Inhibition Of Digestive Enzymes Research Articles

Morus alba: natural and valuable effects in weight loss management.

Overweight and obesity are conditions associated with serious comorbidities, such as diabetes and cardiovascular disease. Prevalence of excessive fat accumulation is increasing worldwide, and thus the need for efficient and sustainable weight loss regimes has become a major issue in clinical practice. Despite the important advances in the development of anti-obesity medications (AOM), their side effects, cost, and accessibility, are limiting factors for their routine use. Conversely, the studies of medicinal plants for weight management holds strong promise as a growing area of research. This review consolidates the representative evidence about the beneficial impacts of Morus alba on weight management and associated metabolic parameters, encompassing: inhibition of digestive enzymes, and thus contribution to the energy deficit required for weight loss, improvements in glucose and lipid metabolism, and attenuation of adiposity. Findings from in vitro, in vivo, and clinical investigations reviewed in the paper, demonstrate that white mulberry extracts have the potency to supplement efficiently and safely a healthy weight management approach.

Structural changes of potato starch and activity inhibition of starch digestive enzymes by anthocyanin from lingonberry (Vaccinium uliginosum L.) retarded starch digestibility

The effects of anthocyanins on in vitro and in vivo digestibility of potato starch were evaluated in this study. Then the influence of anthocyanins on physicochemical property of potato starch and the activity of starch digestive enzymes (α-amylase and α-glucosidase) were also investigated to understand the mechanism of anthocyanins on starch digestibility. Results have shown that dietary anthocyanins could effectively inhibit the biological activities of α-amylase and α-glucosidase to delay the peak of postprandial blood glucose. Characterization of physicochemical properties of potato starch indicates a structural change due to the presence of anthocyanins, hindering its access to starch digestive enzymes. Among all anthocyanins, lingonberry anthocyanin significantly promoted the retrogradation of potato starch (7.153 % to 25.913 %) and exert promising inhibition on α-amylase and α-glucosidase. Lingonberry anthocyanins mainly interacted with potato starch through hydrogen bonds, which reduce the amount of amylose molecules leached from potato starch and loosen the three-dimensional (3D) network structure of starch gel. This study could provide theoretical evidence for utilization of anthocyanins in diabetic-management function food.

Preferential inhibition of α-amylase by cinnamaldehyde-based hydrazones: A comparative study

The escalating issue of obesity and related health conditions, including diabetes mellitus and coronary heart disease, necessitates the development of digestive enzyme inhibitors. Targeting pancreatic lipase to inhibit fatty acid generation to attain reduced lipid absorption is a promising approach for identifying effective agents. Orlistat, the only clinically approved pancreatic lipase inhibitor, is associated with gastrointestinal side effects like oily stools, spotting, and flatulence. Concurrently, α-amylase inhibitors can mitigate rapid spikes in blood sugar levels. With the growing significance of natural products in pharmaceutical research, cinnamaldehyde has been recognized as a potential enzyme inhibitor. This study explores the effects of cinnamaldehyde-derived hydrazone Schiff bases on lipase and α-amylase through in vitro experiments. The synthesized compounds exhibited IC50 value for lipase in the same range ((0.41–12.58) × 10−8 M) as exhibited by the commercial drug orlistat (5.76 × 10−8 M). However, for α-amylase inhibition, the compounds (IC50 value = 0.37–9.54 × 10−9 M) were found effective inhibitors of acarbose (IC50 value = 6.76 × 10−6 M) and curcumin (IC50 value = 467 × 10−9 M). In silico DFT studies, molecular docking, drug likeliness, bioactivity score, ADME, and toxicity are also investigated for these compounds.

Phytochemical analysis, digestive enzymes inhibition, and toxicity study of Beta vulgaris

Phytochemical analysis, digestive enzymes inhibition, and toxicity study of Beta vulgaris

Antioxidant and Biological Activity of Mexican Madroño Fruit (Arbutus arizonica).

