in vivo in a Parkinson's disease model. However, the exact mechanism through which arctigenin improves amyloid beta-induced memory impairment by inhibiting the production of the hyperphosphorylated tau protein is unknown. Amyloid β 1-42 was slowly administered via the intracerebroventricular route in a volume of 3 µL (≈ 410 pmmol/mouse) to mice. The mice were administered arctigenin (10, 40, or 150 mg/kg) or vehicle starting from the second day after amyloid β 1-42 injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloid β 1-42 , the mice were sacrificed for biochemical analysis. Arctigenin (10-150 mg/kg) significantly attenuated the impairment of spontaneous alternation behaviours in the Y-maze task, decreased the escape latency in the Morris water maze test, and increased the swimming times and swimming distances to the platform located in the probe test. Arctigenin attenuated the level of phosphorylated tau at the Thr-181, Thr-231, and Ser-404 sites in the hippocampus, and increased the phosphorylation levels of phosphatidylinositol-3-kinase, threonine/serine protein kinase B, and glycogen synthase kinase-3 β . Arctigenin effectively provides protection against learning and memory deficits and in inhibits hyperphosphorylated tau protein expression in the hippocampus. The possible mechanism may occur via the phosphatidylinositol-3-kinase/protein kinase B-dependent glycogen synthase kinase-3 β signalling pathway., (Georg Thieme Verlag KG Stuttgart · New York.)

Eight ethanolic extracts of indigenous Taiwanese plants of the genus Alpinia were tested for tumor cytotoxicity against AGS, Hep G2, HeLa, KB, and HL-60 cells. Among the 50 % and 95 % EtOH extracts of eight Alpinia species, the cytotoxic effects of Alpinia intermedia leaves were the strongest. When the leaf extract of A. intermedia was partitioned using n -hexane and aqueous solvents, the n -hexane layer showed a greater cytotoxic effect and could prolong the survival time of P-388D 1 tumor-bearing CDF1 mice. Two new labdane diterpene derivatives, intermedin A ( 1 ) and intermedin B ( 2 ), and coronarin E ( 3 ) were isolated from the n -hexane layer of A. intermedia . Intermedin A induced apoptosis in HL-60 cells at 30 µg/mL and significantly prolonged the survival time of P-388D 1 tumor-bearing CDF 1 mice by 48.7 % at 20 mg/kg of body weight. We suggest that intermedin A is a major compound of A. intermedia and has a cytotoxic effect on HL-60 and P-388D 1 cells., (Georg Thieme Verlag KG Stuttgart · New York.)

Phyllanthus amarus has been proven to exhibit chondroprotection. Regarding the morphological similarities among Phyllanthus species, we were attracted to evaluate the chondroprotective potential of Phyllanthus species including P. amarus obtained from Chiang Mai and Phuket, Phyllanthus urinaria L., Phyllanthus urinaria subsp . chamaepeuce, Phyllanthus debilis , and Phyllanthus airy-shawii using interleukin-1 β -induced degradation of cartilage explants. The ethanolic extracts of the plants were evaluated for major lignans, phyllanthin, and hypophyllanthin by HPLC and further measurements of the total contents of flavonoids and phenolic compounds along with the assays for antioxidant and anti-collagenase activities. The interleukin-1 β -induced cartilage explant degradation was performed with/without the extracts at concentrations of 50-250 µg/mL. After 4-14 days of incubation, the medium was assayed for the level of sulfated glycosaminoglycans while the explants were measured for the remaining content of uronic acid. Proteoglycan intensity in the explants was determined by safranin O staining. Diacerein, the antiarthritic agent, was used as the positive control. Although the two major lignans were found in P. amarus from Chiang Mai, P. amarus from Phuket, and P. urinaria L. extracts, similar chondroprotective activities were observed in all Phyllanthus extracts. Total phenolic content and total flavonoid content of the extracts showed a correlation with antioxidation, whereas the total phenolic content correlated with anti-collagenase activity. Among the six extracts, P. airy-shawii showed the greatest antioxidant and collagenase inhibitory activities. The results revealed that chondroprotective activities of all of the extracts of Phyllanthus species might result from an additive or synergistic influence of some constituents of these plants, which could be considered for antiarthritic purposes., (Georg Thieme Verlag KG Stuttgart · New York.)

