RESUMO
3-(Trihydroxygermyl)propanoic acid (THGP), a hydrolysate of poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132, also known as repagermanium), can inhibit glycation between glucose/ribose and amino compounds. In addition, THGP may inhibit glycation by inhibiting reactions that occur after Amadori rearrangement and inducing the reversible solubilization of AGEs. In this study, we first investigated the effects and mechanisms on the glycation of fructose and amino compounds by THGP, as a greater reactivity was obtained with fructose than with glucose. Unlike other anti-glycation materials, THGP can form a complex with fructose, the initial compound of glycation. THGP also inhibited the production of AGEs and suppressed the reduction of fructose in a reaction between fructose and arginine. These results indicate that THGP forms a complex with cyclic fructose possessing a cis-diol structure at a reducing end, and that it suppresses the ring-opening of fructose and the progress of the initial glycation reaction. We next tried to evaluate the suppressive effect of glucosyl hesperidin (GHes) and THGP on the reaction of glycation between fructose and collagen. Both compounds effectively reduced the production of AGEs individually, and the combination of them led to a synergistic suppression. Therefore, through combination with other antiglycation materials, THGP may cooperatively exhibit glycation-inhibitory effects and be able to suppress the AGE production.
Assuntos
Frutose , Frutose/química , Frutose/farmacologia , Glicosilação/efeitos dos fármacos , Propionatos/farmacologia , Propionatos/química , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/metabolismo , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Colágeno/metabolismo , AnimaisRESUMO
Di-d-psicose anhydride (DPA), derived from functional rare saccharide as d-psicose, is investigated for its strong chelating ability. Methylglyoxal (MGO), an important precursor of advanced glycation end-products (AGEs), promotes obesity, and causes complications such as diabetic nephropathy. On mesangial cells, DPA can substantially reduce the negative effects of MGO. DPA effectively trapping MGO in mesangial cells. The bonding properties of the DPA-MGO adduct were discussed by mass spectrometry and nuclear magnetic resonance (NMR). The NMR spectra of the DPA-MGO adduct provide evidence for chelation bonding. The inhibition of AGE formation and the mass spectrometry results of the DPA-MGO adduct indicate that DPA can scavenge MGO at a molar ratio of 1:1. DPA suppressed 330 % of the up-regulated receptor for an AGEs protein expression to a normal level and restored the suppressed glyoxalase 1 level to 86 % of the normal group. This research provides important evidence and theoretical basis for the development of AGE inhibitors derived from rare saccharide.
Assuntos
Nefropatias Diabéticas , Produtos Finais de Glicação Avançada , Aldeído Pirúvico , Aldeído Pirúvico/química , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/prevenção & controle , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Lactoilglutationa Liase/antagonistas & inibidores , Lactoilglutationa Liase/metabolismo , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Anidridos/química , Quelantes/química , Quelantes/farmacologiaRESUMO
Glucose, the predominant carbohydrate in the human body, initiates nonenzymatic reactions in hyperglycemia, potentially leading to adverse biochemical interactions. This study investigates the interaction between glucose and Bovine Serum Albumin (BSA), along with the protective effects of Spirulina platensis PCC 7345 aqueous extract. Phycobiliproteins (phycocyanin, phycoerythrin, and allophycocyanin) in the extract were quantified using spectrophotometry. The extract's anti-glycation potential was assessed by analyzing its effects on albumin glycation, fluorescent advanced glycation end products (AGEs), thiol group oxidation, and ß-amyloid structure generation. Additionally, its antidiabetic potential was evaluated by measuring α-amylase and α-glucosidase enzyme inhibition. Results indicate that the Spirulina extract significantly mitigated ketoamine levels, fluorescence, and protein-carbonyl production induced by glucose, demonstrating a 67.81 % suppression of AGE formation after 28â days. Moreover, it effectively inhibited amyloid formation in BSA cross-linkages. These findings suggest the potential of S. platensis as an anti-glycation and antidiabetic agent, supporting its consideration for dietary inclusion to manage diabetes and associated complications.