The fruit of the Mexican madroño (Arbutus arizonica) has been consumed since pre-Columbian times by North American tribes and native groups in Mexico. Despite this, reports on its chemical composition and biological activity are limited. This work aims to determine the antioxidant, antiproliferative, and digestive enzyme inhibition activities of the methanol amberlite-retained extract of Mexican madroño. Results showed that madroño fruit is rich in antioxidants: DPPH (EC50 = 0.89 ± 0.03 mg/mL), TEAC (1078 ± 4.9 μM/g), and hemolysis inhibition (IC50 = 358.07 μg/mL), with high phenolic and flavonoid content at 15.92 ± 3.2 mg GAE/g and 4.33 ± 0.3 mg CA/g, respectively. Using analytical chromatography, gallic acid, vanillic acid, chlorogenic acid, ferulic acid, quercetin, and rutin were quantified. The extract also showed α-glucosidase inhibition (IC50 = 3.1 ± 0.17 mg/mL), but no inhibition against α-amylase and lipase (>5 mg/mL), while showing antiproliferative activity against HeLa, HT-29, and MCF-7 cancer cell lines. These results point towards an interesting potential for the fruit of the A. arizonica as chemopreventive and hold potential for elaborating functional foods.

Electron beam irradiation coupled ultrasound-assisted natural deep eutectic solvents extraction: A green and efficient extraction strategy for proanthocyanidin from walnut green husk

Proanthocyanidin (PAC) is recognized as a potent natural antioxidant that prevents various diseases. As societal awareness increases, eco-friendly and efficient natural product extraction technologies are gaining more attention. In this study, an electron beam irradiation (EBI) coupled with ultrasound-assisted natural deep eutectic solvents (NADES) extraction method was developed to enable the green and highly efficient extraction of PAC from walnut green husk (WGH). NADES, prepared with choline chloride and ethylene glycol, demonstrated excellent extraction capacity and storage stability for PAC. Molecular dynamics simulations elucidated the high compatibility between NADES and PAC, attributed mainly to a higher SASA value (207.85 nm2), a greater number of hydrogen bonds (330.99), an extended hydrogen bonding lifetime (4.54 ps), and lower inter-molecular interaction energy. Based on these findings, the optimal conditions (13 kGy EBI, 42 mL/g liquid-solid ratio, 38 °C extraction temperature, 70 min extraction time) resulted in a maximum PAC extraction yield of 56.34 mg/g. Notably, this yield was 32.93 % higher than that observed in samples not treated with EBI and ultrasound-assisted extraction (UAE). Analysis of tissue morphology, extract functional groups and thermal behavior suggested a possible mechanism for the synergistically enhanced PAC extraction by the EBI-NADES-UAE method. Additionally, the PAC extracted using the NADES by the EBI coupled with ultrasound-assisted method exhibited outstanding antioxidant activity (comparable to Vc), digestive enzyme inhibition (IC50: 17–0.61 mg/mL), and anti-glycation capacity (IC50: 86.49 μg/mL). Overall, this work provided a green and efficient strategy for PAC extraction from WGH, elucidated the extraction mechanism and bioactivities, and offered valuable insights for potential industrial applications.

Nanoencapsulation of quinoa oil enhanced the antioxidant potential and inhibited digestive enzymes

