Solid-State Structures and Properties of Lignin Hydrogenolysis Oil Compounds: Shedding a Unique Light on Lignin Valorization.

This article explores the important, and yet often overlooked, solid-state structures of selected bioaromatic compounds commonly found in lignin hydrogenolysis oil, a renewable bio-oil that holds great promise to substitute fossil-based aromatic molecules in a wide range of chemical and material industrial applications. At first, single-crystal X-ray diffraction (SCXRD) was applied to the lignin model compounds, dihydroconiferyl alcohol, propyl guaiacol, and eugenol dimers, in order to elucidate the fundamental molecular interactions present in such small lignin-derived polyols. Then, considering the potential use of these lignin-derived molecules as building blocks for polymer applications, structural analysis was also performed for two chemically modified model compounds, i.e., the methylene-bridging propyl-guaiacol dimer and propyl guaiacol and eugenol glycidyl ethers, which can be used as precursors in phenolic and epoxy resins, respectively, thus providing additional information on how the molecular packing is altered following chemical modifications. In addition to the expected H-bonding interactions, other interactions such as π-π stacking and C-H∙∙∙π were observed. This resulted in unexpected trends in the tendencies towards the crystallization of lignin compounds. This was further explored with the aid of DSC analysis and CLP intermolecular energy calculations, where the relationship between the major interactions observed in all the SCXRD solid-state structures and their physico-chemical properties were evaluated alongside other non-crystallizable lignin model compounds. Beyond lignin model compounds, our findings could also provide important insights into the solid-state structure and the molecular organization of more complex lignin fragments, paving the way to the more efficient design of lignin-based materials with improved properties for industrial applications or improving downstream processing of lignin oils in biorefining processes, such as in enhancing the separation and isolation of specific bioaromatic compounds).

Selective regulation of products for guaiacol hydrodeoxygenation by adjusting type and acidity of supports.

Upgrading lignin-oil into advanced fuels or chemicals has been widely studied in recent years. To understand the effect of support type and acidity on the hydrodeoxygenation (HDO) of guaiacol (lignin-oil model compound), Ni-based catalysts were prepared with SiO2, Al2O3 and ZSM-5 as supports, respectively. The catalysts were characterized by X-ray diffraction (XRD), N2 adsorption desorption, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and Pyridine adsorption Fourier-transform infrared (Py-IR). The research results indicate that selective regulation of guaiacol hydrogenation products can be achieved by changing the type and acidity of support. Cyclohexanol is the main product over Ni/SiO2, while cyclohexane is the main product over Ni/ZSM-5 series catalysts. Moreover, as the Si/Al ratio increases, the catalytic activity of Ni/ZSM-5 slightly decreases, and the yield of cyclohexane also decreases. The Brønsted acidity of the support is the key to promoting the conversion of cyclohexanol to cyclohexane. The formation of NiAl2O4 is the main reason for the relatively low activity of Ni/Al2O3. The conversion of guaiacol is as high as 99.2 %, and the yield of cyclohexane is as high as 86.6 % over Ni/ZSM-5(Si/Al = 27). In addition, complete conversion of guaiacol and 92.6 % yield of cyclohexanol were achieved over Ni/SiO2. More importantly, Ni/SiO2 and Ni/ZSM-5(27) are suitable for aromatic substrates with different substituents, respectively.

Ferulic acid triggering a co-production of 4-vinyl guaiacol and fumaric acid from lignocellulose-based carbon source by Rhizopus oryzae.

Plant secondary metabolites have attracted considerable attention due to the increasing demand for finite fossil resources and environmental concerns. However, the biosynthesis of aromatic aldehydes or alcohols from renewable resources remains challenging and costly. This study explores a novel approach performed by the aromatic catabolizing organism Rhizopus oryzae, which enables a ferulic acid-activated co-production of 4-vinyl guaiacol (4-VG) and fumaric acid. The strain produced 4.60 g/L 4-VG and 11.25 g/L fumaric acid from a mixed carbon source of glucose and xylose, suggesting that this new pathway allows the potential production of natural 4-VG from low-cost substrates. This green route, which utilizes Rhizopus oryzae's ability to efficiently convert various renewable resources into valuable chemicals, paves the way for improved catalytic efficiency in 4-VG production.