Assuntos
Glucose , Produtos Finais de Glicação Avançada , Soroalbumina Bovina , Spirulina , Spirulina/química , Soroalbumina Bovina/metabolismo , Soroalbumina Bovina/química , Glicosilação/efeitos dos fármacos , Animais , Bovinos , Glucose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Água/química , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismoRESUMO
Advanced glycation end products (AGEs) can be caused during a glycoxidation reaction. This reaction is associated with complications of diabetes and the consequences of health problems. Therefore, we are exploring the prohibitory effect of highland barley protein hydrolysates (HBPHs) on AGE formation. Herein, first extracted the protein from highland barley with various pH conditions and then hydrolyzed using four different proteolytic enzymes (flavourzyme, trypsin, papain, pepsin) under different degrees of hydrolysis. We assessed three degrees of hydrolysates (lowest, middle, highest) of enzymes used to characterize the antioxidant activity and physicochemical properties. Among all the hydrolysates, flavourzyme-treated hydrolysates F-1, F-2, and F-3 indicated the high ability to scavenge DPPH (IC50 values of 0.97 %, 0.63 %, and 0.90 %), structural and functional properties. Finally, the inhibitory effect of the most active hydrolysates F-1, F-2, and F-3 against the AGEs formation was evaluated in multiple glucose-glycated bovine serum albumin (BSA) systems. Additionally, in a BSA system, F-3 exhibited the strong antiglycation activity, effectively suppressed the non-fluorescent AGE (CML), and the fructosamine level. Moreover, it decreased carbonyl compounds while also preventing the loss of thiol groups. Our results would be beneficial in the application of the food industry as a potential antiglycation agent for several chronic diseases.
Assuntos
Produtos Finais de Glicação Avançada , Hordeum , Proteínas de Plantas , Hidrolisados de Proteína , Soroalbumina Bovina , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Hordeum/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Soroalbumina Bovina/química , Proteínas de Plantas/química , Proteínas de Plantas/farmacologia , Hidrólise , Antioxidantes/farmacologia , Antioxidantes/química , Animais , Glicosilação/efeitos dos fármacosRESUMO
In our quest to discover advanced glycation end products (AGEs) inhibitors from Clinacanthus nutans (Burm.f.) Lindau leaves, we conducted a bioactivity-based molecular networking. This approach integrates LC-MS2 profiling and in vitro antiglycation data to predict bioactive compounds. We began by screening three extracts: 100% ethanol, 70% ethanol and 100% water alongside the in vitro antioxidant activity, total phenolics content (TPC) and schaftoside content. Among these extracts, 100% ethanol extract exhibited the highest total AGEs inhibition effects (IC50 = 80.18 ± 11.6 µg/mL), DPPH scavenging activity (IC50 = 747.40 ± 10.30 µg/mL) and TPC (26.54 ± 2.09 µg GAE /mg extract). Intriguingly, 100% ethanol extract contained the lowest amount of schaftoside, suggesting the involvement of other phytochemicals in the antiglycation effects. The molecular networking and in silico structural annotations of 401 LC-MS features detected in the fractions from 100% ethanol extract predicted 21 bioactive compounds (p < 0.05, r > 0.90), including several C40 carotenoids, alkaloids containing tetrapyrrole structures and fatty acids. On the contrary, all phenolics showed weak correlations with antiglycation effects. These predictions were further validated in vitro, where carotenoid lutein showed half maximal inhibitory concentration, IC50 = 96 ± 8 µM and selected flavonoid-C-glycosides exhibited weaker inhibitions (IC50 between 568 and 1922 µM). Notably, lutein content was higher in freeze-dried leaves (12.42 ± 0.82 mg/100 g) than oven-dried, although the former was associated with elevated mercury levels. In summary, C. nutans exhibited potential antiglycation and antioxidant activity, and lutein was identified as the main bioactive principle.
