RESUMO
Recently, nanoparticles have received considerable attention owing to their efficiency in overcoming the limitations of traditional chemotherapeutic drugs. In our study, we synthesized a vanillic acid nanocomposite using both chitosan and silver nanoparticles, tested its efficacy against lung cancer cells, and analyzed its antimicrobial effects. We used several characterization techniques such as ultraviolet-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to determine the stability, morphological characteristics, and properties of the biosynthesized vanillic acid nanocomposites. Furthermore, the vanillic acid nanocomposites were tested for their antimicrobial effects against Escherichia coli and Staphylococcus aureus, and Candida albicans. The data showed that the nanocomposite effectively inhibited microbes, but its efficacy was less than that of the individual silver and chitosan nanoparticles. Moreover, the vanillic acid nanocomposite exhibited anticancer effects by increasing the expression of pro-apoptotic proteins (BAX, Casp3, Casp7, cyt C, and p53) and decreasing the gene expression of Bcl-2. Overall, vanillic acid nanocomposites possess promising potential against microbes, exhibit anticancer effects, and can be effectively used for treating diseases such as cancers and infectious diseases.
Assuntos
Anti-Infecciosos , Antineoplásicos , Nanocompostos , Ácido Vanílico , Ácido Vanílico/química , Ácido Vanílico/farmacologia , Nanocompostos/química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Prata/química , Prata/farmacologia , Quitosana/química , Quitosana/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Nanopartículas Metálicas/química , Linhagem Celular TumoralRESUMO
BACKGROUND AND OBJECTIVES: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. METHODS: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. RESULTS: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). CONCLUSION: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.
Assuntos
Fraturas do Fêmur , Consolidação da Fratura , Ratos Wistar , Ácido Vanílico , Animais , Ácido Vanílico/farmacologia , Ácido Vanílico/uso terapêutico , Consolidação da Fratura/efeitos dos fármacos , Masculino , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Fêmur/patologia , Ratos , Modelos Animais de Doenças , Fenômenos Biomecânicos/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Fêmur/patologia , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/patologiaRESUMO
BACKGROUND: Vanillic acid (VA; 4-hydroxy-3-methoxybenzoic acid) is a flavouring agent found in various natural sources such as olives, fruits, and green tea. While VA exhibits numerous pharmacological effects, its potential protective effects against gastric injury warrants further investigation. Therefore, the primary objective of this study is to elucidate investigate the gastroprotective properties of VA against ethanol-induced gastric injury. METHODS AND RESULTS: Rats were orally administered either saline or VA at different doses (50, 100, and 200 mg/kg/day), with omeprazole (20 mg/kg) serving as a positive control, for fourteen consecutive days before ethanol administration. Blood and gastric tissue samples were collected one hour after ethanol administration for biochemical, molecular, and histological analyses. Pre-treatment with VA before ulcer induction alleviated both macroscopic and microscopic damage. It also increased antioxidant glutathione levels and decreased malondialdehyde and myeloperoxidase activity, along with reducing inflammatory markers such as tumour necrosis factor (TNF)-α, interleukin (IL)-6, and nuclear factor kappa B (NF-κB). Additionally, VA pre-treatment reversed the elevation of Bax mRNA expression and gastric caspase-3 levels induced by gastric damage. It also mitigated the reduction in Bcl-2 mRNA expression. CONCLUSION: These findings suggest that VA exerts protective effects against ethanol-induced gastric injury in rats. It achieves this by augmenting gastric antioxidant capacity and mitigating oxidative, inflammatory, and apoptotic damage.
