4-hydroxybenzyl Alcohol Research Articles

Stability assessment of PITT tracer candidate compounds: The case of benzyl alcohols

The selection of compounds used as inter-well tracers has traditionally been done taking into consideration the goal of the test and the ease in analyzing the chemicals used. This often led to improper selection of the tracers and insufficient knowledge about their behavior under typical reservoir conditions, resulting in several unsuccessful inter-well tracer tests. One of the critical characteristics of any conservative tracer is its stability under various reservoir conditions. In this document we present the study methodology and the findings from stability experiments carried out on 5 benzyl alcohols investigated as oil/water partitioning tracers for partitioning inter-well tracer tests (PITT). This is the first of three documents reporting such studies on 3 families of chemicals.A PITT consists of the simultaneous injection of one or more mass-conservative passive and phase-partitioning (one type of active) tracers. PITT is primarily conceived for mature water-flooded oil fields and measures the residual (or even remaining) oil saturation (SOR) in the swept volumes between wells. Knowledge of SOR may be used to identify EOR targets, assess efficiency of EOR operations, and the efficiency of volumetric sweep between wells. This is important information, in particular for the increasing number of mature oil-fields where EOR projects are under consideration and/or development. A thorough knowledge about the static and dynamic properties of the tracers under reservoir conditions is required both to ensure successful field tests, and also to increase accuracy of the data obtained from them.4-Chlorobenzyl alcohol, 2,6-Dichlorobenzyl alcohol, 4-Methoxybenzyl alcohol, 3,4-Dimethoxybenzyl alcohol, and 4-Hydroxybenzyl alcohol were tested in brine under simulated reservoir conditions with temperatures up to 150 °C during 12 weeks, at different pH values, and in the presence of typical sedimentary basin rock materials, sandstone, carbonate rock (limestone), and clay (kaolinite). 4-Chlorobenzyl alcohol and 2,6-Dichlorobenzyl alcohol were found to be fully stable at all tested conditions. 4-Methoxybenzyl alcohol and 3,4-Dimethoxybenzyl alcohol exhibit thermally induced degradation above 125 °C, but may still be considered for use below this temperature. 4-Hydroxybenzyl alcohol exhibits thermally induced degradation which was found to follow a first order kinetics. The apparent activation energy and pre-exponential constant in the Arrhenius law for the degradation reaction were determined and a kinetic model built. This opens the possibility for use of 4-Hydroxybenzyl alcohol as a non-conservative reservoir tracer to measure temperature or detect thermal fronts.

Recent Research Progress on the Antidepressant-like Effect and Neuropharmacological Potential of Gastrodia elata Blume

Depression is a difficult and currently incurable mood disorder and the conventional therapies used as treatment are unsatisfactory nowadays. Therefore, there is an urgent demand to find alternative or complementary approaches to deal with depression. Gastrodia elata Blume (GE) is not only a traditional Chinese medicine but also a food material that has been widely used in treating numerous neurological disorders in East Asia, including migraine, seizure, and mood disorders. In the present review article, we summarized the antidepressant-like effects of GE that have been reported in animal studies and elucidate its cellular mechanisms. GE and its active compounds, gastrodin, 4-hydroxybenzyl alcohol, vanillin, and their derivatives have recently been reported to have intensive antidepressant-like effects in several animal models of depression, such as the forced swim test, the tail suspension test, and the chronic mild stress. The molecular mechanisms of GE-induced antidepressant-like effect are likely through regulation of neurotransmitters, antioxidation, antiinflammation, modulation of hypothalamic-pituitary-adrenal axis, neurotrophic effects, regulation of stem cell, and enhancement of neuroplasticity and neuroprotection. GE and its bioactive components have been shown to possess antidepressant-like effects in several well-conducted animal studies. Additionally, GE has been applied to manipulate mood disorders in Chinese medicine for many years. However, more accurate and specific initial targeting of the mechanism of action of GE, as well as the application of clinical trials, are warranted and deserve further investigation.