Quinoa oil is rich in unsaturated fatty acids and vitamin E, but its instability limits its application in food, pharmaceutical, and cosmetic products. Nanoencapsulation emerges as a promising strategy to promote water dispersibility, preserve and enhance functional properties, and increase the bioavailability of bioactive compounds. This study encapsulated quinoa oil through O/W emulsification, using porcine gelatin (OG) and isolated whey protein (OWG) as encapsulating agents. The particles were characterized by different physical and chemical methods and evaluated in vitro for cytotoxicity using Chinese hamster ovary (CHO) cells, human hepatocarcinoma cells (HepG2) and epithelial cells, and bioactive potential through the determination of Total Antioxidant Capacity (CAT) (acidic and neutral media) and iron chelation, and inhibition of digestive enzymes (α-amylase and amyloglucosidase). OG and OWG particles presented smooth surfaces, with an average size between 161 ± 7 and 264 ± 6 nm, with a polydispersity index of 0.11 ± 0.03 and 0.130 ± 0.04, encapsulation efficiency of 74 ± 1.47 % and 83 ± 2.92 %, and water dispersibility >70 %, respectively. Free and nanoencapsulated quinoa oil did not show cytotoxic effects (cell viability >70 %). Nanoencapsulation promoted the enhancement of the antioxidant activity of quinoa oil in the range of 50–63 % in a neutral medium and 96–153 % in an acidic medium than free oil (p < 0.05). OG and OWG also enhanced the inhibition of the enzymes α-amylase (by 5–7 %) and amyloglucosidase (6–9 times more) than free oil (p < 0.05). The results showed that nanoencapsulation increased the potential for quinoa oil application, enabling the development of innovative products.

In vitro and in vivo evaluation of hypoglycemic potential and acute toxicity of microencapsulated turmeric instant powder

BackgroundCurcuma longa L. (turmeric), traditionally used to treat various ailments including diabetes, has demonstrated beneficial health effects. However, its potential in food formulations requires further investigation. PurposeThis study examined the hypoglycemic effects of an instant powder containing microencapsulated turmeric oleoresin both in vitro and in vivo, alongside an acute toxicity assessment in Holtzman rats. MethodsThis study encompassed both in vitro and in vivo evaluations. In vitro, the α-glucosidase (a digestive enzyme) inhibition assay was employed to determine the powder's effectiveness. In vivo assessments included: (1) evaluation of the hypoglycemic effect in mice; (2) conducted safety testing following international guidelines, administering a 2000 mg/kg dose to rats with subsequent monitoring of biochemical parameters; and (3) histological examination of liver, kidney, and spleen tissues for potential harmful effects. ResultsThe instant powder with turmeric oleoresin microencapsulation demonstrated significant α-glucosidase inhibition in vitro and hypoglycemic effects in vivo. The acute toxicity test at 2000 mg/kg showed no mortality but revealed significant alterations in erythrocyte parameters and hemoglobin percentage. Histological examinations of liver, kidney, and spleen tissues did not differ from those of the control group, though pancreatic tissue was not evaluated in this study. ConclusionAccording to this study, the microencapsulated turmeric oleoresin instant powder exhibited antidiabetic effects without signs of overt toxicity at doses up to 2000 mg/kg in rats.

The screening of α-glucosidase inhibitory peptides from β-conglycinin and hypoglycemic mechanism in HepG2 cells and zebrafish larvae

Inhibition of carbohydrate digestive enzymes is a key focus across diverse fields, given the prominence of α-glucosidase inhibitors as preferred oral hypoglycaemic drugs for diabetes treatment. β-conglycinin is the most abundant functional protein in soy; however, it is unclear whether the peptides produced after its gastrointestinal digestion exhibit α-glucosidase inhibitory properties. Therefore, we examined the α-glucosidase inhibitory potential of soy peptides. Specifically, β-conglycinin was subjected to simulated gastrointestinal digestion by enzymatically cleaving it into 95 peptides with gastric, pancreatic and chymotrypsin enzymes. Eight soybean peptides were selected based on their predicted activity; absorption, distribution, metabolism, excretion and toxicity score; and molecular docking analysis. The results indicated that hydrogen bonding and electrostatic interactions play important roles in inhibiting α-glucosidase, with the tripeptide SGR exhibiting the greatest inhibitory effect (IC50 = 10.57 μg/mL). In vitro studies revealed that SGR markedly improved glucose metabolism disorders in insulin-resistant HepG2 cells without affecting cell viability. Animal experiments revealed that SGR significantly improved blood glucose and decreased maltase activity in type 2 diabetic zebrafish larvae, but it did not result in the death of zebrafish larvae. Transcriptomic analysis revealed that SGR exerts its anti-diabetic and hypoglycaemic effects by attenuating the expression of several genes, including Slc2a1, Hsp70, Cpt2, Serpinf1, Sfrp2 and Ggt1a. These results suggest that SGR is a potential food-borne bioactive peptide for managing diabetes.

Inhibition mechanism of different structural polyphenols against α-amylase studied by solid-state NMR and molecular docking

Polyphenol has the considerable effects for inhibition of digestive enzymes, however, inhibition mechanism of molecular size-dependent polyphenols on enzyme activity is still lacking. Herein, inhibition effect and binding interactions of three different structural polyphenols (catechol, quercetin and hesperidin) on α-amylase were studied. Inhibition assays proved that polyphenols significantly inhibited α-amylase and their effects were increased with their molecular sizes. Hesperidin showed the highest inhibition ability of α-amylase, which was determined as IC50 = 0.43 mg/mL. Fluorescence and FT-IR spectroscopy proved that inter-molecular interactions between polyphenols and α-amylase occurred through non-covalent bonds. Besides, the secondary structure of α-amylase was obviously changed after binding with polyphenols. Inter-molecular interactions were investigated using solid-state NMR and molecular docking. Findings proved that hydrogen bonds and π-π stacking interactions were the mainly inter-molecular interactions. We hope this contribution could provide a theoretical basis for developing some digestive enzyme inhibitors from natural polyphenols.

Psidium guajava Linn Leaves Extracts: A Potential Digestive Enzyme Inhibitor in the Treatment of Obesity

Obesity is a major worldwide problem and is associated with metabolic disorders, including hyperglycemia and hyperlipidemia. Many researchers focus on herbal plants rich with polyphenols are potent inhibitors of digestive enzymes and could be used as antihyperlipidemic and antihyperglycemic and hence useful in obesity treatment. The present work deals with the determination of the inhibitory effect of Psidium guajava Linn (Guava) leaves extract on digestive enzymes. Our findings confirmed that guava leaf extracts inhibit two primary enzymes, α-amylase and α-glucosidase. Similarly, investigated pancreatic lipase inhibition potential. The leaf extracts of P. guajava demonstrated significant anti-obesity properties by inhibiting key enzymes associated with obesity development. The aqueous extract exhibited pancreatic lipase inhibition ranging from 19.25 to 38.51%, while the methanolic extract showed inhibition between 22.96 to 46.66%. Additionally, the aqueous extract displayed α-amylase inhibition ranging from 43.10 to 62.06%, and the methanolic extract showed inhibition between 48.27 to 62.06%. Moreover, the aqueous extract demonstrated α-glucosidase inhibition between 13.11 to 49.18%, and the methanolic extract displayed inhibition ranging from 29.50 to 60.65% for 200 to 1000 μg/mL concentrations. The inhibitory activity observed was dosedependent for all three enzymes.

Free radical-induced soybean protein isolate -curcumin conjugates: Characterization, antioxidant and in vitro digestion characteristics

Natural soybean protein isolate（SPI) is vulnerable to environmental factors that compromise its functionality. One effective method to improve this functionality is through free radical induction. In this study, SPI and curcumin (Cur) were utilized to prepare SPI-Cur conjugates using the free radical induction method. The formation mechanism, structure, and functional properties of these conjugates were subsequently. The results indicated that at pH 9, the SPI-Cur conjugate formed hydroxyquinone dimers, which exhibited higher inhibition of digestive enzymes and increased stability through free radical-induced reactions. Furthermore, the antioxidant properties of SPI-Cur conjugates increased significantly, with increases of 9.17-, 2.3-, and 7.70-fold in DPPH, ABTS, and reducing power, respectively (p < 0.05). Circular dichroism analysis revealed increases in the secondary structure of proteins in SPI-Cur conjugates α-helix from 0.40% to 1.47%, β-sheet from 28.70% to 98.38% (pH 3 to pH 9), β-turns from 70.83% to 0.15%, and Random coils from 0.00% to 81.21%. These results suggest a novel approach for creating SPI-Cur conjugates through free radical-induced reactions, which could aid in the development of a continuous delivery system for polyphenols based on SPI and improve the high-value utilization of SPI.

Nanotechnology Enabled Advances in Oral Delivery of Therapeutic Peptides: Mechanistic Insights for Translation to Clinic

Abstract: Peptides represent a rapidly expanding class of novel treatments with distinct pharmacokinetic properties when compared to macromolecular proteins or small-molecule medications. Peptides are polymers with a molecular mass of less than 10 kDa. Protein-protein interactions have been the primary goal of oral delivery of peptide drugs for the last two decades. Recent trends suggest the possibility of mechanistically targeting challenging binding interfaces with the right binding affinity and specificity for molecules like peptides that bring conformational flexibility. Over 80 peptide medications have received regulatory approval to treat a range of conditions, from human immunodeficiency infection caused by viruses to fatal diseases like cancer. This review covers the need for peptide delivery via the oral route and offers insights to overcome the challenges. For successful translation to the clinic, oral delivery of therapeutic peptides coupled with nano formulation strategies has gained increased attention in recent years. The role of permeation boosters, and digestive enzyme inhibitors to overcome major hurdles such as degradation in the gastrointestinal tract and low intestinal permeability are presented here. Alteration of physicochemical characteristics of peptide molecules, the addition of functional excipients to specifically designed drug delivery systems, nanoformulation approaches, amongst other recent methodologies, to increase the oral bioavailability of peptide medications, are also presented herein. Numerous peptide candidates, both approved and under clinical trials, are included in this review.

Functional Model Beverages of Saffron Floral By-Products: Polyphenolic Composition, Inhibition of Digestive Enzymes, and Rheological Characterization.

Despite the rapid and dynamic evolution of research into dietary polyphenols, there is still a knowledge gap regarding their bioaccessibility since it could be influenced by the chemical and nutritional compositions of the food matrix. This study aimed to describe the impact of food thickeners (xanthan gum, guar gum, β-glucan, pectin) on the bioactivity of flavonoids from saffron floral by-products in model beverages before and after thermal processing. The different beverage formulas were characterized in terms of polyphenolic composition using HPLC-DAD-ESI-MSn and rheological properties. The impact of food thickeners and thermal processing on the inhibition of digestive enzymes was also determined. The model beverages mainly presented glycosylated flavonols (of kaempferol, quercetin, and isorhamnetin), with a reduced content in some heat-treated samples. The inhibitory effect on α-amylase was only detected in heat-treated beverages, showing the formulation without any thickener to have the greatest inhibitory effect. Finally, the presence of saffron floral by-products in the beverages showed a tendency to decrease the flow consistency index (K) and an increase in the flow behavior index (n), most probably driven by the aggregation of phenolics with thickeners. Therefore, this research provides new insights into the development of flavonoid-rich beverages in order to ensure that they exert the expected beneficial effects after their ingestion.

Strategic One-Pot Synthesis of 1,2,3-Triazole-Based Dihydropyrimidinone Hybrids Using Magnetic CuFe2O4 NPS as Heterogeneous Catalyst and Their DFT, Molecular Docking Studies

A rapid and enormously professional new-flanged 3,5-disubstituted triazole derivatives were synthesized by the one-pot five-component condensation reaction in the course of transesterification followed by the Biginelli/Click reaction in aqueous medium using magnetic CuFe2O4 NPs as heterogeneous catalyst beneath ultrasonic acceleration in aqueous medium. The synthesized 3,5-disubstituted triazole derivatives were finely characterized and the characterized desired target molecules were employed for the quantum chemical calculations for each reactant and product have been well thought-out using density functional theory. Furthermore, the molecular docking and ADMET revision of all the derivatives have been achieved as digestive enzyme and Cathepsin-B inhibitors and their connections with BSA to treat different diseases.

