2,4,6-Trihydroxybenzaldehyde

Anthocyanin Metabolites in Human Urine after the Intake of New Functional Beverages.[Pubmed:31963236]

Molecules. 2020 Jan 16;25(2). pii: molecules25020371.

Sugar intake abuse is directly related with the increase of metabolic diseases such as type 2 diabetes, obesity, and insulin resistance. Along this line, the development of new beverages using alternative sweeteners could help with combatting the pathophysiological disorders associated to the consumption of sugar. To provide evidence on this issue, in the present work, the bioavailability of anthocyanins was evaluated after the acute ingestion of a new maqui-citrus-based functional beverage rich in polyphenols, and supplemented with a range of sweeteners including sucrose (natural high caloric), stevia (natural non-caloric), and sucralose (artificial non-caloric), as an approach that would allow reducing the intake of sugars while providing bioactive phenolic compounds (anthocyanins). This approach allowed the evaluation of the maximum absorption and the diversity of metabolites excreted through urine. The beverages created were ingested by volunteers (n = 20) and the resulting anthocyanin metabolites in their urine were analyzed by UHPLC-ESI-MS/MS. A total of 29 degradation metabolites were detected: Caffeic acid, catechol, 3,4-dihidroxifenilacetic acid, hippuric acid, trans-ferulic acid, 2,4,6-Trihydroxybenzaldehyde, trans-isoferulic acid, and vanillic acid derivatives, where peak concentrations were attained at 3.5 h after beverage intake. Sucralose was the sweetener that provided a higher bioavailability for most compounds, followed by stevia. Sucrose did not provide a remarkably higher bioavailability of any compounds in comparison with sucralose or stevia. The results propose two sweetener alternatives (sucralose and stevia) to sucrose, an overused high calorie sweetener that promotes some metabolic diseases.

Bioaccessibility and biotransformation of anthocyanin monomers following in vitro simulated gastric-intestinal digestion and in vivo metabolism in rats.[Pubmed:31486446]

Food Funct. 2019 Sep 1;10(9):6052-6061.

Anthocyanins (ANCs) are phytochemicals with several health effects and undergo significant degradation and subsequent biotransformation during complex metabolic processes. The aim of the present study was to determine the bioaccessibility and biotransformation of cyanidin-3-glucoside (C3G) during the simulated gastric-intestinal digestion in vitro and the metabolism in rats in vivo. Characterization of C3G and its metabolites was conducted by HPLC-ESI-MS/MS. After gastric-intestinal digestion, C3G was detected with a recovery of 88.31% in the gastric-digestive system, and a small amount of methylated-C3G occurred. In the intestinal-digestive system, C3G occurred with a recovery of 6.05%, and mainly decomposed into protocatechuic acid (PCA) and 2,4,6-Trihydroxybenzaldehyde. The pharmacokinetic trial of C3G in rats showed rapid elimination in plasma. In tissues, C3G underwent rapid absorption and metabolism into phenolic acids or their derivatives. C3G and methylated-C3G passed through the blood-brain barrier and caused rapid distribution of C3G in the brain. Understanding the conversion of C3G and its metabolites helps in the future design of dietary interventions and the exploration of biological activities of ACNs.

Phenolic Breakdown Products of Cyanidin and Quercetin Contribute to Protection against Mitochondrial Impairment and Reactive Oxygen Species Generation in an In Vitro Model of Hepatocyte Steatosis.[Pubmed:31117508]

J Agric Food Chem. 2019 Jun 5;67(22):6241-6247.

A question in cell culture and dietary studies on protection by flavonoids against conditions such as hepatocyte steatosis is whether effects might be due to phenolic breakdown/digestion products. In HepG2 hepatocytes, treatment with quercetin, cyanidin, or their phenolic breakdown/digestion products (protocatechuic acid, 2,4,6-Trihydroxybenzaldehyde, and caffeic acid), starting 2 h prior to oleic acid for 24 h, protected similarly against increases in intracellular lipid and reactive oxygen species and decreased mitochondrial membrane potential. Cyanidin or the phenolic products also protected against decreased mitochondrial content. After preincubation for only 1 h (to limit spontaneous degradation) and removal prior to oleic acid, only the phenolic products protected against decreased mitochondrial content, and without adding oleic acid, only protocatechuic acid and caffeic acid, and less so cyanidin, induced mitochondrial content. The results suggest that phenolic breakdown/digestion products of cyanidin and quercetin contribute to the protective effects in vitro, and perhaps in vivo.