Five new compounds, including a rare phenyldihydronaphthalene lignanamide (1), an unusual hybrid-norlignan derivative (2), a rare cycloheptenone oxide derivative (3), one new acorane-type sesquiterpenoid (4), and one new guaiane-type sesquiterpenoid (5), together with seven known compounds (6-12), have been isolated from the rhizomes of Acorus tatarinowii. The structures of compounds 1-5 were determined by means of extensive spectroscopic methods. To the best of our knowledge, this is first report of a phenyldihydronaphthalene lignanamide and hybrid-norlignan and cycloheptenone oxide derivatives from the genus Acorus. In addition, compound 5 represents the first guaiane-type sesquiterpenoid with an epoxy group located between C-6 and C-9 from natural sources. Compounds 1-12 were evaluated for their in vitro cytotoxicity against five tumor cell lines. Among them, 2, 3, 5, and 10 exhibited moderate cytotoxicity with IC50 values of 2.11-9.23 µM., (Georg Thieme Verlag KG Stuttgart · New York.)

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.)

Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion., (Georg Thieme Verlag KG Stuttgart · New York.)

Investigation on the fruits of Melia toosendan afforded seven new lignans (1-7), along with seventeen known compounds (8-24). The structures of the new compounds, involving four neo-lignans (1-4), two sesquilignans (5-6), and a nor-lignan (7), were elucidated based on extensive spectroscopic analyses (high-resolution electrospray ionization mass spectra, ultraviolet, infrared, one-dimensional and two-dimensional nuclear magnetic resonance). Compound 24 exhibited activity on melatonin receptor type 1 with an agonistic rate of 57.77% at 1.02 mM according to the assay on HEK293 cell lines in vitro., (Georg Thieme Verlag KG Stuttgart · New York.)

Six new diketopiperazines (1-6), two new sesquilignans (7-8), and ten known compounds (9-18) were isolated from the branches and leaves of Claoxylon polot. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1-3 were assigned by computational methods. Compounds 1 and 2 exhibited antiviral activity against Coxsackie B3 virus with IC50 values of 14.6 and 25.9 µM, respectively., (Georg Thieme Verlag KG Stuttgart · New York.)

Cancer cells may rapidly acquire multidrug resistance, mainly due to the presence of adenosine triphosphate-binding cassette transporters, epidermal growth factor receptor, or mutations in the p53 tumor suppressor gene. This work was designed to assess the cytotoxicity of the methanol crude extracts and compounds from the fruits of Uapaca togoensis, namely, β-amyryl acetate (1), 11-oxo-α-amyryl acetate (2), lupeol (3), pomolic acid (4), futokadsurin B (5), arborinin (6), and 3-O-β-D-glucopyranosyl sitosterol (7) against nine drug sensitive and multidrug-resistant cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of the fruits of U. togoensis and compounds, whilst the caspase-Glo assay was used to detect the activation of caspase enzymes by the fruits of U. togoensis and compound 6. Cell cycle, mitochondrial membrane potential, and levels of reactive oxygen species were all analyzed via flow cytometry. The acridone alkoid 6 and the crude extract from the fruits of U. togoensis were active on all of the nine tested cancer lines with IC50 values below 32 µM and 30 µg/mL, respectively. Compounds 2 and 5 showed selective activities and IC50 values below 99 µM or 42 µM, respectively, which were obtained towards 3/9 and 6/9 tested cancer cell lines. Compound 6 displayed IC50 values below 10 µM towards seven of the nine tested cancer cell lines. The IC50 values ranged from 3.55 µM (against CEM/ADR5000 cells) to 31.77 µM (against CCRF-CEM cells) for alkaloid 6 and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. The crude extract of the fruits of U. togoensis induced apoptosis in the CCRF-CEM leukemia cells, which was mediated by the disruption of the mitochondrial membrane potential. Compound 6 also strongly induced apoptosis in CCRF-CEM cells and cell cycle arrest in the G0/G1 and S phases. The crude extract from the fruits of this plant as well as aborinin are potential antiproliferative natural products that deserve further investigation to develop novel cytotoxic drugs to fight sensitive and otherwise drug-resistant phenotypes., (Georg Thieme Verlag KG Stuttgart · New York.)