Phytoconstituent-derived zingerone nanoparticles disrupt the cell adhesion mechanism and suppress cell motility in melanoma B16F10 cells.

Combining phytochemicals and nanotechnology to improve the unfavorable innate properties of phytochemicals and develop them into potent nanomedicines to enhance antitumor efficacy has become a novel strategy for cancer chemoprevention. Melanoma is the most aggressive, metastatic, and deadly disease of the primary cutaneous neoplasms. In this study, we fabricated phytoconstituent-derived zingerone nanoparticles (NPs) and validated their effects on cell adhesion and motility in melanoma B16F10 cells. Our data indicated that zingerone NPs significantly induced cytotoxicity and anti-colony formation and inhibited cell migration and invasion. Moreover, zingerone NPs dramatically interfered with the cytoskeletal reorganization and markedly delayed the period of cell adhesion. Our results also revealed that zingerone NPs-mediated downregulation of MMPs (matrix metalloproteinases) activity is associated with inhibiting cell adhesion and motility. We further evaluated the effects of zingerone NPs on Src/FAK /Paxillin signaling, our data showed that zingerone NPs significantly inhibited the protein activities of Src, FAK, and Paxillin, indicating that they play important roles in zingerone NP-mediated anti-motility and anti-invasion in melanoma cells. Accordingly, the phytoconstituent-zingerone NPs can strengthen the inhibition of tumor growth, invasion, and metastasis in malignant melanoma. Altogether, these multi-pharmacological benefits of zingerone NPs will effectively achieve the purpose of melanoma prevention and invasion inhibition.

Polyelectrolyte complexes of chitosan and hyaluronic acid or carboxymethylpullulan and their aminoguaiacol derivatives with biological activities as potential drug delivery systems.

Polyelectrolyte complexes (PECs) were elaborated from chitosan as cationic polymer and carboxy-methylpullulan (CMP), hyaluronic acid (HA) and their derivatives grafted with aminoguaiacol (G) with different degrees of substitution (DSGA) with the aim of obtaining nanogels for drug delivery. For each couple of polysaccharides, the charge ratios giving the smaller size with the lower PDI were selected to produce PECs. CMP_CHIT and CMP-G_CHIT PECs had smaller sizes (220-280 nm) than HA_CHIT and HA-G_CHIT PECs (280-390 nm). PECs were stable at 4 °C during 28 days at pH 5. In phosphate buffer saline (PBS) at pH 7.4, at 4 °C, a better stability of PECs based on CMP-G derivatives was observed. The hydrophobic associations between aminoguaiacol groups (highlighted by measurements of pyrene fluorescence) led to a better PECs' stabilization in PBS. The PECs' antioxidant and antibacterial activities were demonstrated and related to the DSGA. Diclofenac and curcumin were used as drug models: their loading reached 260 and 53 µg/mg PEC, respectively. The release of diclofenac in PBS at 37 °C followed a quasi-Fickian diffusion mechanism with release constant between 0.88 and 1.04 h-1. The curcumin release followed a slow linear increase in PBS/EtOH (60/40 V/V) with an effect of DSGA.

Synthesis of new trypanocidal agents from the hybridisation of metronidazole and eugenol analogues.

Nitroimidazole compounds are well-known bioactive substances, and the structural activity relationship has been reported whereby the position of the nitro group within the imidazole ring has a large influence on the activity. This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds). The in vitro trypanocidal tests show good results for both AC and AD hybrid compounds against both epimastigote and trypomastigote forms of T. cruzi. In silico studies showed positive data for most of the synthesised compounds and, in general present low toxicological risks. The AC compounds present lower ClogP (lipophilicity) values than those found for the AD series and higher TPSA (topological polar surface area) values, suggesting lower lipophilicity may be related to the presence of the triazole connector. The AD series compounds have higher Drug Score values than the AC series derivatives, suggesting better general properties for a pharmacological action.

Toxicity of nitrophenolic pollutant 4-nitroguaiacol to terrestrial plants and comparison with its non-nitro analogue guaiacol (2-methoxyphenol).

