Intersections in Neuropsychiatric and Metabolic Disorders: Possible Role of TRPA1 Channels

Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations. Despite decades of research, the mechanism deciphering the link between neuropsychiatric and metabolic disorders is still unclear. In recent years, transient receptor potential Ankyrin 1 (TRPA1) channel has emerged as a potential therapeutic target for modulators. TRPA1 agonists/antagonists have shown efficacy in both neuropsychiatric disorders and appetite regulation and thus provide a crucial link between both. TRPA1 channels are activated by compounds such as cinnamaldehyde, allyl isothiocyanate, allicin and methyl syringate, which are present naturally in food items such as cinnamon, wasabi, mustard, garlic, etc. As these are present in many daily food items, it could also improve patient compliance and reduce the patients’ monetary burden. In this review, we have tried to present evidence of the possible involvement of TRPA1 channels in neuropsychiatric and metabolic disorders and a possible hint towards using TRPA1 modulators to target appetite, lipid metabolism, glucose and insulin homeostasis and inflammation associated with NPDs.

Methyl syringate and isovanilic acid from the bark of Alphonsea elliptica

A phytochemical study of dichloromethane extract of Alphonsea elliptica has led to the isolation of two compounds previously unreported from the species methyl syringate and isovanilic acid. Stigmasterol which has been previously reported was also isolated. The structures were determined by spectroscopic techniques and by comparison with data reported in the literature. The findings of this study will contribute to the chemotaxonomic and phylogenetic aspects of the Alphonsea sp.

Production of Recombinant Laccase From Coprinopsis cinerea and Its Effect in Mediator Promoted Lignin Oxidation at Neutral pH

Laccases are multi-copper oxidases that use molecular oxygen as the electron acceptor to oxidize phenolic and indirectly also non-phenolic substrates by mechanisms involving radicals. Due to their eco-friendliness and broad substrate specificity, laccases span a wide range of biotechnological applications. We have heterologously expressed a laccase from the coprophilic basidiomycete Coprinopsis cinerea (CcLcc9) in the methylotrophic yeast Pichia pastoris. The recombinant CcLcc9 (rCcLcc9) oxidized 2,6-dimethoxyphenol in the neutral pH range, and showed thermostability up to 70°C. The rCcLcc9 efficiently oxidized veratryl alcohol to veratraldehyde in the presence of low molecular weight mediators syringyl nitrile, methyl syringate and violuric acid, which are syringyl-type plant phenolics that have shown potential as natural co-oxidants for lignocellulosic materials. In addition, rCcLcc9 is able to depolymerize biorefinery hardwood lignin in the presence of methyl syringate and syringyl nitrile as indicated by gel permeation chromatography, and infrared spectral and nucleic magnetic resonance analyses. Furthermore, we showed that several added-value aromatic compounds, such as vanillin, vanillic acid, syringaldehyde, syringic acid and p-hydroxybenzoic acid, were formed during sequential biocatalytic chemical degradation of biorefinery lignin, indicating that rCcLcc9 harbors a great potential for sustainable processes of circular economy and modern biorefineries.

Antibacterial Activity of Moroccan Zantaz Honey and the Influence of Its Physicochemical Parameters Using Chemometric Tools

The emergence of multidrug-resistant bacteria has prompted the development of alternative therapies, including the use of natural products with antibacterial properties. The antibacterial properties of Zantaz honey produced in the Moroccan Atlas Mountains against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus was evaluated and analyzed using chemometric tools. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against S. aureus were the lowest (112.5 ± 54.5 mg/mL), revealing that this species was most sensitive to Zantaz honey. P. aeruginosa showed an intermediate sensitivity (MIC= 118.75 ± 51.9 mg/mL), while E. coli was the most resistant to treatment (MIC = 175 ± 61.2 mg/mL). Content of monosaccharides, certain minerals, and phenolic compounds correlated with antibacterial activity (p < 0.05). Principal component analysis of physicochemical characteristics and antibacterial activity indicated that the parameters most associated with antibacterial activity were color, acidity, and content of melanoidins, fructose, epicatechin, methyl syringate, 4-coumaric acid, and 3-coumaric acid.

HPLC-ESI-MS and GC-EI-MS Identification and Quantitation of Polyphenolics and Alkaloids in Moroccan Jujube Honeys