In obese adipose tissue, tumor necrosis factor-α secreted from macrophages plays an important role in the adipocyte dysfunctions, including insulin resistance, lipolytic acceleration, and changes of adipokines, which promote the development of obesity-related complications. Phillyrin, an active ingredient found in many medicinal plants and certain functional foods, elicits anti-obesity and anti-inflammatory properties in vivo. The aim of the current study was to investigate the role of phillyrin in preventing tumor necrosis factor α-induced insulin resistance or lipolytic acceleration in 3T3-L1 adipocytes. Our results showed that phillyrin partially restored insulin-stimulated 2-DOG uptake, which was reduced by tumor necrosis factor-α, with concomitant restoration in serine phosphorylation of insulin receptor substrate-1 and insulin-stimulated Glut4 translocation to plasma membrane. Phillyrin also dose-dependently prevented tumor necrosis factor α-stimulated adipocyte lipolysis with preserved downregulation of perilipin. The mitogen-activated protein kinases and I kappaB kinase activation was promoted in tumor necrosis factor α-stimulated adipocytes, but pretreatment with 40 µM phillyrin inhibited the phosphorylation of extracellular signal-regulated kinases1/2, stress-activated protein kinase/Jun N-terminal kinase and I kappaB kinase (p<0.05). Moreover, phillyrin could inhibit the expressions of interleukin-6 and monocyte chemoattractant protein-1 induced by tumor necrosis factor-α. Using transwell coculture method with 3T3-L1 adipocytes and RAW 264.7 macrophages, the enhanced productions of tumor necrosis factor-α and free fatty acids in the medium were significantly reduced by phillyrin (p<0.05). These results indicate that phillyrin exerts a beneficial effect on adipocyte dysfunctions induced by tumor necrosis factor-α through suppression of the activation of I kappaB kinase and N-terminal kinase. Phillyrin may have the potential to ameliorate the inflammatory changes and insulin resistance in obese adipose tissue., (Georg Thieme Verlag KG Stuttgart · New York.)

To explore the relationship of the dibenzocyclooctadiene lignans from Schisandra chinensis to their anti-inflammatory activities, series of dibenzocyclooctadiene lignans were isolated and assessed by testing their inhibitory effects on nitric oxide production in lipopolysaccharide-induced BV2 mouse microglia. It was found, for the first time, that dibenzocyclooctadiene lignans which have S-biphenyl and methylenedioxy groups strongly inhibited LPS-induced microglia activation. The methoxy group on the cyclooctadiene introduced more effectiveness, but the presence of an acetyl group on the cyclooctadiene or hydroxyl group on C-7 decreased the inhibitory activity., (Georg Thieme Verlag KG Stuttgart · New York.)

Eight new aryltetralin lignans, cleisindosides A-F (1-6), picroburseranin (7), and 7-hydroxypicropolygamain (8), were isolated from the fruits of Cleistanthus indochinensis (Euphorbiaceae). The structures of the isolates were established on the basis of their one- and two-dimensional NMR spectral data, as well as their mass spectrometric data. Compound 7 was found to have potent cytotoxicity against oral epidermoid carcinoma cells with an IC50 value of 0.062 µM, whereas glycosylation to 3 (IC50 7.5 µM) and stereochemical changes to 8 (IC50 10.8 µM) led to marked decreases in biological activity. Thus, it was determined that the C-7 and C-8' positions are critical for the biological activity of the lignans from this plant., (Georg Thieme Verlag KG Stuttgart · New York.)