Assuntos
Acanthaceae , Antioxidantes , Produtos Finais de Glicação Avançada , Fenóis , Compostos Fitoquímicos , Extratos Vegetais , Folhas de Planta , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Folhas de Planta/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Acanthaceae/química , Fenóis/farmacologia , Fenóis/análise , Fenóis/isolamento & purificação , Estrutura MolecularRESUMO
BACKGROUND: Food products undergo a pronounced Maillard reaction (MR) during the cooking process, leading to the generation of substantial quantities of Maillard reaction products (MRPs). Within this category, advanced glycation end products (AGEs), acrylamide (AA), and heterocyclic amines (HAs) have been implicated as potential risk factors associated with the development of diseases. PURPOSE: To explore the effects of polyphenols, a class of bioactive compounds found in plants, on the inhibition of MRPs and related diseases. Previous research has mainly focused on their interactions with proteins and their effects on the gastrointestinal tract and other diseases, while fewer studies have examined their inhibitory effects on MRPs. The aim is to offer a scientific reference for future research investigating the inhibitory role of polyphenols in the MR. METHODS: The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research. RESULTS: Polyphenols have the potential to inhibit the formation of harmful MRPs and prevent related diseases. The inhibition of MRPs by polyphenols primarily occurs through the following mechanisms: trapping α-dicarbonyl compounds, scavenging free radicals, chelating metal ions, and preserving protein structure. Simultaneously, polyphenols exhibit the ability to impede the onset and progression of related diseases such as diabetes, atherosclerosis, cancer, and Alzheimer's disease through diverse pathways. CONCLUSION: This review presents that inhibition of polyphenols on Maillard reaction products and their induction of related diseases. Further research is imperative to enhance our comprehension of additional pathways affected by polyphenols and to fully uncover their potential application value in inhibiting MRPs.
Assuntos
Produtos Finais de Glicação Avançada , Reação de Maillard , Polifenóis , Polifenóis/farmacologia , Polifenóis/química , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Humanos , Acrilamida/química , Doença de Alzheimer/tratamento farmacológico , Neoplasias/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , AnimaisRESUMO
The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.
Assuntos
Produtos Finais de Glicação Avançada , Antagonistas dos Receptores Histamínicos H1 , Simulação de Acoplamento Molecular , Soroalbumina Bovina , Soroalbumina Bovina/metabolismo , Soroalbumina Bovina/química , Antagonistas dos Receptores Histamínicos H1/farmacologia , Animais , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Glicosilação/efeitos dos fármacos , Bovinos , Receptores Histamínicos H1/metabolismoRESUMO
As the irreversible products of the non-enzymatic reduction of sugars and the amino groups of proteins or peptides, advanced glycation end products (AGEs) are metabolized and excreted via the kidneys. However, if AGEs are not metabolized, they are deposited in the kidneys and bind to AGE receptors (RAGE), which can induce various pathological changes, including oxidative stress, apoptosis, and inflammation. This study used the D-galactose (DG)-induced rat model to explore the potential role and mechanism of L-theanine in inhibiting AGEs/RAGE-related signaling pathways in renal tissues. L-theanine increased the activities of glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) while downregulating the contents of malondialdehyde (MDA) and AGEs in renal tissues induced by DG (P < 0.05). By inhibiting the upregulation of RAGE protein expression attributed to AGEs accumulation (P < 0.05), L-theanine downregulated phosphorylated nuclear factor (p-NF-κB (p65)), Bax, and cleaved-caspase-3 expression and increased Bcl-2 protein expression (P < 0.05), thereby alleviating the oxidative stress damage and reducing the inflammation and cell injury induced by DG. In addition, the Congo red staining section of renal tissue also showed that the natural product L-theanine can protect against AGEs-induced renal damage in DG-induced rat model.