Assuntos
Apoptose , Etanol , NF-kappa B , Transdução de Sinais , Úlcera Gástrica , Ácido Vanílico , Animais , NF-kappa B/metabolismo , Etanol/toxicidade , Etanol/efeitos adversos , Ratos , Apoptose/efeitos dos fármacos , Ácido Vanílico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Masculino , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/lesões , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Substâncias Protetoras/farmacologia , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Glutationa/metabolismoRESUMO
Alzheimer's disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist of muscarinic acetylcholine receptors that exhibits the behavioral and molecular hallmarks of AD. Vanillic acid (VA), a phenolic compound, is obtained from the roots of a traditional plant called Angelica sinensis, and has several pharmacologic effects, including antimicrobial, anti-inflammatory, anti-angiogenic, anti-metastatic, and antioxidant properties. Nevertheless, VA's neuroprotective potential associated with the memory has not been thoroughly investigated. Therefore, this study investigated whether VA treatment has an ameliorative effect on the learning and memory impairment induced by SCOP in rats. Behavioral experiments were utilized to assess the learning and memory performance associated with the hippocampus. Using western blotting analysis and assay kits, the neuronal damage, oxidative stress, and acetylcholinesterase activity responses of hippocampus were evaluated. Additionally, the measurement of long-term potentiation was used to determine the function of synaptic plasticity in organotypic hippocampal slice cultures. In addition, the synaptic vesicles' density and the length and width of the postsynaptic density were evaluated using electron microscopy. Consequently, the behavioral, biochemical, electrophysiological, and ultrastructural analyses revealed that VA treatment prevents learning and memory impairments caused by SCOP in rats. The study's findings suggest that VA has a neuroprotective effect on SCOP-induced learning and memory impairment linked to the hippocampal cholinergic system, oxidative damage, and synaptic plasticity. Therefore, VA may be a prospective therapeutic agent for treating AD.
Assuntos
Hipocampo , Transtornos da Memória , Plasticidade Neuronal , Fármacos Neuroprotetores , Estresse Oxidativo , Escopolamina , Ácido Vanílico , Animais , Estresse Oxidativo/efeitos dos fármacos , Ácido Vanílico/farmacologia , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/induzido quimicamente , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Fármacos Neuroprotetores/farmacologia , Ratos Wistar , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Antioxidantes/farmacologia , Ratos Sprague-DawleyRESUMO
Caldimonas thermodepolymerans, a Gram-negative, moderately thermophilic bacterium, exhibits a remarkable biotechnological potential. Given the presence of genes in its genome dedicated to the metabolization of ferulic acid (FA), this study aimed to explore the bacterium's capability for biotransforming FA into high-value metabolites. The results unequivocally demonstrate the bacterium's proficiency in the efficient and rapid conversion of FA into vanillyl alcohol (VOH) and vanillic acid (VA). By manipulating key cultivation parameters, such as adjusting initial FA doses and varying cultivation periods, the product profile can be tailored. Higher initial doses and shorter cultivation periods favor the production of VOH, while lower FA doses and extended cultivation periods lead to the predominant formation of VA. Furthermore, the process can be operated in a repeated-batch scenario. This underscores the potential of C. thermodepolymerans for industrial biotransformation of FA, presenting a promising avenue for leveraging its capabilities in practical applications.
Assuntos
Álcoois Benzílicos , Biotransformação , Ácidos Cumáricos , Ácido Vanílico , Ácidos Cumáricos/metabolismo , Ácido Vanílico/metabolismo , Álcoois Benzílicos/metabolismo , Microbiologia IndustrialRESUMO
It has been reported that lipophilic statins such as atorvastatin can more readily penetrate into ß-cells and reach the mitochondria, resulting in mitochondrial dysfunction, oxidative stress, decrease in insulin release. Many studies have shown that natural products can protect mitochondrial dysfunction induced by drug in different tissue. We aimed to explore mitochondrial protection potency of hesperidin, vanillic acid, and sinapic acid as natural compounds against mitochondrial dysfunction induced by atorvastatin in pancreas isolated mitochondria. Mitochondria were isolated form rat pancreas and directly treated with toxic concentration of atorvastatin (500 µM) in presence of various concentrations hesperidin, vanillic acid, and sinapic acid (1, 10, and 100 µM) separately. Mitochondrial toxicity parameters such as the reactive oxygen species (ROS) formation, succinate dehydrogenases (SDH) activity, mitochondrial swelling, depletion of glutathione (GSH), mitochondrial membrane potential (MMP) collapse, and malondialdehyde (MDA) production were measured. Our findings demonstrated that atorvastatin directly induced mitochondrial toxicity at concentration of 500 µM and higher in pancreatic mitochondria. Except MDA, atorvastatin caused significantly reduction in SDH activity, mitochondrial swelling, ROS formation, depletion of GSH, and collapse of MMP. While, our data showed that all three protective compounds at low concentrations ameliorated atorvastatin-induced mitochondrial dysfunction with the increase of SDH activity, improvement of mitochondrial swelling, MMP collapse and mitochondrial GSH, and reduction of ROS formation. We can conclude that hesperidin, vanillic acid, and sinapic acid can directly reverse the toxic of atorvastatin in rat pancreas isolated mitochondria, which may be beneficial for protection against diabetogenic-induced mitochondrial dysfunction in pancreatic ß-cells.