New titanium(IV) coordination compounds with 2-hydroxybenzyl alcohol derivatives used in the preparation of ultra-high molecular weight polyethylene

A reaction of 2,4-bis(α,α-dimethylbenzyl)phenol with TiCl2(ОPri)2 and Ti(ОPri)4 was used to obtain the coordination compounds (HL)2L2Ti2Cl2•MeC6H5 and L4Ti4(OPri)8, respectively. The compounds were characterized by elemental analysis, NMR spectroscopy, and X-ray diffraction. The titanium(IV) coordination compounds obtained polymerize ethylene in the presence of binary cocatalysts {3Et2AlCl + Bu2Mg} or {3Et3Al2Cl3 + Bu2Mg} at moderate to high rates, giving rise to ultra-high molecular weight polyethylene with a wide range of molecular masses. The highest values of tensile strength (2.4 GPa) and modulus of elasticity (e = 2.67%) were obtained for the sample with a molecular mass of 3.14•106 Da under comparable conditions of orientation drawing of the film filaments. This sample was obtained when complex (HL)2L2Ti2Cl2 was activated by a 3: 1 mixture of Et2AlCl—Bu2Mg.

Evaluation of the Mitochondria-Related Redox and Bioenergetics Effects of Gastrodin in SH-SY5Y Cells Exposed to Hydrogen Peroxide.

Mitochondrion is the main site of ATP production in animal cells and also orchestrates signaling pathways associated with cell survival and death. Mitochondrial dysfunction has been linked to bioenergetics and redox impairment in human diseases, such as neurodegeneration and cardiovascular disease. Protective agents able to attenuate mitochondrial impairment are of pharmacological interest. Gastrodin (GAS; 4-hydroxybenzyl alcohol 4-O-beta-D-glucoside) is a phenolic glucoside obtained from the Chinese herbal medicine Gastrodia elata Blume and exhibits antioxidant, anti-inflammatory, and antiapoptotic effects in several cell types. GAS is able to cross the blood-brain barrier, reducing the impact of different stressors on the cognition of experimental animals. In the present work, we investigated whether GAS would protect mitochondria of human SH-SY5Y neuroblastoma cells against an exposure to a pro-oxidant agent. The cells were treated with GAS at 25μM for 30min before the administration of hydrogen peroxide (H2O2) at 300μM for an additional 3 or 24h, depending on the assay. We evaluated both mitochondrial redox state and function parameters and analyzed the mechanism by which GAS protected mitochondria in this experimental model. Silencing of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor suppressed the GAS-induced mitochondrial protection seen here. Moreover, Nrf2 knockdown abrogated the effects of GAS on cell viability, indicating a potential role for Nrf2 in both mitochondrial and cellular protection promoted by GAS. Further research would be necessary to investigate whether GAS would be able to induce similar effects in in vivo experimental models.

4-Hydroxybenzyl alcohol derivatives and their sedative–hypnotic activities

4-Hydroxybenzyl alcohol (HBA), one of the characteristic active components of Gastrodia elata, exhibits obvious effects on the human central nervous system. In order to acquire compounds with superior bioactivity, 10 derivatives of HBA were synthesized from HBA and carboxylic acids. The sedative effects of the 10 HBA derivatives were evaluated using a spontaneous locomotor activity test (SLT) in mice, and their hypnotic effects were determined to be synergistic with pentobarbital-induced sleep. The results showed that 4-hydroxybenzyl alcohol 3-furancarboxylic acid diester (2FHBA, 10 mg kg−1) exhibited the strongest sedative–hypnotic activity among HBA and its derivatives, and 2FHBA could reverse the insomnia caused by p-chlorophenylalanine (pCPA), flumazenil (FLU) and thiosemicarbazide (TSC). Meanwhile, 2FHBA and 5-hydroxytryptophan (5-HTP) showed a synergistic effect. The results suggested that 2FHBA might be a potential agent against insomnia, which might be mediated by the serotonergic and GABAergic systems.

Novel titanium(IV) complexes stabilized by 2-hydroxybenzyl alcohol derivatives as catalysts for UHMWPE production

A series of titanium (IV) complexes (2, 5-7) stabilized by a substituted 2-hydroxybenzyl alcohols (1, 4) – were synthesized. Structures of complexes 6-7 were determined by X-ray diffraction. Titanium atom in the tetrameric complex 6 has an octahedral environment created by chlorine atom and five oxygen atoms. The main structural feature of 7 is a centrosymmetric Ti4O6 cage which is built of two seco-norcubanes Ti4O3 sharing a common Ti2O2-face. A coordination polyhedron around the titanium atoms is the distorted octahedron, with the long Ti─μ-O and short Ti─O bonds. All resulting complexes are moderately or highly active in ethylene polymerization in the presence of {3Et2AlCl + Bu2Mg} binary co-catalyst. Resulting polymers are linear ultrahigh molecular weight polyethylenes (up to 7.9 106 g/mole). Polymers are suitable for the modern processing methods – the solvent-free solid state formation of super high-strength (tensile strength over 2.0–2.4 GPa) and high-modulus (elastic modulus up to 130 GPa) oriented film tapes.