Assuntos
Galactose , Glutamatos , Produtos Finais de Glicação Avançada , Receptor para Produtos Finais de Glicação Avançada , Animais , Galactose/farmacologia , Glutamatos/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/metabolismo , Inflamação/metabolismo , Rim/metabolismo , Estresse Oxidativo , Ratos , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The glycation process has been recognized as one of the critical parameters that accelerate signs of skin aging, especially in skin exposed to environment factors, such as ultraviolet radiation. Although previous studies showed the anti-inflammatory and antiaging properties of the hydrolyzed collagen tripeptide (CTP), its exact mechanism is not fully understood. Therefore, in this study, we sought to investigate the effect of a topical CTP on facial skin. Our group designed a 4 week prospective, single-arm study of 22 Asian women who applied topical CTP. We observed significant improvements in skin wrinkles, elasticity, and density with a reduction in skin accumulation of advanced glycated end products (AGEs) at week 4 without any adverse effects. The in vitro study revealed a preventive effect of the topical CTP on the accumulation of AGEs, denatured collagen production, and reactive oxygen species in dermal fibroblasts. Moreover, treatment with the CTP decreased induction of matrix metalloproteinases while increasing the collagen 1 level. These results suggest that the application of a topical CTP might improve clinical aging phenotypes via the inhibition of glycation and oxidative stress, leading to a delay in cellular aging.
Assuntos
Senescência Celular/efeitos dos fármacos , Colágeno/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Estresse Oxidativo , Fragmentos de Peptídeos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Elasticidade , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Glicosilação , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Envelhecimento da Pele/patologiaRESUMO
Hyperglycemia, when sustained over a long time in diabetes mellitus (DM), leads to biochemical and cellular abnormalities, primarily through the formation of advanced glycation end-products (AGEs). In the treatment of diabetes, beside blood-sugar-lowering medications, a consumption of herbal products that can inhibit the AGEs' formation is recommended. This study investigated the in vitro antiglycoxidative potential of extracts and fractions from the rhizomes of Japanese, Giant, and Bohemian knotweeds (Reynoutria japonica (Houtt.), R. sachalinensis (F. Schmidt) Nakai, and R.× bohemica Chrtek et Chrtkova). Their effects on glycooxidation of bovine and human serum albumin were evaluated by incubation of the proteins with a mixture of glucose and fructose (0.5 M) and 150 µg/mL of extract for 28 days at 37 °C, followed by measuring early and late glycation products, albumin oxidation (carbonyl and free thiol groups), and amyloid-ß aggregation (thioflavin T and Congo red assays). The highest antiglycoxidative activity, comparable or stronger than the reference drug (aminoguanidine), was observed for ethyl acetate and diethyl ether fractions, enriched in polyphenols (stilbenes, phenylpropanoid disaccharide esters, and free and oligomeric flavan-3-ols). In conclusion, the antiglycoxidative compounds from these three species should be further studied for potential use in the prevention and complementary treatment of DM.
Assuntos
Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Reynoutria , Rizoma , Acetatos/farmacologia , Animais , Bovinos , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Éter/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Glicosilação/efeitos dos fármacos , Humanos , Oxirredução/efeitos dos fármacos , Polifenóis/farmacologia , Albumina Sérica/metabolismo , Soroalbumina Bovina/metabolismoRESUMO
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Many studies have shown a significant increase in the marker signal of the receptor for advanced glycation end-products (RAGE) with the malignant progression of tumor growth, metastasis and recurrence of breast cancer, including TNBC of primary tumors and lymph node metastases. Azeliragon is a RAGE inhibitor and it has been shown to actively inhibit the TNBC cell line, SUM149 (IC50 = 5.292 ± 0.310 µM). In order to develop a new anti-TNBC agent, we designed, synthesized and screened 26 Azeliragon triazole analogues to determine their anti-TNBC activities in vitro. The most active compound was KC-10 with an IC50 value of 0.220 ± 0.034 µM.
Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Imidazóis/farmacologia , Triazóis/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Imidazóis/síntese química , Imidazóis/química , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Natural products exist in various natural foods such as plants, herbs, fruits, and vegetables. Furthermore, marine life offers potential natural products with significant biological activity. The biochemical reaction is known as advanced glycation end products (AGEs) occurs in the human body. On the other hand, foods are capable of a wide range of processing conditions resulting in the generation of exogenous AGEs adducts. Protein glycation and the formation of advanced glycation end products both contribute to the pathogenesis of hyperglycemic complications. AGEs also play a pivotal role in microvascular and macrovascular complications progression by receptors for advanced glycation end products (RAGE). RAGE activate by AGEs leads to up-regulation of transcriptional factor NF-kB and inflammatory genes. Around the globe, researchers are working in various approaches for therapeutical implications on controlling AGEs mediated disease complications. In this regard, one of the potential promising agents observed with a wide range of AGEs inhibition by food-derived natural products. Current biotechnological tools have been turned to natural products or phytochemicals to manufacture the molecules without compromising their functionality. Metabolic engineering and bioinformatics perspectives have recently enabled the generation of a few potent metabolites with anti-diabetic activity. As the primary focus, this review article will also discuss multidisciplinary approaches that emphasize current advances in anti-diabetic therapeutic action and future perspectives of natural products.
Assuntos
Produtos Biológicos/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Hipoglicemiantes/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Fitoterapia , Preparações de Plantas/uso terapêutico , Animais , Produtos Biológicos/isolamento & purificação , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus/sangue , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hipoglicemiantes/isolamento & purificação , Resistência à Insulina , Compostos Fitoquímicos/isolamento & purificação , Preparações de Plantas/isolamento & purificaçãoRESUMO
Oxidative stress is one of the significant precursors of various metabolic diseases such as diabetes, Parkinson's disease, cardiovascular diseases, cancer, etc. Various scientific reports have indicated that secondary plant metabolites play an important role in preventing oxidative stress and its harmful effects. In this respect, this study was planned to investigate the phenolic profile and antioxidant and antidiabetic potentials of the aqueous extracts from Turkish Cistus species by employing in vitro methods. In vitro digestion simulation procedure was applied to all extracts to estimate the bioavailability of their phenolic contents. Total phenolic, flavonoid, phenolic acid and proanthocyanidin contents were determined for all phases of digestion. In addition, changes in the quantity of the assigned marker flavonoids (tiliroside, hyperoside and quercitrin) were monitored by High-Performance Thin Layer Chromatography (HPTLC) analysis. The antioxidant activity potentials of the extracts were studied by various methods to reveal their detailed activity profiles. On the other hand, in vitro α-amylase and α-glucosidase enzymes and advanced-glycation end product (AGE) inhibitory activities of the extracts were determined to evaluate the antidiabetic potentials of extracts. The results showed that aqueous extracts obtained from the aerial parts of Turkish Cistus species have rich phenolic contents and potential antioxidant and antidiabetic activities; however, their bioactivity profiles and marker flavonoid concentrations might significantly be affected by human digestion. The results exhibited that total phenolic contents, antioxidant activities and diabetes-related enzyme inhibitions of the bioavailable samples were lower than non-digested samples in all extracts.
Assuntos
Antioxidantes/farmacologia , Cistus/química , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Compostos de Bifenilo/antagonistas & inibidores , Cistus/metabolismo , Diabetes Mellitus/metabolismo , Relação Dose-Resposta a Droga , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Fenóis/metabolismo , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Relação Estrutura-Atividade , Turquia , Água/química , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismoRESUMO
Investigation of chemical constituents of Masclura tricuspidata leaves resulted in the isolation of 47 isoflavonoids possessing prenyl groups with different numbers and structures. Among them, sixteen compounds named cudracusisoflavones A-P (1-16) were first isolated from nature. The isoflavonoids isolated from M. tricuspidata leaves showed anti-diabetic effects as measured by inhibition on α-glucosidase activity and advanced glycation end-products (AGEs) formations. Especially, cudracusisoflavone L (12), a new compound, together with gancaonin M (27), erysenegalensein E (41) and millewanin G (44) showed strong α-glucosidase inhibition with IC50 values <10.0 µM. In addition, cudracusisoflavones A (1), D (4), M (13) and N (14), together with known prenylated isoflavonoids efficiently inhibited methylglyoxal (MGO)- or glyoxal (GO)-induced AGE formations. Structure activity relationship together with molecular docking analysis suggested the importance of hydroxy group and linear type of prenyl moiety for α-glucosidase inhibition. Conclusively, diverse prenylated isoflavonoids in M. tricuspidata leaves might ameliorate glycotoxicity-induced metabolic diseases.