Assuntos
Atorvastatina , Ácidos Cumáricos , Hesperidina , Potencial da Membrana Mitocondrial , Mitocôndrias , Dilatação Mitocondrial , Pâncreas , Espécies Reativas de Oxigênio , Ácido Vanílico , Animais , Atorvastatina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/metabolismo , Ácidos Cumáricos/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Masculino , Dilatação Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ácido Vanílico/farmacologia , Hesperidina/farmacologia , Glutationa/metabolismo , Ratos Wistar , Succinato Desidrogenase/metabolismo , Malondialdeído/metabolismoAssuntos
Colite , Ferroptose , Homeostase , Mucosa Intestinal , Ácido Vanílico , Ferroptose/efeitos dos fármacos , Animais , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Colite/tratamento farmacológico , Colite/metabolismo , Humanos , Ácido Vanílico/farmacologia , Ácido Vanílico/uso terapêutico , Canais de Cálcio/metabolismo , Canais de Cálcio/efeitos dos fármacosRESUMO
To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.
Assuntos
Amomum , Benzotiazóis , Catequina , Hidroxibenzoatos , Óleos Voláteis , Ácidos Sulfônicos , Radical Hidroxila , Ácido Vanílico , Antioxidantes/química , Água , Etanol , Óleos Voláteis/químicaRESUMO
Vanillic acid (4-hydroxy-3-methoxybenzoic acid) (VA) is a natural benzoic acid derivative commonly found in herbs, rice, maize, and some fruits and vegetables. However, due to the wide use of VA in various industrial sectors, its presence in the environment might harm living organisms. This study evaluated the toxicity of VA and its isomers, iso-VA and orto-VA. Firstly, the antimicrobial effect of VA and its isomers iso-VA and orto-VA (in doses of 1000; 100, 10, 1; 0.1; 0.01â¯mg/L) against Escherichia coli, Sarcina spp., Enterobacter homaechei, Staphylococcus aureus and Candida albicans were identified. The toxic effect and protein degradation potential of VA and its isomers were determined using E. coli grpE:luxCDABE and lac:luxCDABE biosensor strains. However, the genotoxicity and oxidative stress generation were assessed with the E. coli recA:luxCDABE biosensor and E. coli strain. The results showed that VA, iso-VA, and orto-VA exhibited antimicrobial activity against all tested bacterial strains. However, VA's antimicrobial effect differed from iso-VA and orto-VA. Similar toxic, genotoxic, and oxidative stress-inducing effects were observed for VA and its isomers. Each compound exhibited toxicity, cellular protein degradation, and genotoxic activity against E. coli grpE:luxCDABE, E. coli lac:luxCDABE, and E. coli recA:luxCDABE strains. Analysis of reactive oxygen species (ROS) generation within E. coli cells highlighted oxidative stress as a contributing factor to the toxicity and genotoxicity of VA and its isomers. While the findings suggest potential applications of VA compounds as food preservatives, their presence in the environment raises concerns regarding the risks posed to living organisms due to their toxic and genotoxic characteristics.
Assuntos
Escherichia coli , Estresse Oxidativo , Ácido Vanílico , Ácido Vanílico/farmacologia , Ácido Vanílico/toxicidade , Escherichia coli/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Testes de Mutagenicidade , Antibacterianos/toxicidade , Antibacterianos/farmacologia , Anti-Infecciosos/toxicidade , Anti-Infecciosos/farmacologiaRESUMO
The aim is to investigate the possible pulmonary protective effect of vanillic acid (VA) in liposome-TPGS nanoparticles, to overcome VA's poor bioavailability. VA was successfully extracted. Liposomes were prepared using thin film hydration. Central composite design was adopted for optimisation of liposomes to get the maximum entrapment efficiency (EE%) and the minimum mean diameter, where the liposomes were further modified with TPGS, and tested for PDI, zeta-potential, and in-vitro drug release. In-vivo study on mice with LPS-acute pulmonary toxicity was tested. TPGS-modified VA-liposomes showed EE% of 69.35 ± 1.23%, PS of 201.7 ± 3.23 nm, PDI of 0.19 ± 0.02, and zeta-potential of -32.2 ± 0.32 mv. A sustained drug release of the TPGS-modified VA-liposomes was observed compared to standard VA, and a pulmonary-protective effect through decreasing miR-217 expression with subsequent anti-inflammatory effect through suppression of MAPK and PI3K/NF-κB pathways was also demonstrated in the current study. TPGS-modified VA-liposomes showed an enhanced bioavailability and a sustained drug release with promising pulmonary protective effects against acute pulmonary injury diseases.