Synthesis of 2-(ethynyloxy)naphthaene-1-carbaldehyde using 2-hydroxy benzyl alcohol and propargyl bromide in aqueous micellar media

A highly convenient method has been developed for the synthesis of 2-(ethynyloxy) napthaene-1-carbaldehyde and its derivatives. Substituted naphthalene derivatives, having hydroxyl and carbonyl group, in the presence of K2CO3 base, react with propargyl bromide. Not only the product was obtained in good yield, but also the low cost and easy availability of the starting materials makes this synthesis a convenient one. In micellar solution, organic substrates are pushed away from water molecules towards the hydrophobic core of micelle droplets, thus inducing efficient collisions between organic substrates that eventually enhance the reaction rate and yield, which is ten times greater and two and half hours lesser time than in absence of micellar medium. An electron withdrawing group favours the formation of a stable phenoxide ion, which in turn favours the formation of product. The product is confirmed by FT-IR, 1H-NMR, and MASS spectroscopy. A green and useful method has been developed for the O-alkylation of aryl in aqueous surfactant media.

Anti-Zn2+-Toxicity of 4-Hydroxybenzyl Alcohol in Astrocytes and Neurons Contribute to a Robust Neuroprotective Effects in the Postischemic Brain.

4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn2+ toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects. Intraperitoneal administration of 4-HBA (20mg/kg) in Sprague-Dawley rats 1h after MCAO reduced infarct volumes to 27.1±9.2% of that of MCAO controls and significantly ameliorated motor impairments and neurological deficits. Significant suppressions of Zn2+-induced cell death, ROS generation, and PARP-1 induction by 4-HBA were observed in primary cortical cultures. 4-HBA also protected astrocytes from Zn2+-induced toxicity and suppressing ROS generation by employing slightly different molecular mechanisms, i.e., suppressing PARP-1 induction and NAD depletion under acute Zn2+-treatment and suppressing p67 NADPH oxidase subunit induction under chronic Zn2+-treatment. Results indicate that the protective effects of 4-HBA against Zn2+-toxicity in neurons and astrocytes contribute to its robust neuroprotective effects in the postischemic brain. Considering the pleiotropic effects of 4-HBA, which have been reported in previous reports and added in the present study, it has therapeutic potential for the amelioration of ischemic brain damage.

Anti-oxidative effects of 4-hydroxybenzyl alcohol in astrocytes confer protective effects in autocrine and paracrine manners.

4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata Blume (GEB), a traditional herbal medicine used in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in the brain, and in particular, its anti-inflammatory, anti-oxidative, and anti-zinc-toxic effects have been implicated in the postischemic brain. Here, the authors investigated the anti-oxidative effect of 4-HBA on astrocytes and sought to identify the underlying molecular mechanisms involved. 4-HBA dose-dependently suppressed H2O2-induced astrocyte cell death. More specifically, pre-incubation of C6 cells (an astrocyte cell line) with 100 μM 4-HBA for 6 hrs increased survival when cells were treated with H2O2 (100 μM, 1 hr) from 54.2±0.7% to 85.9±1.5%. In addition, 4-HBA was found to up-regulate and activate Nrf2, and subsequently, to induce the expressions of several anti-oxidative genes, such as, HO-1, NQO1, and GCLM. Notably, HO-1 was induced by 3.4-fold in 4-HBA-treated C6 cells, and siRNA-mediated HO-1 knockdown demonstrated that Nrf2 activation and HO-1 induction were responsible for the observed cytoprotective effect of 4-HBA. ERK and Akt signaling pathways were activated by 4-HBA in C6 cells, suggesting their involvements in protective effect of 4-HBA. In addition, 4-HBA-conditioned astrocyte culture medium was found to have neuroprotective effects on primary neuronal cultures or fresh C6 cells exposed to oxidative stress, and these effects seemed to be mediated by glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), which both accumulated in 4-HBA-treated astrocyte culture media. Thus, the 4-HBA-mediated activation of Nrf2 and induction of HO-1 in astrocytes were found to act via autocrine and paracrine mechanisms to confer protective effects. Furthermore, given the pleiotropic effects of 4-HBA with respect to its targeting of various brain cell types and functions, it would appear that 4-HBA has therapeutic potential for the prevention and amelioration of various brain diseases.