Topical preparations of Anemopsis californica have been used by Native American tribes in the southwestern United States and northern Mexico to treat inflammation and infections. We report results of bioassay-guided isolation conducted on a sample of A. californica roots. The furofuran lignans sesamin (1) and asarinin (2) were isolated and shown to have MIC values ranging from 23 to 395 µM against five different species of environmental nontuberculous mycobacteria. These findings are significant given that these bacteria can cause skin, pulmonary, and lymphatic infections. Crude A. californica extracts were analyzed by liquid chromatography-mass spectrometry, and it was determined that sesamin and asarinin were extracted at relatively high levels from the roots (1.7-3.1 g/kg and 1.1-1.7 g/kg, respectively), but at lower levels from the leaves (0.13 g/kg for both compounds). Our findings suggest that the majority of activity of crude A. californica root extracts against nontuberculous mycobacteria can be attributed to the presence of sesamin and asarinin. This paper is the first to report the isolation of these compounds from a member of the Saururaceae family, and the first to describe their activity against nontuberculous mycobacteria., (Georg Thieme Verlag KG Stuttgart · New York.)

Multiple sclerosis is an inflammatory disease of the central nervous system. Chronic pain is one of the main symptoms, affecting many patients. Studies show that the lignans or the apolar extracts of Phyllanthus amarus have antinociceptive effects in different animal models. To evaluate the antihypernociceptive effect of a hexanic extract of P. amarus in experimental autoimmune encephalomyelitis in mice, the chemical composition of the hexanic extract was analyzed by gas chromatography mass spectrometry. After EAE induction, animals were treated with the hexanic extract of P. amarus for 26 consecutive days. Motor coordination and mechanical hypernociception were evaluated on alternate days. The principal lignans found were phyllanthin, niranthin, and 5-demethoxyniranthin. The hexanic extract of P. amarus at a dose of 100, 200, or 400 mg/kg did not affect the development of the disease. The motor coordination and pain threshold of the treated animals were not altered in this experiment. In conclusion, in this test, the hexanic extract of P. amarus did not show evidence of antihypernociceptive activity in experimental autoimmune encephalomyelitis., (Georg Thieme Verlag KG Stuttgart · New York.)

The potential protective effects of arctigenin on 1-methyl-4-phenylpyridinium ion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity were examined, and the results indicated that arctigenin could improve the movement behaviors and upregulate dopamine and γ-aminobutyric acid levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity mouse model. A further in vitro experiment showed that the pretreatment with arctigenin on cultured human neuroblastoma SH-SY5Y cells could obviously attenuate the decrease of cell survival rates caused by treatment with 1-methyl-4-phenylpyridinium ion by way of acting against cell apoptosis through the decrease of Bax/Bcl-2 and caspase-3, and by antioxidative action through reduction of the surplus reactive oxygen species production and downregulation of mitochondrial membrane potential. It is for the first time that a neuroprotective activity of arctigenin in both in vitro and in vivo experiments was reported, enlightening that arctigenin could be useful as a potential therapeutic agent for Parkinson's disease., (Georg Thieme Verlag KG Stuttgart · New York.)

Five new neolignans with a bicyclo[2.2.2]octene framework were isolated from an ethanolic extract of the bark of Cordia americana. The structures and relative configurations of the compounds were elucidated by a combination of spectroscopic methods. All the isolated compounds showed good antioxidant activities in the DPPH radical scavenging (0.5-100 µg/mL) and Ferric-reducing antioxidant power (FRAP, 1-100 µg/mL) assays. One of the compounds displayed mild fungistatic activity at 0.1 µmol/spot against Fusarium virguliforme while, at the same time, all compounds were inactive against several strains of Gram (+) and Gram (-) bacteria at all assayed concentrations (10-1,000 µg/mL)., (Georg Thieme Verlag KG Stuttgart · New York.)

Six new benzofuran neolignans (1-6) were isolated from the EtOAc-soluble fraction of the aerial part of Aristolochia fordiana, together with twelve known analogues (7-18). The structures of the isolated compounds were elucidated by spectroscopic methods. All isolates were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccaride-activated RAW264.7 macrophages and for their cytotoxic activities on three human cancer cell lines. Compound 2 showed significant nitric oxide production inhibitory activity with an IC50 value of 10.00 µM, while compound 16 exhibited cytotoxic activity with an IC50 value of 11.9 µM against MG-63 and compound 18 of 9.15 µM against HepG2 cell lines, respectively., (Georg Thieme Verlag KG Stuttgart · New York.)