Assuntos
Lipossomos , MicroRNAs , NF-kappa B , Ácido Vanílico , Vitamina E , Animais , NF-kappa B/metabolismo , Ácido Vanílico/farmacologia , Ácido Vanílico/análogos & derivados , Vitamina E/química , Vitamina E/farmacologia , Vitamina E/análogos & derivados , Camundongos , Transdução de Sinais/efeitos dos fármacos , Masculino , Pulmão/efeitos dos fármacosRESUMO
The production of nanoparticles enhances the bioactivity of biological molecules for drug delivery to diseased sites. This study explains how silver nanoparticle (AgNP) coating enhanced the protection effects of vanillic acid in male diabetic rats with streptozotocin- (STZ-) induced diabetes. Twenty-four rats were divided into four groups (n = 6) for this investigation. The first group (G1) is untreated, whereas diabetes was induced in the other three groups through STZ injection. Diabetic rats that were not getting therapy were included in the second group (G2, STZ-positive), whereas the other diabetic rats were divided into the third group (G3, vanillic acid-treated) and the fourth group (G4, vanillic acid-coated AgNPs treated). The treatment lasted four weeks. In G2, the induction of diabetes significantly (at P = 0.05) increased in serum glucose, glycated proteins, renal indices, interleukin-6 (IL-6), K+, immunoglobulins, and lipid peroxidation, while decreased Ca++, Na+, and other antioxidants in the kidney tissue homogenate. In addition, pathological altered signs were present in the pancreas and kidneys of diabetic rats. The renal and pancreatic tissues were effectively enhanced by vanillic acid or vanillic acid-coated AgNPs, bringing them very close to their prediabetic conditions. Vanillic acid-coated AgNPs offered a stronger defense against STZ-induced diabetes and lessened the effects of hyperglycemia compared to ordinary vanillic acid. Additionally, using vanillic acid coated with silver nanoparticles greatly increased the antioxidant and antidiabetic activity and reduced inflammation when compared to using vanillic acid alone.
Assuntos
Diabetes Mellitus Experimental , Nanopartículas Metálicas , Ratos , Masculino , Animais , Estreptozocina/farmacologia , Ácido Vanílico/farmacologia , Ácido Vanílico/uso terapêutico , Prata/farmacologia , Prata/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Antioxidantes/uso terapêutico , Estresse OxidativoRESUMO
Vanillin is a valuable natural product that can be used as a fragrance and additive. Recent research in the biosynthesis of vanillin has brought attention to a key enzyme, carboxylic acid reductase (CAR), which catalyzes the reduction of vanillic acid to vanillin. Nevertheless, the biosynthesis of vanillin is hampered by the low activity and stability of CAR. As such, a rational design campaign was conducted on a well-documented carboxylic acid reductase from Segniliparus rugosus (SrCAR), using vanillic acid as the model substrate. After combined active site saturation and iterative site-specific mutagenesis, the best quadruple mutant N292H/K524S/A627L/E1121W (M3) was successfully obtained. In comparison to the wildtype SrCAR, M3 demonstrated a 4.2-fold increase in catalytic efficiency (kcat/Km), and its half-life (t1/2) was enhanced by 3.8 times up to 385.08â¯minutes at 40⯰C. In silico docking and molecular dynamics simulation provided insights into the improved activity and stability. In the subsequent preparative-scale reaction with 100â¯mM (16.8â¯gâ¯L-1) vanillic acid, the whole cell catalysis utilizing M3 produced 10.15â¯g·L-1 of vanillin and 1.11â¯g·L-1 of vanillyl alcohol, respectively. This work demonstrates a dual improvement in the activity and thermal stability of SrCAR, thereby potentially facilitating the application of carboxylic acid reductase in the biosynthesis of vanillin.
Assuntos
Oxirredutases , Ácido Vanílico , Oxirredutases/química , BenzaldeídosRESUMO
Vanillic acid (VA) - a naturally occurring phenolic compound in plants - is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson's alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a-1i, 2a-2i, 3, 3a-3i, 4a-4i, 5a-5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b-3d, 4a-4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.