4-Hydroxybenzyl Alcohol Prevents Epileptogenesis As Well As Neuronal Damage in Amygdaloid Kindled Seizures

Background: 4-Hydroxybenzyl alcohol (4-HBA), one of the major active phenolic constituents of Gastrodia elata Blume, has been shown to be a neuroprotective agent. Previous studies have demonstrated the anticonvulsive effect of Gastrodia elata, while no studies have investigated the antiepileptogenic effect of 4-HBA. Methods: We examined the effect of 4-HBA (25 mg/kg, 50 mg/kg or 100 mg/kg i.p.) on amygdaloid kindled seizures. Fully kindled seizures were achieved by daily electrical stimulation of the amygdala. Seizure stage and afterdischarge duration (ADD) were assessed daily. The effects of 4-HBA on neuronal loss were observed before kindling and 20 days after kindling by Nissl staining. Results: We found that treatment with 50 mg/kg 4-HBA delayed seizure stage progression, and 25 mg/kg and 50 mg/kg 4-HBA shortened the corresponding ADD. Rats pretreated with 50 mg/kg 4-HBA needed more kindling stimulations to reach stages 4-5 and exhibited more cumulative ADD to stage 5. Pretreatment with 50 mg/kg 4-HBA shortened the number of days in stages 4–5 and decreased the incidence of generalized seizures. Pretreatment with 4-HBA showed no effect on fully kindled rats. Moreover, 50 mg/kg 4-HBA attenuated neuronal loss in the ipsilateral CA1 and the bilateral entorhinal cortex. Conclusion: Our data suggests that 4-HBA can protect against epileptogenesis by preventing the after-discharge propagation in amygdaloid kindled seizures. In addition, the anti-epileptogenic activity may be related to the neuroprotective function of 4-HBA in the late stage of kindling.

Vanillin and 4-hydroxybenzyl alcohol attenuate cognitive impairment and the reduction of cell proliferation and neuroblast differentiation in the dentate gyrus in a mouse model of scopolamine-induced amnesia.

4-Hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxybenzyl alcohol (4-HBA) are natural phenolic compounds, which present in many plants and have diverse biological properties. In this study, we examined effects of vanillin and 4-HBA on learning and memory function, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a mouse model of scopolamine-induced amnesia. Scopolamine (SCO; 1 mg/kg/day, intraperitoneally), vanillin, and 4-HBA (40 mg/kg/day, orally) were administered for 28 days. Treatment with scopolamine alone impaired learning and memory function in the Morris water maze and passive avoidance tests, in addition, the treatment significantly reduced cell proliferation and neuroblast differentiation in the dentate gyrus, which were examined by immunohistochemistry for Ki-67 (a classic marker for cell proliferation) and doublecortin (a marker for neuroblasts). However, treatment with vanillin or 4-HBA significantly attenuated SCO-induced learning and memory impairment as well as the reduction of cell proliferation and neuroblast differentiation in the dentate gyrus. These results indicate that vanillin and 4-HBA may be helpful in improving cognitive function and in increasing endogenous neuronal proliferation in the brain.

Fabrication of continuous ZrB2 nanofibers derived from boron-containing polymeric precursors

Continuous ceramic nanofibers of ZrB2 were synthesized via electrospinning combining with polymeric precursor method. The electrospinning solution was prepared from the reaction of Polyzirconoxane (PZO) with 2-Hydroxybenzyl alcohol and boric acid followed by the addition of polyvinylpyrrolidone (PVP). The influences of the solution properties and B/Zr molar ratio on electrospinning were investigated. The electrospun precursors and heat-treated nanofibers were characterized by XRD, SEM, EDS, TEM and Raman. The results showed that pyrolysis at 350 °C helped to stabilize the fibers morphology and ZrB2 nanofibers were obtained by pyrolyzing the precursor fibers at 1400 °C for 2 h in argon. ZrB2 nanofibers maintained the excellent fibrous morphology in all the samples. ZrB2 nanofibers are composed of uniformly nanosized ZrB2 particles. The average crystallite size of ZrB2 particles using Scherrer equation is 25 nm. The atomic percentages of zirconium and boron in the product formed in argon at 1400 °C were 17.06% and 33.73% respectively, which is very close to the stoichiometric ZrB2.