Three new sauchinone analogues, sauchinones B-D (1-3), together with sauchinone (4), were isolated from the aerial part of Saururus chinensis. Structures of the new compounds were determined by extensive spectroscopic data as well as X-ray analysis. Compounds 3 and 4 inhibited nitric oxide production in lipopolysaccharide stimulated RAW 264.7 cells with IC50 values of 13.0 and 14.2 µM, respectively., (Georg Thieme Verlag KG Stuttgart · New York.)

Carya cathayensis is a fruit-bearing plant that belongs to the Juglandaceae family and is widely distributed throughout the world. It possesses various important biological activities. We have previously isolated an antitumor compound from the shell of C. cathayensis fruits and named it E2S ((E)-3-[(2S,3R)-2,3-dihydro-2-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-1-benzo[b]furan-5-yl]-2-propenal). In this study, we investigated the antitumor activity of E2S against various human colorectal cancer cell lines (HCT116, HT29, SW480, LoVo). The results showed that E2S could significantly inhibit the growth of cancer cells in a dose-dependent manner, as well as disrupt the progression of the cell cycle. Mechanistic study revealed that E2S could decrease the protein levels of β-catenin and its downstream targets (such as c-myc, a key transcriptional target of β-catenin) in the cells. In addition, it also significantly suppressed β-catenin/TCF transcriptional activity. Taken together, the results suggested that E2S might partially exert an antiproliferative effect on human colorectal cancer cells by targeting β-catenin signaling, a finding that might potentially translate into a chemotherapeutic strategy for the treatment of cancer. It might also have implications for cancer prevention strategies., (Georg Thieme Verlag KG Stuttgart · New York.)

Three new lignans (1, 2, and 8) and ten known ones (3-7, 9-13) were isolated from the roots of Vladimiria muliensis. Their structures and configurations were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. The isolated compounds were evaluated for their antioxidant and antibacterial activities. The antioxidant activity was the greatest for lignans 7 and 10 with IC50 values of 11.2 and 7.3 µM against DPPH radical, and of 1.6 and 1.7 µM against ABTS+ radical, respectively. Moreover, 7 also displayed broad-spectrum antibacterial activity with MIC values around 7.25 µg/mL., (Georg Thieme Verlag KG Stuttgart · New York.)

Three new neolignans, named 9-methoxyobovatol (6), magnobovatol (7), and 2-hydroxyobovaaldehyde (9), along with six known ones, magnolol (1), honokiol (2), isomagnolol (3), obovatol (4), obovatal (5), and obovaaldehyde (8), were isolated from the fruits of Magnolia obovata using silica gel and ODS column chromatography. From the results of spectroscopic data including EIMS, IR, 1H- and 13C-NMR, DEPT, and 2D-NMR (gCOSY, gHSQC, gHMBC), the chemical structures were determined. All isolated compounds were evaluated for inhibition activity on nitric oxide production in LPS-induced RAW 264.7 cells, and compounds 1-4, 6, 7, and 9 showed significant activity with IC50 values of 15.8 ± 0.3, 3.3 ± 1.2, 14.1 ± 0.9, 6.2 ± 1.2, 14.8 ± 2.3, 14.2 ± 1.2, and 14.8 ± 3.2 µM, respectively, without any visible toxic effect., (Georg Thieme Verlag KG Stuttgart · New York.)

Five new dibenzocyclooctane lignans, schisanwilsonins K-O, together with eighteen known lignans were isolated from the stems of Schisandra wilsoniana. The structures of these new compounds were elucidated by spectroscopic methods, including 2D-NMR techniques. Several compounds were found to show anti-HIV and anti-HBV activity., (Georg Thieme Verlag KG Stuttgart · New York.)