Assuntos
Flavonoides/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Moraceae/química , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosilação/efeitos dos fármacos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Folhas de Planta/química , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-AtividadeRESUMO
Advanced glycation end-products (AGEs) are produced during protein glycation and associated with diabetic complications. Peanut skin is rich in procyanidins, which may be used as an inhibitor of glycation. This study evaluated the potential anti-glycation effect of peanut skin extract (PSE) and dissected the underlying mechanism. PSE could effectively inhibit the formation of AGEs in BSA-Glc and BSA-MGO/GO models, with 44%, 37% and 82% lower IC50 values than the positive control (AG), respectively. The inhibitory effect of PSE on BSA glycation might be ascribed to its binding interaction with BSA, attenuated formation of early glycation products and trapping of reactive dicarbonyl compounds. Notably, PSE showed a remarkably stronger inhibitory effect on Amadori products than AG. Furthermore, three new types of PSE-MGO adducts were formed as identified by UPLC-Q-TOF-MS. These findings suggest that PSE may serve as an inhibitor of glycation and provide new insights into its application.
Assuntos
Arachis/química , Produtos Finais de Glicação Avançada/química , Extratos Vegetais/química , Frutosamina/química , Glucose/química , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Extratos Vegetais/análise , Proantocianidinas/análise , Proantocianidinas/química , Aldeído Pirúvico/química , Soroalbumina Bovina/químicaRESUMO
Advanced glycation end products (AGEs) are a group of complex compounds generated by nonenzymatic interactions between proteins and reducing sugars or lipids. AGEs accumulate in vivo and activate various signaling pathways closely related to the occurrence of various chronic metabolic diseases. In this paper, we describe the process through which AGEs are formed, the classification of AGEs, and biological effects of AGEs on human health. Most importantly, we review recent progress in natural compound-based AGE formation inhibitors. Major classes of natural inhibitors, including polyphenols, polysaccharides, terpenoids, vitamins and alkaloids, have been described. Their mechanisms of action have been summarized as scavenging free radicals, chelating metal ions, capturing active carbonyl compounds, protecting protein glycation sites, and lowering blood glucose levels. Although these natural compounds have good antiglycation activity, to date, they are not widely used in the clinic, likely because of their low content levels. However, these natural compounds and their molecular frameworks will play a valuable role in inspiring drug discovery.
Assuntos
Produtos Biológicos/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Animais , Produtos Finais de Glicação Avançada/metabolismo , HumanosRESUMO
The role of advanced glycation end products (AGEs) is not limited to diabetes and diabetes-related complications. There are multiple modulators, including the receptor for advanced glycation end products, high mobility group box 1, glyoxalase 1, nuclear factor-kappa B, tumor necrosis factor-α, chronic unpredictable stress, reactive oxygen species, and inflammatory cytokines, which interact with AGE signaling and control diabetes, modulating these interacting modulators. The progression of diabetes, as well as related complications, can be controlled and treated. Natural products rich in bioactive constituents can interact with AGEs and their related mediators through various signaling cascades, thereby controlling and preventing the progression of diabetes. This review provides a deeper assessment of the signaling pathway, interactions between phytochemicals and AGEs, and its mediators, to develop a multifold therapeutic approach to prevent and treat diabetes and its related complications.