Phenols, and especially their nitrated analogues, are ubiquitous pollutants and known carcinogens which have already been linked to forest decline. Although nitrophenols have been widely recognized as harmful to different aquatic and terrestrial organisms, we could not find any literature assessing their toxicity to terrestrial plants. Maize (monocot) and sunflower (dicot) were exposed to phenolic pollutants, guaiacol (GUA) and 4-nitroguaiacol (4NG), through a hydroponics system under controlled conditions in a growth chamber. Their acute physiological response was studied during a two-week root exposure to different concentrations of xenobiotics (0.1, 1.0, and 10 mM). The exposure visibly affected plant growth and the effect increased with increasing xenobiotic concentration. In general, 4NG affected plants more than GUA. Moreover, sunflower exhibited an adaptive response, especially to low and moderate GUA concentrations. The integrity of both plant species deteriorated during the exposure: biomass and photochemical pigment content were significantly reduced, which reflected in the poorer photochemical efficiency of photosystem II. Our results imply that 4NG is taken up by sunflower plants, where it could enter a lignin biosynthesis pathway.

6-Gingerol and Semisynthetic 6-Gingerdione Counteract Oxidative Stress Induced by ROS in Zebrafish.

6-Gingerol (1) is one of the major components in ginger and developing new synthetic methodologies could bring semisynthetic analogs with improved therapeutic properties. Towards this, multigram scale isolation of 6-gingerol with excellent purity was optimized using a simple and robust extraction, followed by column purification. Synthesis of 6-gingerdione, 7 from 6-gingerol was then achieved through selective -OTBDMS protection, DMP oxidation and deprotection reaction sequence for the first time. Compounds 1, 7 and 8 (dehydrozingerone) exhibited excellent cell-free antioxidant properties in DPPH, ABTS, superoxide radical scavenging assay and H2 O2 assay at 10-50 µM concentrations. The hemolytic study suggests that up to 50 µM, all three compounds did not exhibit toxicity to human erythrocytes. When H2 O2 treated zebrafish larvae groups (96hpf) were exposed to compounds 1, 7 and 8, it increases the SOD (19, 19.1 and 18.7 U/mg protein), CAT (18.1, 16.5, and 15.8 µmol/mg levels and decreases the lipid peroxidation level (13, 15 and 18 nmol/mg protein), respectively. In vivo ROS levels and degree of cell death were studied using DCFDA and Acridine orange assays. Compounds 1, 7 and 8 decreases the ROS and cell death level significantly. Taken together, compounds 1, 7 and 8 exhibit excellent antioxidant properties, counteract H2 O2 induced oxidative stress, reduces cell death in zebrafish larvae.

Ginger, a Possible Candidate for the Treatment of Dementias?

As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (Zingiber officinale) and explore its properties against Alzheimer's Disease and Vascular Dementia, two of the most common and devastating forms of dementia. This work resumes the beneficial effects of Ginger compounds, tested in computational in vitro and in vivo models of Alzheimer's Disease and Vascular Dementia, along with some human tests. All these evidences suggest a potential role of the compounds of ginger not only in the treatment of the disease, but also in its prevention.

Enzymatic Degradation of Multiple Major Mycotoxins by Dye-Decolorizing Peroxidase from Bacillus subtilis.

The co-occurrence of multiple mycotoxins, including aflatoxin B1 (AFB1), zearalenone (ZEN) and deoxynivalenol (DON), widely exists in cereal-based animal feed and food. At present, most reported mycotoxins degrading enzymes target only a certain type of mycotoxins. Therefore, it is of great significance for mining enzymes involved in the simultaneous degradation of different types of mycotoxins. In this study, a dye-decolorizing peroxidase-encoding gene BsDyP from Bacillus subtilis SCK6 was cloned and expressed in Escherichia coli BL21/pG-Tf2. The purified recombinant BsDyP was capable of oxidizing various substrates, including lignin phenolic model compounds 2,6-dimethylphenol and guaiacol, the substrate 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), anthraquinone dye reactive blue 19 and azo dye reactive black 5, as well as Mn2+. In addition, BsDyP could efficiently degrade different types of mycotoxins, including AFB1, ZEN and DON, in presence of Mn2+. More important, the toxicities of their corresponding enzymatic degradation products AFB1-diol, 15-OH-ZEN and C15H18O8 were significantly lower than AFB1, ZEN and DON. In summary, these results proved that BsDyP was a promising candidate for the simultaneous degradation of multiple mycotoxins in animal feed and food.

Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives.

Demethylating methyl phenyl ethers is challenging, especially when the products are catechol derivatives prone to follow-up reactions. For biocatalytic demethylation, monooxygenases have previously been described requiring molecular oxygen which may cause oxidative side reactions. Here we show that such compounds can be demethylated anaerobically by using cobalamin-dependent methyltransferases exploiting thiols like ethyl 3-mercaptopropionate as a methyl trap. Using just two equivalents of this reagent, a broad spectrum of substituted guaiacol derivatives were demethylated, with conversions mostly above 90 %. This strategy was used to prepare the highly valuable antioxidant hydroxytyrosol on a one-gram scale in 97 % isolated yield.

Design, synthesis, molecular docking, anti-quorum sensing, and anti-biofilm activity of pyochelin-zingerone conjugate.

In this article, we report the chemical synthesis of pyochelin-zingerone conjugate via a hydrolysable ester linkage for drug delivery as a "Trojan Horse Strategy." It is a new therapeutic approach to combat microbial infection and to address the issue of multi drug resistance in Gram-negative, nosocomial pathogen Pseudomonas aeruginosa. Pyochelin (Pch) is a catecholate type of phenolate siderophore produced and utilized by the pathogen P. aeruginosa to assimilate iron when colonizing the vertebrate host. Zingerone, is active component present in ginger, a dietary herb known for its anti-virulent approach against P. aeruginosa. In the present study, zingerone was exploited to act as a good substitute for existing antibiotics, known to have developed resistance by most pathogens. Encouraging results were obtained by docking analysis of pyochelin-zingerone conjugate with FptA, the outer membrane receptor of pyochelin. Conjugate also showed anti-quorum sensing activity and also inhibited swimming, swarming, and twitching motilities as well as biofilm formation in vitro.

Potential natural inhibitors of xanthine oxidase and HMG-CoA reductase in cholesterol regulation: in silico analysis.

BACKGROUND: Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generate atherosclerosis and cholesterol crystals. ß-Hydroxy ß-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced cholesterol levels, most of them have failed to meet potential drug candidates' requirements. Here, we have carried out an in-silico analysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR in a wet lab setup. METHODS: Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were selected based on the IC50 values reported in in vitro assays. Further, receptor-based virtual screening was carried out against secondary metabolites using GOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-silico ADMET analysis was carried out to explore their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. RESULTS: The molecular docking of amentoflavone (GOLD score 70.54, ∆G calc. = - 10.4 Kcal/mol) and ganomycin I (GOLD score 59.61, ∆G calc. = - 6.8 Kcal/mol) displayed that the drug has effectively bound at the competitive site of XO and HMGR, respectively. Besides, 6-paradol and selgin could be potential drug candidates inhibiting XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl (6' → 1″)-O-α-D-glucopyranoside could be potential drug candidates to maintain serum cholesterol. In-silico ADMET analysis has shown that these sixteen metabolites were optimal within the categorical range compared to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through ProTox-II revealed that 6-gingerol, ganoleucoin K, and ganoleucoin Z are toxic for human use. CONCLUSION: This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.

Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat.

Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and the TRPV1 is activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32-35 °C) following a sustained exposition. Also, the effect was reversed 6 h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed.

Biamphiphilic ionic liquid based aqueous microemulsions as an efficient catalytic medium for cytochrome c.