Antioxidant and Antiradical Properties of Selected Flavonoids and Phenolic Compounds.[Pubmed:29158919]

Biochem Res Int. 2017;2017:7616791.

Phenolic compounds and flavonoids are known by their antioxidant properties and one of the most important sources for humans is the diet. Due to the harmful effects of synthetic antioxidants such as BHA and BHT, natural novel antioxidants have become the focus of attention for protecting foods and beverages and reducing oxidative stress in vivo. In the current study, we investigated the total antioxidant, metal chelating, Fe(3+) and Cu(2+) reduction, and free radical scavenging activities of some phenolic and flavonoid compounds including malvin, oenin, ID-8, silychristin, callistephin, pelargonin, 3,4-dihydroxy-5-methoxybenzoic acid, 2,4,6-Trihydroxybenzaldehyde, and arachidonoyl dopamine. The antioxidant properties of these compounds at different concentrations (10-30 mug/mL) were compared with those of reference antioxidants such as BHA, BHT, alpha-tocopherol, and trolox. Each substance showed dose-dependent antioxidant activity. Furthermore, oenin, malvin, arachidonoyl dopamine, callistephin, silychristin, and 3,4-dihydroxy-5-methoxybenzoic acid exhibited more effective antioxidant activity than that observed for the reference antioxidants. These results suggest that these novel compounds may function to protect foods and medicines and to reduce oxidative stress in vivo.

Biotransformation and metabolism of three mulberry anthocyanin monomers by rat gut microflora.[Pubmed:28764082]

Food Chem. 2017 Dec 15;237:887-894.

Anthocyanins (ACNs) are naturally occurring components of human diet. Evidence has accumulated regarding the positive association of their intake with chronic disease. Because microbiota has been considered as a metabolic organ, the bacterial-dependent metabolisms of three types of ACNs from mulberry fruits (cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), delphinidin-3-rutinoside (D3R)) during a simulation of large intestine conditions were investigated. ACNs and metabolites were analysed and characterized by high performance liquid chromatography-electrospray ionization-mass spectrum (HPLC-ESI-MS/MS). C3G disappeared after 6h of metabolism, while C3R and D3R were no longer detected after 8h. The metabolism of C3G and C3R mainly resulted in the formation of protocatechuic, vanillic, and p-coumaric acids, as well as 2,4,6-Trihydroxybenzaldehyde, while the main metabolites of D3R were gallic acid, syringic acid and 2,4,6-Trihydroxybenzaldehyde. This research indicated that the intake of ACNs may result in the appearance of specific metabolites that exert a protective effect in the host physiology.

Comparison of dietary polyphenols for protection against molecular mechanisms underlying nonalcoholic fatty liver disease in a cell model of steatosis.[Pubmed:28317281]

Mol Nutr Food Res. 2017 Sep;61(9).

SCOPE: Dietary polyphenols have shown promise in protecting the liver against nonalcoholic fatty liver disease. The relative effectiveness and mechanisms of different polyphenols however is mostly unknown. METHODS AND RESULTS: In a model of steatosis using HepG2 hepatocytes, we evaluated the protective effects of different classes of polyphenols and the contributing mechanisms. The treatment of the cells with oleic acid increased reactive oxygen species (ROS) generation and expression of tumor necrosis factor alpha (TNF-alpha), decreased expression of uncoupling protein 2, and decreased mitochondrial content and markers of biogenesis. The treatment with 1-10 muM polyphenols (resveratrol, quercetin, catechin, cyanidin, kuromanin, and berberine), as well as phenolic degradation products (caffeic acid, protocatechuic acid, and 2,4,6-Trihydroxybenzaldehyde), all protected by more than 50% against the oleic acid induced increase in ROS. In other mechanisms involved, the polyphenols except anthocyanins strongly prevented or reversed the effect on mitochondrial content/biogenesis, increased expression of manganese superoxide dismutase, and prevented the large increase in TNF-alpha expression. Most polyphenols also prevented the decrease in uncoupling protein 2. The anthocyanins were unique in decreasing ROS generation without inducing mitochondrial biogenesis or manganese superoxide dismutase expression. CONCLUSION: While different polyphenols similarly decreased cellular ROS in this model of steatosis, they differed in their ability to suppress TNF-alpha expression and induce mitochondrial biogenesis and content.