Assuntos
Diabetes Mellitus/tratamento farmacológico , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Hipoglicemiantes/antagonistas & inibidores , Compostos Fitoquímicos/farmacologia , Animais , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Compostos Fitoquímicos/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Ginseng (Panax ginseng and red ginseng) extract has been reported to inhibit the formation of advanced glycation end-products (AGEs); however, the potential inhibitory activity of its major constituents (ginsenosides) against AGE formation is still unknown. In the present study, we investigated the inhibitory effect of ginsenoside derivatives on AGE formation. Herein, we assessed the activity of 22 ginsenosides, most of which significantly inhibited fluorescent AGE formation. Notably, ginsenoside Rh2, ginsenoside Rh1, and compound K exhibited the most potent AGE inhibitory potential with IC50 values of 3.38, 8.42, and 10.85 µM, respectively. The structure- activity relationship revealed that the presence of sugar moieties, hydroxyl groups, and their linkages, and the stereostructure of the ginsenoside skeleton played an important role in the inhibition of AGE formation. Furthermore, the inhibitory activity of the most active ginsenoside Rh2 on fructose-glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was explored. Rh2 (0.1-12.5 µM) inhibited the formation of fluorescent AGE and non-fluorescent AGE, as well as the level of fructosamine and prevented protein oxidation by decreasing protein carbonyl formation and protein thiol group modification. Rh2 also suppressed the formation of the ß-cross amyloid structure of BSA. Ginsenosides might be promising new anti-glycation agents for the prevention of diabetic complications via inhibition of AGE formation and oxidation-dependent protein damage.
Assuntos
Descoberta de Drogas , Ginsenosídeos/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Panax/química , Soroalbumina Bovina/antagonistas & inibidores , Animais , Bovinos , Relação Dose-Resposta a Droga , Frutose/metabolismo , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Glucose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Glicosilação/efeitos dos fármacos , Estrutura Molecular , Soroalbumina Bovina/metabolismo , Relação Estrutura-AtividadeRESUMO
(-)-Epigallocatechin gallate (EGCG) and olivetol hybrid molecules 1-4 were conveniently synthesized using dielectric barrier discharge plasma irradiation. The structures of these unprecedented hybrid molecules were determined by interpretation of spectroscopic data. The unusual hybrid 1 showed improved antiglycation potency toward the advanced formation of glycation end products than the original EGCG and olivetol. The novel hybrid 1 is an interesting new class of antiglycation candidate that requires further investigation.
Assuntos
Catequina/análogos & derivados , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Resorcinóis/química , Soroalbumina Bovina/química , Animais , Catequina/química , Catequina/farmacologia , Bovinos , Técnicas de Química Sintética , Frutose/química , Glucose/química , Produtos Finais de Glicação Avançada/química , Glicosilação/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Gases em Plasma/química , Resorcinóis/farmacologia , SoluçõesRESUMO
Caffeic acid is one of the most abundant hydroxycinnamic acids in fruits, vegetables, and beverages. This phenolic compound reaches relevant concentrations in the colon (up to 126 µM) where it could come into contact with the intestinal cells and exert its anti-inflammatory effects. The aim of this investigation was to study the capacity of caffeic acid, at plausible concentrations from an in vivo point of view, to modulate mechanisms related to intestinal inflammation. Consequently, we tested the effects of caffeic acid (50-10 µM) on cyclooxygenase (COX)-2 expression and prostaglandin (PG)E2, cytokines, and chemokines (IL-8, monocyte chemoattractant protein-1 -MCP-1-, and IL-6) biosynthesis in IL-1ß-treated human myofibroblasts of the colon, CCD-18Co. Furthermore, the capacity of caffeic acid to inhibit the angiotensin-converting enzyme (ACE) activity, to hinder advanced glycation end product (AGE) formation, as well as its antioxidant, reducing, and chelating activity were also investigated. Our results showed that (i) caffeic acid targets COX-2 and its product PGE2 as well as the biosynthesis of IL-8 in the IL-1ß-treated cells and (ii) inhibits AGE formation, which could be related to (iii) the high chelating activity exerted. Low anti-ACE, antioxidant, and reducing capacity of caffeic acid was also observed. These effects of caffeic acid expands our knowledge on anti-inflammatory mechanisms against intestinal inflammation.