Considering the remarkable applicability of ionic liquids (ILs) in bio-catalysis involving enzymes, herein, we report new IL based aqueous microemulsions as a catalytic reactor for cytochrome c (Cyt-c). Microemulsions (µEs), comprising water as the polar component, imidazolium (cation) and dioctylsulfosuccinate (AOT) (anion) based biamphiphilic ionic liquid (BAIL) as the surfactant and a hydrophobic ionic liquid (HIL) as the non-polar component have been prepared and characterized. The use of BAIL has promoted the formation of µEs without any co-surfactant, owing to its higher surface activity. The effect of ester- or amide-functionalization of the alkyl chain of the imidazolium cation of BAILs on the phase behavior of µEs has been investigated. The prepared µEs have been characterized via conductivity, dynamic light scattering (DLS), UV-vis absorption and steady-state fluorescence (using external polarity probes) techniques. The prepared µEs have been employed as nano-reactors for exploring the catalytic activity of Cyt-c. The formed BAIL-water nano-interfaces in reverse µEs have exerted a positive effect on the catalytic activity of Cyt-c stored in a water pool of reverse µEs. A five-fold higher rate constant in µEs as compared to buffer establishes µEs as a better catalytic medium. Furthermore, the differing nature of nano-interfaces created by BAILs and water in reverse µEs, depending on the functionalization of the alkyl chain of the cationic part of BAIL, has exerted varying influence on the catalytic activity of Cyt-c. It is expected that the present work will result in providing a versatile platform for the creation of new IL and water based µEs for bio-catalytic applications.

Generation of 4-vinylguaiacol through a novel high-affinity ferulic acid decarboxylase to obtain smoke flavours without carcinogenic contaminants.

Traditional smoke flavours bear the risk of containing a multitude of contaminating carcinogenic side-products. Enzymatic decarboxylation of ferulic acid released from agro-industrial side-streams by ferulic acid esterases (FAE) enables the sustainable generation of pure, food grade 4-vinylguaiacol (4-VG), the impact compound of smoke flavour. The first basidiomycetous ferulic acid decarboxylase (FAD) was isolated from Schizophyllum commune (ScoFAD) and heterologously produced by Komagataella phaffii. It showed a molecular mass of 21 kDa, catalytic optima at pH 5.5 and 35°C, and a sequence identity of 63.6% to its next relative, a FAD from the ascomycete Cordyceps farinosa. The ScoFAD exhibited a high affinity to its only known substrate ferulic acid (FA) of 0.16 mmol L-1 and a turnover number of 750 s-1. The resulting catalytic efficiency kcat KM-1 of 4,779 L s-1 mmol-1 exceeded the next best known enzyme by more than a factor of 50. Immobilised on AminoLink Plus Agarose, ScoFAD maintained its activity for several days. The combination with FAEs and agro-industrial side-streams paves the way for a new generation of sustainable, clean, and safe smoke flavours.

6-Paradol and its glucoside improve memory disorder in mice.

In this study, the effects of 6-paradol (6P) and 6-paradol-ß-glucoside (6PG) on neuritogenesis were investigated using PC12 cells. Treatment with 200 µM 6P or 6PG and nerve growth factor (NGF) (5 ng mL-1) increased the number of elongated dendritic cells 8.7 and 5.4 times, respectively, compared to that with NGF (5 ng mL-1) treatment alone. 6P and 6PG did not stimulate the phosphorylation of extracellular regulated protein kinases (ERK)1/2 and cAMP response element-binding protein (CREB) in the tropomyosin receptor kinase A (TrkA) pathway as their activities were suppressed by the pathway inhibitor, k252a. 6P enhanced Ca2+ influx into the cells, whereas 6PG had no effect on Ca2+ influx, although it stimulated PC12 cell differentiation. High-performance liquid chromatography (HPLC) analysis of 6PG in PC12 culture medium suggested that 6PG was deglycosylated to generate 6P, which exhibited the effect. Furthermore, the bioactivities of 6P and 6PG were investigated in mice, and the results revealed that they ameliorated short-term memory loss in animals during behavioral testing.

Characterization of alkylguaiacol-degrading cytochromes P450 for the biocatalytic valorization of lignin.