Epidemiological studies have highlighted the ability of phytochemicals to reduce the risk of breast cancer by attenuating specific intracellular signaling pathways that regulate cell proliferation and survival. γ-Tocotrienol is a natural form of vitamin E that displays potent anticancer activity at doses that have no discernible toxicity toward normal cells. Sesamin is an abundant phytochemical found in sesame seed oil that also shows antiproliferative and antiangiogenic activity against human breast cancer cells. In this study, the combined treatment of subeffective doses of γ-tocotrienol and sesamin caused a synergistic inhibition of murine +SA mammary epithelial cell growth, as determined by the MTT assay and immunofluorescent Ki-67 staining. Western blot studies revealed that combined low-dose treatment of γ-tocotrienol and sesamin caused a marked reduction in EGF-induced ErbB3 and ErbB4 receptors phosphorylation (activation) and a relatively large decrease in intracellular levels of total and/or phosphorylated c-Raf, MEK1/2, ERK1/2, PI3K, PDK1, Akt, p-NFκB, Jak1, Jak2, and Stat1, as compared to cells treated with only one compound or in the vehicle-treated control group. These findings demonstrate that the synergistic growth inhibitory effects of γ-tocotrienol and sesamin treatment are associated with suppression of EGF-dependent mitogenic signaling in mammary tumor cells and suggest that dietary supplementation with these phytochemicals may provide some benefits in the prevention and/or treatment of breast cancer., (Georg Thieme Verlag KG Stuttgart · New York.)

A phytochemical investigation of acetone and chloroform extracts of the aerial parts of Onopordum cynarocephalum Boiss. et Blanche was carried out. It led to the isolation of two new sesquiterpenes, the elemane aldehyde (2) and the eudesmane (11), together with 15 known compounds: two lignans (1 and 15) and 13 sesquiterpenes (3-10, 12-14, 16, 17). The structures were elucidated by spectroscopic analyses, especially 1D and 2D NMR spectra. The anti-growth effect against three human melanoma cell lines, M14, A375, and A2058, of the different extracts and compounds of O. cynarocephalum was also investigated. Among them, the chloroform extract exhibited the strongest biological activity, while the most active compounds were the lignan arctigenin (1), and the sesquiterpenes, compounds 3, 5, and 6 belonging to the elemane type, and 7 belonging to the eudesmane type. Our data also demonstrate that acetone and chloroform extracts induce, in the A375 cell line, apoptotic cell death that could be related to an overall action of the compounds present, but in particular to the lignans arctigenin (1) and the sesquiterpenes compounds 3-8 and 16. In fact, these molecules were able to induce a high DNA fragmentation, correlated to a significant increase of the caspase-3 enzyme activity. Furthermore, apoptosis appears to be mediated, at least in part, via PTEN activity and the inhibition of Hsp70 expression., (Georg Thieme Verlag KG Stuttgart · New York.)

From the aerial part of Abies recurvata, 62 miscellaneous chemical constituents were isolated including 6 new and 56 known ones. The new compounds comprised three monoterpenes, two diterpenes, and one lignan. Their chemical structures were characterized on the basis of various spectroscopic techniques. Dihydrodehydrodiconiferyl alcohol (35) showed the strongest inhibitory effects against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC₅₀ value of 66.4 µM., (Georg Thieme Verlag KG Stuttgart · New York.)

Six new triterpenoids, euscaphic acids G-L (1-6), along with nine known triterpene acids, and two known lignans were isolated from the ethanolic extract of the twigs of Euscaphis japonica. This is the first report concerning 1α,3β-dihydroxy-12-oleanen-28-oic acid isolated from a natural source. The structures of the new compounds were established by spectroscopic analysis. The cytotoxic and anti-NO production activities for the isolates are also evaluated and discussed; compound 1, hederagenin (11), and arjunic acid (12) showed significant cytotoxicity against NCI-H460 cells, HT-29 cells, and CEM cells (IC₅₀ = 1.64 ± 0.87, 2.11 ± 1.54, 1.73 ± 0.64 µM, respectively). Some of the isolated triterpenoids showed marginal inhibitions on NO production induced by LPS., (Georg Thieme Verlag KG Stuttgart · New York.)