The aim of this study was to determine the phytochemical content of Moroccan Jujube Honey and to establish the principal components of this staple Moroccan food, which contributes health benefit for the local population. Total phytochemical compounds as determined by analytical HPLC-ESI-MS in the honey extracts were 29.39±5.21 mg/kg (range 16.64–42.16) wet weight. The individual phytochemical compounds definitively identified by HPLC-DAD-ESI-MS in the Jujube honeys were the alkaloids: (I) 4-hydroxyquinoline glucoside, (II) 4-hydroxyquinoline and (V) kynurenic acid (17.66±0.87 mg/kg), and the phenolic compounds: (III) p-hydroxybenzoic acid, (IV) caffeic acid and (VI) methyl syringate (11.73±0.50 mg/kg). The structures were confirmed by GC-EI-MS apart from 4-hydroxyquinoline-glucoside. The major components were methyl syringate (8.34±2.49 mg/kg), 4-hydroxyquinoline (6.61±3.23 mg/kg) and kynurenic acid (6.56±0.97 mg/kg). The mean content of polyphenolic compounds (11.73±0.50 mg/kg) of Moroccan Jujube honeys compared favorably with those described for six Chinese Jujube honeys (2.49 mg/kg), five commercial Jujube honeys from different countries (0.92 mg/kg) and twelve Jujube honeys from Yemen (25.71 mg/kg). Reference studies did not identify alkaloids as components of Jujube honey, and therefore the phytochemical profile of Moroccan Jujube honey appears to be unique.

Phytotoxic Activity and Identification of Phytotoxic Substances from Schumannianthus dichotomus

The phytotoxic potential of plants and their constituents against other plants is being increasingly investigated as a possible alternative to synthetic herbicides to control weeds in crop fields. In this study, we explored the phytotoxicity and phytotoxic substances of Schumannianthus dichotomus, a perennial wetland shrub native to Bangladesh, India, and Myanmar. Leaf extracts of S. dichotomus exerted strong phytotoxicity against two dicot species, alfalfa and cress, and two monocot species, barnyard grass and Italian ryegrass. A bioassay-driven purification process yielded two phenolic derivatives, syringic acid and methyl syringate. Both constituents significantly inhibited the growth of cress and Italian ryegrass in a concentration-dependent manner. The concentrations required for 50% growth inhibition (I50 value) of the shoot and root growth of cress were 75.8 and 61.3 μM, respectively, for syringic acid, compared with 43.2 and 31.5 μM, respectively, for methyl syringate. Similarly, to suppress the shoot and root growth of Italian rye grass, a greater amount of syringic acid (I50 = 213.7 and 175.9 μM) was needed than methyl syringate (I50 = 140.4 to 130.8 μM). Methyl syringate showed higher phytotoxic potential than syringic acid, and cress showed higher sensitivity to both substances. This study is the first to report on the phytotoxic potential of S. dichotomus and to identify phytotoxic substances from this plant material.

Degradation of Aflatoxin B1 and Zearalenone by Bacterial and Fungal Laccases in Presence of Structurally Defined Chemicals and Complex Natural Mediators

Aflatoxin B1 (AFB1) and zearalenone (ZEN) exert deleterious effects to human and animal health. In this study, the ability of a CotA laccase from Bacillus subtilis (BsCotA) to degrade these two mycotoxins was first investigated. Among the nine structurally defined chemical compounds, methyl syringate was the most efficient mediator assisting BsCotA to degrade AFB1 (98.0%) and ZEN (100.0%). BsCotA could also use plant extracts, including the Epimedium brevicornu, Cucumis sativus L., Lavandula angustifolia, and Schizonepeta tenuifolia extracts to degrade AFB1 and ZEN. Using hydra and BLYES as indicators, it was demonstrated that the degraded products of AFB1 and ZEN using the laccase/mediator systems were detoxified. Finally, a laccase of fungal origin was also able to degrade AFB1 and ZEN in the presence of the discovered mediators. The findings shed light on the possibility of using laccases and a mediator, particularly a natural plant-derived complex mediator, to simultaneously degrade AFB1 and ZEN contaminants in food and feed.

A commercial laccase-mediator system to delignify and improve saccharification of the fast-growing Paulownia fortunei (Seem.) Hemsl.

It was demonstrated for the first time that a laccase-based enzymatic pretreatment is able to delignify fast-growing paulownia species. The treatment was performed with a commercial low-redox potential laccase isolated from Myceliophthora thermophila (Apinis) Oorschot and methyl syringate (MeS) as a natural phenolic mediator. Up to 24% lignin removal was attained by the laccase-MeS treatment (L/MeS), followed by alkaline peroxide extraction in a multistage sequence. The reduction in lignin content was accompanied by a significant improvement in the subsequent enzymatic saccharification, with increases of up to 38% glucose and 34% xylose yields. The structural modifications of the lignin were analyzed in situ by two dimensional-nuclear magnetic resonance (2D-NMR) spectroscopy. A considerable removal of guaiacyl and syringyl lignin units with respect to the carbohydrate signals was visible as well as the cleavage of β-O-4′, β-5′ and β-β′ linkages leading to elevated amounts of Cα-oxidized guaiacyl and syringyl units. The presence of oxidized lignin compounds in the filtrates of the enzymatic treatments – such as vanillin, vanillic acid, syringaldehyde and syringic acid – conclusively demonstrates the ability of L/MeS treatment to oxidize and depolymerize the lignin in paulownia wood.