Cytochrome P450 enzymes have tremendous potential as industrial biocatalysts, including in biological lignin valorization. Here, we describe P450s that catalyze the O-demethylation of lignin-derived guaiacols with different ring substitution patterns. Bacterial strains Rhodococcus rhodochrous EP4 and Rhodococcus jostii RHA1 both utilized alkylguaiacols as sole growth substrates. Transcriptomics of EP4 grown on 4-propylguaiacol (4PG) revealed the up-regulation of agcA, encoding a CYP255A1 family P450, and the aph genes, previously shown to encode a meta-cleavage pathway responsible for 4-alkylphenol catabolism. The function of the homologous pathway in RHA1 was confirmed: Deletion mutants of agcA and aphC, encoding the meta-cleavage alkylcatechol dioxygenase, grew on guaiacol but not 4PG. By contrast, deletion mutants of gcoA and pcaL, encoding a CYP255A2 family P450 and an ortho-cleavage pathway enzyme, respectively, grew on 4-propylguaiacol but not guaiacol. CYP255A1 from EP4 catalyzed the O-demethylation of 4-alkylguaiacols to 4-alkylcatechols with the following apparent specificities (kcat/KM): propyl > ethyl > methyl > guaiacol. This order largely reflected AgcA's binding affinities for the different guaiacols and was the inverse of GcoAEP4's specificities. The biocatalytic potential of AgcA was demonstrated by the ability of EP4 to grow on lignin-derived products obtained from the reductive catalytic fractionation of corn stover, depleting alkylguaiacols and alkylphenols. By identifying related P450s with complementary specificities for lignin-relevant guaiacols, this study facilitates the design of these enzymes for biocatalytic applications. We further demonstrated that the metabolic fate of the guaiacol depends on its substitution pattern, a finding that has significant implications for engineering biocatalysts to valorize lignin.

Immune modulatory effect of a novel 4,5-dihydroxy-3,3´,4´-trimethoxybibenzyl from Dendrobium lindleyi.

Dendrobium bibenzyls and phenanthrenes such as chrysotoxine, cypripedin, gigantol and moscatilin have been reported to show promising inhibitory effects on lung cancer growth and metastasis in ex vivo human cell line models, suggesting their potential for clinical application in patients with lung cancer. However, it remains to be determined whether these therapeutic effects can be also seen in primary human cells and/or in vivo. In this study, we comparatively investigated the immune modulatory effects of bibenzyls and phenanthrenes, including a novel Dendrobium bibenzyl derivative, in primary human monocytes. All compounds were isolated and purified from a Thai orchid Dendrobium lindleyi Steud, a new source of therapeutic compounds with promising potential of tissue culture production. We detected increased frequencies of TNF- and IL-6-expressing monocytes after treatment with gigantol and cypripedin, whereas chrysotoxine and moscatilin did not alter the expression of these cytokines in monocytes. Interestingly, the new 4,5-dihydroxy-3,3',4'-trimethoxybibenzyl derivative showed dose-dependent immune modulatory effects in lipopolysaccharide (LPS)-treated CD14lo and CD14hi monocytes. Together, our findings show immune modulatory effects of the new bibenzyl derivative from Dendrobium lindleyi on different monocyte sub-populations. However, therapeutic consequences of these different monocyte populations on human diseases including cancer remain to be investigated.

Increasing the level of 4-vinylguaiacol in top-fermented wheat beer by secretory expression of ferulic acid decarboxylase from Bacillus pumilus in brewer's yeast.

OBJECTIVE: The objective is to explore the effects of enhancing the activity of yeast ferulic acid decarboxylase (FDC1) on the level of 4-vinylguaiacol (4-VG) and the consumption of its precursor ferulic acid (FA) in top-fermented wheat beer. RESULTS: Expression of Bacillus pumilus FDC1 in brewer's yeast showed a better effect on the FDC1 activity than overexpression of the endogenous enzyme. The 4-VG content was increased by 34%, and the consumption time of FA was shortened from 48 to 12 h. Since the intracellular accumulation of the FDC1 substrate did not increase over time, to reduce the FA transport burden on cells and shorten the decarboxylation time, B. pumilus FDC1 was further secreted extracellularly. The resulted strain showed a 65% increase in 4-VG content in the FA-containing medium, and produced about 3 mg L-1 4-VG in the top-fermented wheat beer, increasing by 61% than control. However, further increasing the secretory expression level of FDC1 only accelerated FA consumption. CONCLUSIONS: These results suggested that appropriate secretion of bacterial FDC1 into wort could be used as a potential alternative strategy to increase the level of 4-VG in top-fermented wheat beer.