Synthesis and Antiacetylcholinesterase Activity Evaluation of New 2-aryl Benzofuran Derivatives

Starting from 2-hydroxybenzyl alcohol, a series of 2-arylbenzofurans have been synthesized and evaluated as acetylcholinesterase inhibitors at 23 µM by using modified colorimetric Ellman’s method. The reaction sequence was completed in four steps. All of the fourteen synthesized products were obtained in excellent yields without the need to tedious work-up step. In the last step, different derivatives were obtained by the substitution of bromine with five and six-membered cyclic and acyclic amines. Among the synthesized compounds, the best activity was observed in 1-(4- (Benzofuran-2-yl) benzyl)piperidine 5c with 74% activity compared to donepezil as a reference drug. Keywords: Benzofuran, acetylcholinesterase, N-bromosuccinimide (NBS), wittig reagent; alzheimer’s disease, 2-hydroxybenzyl alcohol.

The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures.

Tian ma (Gastrodia elata, GE) is an ancient Chinese herbal medicine that has been suggested to be effective as an anticonvulsant and analgesic, and to have sedative effects against vertigo, general paralysis, epilepsy and tetanus. The primary active ingredient isolated from GE is termed gastrodin, which is the glucoside of 4-hydroxybenzyl alcohol (4-HBA). Gastrodin can abolish hypoxia-, glutamate- and N-methyl-D-aspartate (NMDA) receptor-induced toxicity in primary culture of rat cortical neurons, and reduces seizure severity in seizure-sensitive gerbils. We evaluated the effect of gastrodin on NMDA excitotoxicity in hippocampal slice cultures (HSCs) with propidium iodide (PI) fluorescence measurement. We also evaluated the effects of gastrodin for treating active in vivo temporal lobe seizures induced by lithium/pilocarpine. Seizure severity, time span to seizure onset, mortality rate and hippocampal histology for survivors were compared. The effect of gastrodin was evaluated for treating in vitro seizures induced by Mg²⁺-free medium in hippocampal slices. Frequencies and amplitudes of epileptiform discharges were compared. The effect of gastrodin on synaptic transmission was evaluated on hippocampal CA1 Schaffer collaterals. Application of 25 μM gastrodin significantly suppressed NMDA excitotoxicity in CA3 but not in CA1 hippocampus and dentate gyrus. Intraventricular gastrodin accelerated seizure onset for 12 min after intraperitoneal pilocarpine injection (P = 0.051). Three of five rats (60%) in the gastrodin group, and three of four (75%) in the dimethyl sulfoxide (DMSO) group died within 3 days after status epilepticus (SE). Gastrodin also failed to inhibit epileptiform discharges in hippocampal slices induced by Mg²⁺-free medium, believed to be NMDA receptor-mediated spontaneous activity. The frequencies of the spontaneous epileptiform discharges were similar under treatments with 25 μM gastrodin, 200 μM gastrodin and DMSO. For the evaluation of gastrodin on synaptic transmission, application of DMSO, 25 μM or 200 μM gastrodin had no significant effect on excitatory postsynaptic potential (EPSP) slopes. Gastrodin at 200 μM decreased paired-pulse facilitation (PPF) from 1.23 ± 0.04 to 1.12 ± 0.04 (P = 0.002). In conclusion, gastrodin failed to suppress in vivo and in vitro seizures in our study. Gastrodin showed no effect on hippocampal Schaffer collateral EPSP. These findings suggest that gastrodin does not interact with ionotropic glutamate receptors to inhibit NMDA receptor-facilitated seizures. However, gastrodin showed protective effects against NMDA toxicity on cultured hippocampal slices. Nevertheless, gastrodin is still a potential neuroprotective agent against NMDA excitotoxicity, with potential benefits for stroke and patients with epilepsy.