Total Synthesis of Kehokorins A-E, Cytotoxic p-Terphenyls.[Pubmed:28267327]

J Org Chem. 2017 Mar 17;82(6):3159-3166.

This paper describes a general method for the synthesis of kehokorins A-E, novel cytotoxic p-terphenyls. 2,4,6-Trihydroxybenzaldehyde served as a common building block for preparation of the central aromatic ring. Construction of their p-terphenyl skeletons was achieved by a stepwise Suzuki-Miyaura coupling, whereas the phenyldibenzofuran moiety was built up by an intramolecular Ullmann reaction. Introduction of an l-rhamnose residue into partly protected kehokorin B was performed by the trichloroacetimidate method.

Biocatalytic Properties and Structural Analysis of Phloroglucinol Reductases.[Pubmed:27874239]

Angew Chem Int Ed Engl. 2016 Dec 12;55(50):15531-15534.

Phloroglucinol reductases (PGRs) are involved in anaerobic degradation in bacteria, in which they catalyze the dearomatization of phloroglucinol into dihydrophloroglucinol. We identified three PGRs, from different bacterial species, that are members of the family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs). In addition to catalyzing the reduction of the physiological substrate, the three enzymes exhibit activity towards 2,4,6-Trihydroxybenzaldehyde, 2,4,6-trihydroxyacetophenone, and methyl 2,4,6-trihydroxybenzoate. Structural elucidation of PGRcl and comparison to known SDRs revealed a high degree of conservation. Several amino acid positions were identified as being conserved within the PGR subfamily and might be involved in substrate differentiation. The results enable the enzymatic dearomatization of monoaromatic phenol derivatives and provide insight into the functional diversity that may be found in families of enzymes displaying a high degree of structural homology.

Vanillin Analogues o-Vanillin and 2,4,6-Trihydroxybenzaldehyde Inhibit NFkB Activation and Suppress Growth of A375 Human Melanoma.[Pubmed:27793895]

Anticancer Res. 2016 Nov;36(11):5743-5750.

BACKGROUND/AIM: Constitutive activation of nuclear factor kappa-B (NFkB) is a hallmark of various cancer types, including melanoma. Chemotherapy may further increase tumour NFkB activity, a phenomenon that, in turn, exacerbates drug resistance. This study aimed at preliminary screening of a panel of aromatic aldehydes, including vanillin, for cytotoxicity and suppression of tumour cell NFkB activity. MATERIALS AND METHODS: The cytotoxic and NFkB-inhibitory effects of 10 aromatic aldehydes, including vanillin, were investigated in cultured A375 human melanoma cells. Each compound was assayed alone and in combination with the model NFkB-activating drug doxorubicin. The most promising analogues were then tested alone and in combination with 4-hydroperoxycyclophosphamide in vitro, and with cyclophosphamide in mice bearing A375 xenografts. RESULTS: The vanillin analogues o-vanillin and 2,4,6-Trihydroxybenzaldehyde exhibited cytotoxicity against cultured A375 cells, and inhibited doxorubicin- and 4-hydroperoxycyclophosphamide-induced NFkB activation. They also suppressed A375 cell growth in mice. CONCLUSION: o-vanillin and 2,4,6-Trihydroxybenzaldehyde deserve further evaluation as potential anticancer drugs.

A New Group of Disinfection Byproducts in Drinking Water: Trihalo-hydroxy-cyclopentene-diones.[Pubmed:27286323]

Environ Sci Technol. 2016 Jul 19;50(14):7344-52.