In the present study, we examined the effects of deoxyschisandrin (DS) from Schisandra chinensis on the amyloid-beta₁₋₄₂ (Aβ₁₋₄₂)-induced memory impairment in mice and investigated the possible antioxidative mechanism. Mice were given an intracerebroventricular (i. c. v.) injection with the aggregated Aβ₁₋₄₂ and then treated with DS (4, 12, and 36 mg/kg body weight) or donepezil (DPZ), a positive control drug (0.65 mg/kg), by intragastric infusion for 14 days. Non-cognitive disturbances and cognitive performance were evaluated by the locomotor activity, Y-maze, and water maze tests. Antioxidative enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and levels of malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG) within the cerebral cortex and hippocampus of mice were measured to investigate the mechanism. Our results showed that DS significantly improved Aβ₁₋₄₂-induced short-term and spatial memory impairments in the Y-maze and water maze tests. Furthermore, in the cerebral cortex and hippocampus of mice, the reduced activities of SOD and GSH-px, the GSH level, and the GSH/GSSG ratio were increased, and increased levels of MDA and GSSG were reduced following treatment with DS, although the improvement of GSH and the reduction of GSSG levels were not marked. These results suggest that DS is a potential cognitive enhancer in Alzheimer's disease through its antioxidative action., (Georg Thieme Verlag KG Stuttgart · New York.)

A new orthoquinone, berryammone A (1), and four new naphthalenone derivatives, berryammone B (2), berryammone C (3), 6-O-methylberryammone C (4), and 4-O-methylberryammone C (5), have been isolated from the stem of Berrya ammonilla, together with eleven known compounds (6-16). The structures of these new compounds were determined through spectroscopic and MS analyses. Among the isolates, compounds 1-3, 5, (+)-pinoresinol (6), and betulinic acid (12) exhibited inhibition (IC50 ≤ 4.41 µM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, and 5 also inhibited fMLP/CB-induced elastase release with IC50 values ≤ 3.95 µM., (Georg Thieme Verlag KG Stuttgart · New York.)

Seven new dibenzocyclooctadiene lignans, named propinquain E-K, together with 11 known lignans were isolated from the ethanol extract of the roots of Schisandra propinqua subsp. sinensis. The structures of the new compounds were elucidated by spectroscopic methods, including ¹H- and ¹³C-NMR, 2D-NMR, HR ESI-MS, and CD spectra. Two dibenzocyclooctadienes revealed inhibitory effects on lymphocyte proliferation., (Georg Thieme Verlag KG Stuttgart · New York.)

Four new tetrahydrofuranoid lignans, (-)-tanegool-7'-methyl ether ( 1), (+)-7'-methoxylariciresinol (2), sinolignan C (3), and epipinoresinol-4,4'-di- O- β- D-glucopyranoside (4), were isolated from the roots and rhizomes of SINOPODOPHYLLUM EMODI together with one known lignan (5). Their structures and stereochemistry were elucidated on the basis of spectroscopic and mass spectrometric evidence. The isolation of compounds 1- 5 represents the first report of tetrahydrofuran lignans from the genus SINOPODOPHYLLUM. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines, and compound 1 showed the most potent cytotoxicity with IC₅₀ values of 9.7 µM and 4.7 µM, respectively., (© Georg Thieme Verlag KG Stuttgart · New York.)