Selective photooxidation of ortho-substituted benzyl alcohols and the catalytic role of ortho-methoxybenzaldehyde

Abstract It has been recently reported by Palmisano et al. (2015) [1] that the oxidation of 2-methoxybenzyl alcohol (2-MBA) to 2-methoxybenzaldehyde (2-MBAD) proceeds in water under near-UV light with an unexpected catalytic effect of 2-MBAD. In order to investigate the catalytic role of aldehyde in photolytic oxidation of ortho-substituted benzyl alcohols (OSBAs), reactivity runs were carried out with 2-methylbenzyl alcohol (2-MeBA), 2-nitrobenzyl alcohol (2-NBA), 2-hydroxybenzyl alcohol (2-HBA) and 2-chlorobenzyl alcohol (2-ClBA) in the absence and in the presence of their corresponding aldehyde. None of those alcohols showed a measurable oxidation rate even in the presence of their aldehydes but 2-NBA was oxidised very fast, although no corresponding carbonyl product was obtained. The possible catalytic role of 2-MBAD was investigated for the photolytic oxidation of 4-methoxybenzyl alcohol (4-MBA), 4-nitrobenzyl alcohol (4-NBA), 2-ClBA, 2-HBA, 2-MeBA and ferulic acid (FA). The results showed that 2-MBAD acts as a catalyst only for 4-MBA, 2-HBA and FA. The photocatalytic oxidation of OSBAs in the presence of powdered TiO2 has been also carried out in order to investigate the mutual influences, if any, between homogeneous and heterogeneous processes. The reactivity runs were carried out with TiO2 photocatalyst in water and under near-UV irradiation; a home-prepared (HP) TiO2 sample was used along with Degussa P25. HP catalyst showed the best performance: the 2-MBA half-life time was 5 times smaller and the selectivity to aldehyde 13 times higher than in the presence of Degussa P25.

Mechanism pathway and kinetics of p-cresol photocatalytic degradation over titania nanorods under UV–visible irradiation

Titania nanorods (TNRs) in pure anatase phase were synthesized by a hydrothermal technique and calcined at 450°C. The material was characterized by X-ray diffraction (XRD), N2 adsorption, transmission electron microscopy (TEM), UV-DR spectroscopy, and X-ray photoelectron spectroscopy (XPS). The photocatalytic degradation of p-cresol was carried out under UV–vis irradiation. The photodecomposition of p-cresol could be expressed by pseudo-first order in Langmuir–Hinshelwood kinetic model. The rate constant obtained of the TNRs catalyst was higher than that over P25 catalyst. Intermediates produced during the reaction were 4-methylcatechol, 4-hydroxybenzoic acid, 4-hydroxybenzyl alcohol and 4-hydroxybenzaldehyde. All intermediates are indicated to be less hazardous compared to p-cresol. More than 96% TOC mineralization was achieved during the degradation time. In addition, the reaction mechanism and pathway has been proposed and the rate constants for each elementary reaction were evaluated.

Synthesis of a soluble preceramic polymer for ZrC using 2-hydroxybenzyl alcohol as carbon source

A preceramic polymer for ZrC was successfully synthesised by chemical reaction between zirconium oxychloride (ZrOCl2·8H2O) and 2-Hydroxybenzyl alcohol via a one-pot route. The molecular structure, thermal properties and pyrolysis behaviour of the precursor were investigated. The results indicated that the precursor might be Zr–O–Zr chain polymer with 2-Hydroxybenzyl alcohol as ligand. The precursor was air-stable and exhibited excellent solubility in common organic solvents. The conversions from precursor to ZrC powders were investigated by TG-DTA, X-ray diffraction, Scanning electron microscope, TEM and Raman spectrum. The precursor underwent a thermal decomposition in four steps, and ZrC powders were formed at 1300°C via carbothermal reduction reaction of ZrO2 and carbon in argon with ceramic yield of 63.0%. The ZrC particles were fine and exhibited irregular polyhedron morphology with average size in the range of 100–300 nm.