We report the detection, synthesis, preparative isolation, structure characterization and identification, and formation of a new group of drinking water disinfection byproducts (DBPs): trihalo-hydroxy-cyclopentene-diones (trihalo-HCDs). With ultra performance liquid chromatography (UPLC)/electrospray ionization-triple quadruple mass spectrometry analyses (full scans, multiple reaction monitoring, and product ion scans) and high-resolution mass spectrometry analyses (full scans), the new group of DBPs was identified with formulae and proposed with structures. However, due to a lack of commercially available standard compounds, structure identification of this new group of DBPs was challenging. 2,4,6-Trihydroxybenzaldehyde was found to be a good precursor for the synthesis of the tribromo species (m/z 345/347/349/351) in the new group of DBPs by reacting with bromine at a 2,4,6-Trihydroxybenzaldehyde-to-bromine molar ratio of 1:8. With UPLC/photodiode array analysis (simultaneous 2- and 3-dimensional operations), the new DBP was determined to have a maximum UV absorption at the wavelength of 280 nm. Through isolation with high performance liquid chromatography/UV-triggered collections followed by lyophilization, the pure standard of the new DBP was obtained. Characterized with Fourier transform infrared spectroscopy, the pure standard of the new DBP was finally identified to be tribromo-HCD, and thus the new group of DBPs was identified to be trihalo-HCDs. On the basis of the disclosed structure, formation pathways of tribromo-HCD through reactions of three different precursors and bromine were proposed and partially verified. Moreover, increasing the bromide level in source water shifted the formation of trihalo-HCDs from being more chlorinated to being more brominated; with an increase in the contact time from 1 h to 5 d, the formation of trihalo-HCDs kept increasing in chloramination, whereas they kept decreasing in chlorination; with an increase in the pH from 6.0 to 8.5, the formation of trihalo-HCDs was decreased by approximately 80%. Notably, the concentrations of tribromo-HCD in eight Chinese tap water samples were from below the detection limit to 0.53 mug/L.

Inhibitory effects of some phenolic compounds on the activities of carbonic anhydrase: from in vivo to ex vivo.[Pubmed:26670706]

J Enzyme Inhib Med Chem. 2016 Dec;31(6):1234-40.

Carbonic anhydrase (CA) inhibitors have been used for more than 60 years for therapeutic purposes in many diseases table such as in medications against antiglaucoma and as diuretics. Phenolic compounds are a new class of CA inhibitor. In our study, we tested the effects of arachidonoyl dopamine, 2,4,6-Trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid on esterase and the CO2-hydratase activities of CA I and II isozymes purified from in vivo to ex vivo. The Ki values of arachidonoyl dopamine, 2,4,6-Trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid were 203.80, 1170.00 and 910.00 muM, respectively for hCA I and 75.25, 354.00 and 1510.00 muM, respectively for hCA II. Additionally, IC50 values from in vivo studies were found to be in the range of 173.25-1360.0 muM for CA I and II, respectively, using CO2-hydratase activity methods. These results demonstrated that phenolic compounds used in in vivo studies could be used in different biomedical applications to inhibit approximately 30% of the CO2-hydratase activity of the total CA enzyme of rat erythrocytes.

2,4,6-Trihydroxybenzaldehyde, a potential anti-obesity treatment, suppressed adipocyte differentiation in 3T3-L1 cells and fat accumulation induced by high-fat diet in C57BL/6 mice.[Pubmed:25812771]

Environ Toxicol Pharmacol. 2015 Mar;39(2):962-8.

In the present study, 2,4,6-Trihydroxybenzaldehyde (THB) was evaluated for inhibitory effects on adipocyte differentiation in 3T3-L1 cells and anti-obesity effects in mice with high-fat diet (HFD)-induced obesity. Lipid accumulation measurement indicated that THB markedly inhibited adipogenesis, and this involved down-regulation of the expression of the adipogenesis-related proteins, CCAAT/enhancer-binding protein alpha (C/EBPalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c), in 3T3-L1 pre-adipocyte cells. In a mouse model of HFD-induced obesity, oral administration of THB (5 and 25mg/kg for 13 weeks) reduced the HFD-induced increase in weight gain. THB administration also reduced serum levels of glucose, triglycerides, and total cholesterol. A reduction in the hypertrophy of white adipose tissue was also observed. Furthermore, THB administration inhibited HFD-induced hepatic steatosis. These results provided evidence that administration of THB alleviated HFD-induced obesity in C57BL/6 mice and revealed the potential of THB as a nutraceutical to help prevent or treat obesity and the associated metabolic disorders.

Nematicidal activity of acetophenones and chalcones against Meloidogyne incognita and structure-activity considerations.[Pubmed:25641877]

Pest Manag Sci. 2016 Jan;72(1):125-30.

BACKGROUND: With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita. RESULTS: The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC(50/24 h) values of 12 +/- 5 and 15 +/- 4 mg L(-1) respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC(50/24 h) 0.4 +/- 0.3 mg L(-1)). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-Trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC(50/24 h) value 25 +/- 17 mg L(-1)). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC(50/24) h value 26 +/- 15 mg L(-1)) than 4-methoxyacetophenone (EC(50/24 h) value 43 +/- 10 mg L(-1)). CONCLUSIONS: Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients.