RESUMEN

Background: The twigs and roots of Erythrina subumbrans (Hassk). Merr. Was reported to possess antidiabetic activity by reducing the activity of α-glucosidase and α-amylase. TNF-α is a pro-inflammatory cytokine in obesity and diabetes mellitus (DM). It inhibits the action of insulin, causing insulin resistance. Adiponectin is an anti-inflammatory peptide synthesized in white adipose tissue (WAT) and its high levels are linked with a decreased risk of DM. However, information about the effect of Erythrina subumbrans (Hassk). Merr. on insulin resistance are still lacking. Purpose: To obtain the effects of the ethanol extract of E. subumbrans (Hassk) Merr. leaves (EES) in improving insulin resistance conditions. Methods: The leaves were collected at Ciamis, West Java, Indonesia, and were extracted using ethanol 96%. The effects of EES were studied in fructose-induced adult male Wistar rats by performing the insulin tolerance test (ITT) and assessing blood glucose, TNF-α, adiponectin, and FFA levels. The number of WAT and BAT of the adipose tissues was also studied. The total phenols and flavonoids in EES were determined by the spectrophotometric method and the presence of quercetin in EES was analyzed using the LC-MS method. Results: EES significantly reduced % weight gain, TNF-α levels, and increased adiponectin levels in fructose-induced Wistar rats. EES significantly reduced the FFA levels of fructose-induced Wistar rats and significantly affected the formation of BAT similar to that of metformin. All rats in EES and metformin groups improved insulin resistance as proven by higher ITT values (3.01 ± 0.91 for EES 100 mg/kg BW; 3.01 ± 1.22 for EES 200 mg/kg BW; 5.86 ± 3.13 for EES 400 mg/kg BW; and 6.44 ± 2.58 for metformin) compared with the fructose-induced group without treatment (ITT = 2.62 ± 1.38). EES contains polyphenol compounds (2.7638 ± 0.0430 mg GAE/g extract), flavonoids (1.9626 ± 0.0152 mg QE/g extract), and quercetin 0.246 µg/mL at m/z 301.4744. Conclusion: Erythrina subumbrans (Hassk). Merr. extract may have the potential to be further explored for its activity in improving insulin resistance conditions. However, further studies are needed to confirm its role in alleviating metabolic disorders.

Asunto(s)

Erythrina , Fructosa , Resistencia a la Insulina , Extractos Vegetales , Ratas Wistar , Animales , Ratas , Masculino , Erythrina/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Fructosa/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Hojas de la Planta/química , Relación Dosis-Respuesta a Droga

RESUMEN

Diabetes mellitus (DM) manifests as a complex and chronic metabolic disorder, posing a significant threat to global public health and contributing substantially to mortality rates. It is characterized by elevated blood glucose levels or hyperglycemia and requires effective preventive and therapeutic strategies. One promising approach involves targeting the inhibition of α- glucosidase and α-amylase, key enzymes responsible for carbohydrate hydrolysis. Inhibiting these enzymes proves beneficial in reducing postprandial glucose levels and mitigating postprandial hyperglycemia. However, existing antidiabetic medications are associated with undesirable side effects, highlighting the need to develop new molecules with increased efficacy and reduced side effects. Traditional methods for designing such molecules are often lengthy and costly. To address this, computer-based molecular modeling tools offer a promising approach to evaluate the antidiabetic activities of chemical compounds. This review aims to compile information on chemical compounds assessed for their anti-diabetic activities through molecular modeling, with a particular focus on the period from 2020 to 2023.

RESUMEN

Enhalus acoroides, a tropical seagrass, is known for its significant contribution to marine ecosystems and its potential health benefits due to bioactive compounds. This study aims to compare the carotenoid levels in E. acoroides using green extraction via ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) and to evaluate the biological properties of these extracts against oxidative stress, diabetes, and obesity through in silico and in vitro analyses. E. acoroides samples were collected from Manado City, Indonesia, and subjected to UAE and MAE. The extracts were analyzed using UHPLC-ESI-MS/MS to identify carotenoids, including ß-carotene, lutein, lycopene, ß-cryptoxanthin, and zeaxanthin. In silico analysis was conducted to predict the compounds' bioactivity, toxicity, and drug-likeness using WAY2DRUG PASS and molecular docking with CB-Dock2. The compounds C3, C4, and C7 demonstrated notable interactions, with key metabolic proteins and microRNAs, further validating their potential therapeutic benefits. In vitro assays evaluated antioxidant activities using DPPH and FRAP assays, antidiabetic properties through α-glucosidase and α-amylase inhibition, and antiobesity effects via lipase inhibition and MTT assay with 3T3-L1 cells. Results indicated that both UAE and MAE extracts exhibited significant antioxidant, antidiabetic, and antiobesity activities. MAE extracts showed higher carotenoid content and greater biological activity compared to UAE extracts. These findings suggest that E. acoroides, mainly when extracted using MAE, has promising potential as a source of natural bioactive compounds for developing marine-based antioxidant, antidiabetic, and antiobesity agents. This study supplements existing literature by providing insights into the efficient extraction methods and the therapeutic potential of E. acoroides carotenoids.

Asunto(s)

Fármacos Antiobesidad , Antioxidantes , Carotenoides , Hipoglucemiantes , Simulación del Acoplamiento Molecular , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Carotenoides/farmacología , Carotenoides/aislamiento & purificación , Carotenoides/química , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/aislamiento & purificación , Fármacos Antiobesidad/química , Ratones , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Simulación por Computador , Obesidad/tratamiento farmacológico , Células 3T3-L1 , Espectrometría de Masas en Tándem , Indonesia , Microondas , Estrés Oxidativo/efectos de los fármacos

RESUMEN

The importance of essential oils and their components in the industrial sector is attributed to their chemical characteristics and their application in the development of products in the areas of cosmetology, food, and pharmaceuticals. However, the pharmacological properties of this class of natural products have been extensively investigated and indicate their applicability for obtaining new drugs. Therefore, this review discusses the use of these oils as starting materials to synthesize more complex molecules and products with greater commercial value and clinic potential. Furthermore, the antiulcer, cardiovascular, and antidiabetic mechanisms of action are discussed. The main mechanistic aspects of the chemopreventive properties of oils against cancer are also presented. The data highlight essential oils and their derivatives as a strategic chemical group in the search for effective therapeutic agents against various diseases.

RESUMEN

INTRODUCTION: Traditional and some scientific literature document the antidiabetic effects of the Ziziphi Spinosae Semen (ZSS). However, the bioactive compounds of ZSS responsible for the antidiabetic effects are not well known. OBJECTIVES: This study aimed to investigate the material basis of the antidiabetic effects of ZSS by inhibiting α-amylase. METHODOLOGY: An online analysis platform was established and optimized using an ultra-performance liquid chromatography-photo-diode array-quadrupole-time-of-flight-mass spectrometry-α-amylase-fluorescence detector (UHPLC-PDA-Q-TOF-MS-α-amylase-FLD) system to screen α-amylase inhibitors in ZSS rapidly. The inhibitory effect of these compounds was confirmed by molecular docking screening. and the molecular interactions between α-amylase and active compounds were evaluated, which strongly supported the experimental results. RESULTS: Seventy-eight compounds were identified in the ZSS extract, eleven of which were screened to have significant α-amylase binding activity. CONCLUSION: This study demonstrated the feasibility of using an established platform to screen for effective components in ZSS, providing a practical method for the rapid screening of potential antidiabetic active ingredients in traditional Chinese medicine.

Asunto(s)

Simulación del Acoplamiento Molecular , alfa-Amilasas , alfa-Amilasas/antagonistas & inhibidores , Cromatografía Líquida de Alta Presión/métodos , Ziziphus/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Espectrometría de Masas/métodos

RESUMEN

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.

Asunto(s)

Células 3T3-L1 , Adipocitos , Adipogénesis , Fármacos Antiobesidad , Hipoglucemiantes , PPAR gamma , Extractos Vegetales , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/química , Animales , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Adipogénesis/efectos de los fármacos , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , PPAR gamma/metabolismo , PPAR gamma/genética , Fármacos Antiobesidad/farmacología , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Transportador de Glucosa de Tipo 4/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , alfa-Glucosidasas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Antioxidantes/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Crassulaceae/química , Metabolismo de los Lípidos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos

RESUMEN

Phytochemicals are now increasingly exploited as remedial agents for the management of diabetes due to side effects attributable to commercial antidiabetic agents. This study investigated the structural and molecular mechanisms by which betulinic acid exhibits its antidiabetic effect via in vitro and computational techniques. In vitro antidiabetic potential was analysed via on α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin inhibitory assays. Its structural and molecular inhibitory mechanisms were investigated using Density Functional Theory (DFT) analysis, molecular docking and molecular dynamics (MD) simulation. Betulinic acid significantly (p < 0.05) inhibited α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin enzymes with IC50 of 70.02 µg/mL, 0.27 µg/mL, 1.70 µg/mL and 8.44 µg/mL, respectively. According to DFT studies, betulinic acid possesses similar reaction in gaseous phase and water due to close values observed for highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) and the chemical descriptors. The dipole moment indicates that betulinic acid has high polarity. Molecular electrostatic potential surface revealed the electrophilic and nucleophilic attack-prone atoms of the molecule. Molecular dynamic studies revealed a stable complex between betulinic acid and α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin. The study elucidated the potent antidiabetic properties of betulinic acid by revealing its conformational inhibitory mode of action on enzymes involved in the onset of diabetes.

Asunto(s)

Ácido Betulínico , Quimotripsina , Hipoglucemiantes , Lipasa , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Triterpenos Pentacíclicos , alfa-Amilasas , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , alfa-Amilasas/química , Lipasa/antagonistas & inhibidores , Lipasa/química , Lipasa/metabolismo , Quimotripsina/antagonistas & inhibidores , Quimotripsina/metabolismo , Triterpenos/química , Triterpenos/farmacología , Relación Estructura-Actividad Cuantitativa , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , Diabetes Mellitus/tratamiento farmacológico , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química

RESUMEN

Rapeseed-derived peptides (RPPs) can maintain the homeostasis of human blood glucose by inhibiting Dipeptidyl Peptidase-IV (DPP-IV) and activating the calcium-sensing receptor (CaSR). However, these peptides are susceptible to hydrolysis in the gastrointestinal tract. To enhance the therapeutic potential of these peptides, we developed a chitosan/sodium alginate-based nanocarrier to encapsulate two RPP variants, rapeseed-derived cruciferin peptide (RCPP) and rapeseed-derived napin peptide (RNPP). A convenient three-channel device was employed to prepare chitosan (CS)/sodium alginate (ALG)-RPPs nanoparticles (CS/ALG-RPPs) at a ratio of 1:3:1 for CS, ALG, and RPPs. CS/ALG-RPPs possessed optimal encapsulation efficiencies of 90.7 % (CS/ALG-RNPP) and 91.4 % (CS/ALG-RCPP), with loading capacities of 15.38 % (CS/ALG-RNPP) and 16.63 % (CS/ALG-RCPP) at the specified ratios. The electrostatic association between CS and ALG was corroborated by zeta potential and near infrared analysis. 13C NMR analysis verified successful RPPs loading, with CS/ALG-RNPP displaying superior stability. Pharmacokinetics showed that both nanoparticles were sustained release and transported irregularly (0.43 < n < 0.85). Compared with the control group, CS/ALG-RPPs exhibited significantly increased glucose tolerance, serum GLP-1 (Glucagon-like peptide 1) content, and CaSR expression which play pivotal roles in glucose homeostasis (*p < 0.05). These findings proposed that CS/ALG-RPPs hold promise in achieving sustained release within the intestinal epithelium, thereby augmenting the therapeutic efficacy of targeted peptides.

Asunto(s)

Brassica napus , Quitosano , Nanopartículas , Humanos , Quitosano/química , Portadores de Fármacos/química , Preparaciones de Acción Retardada , Brassica napus/metabolismo , Alginatos/química , Nanopartículas/química , Glucosa , Péptidos

RESUMEN

Allelochemicals are secondary metabolites which function as a natural protection against grazing activities by algae and higher plants. They are one of the major metabolites engaged in the interactions of organisms. The chemically mediated interactions between organisms significantly influence the functioning of the ecosystems. Most of these compounds are secondary metabolites comprising sterols, terpenes, and polyphenols. These compounds not only play a defensive role, but also exhibit biological activities such as antioxidants, anti-cancer, anti-diabetes, anti-inflammation, and anti-microbial properties. This review article discusses the current understanding of the allelochemicals of seaweeds and their bioprospecting potential that can bring benefit to humanity. Specifically, the bioactive substances having specific health benefits associated with the consumption or application of seaweed-derived compounds. The properties of such allelochemicals can have implications for bioprospecting pharmaceutical, nutraceutical and cosmetic applications.

Asunto(s)

Bioprospección , Feromonas , Algas Marinas , Algas Marinas/química , Humanos , Animales , Feromonas/química , Feromonas/aislamiento & purificación , Feromonas/farmacología , Bioprospección/métodos

RESUMEN

Three Schiff bases were synthesised by the condensation reaction between 2-napthaldehyde and aromatic amines to afford (E)-N-mesityl-1-(naphthalen-2-yl)methanimine (L1), (E)-N-(2,6-dimethylphenyl)-1-(naphthalen-2-yl)methanimine (L2) and (E)-N-(2,6-diisopropylphenyl)-1-(naphthalen-2-yl)methanimine (L3). The synthesised compounds were characterised using UV-visible, NMR (13C & 1H), and Fourier transform infrared spectroscopic methods while their purity was ascertained by elemental analysis. Structural analysis revealed that the naphthalene ring is almost coplanar with the imine functional group as evident by C1-C10-C11-N1 torsion angles of 176.4(2)° and 179.4(1)° in L2 and L3, respectively. Of all the various intermolecular contacts, H⋯H interactions contributed mostly towards the Hirshfeld surfaces of both L2 (58.7 %) and L3 (69.7 %). Quantum chemical descriptors of L1 - L3 were determined using Density Functional Theory (DFT) and the results obtained showed that the energy band gap (ΔE) for L1, L2 and L3 are 3.872, 4.023 and 4.004 eV respectively. The antidiabetic potential of the three compounds were studied using α-amylase and α-glucosidase assay. Compound L1 showed very promising antidiabetic activities with IC50 values of 58.85 µg/mL and 57.60 µg/mL while the reference drug (Acarbose) had 405.84 µg/mL and 35.69 µg/mL for α-amylase and α-glucosidase respectively. In-silico studies showed that L1 docking score as well as binding energies are higher than that of acarbose, which are recognized inhibitors of α-amylase together with α-glucosidase. Further insight from the RMSF, RMSD and RoG analysis predicted that, throughout the simulation L1 showcased evident influence on the structural stability of α-amylase. The antioxidant potential of the compounds was carried out using nitric oxide (NO), ferric reducing ability power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The compounds exhibited good to fairly antioxidant properties with L1 as well as L3 having IC50 values of 70.91 and 91.21 µg/mL respectively for NO scavenging activities assay, which comparatively outshined acarbose (reference drug) with IC50 value of 109.95 µg/mL. Pharmacology and pharmacokinetics approximations of L1 - L3 showed minimal violation of Lipinski's Ro5 and this projects them to be less toxic and orally bioavailable as potential templates for the design of therapeutics with antioxidant and antidiabetic activities.

RESUMEN

Ligustrum robustum has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk medicine. From the leaves of L. robustum, ten new monoterpenoid glycosides named ligurobustosides T10 (1a), T11 (1b), T12 (2a), T13 (2b), T14 (3a), T15 (3b), F1 (4b), T16 (5a), T17 (5b), and E1 (6b), together with five known ones (4a, 6a, 7, 8a, 8b), were separated and identified using the spectroscopic method and chemical method in this research. The results of biological tests exhibited that the fatty acid synthase (FAS) inhibitory action of compound 5 (IC50: 4.38 ± 0.11 µM) was as strong as orlistat (IC50: 4.46 ± 0.13 µM), a positive control; the α-glucosidase inhibitory actions of compounds 1-4 and 7-8, and the α-amylase inhibitory actions of compounds 1-8 were medium; the ABTS radical scavenging capacities of compounds 1-3 and 5-8 (IC50: 6.27 ± 0.23 ~ 8.59 ± 0.09 µM) were stronger than l-(+)-ascorbic acid (IC50: 10.06 ± 0.19 µM) served as a positive control. This research offered a theoretical foundation for the leaves of L. robustum to prevent diabetes and its complications.

Asunto(s)

Ligustrum , Ligustrum/química , Glicósidos/farmacología , Glicósidos/química

RESUMEN

Chronic diabetes mellites related hyperglycemia is a major cause of mortality and morbidity due to further complications like retinopathy, hypertension and cardiovascular diseases. Though several synthetic anti-diabetes drugs specifically targeting glucose-metabolism enzymes are available, they have their own limitations, including adverse side-effects. Unlike other natural or marine-derived pharmacologically important molecules, deep-sea fungi metabolites still remain under-explored for their anti-diabetes potential. We performed structure-based virtual screening of deep-sea fungal compounds selected by their physiochemical properties, targeting crucial enzymes viz., α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B involved in glucose-metabolism pathway. Following molecular docking scores and MD simulation analyses, the selected top ten compounds for each enzyme, were subjected to pharmacokinetics prediction based on their AdmetSAR- and pharmacophore-based features. Of these, cladosporol C, tenellone F, ozazino-cyclo-(2,3-dihydroxyl-trp-tyr), penicillactam and circumdatin G were identified as potential inhibitors of α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B, respectively. Our in silico data therefore, warrants further experimental and pharmacological studies to validate their anti-diabetes therapeutic potential.

RESUMEN

Carotenoids come in second among the most frequent natural pigments and are utilized in medications, nutraceuticals, cosmetics, food pigments, and feed supplements. Based on recent complementary work, Virgibacillus was announced for the first time as a member of Wadi El-Natrun salt and soda lakes microbiota, identified as Virgibacillus halodenitrificans, and named V. halodenitrificans DASH; hence, this work aimed to investigate several in vitro medicinal bioactivities of V. halodenitrificans DASH carotenoids. The carotenoid methanolic extract showed antioxidant activity based on diphenylpicrylhydrazyl (DPPH) scavenging capacity with a half-maximal concentration (IC50) of 1.6 mg/mL as well as nitric oxide (NO) scavenging action expressed by an IC50 of 46.4 µg/mL. The extract showed considerable inhibitory activity for alpha-amylase (α-amylase) and alpha-glucosidase (α-glucosidase) enzymes (IC50 of 100 and 173.4 µg/mL, respectively). Moreover, the extract displayed selective anticancer activity against Caco-2 (IC50 = 138.96 µg/mL) and HepG-2 cell lines (IC50 = 31.25 µg/mL), representing colorectal adenocarcinoma and hepatoblastoma. Likewise, the extract showed 98.9 % clearance for human hepatitis C virus (HCV) using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), HCV-NS5B polymerase activity inhibition (IC50 = 27.4 µg/mL), and selective inhibitory activity against human coronavirus (HCoV 229E) using the plaque reduction assay (IC50 = 53.5 µg/mL). As far as we can tell, the anticancer, antiviral, and antidiabetic attributes of Virgibacillus carotenoids are, de novo, reported in this work which accordingly invokes further exploration of the other medicinal, biotechnological, and industrial applications of Virgibacillus and haloalkaliphilic bacteria carotenoids.

RESUMEN

This study evaluated the anti-diabetic effect of polysaccharides isolated from Ornithogalum caudatum and their underlying mechanisms. To achieve this, a type 2 diabetes mellitus mouse model was established using a combination of a high-fat diet and low-dose streptozotocin injection. The mice were treated with Ornithogalumcaudatum polysaccharides (OCPs) for 4 weeks. OCPs treatment significantly decreased body weight loss, fasting blood glucose levels, and plasma insulin levels in diabetic mice. Additionally, compared with the untreated group, OCPs treatment significantly decreased total cholesterol, triacylglycerol, and low-density lipoprotein-cholesterol levels, but increased those of high-density lipoprotein-cholesterol in diabetic mice. Moreover, antioxidant enzyme activity and histopathology results revealed that OCPs effectively alleviated oxidative stress and streptozotocin-induced lesions by increasing antioxidant enzyme activity. Results from mechanistic studies showed that OCPs treatment significantly increased the expression of p-PI3K, p-Akt, and p-GSK-3ß in the liver. Moreover, OCPs optimized the gut microbiota composition of diabetic mice by significantly decreasing the Firmicutes/Bacteroidetes ratio and increasing the levels of beneficial bacteria (Muribaculaceae_norank, Prevotellaceae_UCG-001 and Alloprevotella). Overall, these findings suggest that OCPs exert anti-diabetic effects by triggering the PI3K/Akt/GSK-3ß signaling pathway and regulating the gut microbiota.

RESUMEN

Ursolic acid (UA) is a pentacyclic triterpenoid, which exhibits many biological activities, particularly in anti-cardiovascular and anti-diabetes. The further application of UA is greatly limited due to its low bioavailability and poor water solubility. Up to date, various UA derivatives have been designed to overcome these shortcomings. In this paper, the authors reviewed the development of UA derivatives as the anti-diabetes anti-cardiovascular reagents.

Asunto(s)

Triterpenos , Solubilidad , Triterpenos/farmacología , Triterpenos/uso terapéutico , Ácido Ursólico

RESUMEN

This study presents a phytochemical investigation of Lepionurus sylvestris leaf extracts and their anti-diabetic activities. Traditionally, L. sylvestris leaves were used as vegetables and food in local recipes, but the root extracts of the plant can also be used in body tonic and erectile dysfunction treatments. Following a preliminary anti-diabetic activity screening test, the 80% ethanolic leaf extract exhibited potent anti-alpha glucosidase activity. So, the leaves' active components were selected for further investigation. Firstly, the plant was extracted via maceration using lower to higher polarity solvents such as hexane, ethyl acetate, ethanol, and water, respectively, to obtain the four crude extracts. Then, the phytochemicals contained in this plant were investigated via classical column chromatography and spectroscopy techniques. Anti-diabetic activity was evaluated via anti-alpha glucosidase and insulin secretagogue assays. The results showed that five compounds were isolated from the fractionated ethanolic leaf extract: interruptin A; interruptin C; ergosterol; diglycerol; and 15-16-epoxy-neo-cleoda-3,7(20),13(16),14-tetraene-12,17:18,19-diolide, a new diterpene derivative which is herein referred to as lepionurodiolide. Interruptin A and the new diterpene derivative exhibited the greatest effect on anti-alpha glucosidase activity, showing IC50 values of 293.05 and 203.71 µg/mL, respectively. Then, molecular docking was used to study the sites of action of these compounds. The results showed that interruptin A and the new compound interacted through H-bonds with the GLN279 residue, with a binding energy of -9.8 kcal/mol, whereas interruptin A and C interacted with HIS280 and ARG315 a with binding energy of -10.2 kcal/mol. Moreover, the extracts were investigated for their toxicity toward human cancer cells, and a zebrafish embryonic toxicity model was used to determine herbal drug safety. The results indicated that ethyl acetate and hexane extracts showed cytotoxicity to both Hela cells and human breast adenocarcinomas (MCF-7), which was related to the results derived from using the zebrafish embryonic toxicity model. The hexane and ethyl acetate presented LC50 values of 33.25 and 36.55 µg/mL, respectively, whereas the ethanol and water extracts did not show embryonic toxicity. This study is the first of its kind to report on the chemical constituents and anti-diabetic activity of L. sylvestris, the leaf extract of which has been traditionally used in southern Thailand as a herbal medicine and food ingredient.

RESUMEN

Four undescribed compounds (two 1,5-anhydro-d-glucitol derivatives and two galloyl derivatives) and fourteen known compounds were isolated and structurally identified from leaves of Acer ginnala Maxim. (Amur maple). Structures and absolute configurations of the four undescribed compounds were determined using extensive analysis of NMR spectroscopic, HRESI-MS, modified Mosher ester method, and comparison with spectroscopic data of known compounds. Bioactivity evaluation revealed that the isolated 1,5-anhydro-d-glucitol derivative, galloylated flavonol rhamnosides, and galloylated flavanols had inhibitory effects on both protein tyrosine phosphatase-1B (PTP1B, IC50 values ranging of 3.46-12.65 µM) and α-glucosidase (IC50 values ranging of 0.88-6.06 µM) in comparison with a positive control for PTP1B (ursolic acid, IC50 = 5.10 µM) or α-glucosidase (acarbose, IC50 = 141.62 µM). A combination of enzyme kinetic analysis and molecular docking provided additional evidence in favor of their inhibitory activities and mechanism. These data demonstrate that A. ginnala Maxim. together with its constituents are promising sources of potent candidates for developing novel anti-diabetic medications.

Asunto(s)

Acer , Inhibidores Enzimáticos , Inhibidores Enzimáticos/química , alfa-Glucosidasas/metabolismo , Acer/química , Acer/metabolismo , Flavonoides/metabolismo , Sorbitol/química , Sorbitol/farmacología , Simulación del Acoplamiento Molecular , Cinética , Hojas de la Planta/química , Inhibidores de Glicósido Hidrolasas/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1

RESUMEN

Brown macroalgae (BMG) were used as carriers for ZnO (ZnO/BMG) and cobalt-doped ZnO (Co-ZnO/BMG) via facile microwave-assisted hydrothermal synthesis. The multifunctional structures of synthesized composites were evaluated as enhanced antioxidant and anti-diabetic agents based on the synergistic effects of ZnO, Co-ZnO, and BMG. BMG substrate incorporation and cobalt doping notably enhanced the bioactivity of the synthesized ZnO nanoparticles. As an antioxidant, the Co-ZnO/BMG composite exhibited highly effective scavenging properties for the common free reactive oxygen radicals (DPPH [89.6 ± 1.5%], nitric oxide [90.2 ± 1.3%], ABTS [87.7 ± 1.8%], and O2●- [46.7 ± 1.9%]) as compared to ascorbic acid. Additionally, its anti-diabetic activity was enhanced significantly and strongly inhibited essential oxidative enzymes (porcine α-amylase (90.6 ± 1.5%), crude α-amylase (84.3 ± 1.8%), pancreatic α-glucosidase (95.7 ± 1.4%), crude intestinal α-glucosidase (93.4 ± 1.8%), and amyloglucosidase (96.2 ± 1.4%)). Co-ZnO/BMG inhibitory activity was higher than that of miglitol, and in some cases, higher than or close to that of acarbose. Therefore, the synthetic Co-ZnO/BMG composite can be used as a commercial anti-diabetic and antioxidant agent, considering the cost and adverse side effects of current drugs. The results also demonstrate the impact of cobalt doping and BMG integration on the biological activity of ZnO.

Asunto(s)

Diabetes Mellitus , Nanopartículas del Metal , Sargassum , Algas Marinas , Óxido de Zinc , Animales , Porcinos , Antioxidantes/farmacología , Antioxidantes/química , Sargassum/metabolismo , Óxido de Zinc/farmacología , Óxido de Zinc/química , alfa-Glucosidasas , Hipoglucemiantes/farmacología , alfa-Amilasas , Cobalto/química , Nanopartículas del Metal/química , Algas Marinas/metabolismo

RESUMEN

The chitosan matrix was used as a substrate for ZnO nanoflowers (ZnO/CH) and Ce-doped ZnO nanoflowers (Ce-ZnO/CH) by microwave-induced hydrothermal synthesis processes. The obtained hybrid structures were assessed as enhanced antioxidant and antidiabetic agents considering the synergetic effect of the different components. The integration of chitosan and cerium induced significantly the biological activity of ZnO flower-like particles. Ce-doped ZnO nano-flowers show higher activities than both ZnO nanoflowers and ZnO/CH composite reflecting the strong effect of surface electrons that were formed by the doping process as compared to the high interactive interface of the chitosan substrate. As an antioxidant the synthetic Ce-ZnO/CH composite achieved remarkable scavenging efficiencies for DPPH (92.4 ± 1.33 %), nitric oxide (95.2 ± 1.81 %), ABTS (90.4 ± 1.64 %), and superoxide (52.8 ± 1.22 %) radicals which are significantly higher values than Ascorbic acid as standard and the commercially used ZnO nanoparticles. Also, its antidiabetic efficiency enhanced greatly achieving strong inhibition effects on porcine α-amylase (93.6 ± 1.66 %), crude α-amylase (88.7 ± 1.82 %), pancreatic α-glucosidase (98.7 ± 1.26 %), crude intestinal α-glucosidase (96.8 ± 1.16 %), and amyloglucosidase (97.2 ± 1.72 %) enzymes. The recognized inhibition percentages are notably higher than the determined percentages using miglitol drug and slightly higher than acarbose. This recommends the Ce-ZnO/CH composite as a potential antidiabetic and antioxidant agent compared with the high cost and the reported side effects of the commonly used chemical drug.

Asunto(s)

Quitosano , Óxido de Zinc , Animales , Porcinos , Antioxidantes/farmacología , Quitosano/química , Óxido de Zinc/química , alfa-Glucosidasas , Microondas , Hipoglucemiantes/farmacología , alfa-Amilasas

RESUMEN

Green ZnO-decorated acid-activated bentonite-mediated curcumin extract (ZnO@CU/BE) was prepared as a multifunctional antioxidant and antidiabetic agent based on the extract of curcumin, which was used as a reducing and capping reagent. ZnO@CU/BE showed notably enhanced antioxidant properties against nitric oxide (88.6 ± 1.58%), 1,1-diphenyl-2-picrylhydrazil (90.2 ± 1.76%), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (87.3 ± 1.61%), and superoxide (39.5 ± 1.12%) radicals. These percentages are higher than the reported values of ascorbic acid as a standard and the integrated components of the structure (CU, BE/CU, and ZnO). This signifies the impact of the bentonite substrate on enhancing the solubility, stability, dispersion, and release rate of the intercalated curcumin-based phytochemicals, in addition to enhancing the exposure interface of ZnO nanoparticles. Therefore, effective antidiabetic properties were observed, with significant inhibition effects on porcine pancreatic α-amylase (76.8 ± 1.87%), murine pancreatic α-amylase (56.5 ± 1.67%), pancreatic α-glucosidase (96.5 ± 1.07%), murine intestinal α-glucosidase (92.5 ± 1.10%), and amyloglucosidase (93.7 ± 1.55%) enzymes. These values are higher than those determined using commercial miglitol and are close to the values measured using acarbose. Hence, the structure can be applied as an antioxidant and antidiabetic agent.