Six new lignans, 1- 6, along with six known compounds were obtained from the flower buds of Magnolia liliflora Desr. The new lignans were elucidated as (1 S*,2 R*,5 S*,6 S*)-2-(3,5-dimethoxyphenyl)-6-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (1), (1 R*,2 R*,5 R*,6 S*)-2-(3,5-dimethoxyphenyl)-6-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (2), (1 R*, 2 R*,5 R*,6 S*)-2,6-bis (3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (3), (1 R*,2 S*,5 R*,6 R*)-2-(3,4-methylenedioxyphenyl)-6-(3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane ( 4), (7' S*,8 R*,8' R*)-3,5'-dimethoxy-3',4,9'-trihydroxy-7',9-epoxy-8,8'-lignan (5), and (7' R*,8' S*)-3,3',4,5'-tetramethoxy-7-en-7',9-epoxy-8,8'-lignan (6), by the analysis of 1D and 2D-NMR as well as HRESIMS data. The capacity of compound 1 to protect against damages to the DNA of rat lymphocyte cells induced by UV irradiation was assessed by the comet assay. It showed stronger antigenotoxicity than ascorbic acid from 6×10(-3) mmol·L(-1) to 6×10(-6) mmol·L(-1)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Seven new compounds, including four lignans, (+)-(8S,8′S)-9,9′-dibenzoylsecoisolariciresinol (1), (+)-(8S*,8′R*)-4,4′-dimethyloxomatairesinol (2), (+)-(7S*,8R*,8′R*,9′S*)-9′-n-butoxytsugacetal (3), and pseudolarkaemin A (4), a pyronane glycoside, pseudolarkaemin B (5), an ent-beyerene glycoside, pseudolarkaemin C (6), and a triterpene, 25-epi-pseudolarolide Q (7), along with 25 known compounds (8–32) were isolated from the twigs of Pseudolarix kaempferi. Their structures were elucidated mainly by the analysis of their NMR and MS data. Pseudolarolide C acid (24) was isolated for the first time as a natural product. All compounds were evaluated for antimicrobial activity against Candida albicans and Staphylococcus aureus, and cytotoxic activity against K562, HT-29, B16, BGC-823, BEL-7402, SGC-7901, U251, and A549 cancer cell lines were assayed. Results indicated that the new compounds 3, 7, and some known compounds showed antimicrobial and cytotoxic activities., (© Georg Thieme Verlag KG Stuttgart · New York.)

An anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the Peruvian rainforest, Mikania decora and Cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien-19-oic acid (1), three thymol derivatives, 10-acetoxy-8,9-dehydro-6-methoxythymol butyrate (2), 10-acetoxy-8,9-epoxy-6-methoxythymol isobutyrate (3), and acetylschizoginol (4), as well as one neolignan, (±)-trans-dehydrodiisoeugenol (5). Only the latter was isolated from C. microcarpum. These compounds exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 3 and 4 were also investigated for their in vitro antileishmanial and trypanocidal activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes., (© Georg Thieme Verlag KG Stuttgart · New York.)

Four new compounds: an abietane (1), two isopimarane (2 and 3) diterpenes, and a dihydrobenzofuran neolignan (5), together with a sesquiterpene glycoside (6) firstly isolated from a natural source, and a known phenol glycoside (4) were isolated from leaves of Platycladus orientalis. The structures and relative configurations of these compounds were assigned on the basis of MS, IR, 1D and 2D NMR data. The absolute configuration of compound 1 was determined via density functional theory calculations of its electronic circular dichroism. In addition, the results of bioassays indicated that compounds 4 and 6 showed a potent inhibitory effect on NO production with IC₅₀ values of 24.4 and 11.9 µM, respectively. Meanwhile, compounds 1, 2, and 3 moderately inhibited TNF- α release., (© Georg Thieme Verlag KG Stuttgart · New York.)

From the leaves and bark of Zanthoxylum monophyllum, a new lignan, 3-methoxy-3',4'-methylenedioxylignan-4,8,9,9'-tetraol (1), has been isolated along with 22 known compounds (2- 23), fifteen of them reported for the first time from Z. monophyllum. Their chemical structures were elucidated using detailed spectroscopic studies and chemical analysis. All compounds were evaluated for antimicrobial and antiprotozoal activities. Alkaloids BIS-[6-(5,6-dihydro-chelerythrinyl)] ether (2) and 6-ethoxy-chelerythrine (4) exhibited strong activity against Aspergillus fumigatus and methicillin-resistant Staphylococcus aureus (MRSA). Compound 4-methoxy-N-methyl-2-quinolone (9) exhibited significant activity against MRSA (IC50 value of 8.0 µM) while compound 5,8,4'-trihydroxy-3,7,3'-trimethoxyflavone (10) showed weak activity against Plasmodium falciparum., (© Georg Thieme Verlag KG Stuttgart · New York.)