Assuntos
Antifúngicos , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Ácido Vanílico/farmacologia , Ácido Vanílico/uso terapêutico , Azóis/farmacologia , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Fluconazol/farmacologia , Candida , Candida albicans , Candida glabrata , Inflamação/tratamento farmacológicoRESUMO
The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence of ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced colitis by restoring intestinal epithelium homeostasis via the inhibition of ferroptosis. By the CETSA assay and DARTS assay, we identified carbonic anhydrase IX (CAIX, CA9) as the direct target of VA. The binding of VA to CA9 causes insulin-induced gene-2 (INSIG2) to interact with stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading to the translocation of SCAP-SREBP1 from the endoplasmic reticulum (ER) to the Golgi apparatus for cleavage into mature SREBP1. The activation of SREBP1 induced by VA then significantly facilitated the transcription of stearoyl-CoA desaturase 1 (SCD1) to exert an inhibitory effect on ferroptosis. By inhibiting the excessive death of intestinal epithelial cells caused by ferroptosis, VA effectively preserved the integrity of intestinal barrier and prevented the progression of unresolved inflammation. In conclusion, our study demonstrated that VA could alleviate colitis by restoring intestinal epithelium homeostasis through CA9/STIM1-mediated inhibition of ferroptosis, providing a promising therapeutic candidate for UC.
Assuntos
Colite , Ferroptose , Humanos , Animais , Camundongos , Ácido Vanílico , Molécula 1 de Interação Estromal , Colite/induzido quimicamente , Colite/tratamento farmacológico , Homeostase , Mucosa Intestinal , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Anidrase Carbônica IX , Antígenos de Neoplasias , Proteínas de NeoplasiasRESUMO
Maize bran, an agro-processing waste residue, is a good source of ferulic acid that can be further valorized for vanillin production. However, extraction of ferulic acid from natural sources has been challenging due to low concentrations and intensive extraction procedures. In the present work, ferulic acid streams (purities ranging from 5% to 75%) extracted from maize bran using thermochemical methods were evaluated for biotransformation to vanillin, employing Amycolatopsis sp. as a whole-cell biocatalyst. Initial adaptation studies were critical in improving ferulic acid assimilation and its conversion to vanillin by 65% and 56%, respectively by the fourth adaptation cycle. The effect of cell's physiological states and vanillic acid supplementation on vanillin production was studied using standard ferulic acid as a substrate in an effort to achieve further improvement in vanillin yield. In the presence of vanillic acid, 18 h cultured cells using 2 g/L of standard and isolated ferulic acid produced vanillin concentrations of up to 0.71 and 0.48 g/L, respectively. Furthermore, intermediates involved in the ferulic acid catabolic pathway and their interrelations were studied using GC-MS analysis. Results indicated that two different routes were involved in the catabolism of standard ferulic acid, and similar metabolic routes were observed for an isolated ferulic acid stream. These findings effectively evaluated isolated ferulic acid for sustainable vanillin production while reducing agro-industrial waste pollution.
Assuntos
Amycolatopsis , Zea mays , Amycolatopsis/metabolismo , Zea mays/metabolismo , Ácido Vanílico/metabolismo , Benzaldeídos/metabolismo , Ácidos Cumáricos/metabolismo , BiotransformaçãoRESUMO
The nosocomial bacterium Acinetobacter baumannii is protected from antibiotic treatment by acquiring antibiotic resistances and by forming biofilms. Cell attachment, one of the first steps in biofilm formation, is normally induced by environmental metabolites. We hypothesized that vanillic acid (VA), the oxidized form of vanillin and a widely available metabolite, may play a role in A. baumannii cell attachment. We first discovered that A. baumannii actively breaks down VA through the evolutionarily conserved vanABKP genes. These genes are under the control of the repressor VanR, which we show binds directly to VanR binding sites within the vanABKP genes bidirectional promoter. VA in turn counteracts VanR inhibition. We identified a VanR binding site and searched for it throughout the genome, especially in pili encoding promoter genes. We found a VanR binding site in the pilus encoding csu operon promoter and showed that VanR binds specifically to it. As expected, a strain lacking VanR overproduces Csu pili and makes robust biofilms. Our study uncovers the role that VA plays in facilitating the attachment of A. baumannii cells to surfaces, a crucial step in biofilm formation. These findings provide valuable insights into a previously obscure catabolic pathway with significant clinical implications.