Vanillin and 4-hydroxybenzyl alcohol promotes cell proliferation and neuroblast differentiation in the dentate gyrus of mice via the increase of brain-derived neurotrophic factor and tropomyosin-related kinase B

4-Hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxybenzyl alcohol (4-HBA) are well-known phenolic compounds, which possess various therapeutic properties and are widely found in a variety of plants. In the present study, the effects of vanillin and 4-HBA were first investigated on cell proliferation, as well as neuronal differentiation and integration of granule cells in the dentate gyrus (DG) of adolescent mice using Ki-67, doublecortin (DCX) immunohistochemistry and 5-bromo-2′-de-oxyuridine (BrdU)/feminizing Locus on X 3 (NeuN) double immunofluorescence. In both the vanillin and 4-HBA groups, the number of Ki-67+ cells, DCX+ neuroblasts and BrdU+/NeuN+ neurons were significantly increased in the subgranular zone of the DG, as compared with the vehicle group. In addition, the levels of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB), a BDNF receptor, were significantly increased in the DG in the vanillin and 4-HBA groups compared with the vehicle group. These results indicated that vanillin and 4-HBA enhanced cell proliferation, neuroblast differentiation and integration of granule cells in the DG of adolescent mice. These neurogenic effects of vanillin and 4-HBA may be closely associated with increases in BDNF and TrkB.

Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and 4-hydroxybenzyl alcohol, via the monoaminergic system and neuronal cytoskeletal remodeling

Ethnopharmacology relevanceGastrodia elata Blume is a highly valuable traditional Chinese medicine used in the treatment of depression. However, compounds with antidepressant effects in water extracts of G. elata Bl. (WGE) have not been identified. The aims of this study were to determine the major antidepressant compound in WGE and to evaluate the antidepressant effects of WGE and its active compounds which involved the monoaminergic system and neuronal cytoskeletal remodeling. Materials and methodsGastrodin (GAS) and 4-hydroxybenzyl alcohol (HBA) in WGE, were analyzed with high-performance liquid chromatography (HPLC)-ultraviolet detection.The forced swimming test (FST) was used to induce depression-like symptoms in 9 weeks old male Sprague-Dawley rats. The open field test (OFT) was used to measure anxiety after WGE, GAS, and HBA treatments. The levels of monoamine such as serotonin (5-HT), dopamine (DA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using HPLC-electrochemical detection. Western blotting was used to examine the 5-HT1A receptor and the neuronal cytoskeleton remodeling-related proteins, Slit, dihydropyrimidinase-related protein 2 (DPYSL2, also called CRMP2), Ras homologous member A (RhoA), and profilin 1 (PFN1) in vivo. Slit1 expression was evaluated in Hs683 cell line after treated with WGE (0.5mg/mL), GAS (50, 100 and 100μM), and HBA (50, 100 and 100μM). ResultsOral administration of WGE (500mg/kg bw), GAS (100mg/kg bw), and HBA (100mg/kg bw) exhibited the anti-depressant effect by significantly reducing the immobility time in FST, monoamine metabolism including the 5-HT to 5-HIAA in the hippocampus and DA to DOPAC and HVA ratios in the frontal cortex, amygdala, and hippocampus. In the hippocampus, the expression of the neuronal cytoskeleton remodeling-related negative regulators Slit1 and RhoA were significantly down-regulated. In addition, the positive regulators CRMP2 and PFN1 were significantly up-regulated following GAS, HBA, and WGE treatments. Moreover, WGE, GAS, and HBA were directly down-regulated Slit1 expression in Hs683 cells. ConclusionWGE, GAS, and HBA exhibited potential anti-depressant effects in rats by decreasing monoamine metabolism and modulated cytoskeleton remodeling-related protein expression in the Slit-Robo pathway. These results suggest that WGE can be used as agent for depressive prevention.

De novo biosynthesis of Gastrodin in Escherichia coli

Gastrodin, a phenolic glycoside, is the key ingredient of Gastrodia elata, a notable herbal plant that has been used to treat various conditions in oriental countries for centuries. Gastrodin is extensively used clinically for its sedative, hypnotic, anticonvulsive and neuroprotective properties in China. Gastrodin is usually produced by plant extraction or chemical synthesis, which has many disadvantages. Herein, we report unprecedented microbial synthesis of gastrodin via an artificial pathway. A Nocardia carboxylic acid reductase, endogenous alcohol dehydrogenases and a Rhodiola glycosyltransferase UGT73B6 transformed 4-hydroxybenzoic acid, an intermediate of ubiquinone biosynthesis, into gastrodin in Escherichia coli. Pathway genes were overexpressed to enhance metabolic flux toward precursor 4-hydroxybenzyl alcohol. Furthermore, the catalytic properties of the UGT73B6 toward phenolic alcohols were improved through directed evolution. The finally engineered strain produced 545mgl−1 gastrodin in 48h. This work creates a new route to produce gastrodin, instead of plant extractions and chemical synthesis.