Assuntos
Acinetobacter baumannii , Aderência Bacteriana , Proteínas de Bactérias , Biofilmes , Fímbrias Bacterianas , Regulação Bacteriana da Expressão Gênica , Regiões Promotoras Genéticas , Ácido Vanílico , Acinetobacter baumannii/metabolismo , Acinetobacter baumannii/genética , Acinetobacter baumannii/efeitos dos fármacos , Ácido Vanílico/metabolismo , Ácido Vanílico/farmacologia , Biofilmes/crescimento & desenvolvimento , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Fímbrias Bacterianas/metabolismo , Fímbrias Bacterianas/genética , Óperon , Sítios de Ligação , Benzaldeídos/metabolismo , Benzaldeídos/farmacologiaRESUMO
Vanillic acid (VA), as a plant-derived phenolic acid compound, has widespread applications and good market prospects. However, the traditional production process cannot meet market demand. In this study, Pseudomonas putida KT2440 was used for de novo biosynthesis of VA. Multiple metabolic engineering strategies were applied to construct these P. putida-based cell factories, including the introduction of a Hs-OMTopt, engineering the cofactor S-adenosylmethionine supply pathway through the overexpression of metX and metH, reforming solubility of Hs-OMTopt, increasing a second copy of Hs-OMTopt, and the optimization of the fermentation medium. The resulting strain, XCS17, de novo biosynthesized 5.4 g/L VA from glucose in a fed-batch fermentation system; this is the highest VA production titer reported up to recently. This study showed that P. putida KT2440 is a robust platform for achieving the effective production of phenolic acids.
Assuntos
Pseudomonas putida , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Ácido Vanílico/metabolismo , Engenharia Metabólica , Hidroxibenzoatos/metabolismoRESUMO
Maize (Zea mays L.) is an important crop in Argentina. Aspergillus section Flavi can infect this crop at the pre-harvest stage, and the harvested grains can be contaminated with aflatoxins (AFs). During the production of bioethanol from maize, AF levels can increase up to three times in the final co-products, known as, dry and wet distiller's grain with solubles (DDGS and WDGS), intended for animal feed. Fungal enzymes like laccases can be a useful tool for reducing AF contamination in the co-products obtained from this process. The aim of the present study was to evaluate the ability of laccase enzymes included in enzymatic extracts (EE) produced by different species in the Basidiomycota phylum to reduce AF (AFB1 and AFB2) accumulation under the conditions of in vitro assays. Four laccase activities (5, 10, 15, and 20 U/mL) exerted by nine isolates were evaluated in the absence and presence of vanillic acid (VA), serving as a laccase redox mediator for the degradation of total AFs. The enzymatic stability in maize steep liquor (MSL) was confirmed after a 60 h incubation period. The most effective EE in terms of reducing AF content in the buffer was selected for an additional assay carried out under the same conditions using maize steep liquor obtained after the saccharification stage during the bioethanol production process. The highest degradation percentages were observed at 20 U/mL of laccase enzymatic activity and 1 mM of VA, corresponding to 26% for AFB1 and 26.6% for AFB2. The present study provides valuable data for the development of an efficient tool based on fungal laccases for preventing AF accumulation in the co-products of bioethanol produced from maize used for animal feed.
Assuntos
Aflatoxinas , Basidiomycota , Animais , Zea mays , Descontaminação , Lacase , Ácido VanílicoRESUMO
Substituted benzaldehydes are the most commonly used natural-occurring flavours in the world. The consumer's preference for 'natural or organic' aromas has increased the request for flavours possessing the 'natural' status. The resulting shortage of aromatic aldehydes of extractive origin, such as vanillin, veratraldehyde and piperonal, can be offset by developing a new biotechnological synthesis method. Here, we report a study on the microbiological reduction of five natural benzoic acid derivatives, namely p-anisic, vanillic, veratric, piperonylic and eudesmic acids, to produce the corresponding fragrant aldehydes. We found that different Basidiomycota strains can efficiently perform this transformation, with good chemical selectivity and tolerance to the toxicity of substrates and products. Besides confirming the carboxylic acid reductase activity of the already studied fungi Pycnoporus cinnabarinus, we discovered that other species such as Pleurotus eryngii, Pleurotus sapidus and Laetiporus sulphureus as well as the non-ligninolytic fungi Lepista nuda are valuable microorganisms for the synthesis of anisaldehyde, vanillin, veratraldehyde, piperonal and 3,4,5-trimethoxybenzaldehyde from the corresponding acids. According to our findings, we propose a reliable process for the preparation of the above-mentioned aldehydes, in natural form. KEY POINTS: ⢠Fragrant benzaldehydes were obtained by biotransformation. ⢠Basidiomycota strains reduced substituted benzoic acid to the corresponding aldehydes. ⢠Anisaldehyde, vanillin, veratraldehyde, piperonal and 3,4,5-trimethoxybenzaldehyde were prepared in natural form.