Inhibitory activity of luteolin on α‐glucosidase and pancreatic lipase in vitro and in vivo

SummaryObesity is becoming a top global health problem. Inhibition of digestive enzymes is an effective approach in weight management due to the reduction of energy absorption. In this study, the inhibitory effects of luteolin on α‐glucosidase and pancreatic lipase were investigated in vitro and in vivo via enzyme kinetics, fluorescence quenching, molecular docking and rat experiments. The results showed that luteolin inhibited α‐glucosidase and pancreatic lipase in a mixed‐type and uncompetitive manner with IC50 values of 29.31 and 42.74 μg mL−1 respectively. The binding of luteolin with the two enzymes caused the quenching of intrinsic fluorescence of protein. Molecular docking simulation revealed that luteolin could be located in the active pocket of α‐glucosidase and interact with the key amino acid residues. Moreover, a hydrophobic interaction and a van der Waals force were formed between luteolin and the key amino acid residues of pancreatic lipase (His264 and Ser153). In vivo studies further confirmed that luteolin could significantly decrease the absorption of glucose and triacylglyceride in rats by inhibiting α‐glucosidase and pancreatic lipase.

Investigating the effect of polyphenols from nuts on human carbohydrate digestion in vitro

Recent studies have documented the importance of postprandial hyperglycaemia in the incidence of chronic diseases, including type 2 diabetes. Inhibition of digestive enzymes, including membrane-bound brush-border α-glucosidases, leads to slowed carbohydrate digestion and absorption, and reduced postprandial glycemia. Nuts are widely eaten around the world and have the potential to inhibit α-glucosidases through their content of polyphenols and other bioactive compounds. According to our recent systematic review(1), no study has investigated the inhibitory effects of nut extracts on human α-glucosidase activities. Almost all studies in this area have been conducted on yeast α-glucosidase, with only a few using rat α-glucosidase. While there is no sequence homology between yeast and human α-glucosidase, there is 74% to 78% sequence homology between rat and human α-glucosidases(1). The lack of studies on the effect of bioactive compounds from nuts on human α-glucosidases, along with the growing attention to nuts as an important component of a healthy diet with the potential to reduce the risk of chronic diseases(2), highlights the need for research to evaluate the inhibitory effect of nut extracts on human α-glucosidases. The aim of the current study is to explore the inhibitory effect of extracts from nuts on human carbohydrate digestive enzymes. Walnuts and almonds were ground and defatted with hexane, extracted in 80% (v/v) acetone, and further purified using solid-phase extraction to obtain phenolic-rich extracts. The Folin–Ciocalteu assay was used to approximate the polyphenol content of the samples. Following our recently published detailed protocol(3), cell-free extracts from human intestinal Caco-2/TC7 cells were used as a source of α-glucosidase in enzyme inhibition assays, with sucrose, maltose and isomaltose as substrates and appropriate controls. The assay products were quantified using high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Glucose production in the presence of various concentrations of phenol-rich nut extracts was compared using a one-way ANOVA and half-maximal inhibitory concentration (IC50) values were calculated. The Folin–Ciocalteu data demonstrate that walnut extracts comprise a relatively high polyphenol content, with 18.1 ± 0.23 mg (epigallocatechin gallate [EGCG] equivalent) per gram of fresh weight, while almond extracts contain 0.87 ± 0.03 mg EGCG equivalent/g of fresh weight. The walnut phenolic-rich extract dose-dependently inhibited human intestinal sucrase and maltase activities (both p&lt;0.01), with IC50 values of 1.67 mg/mL and 2.84 mg/mL, respectively. We demonstrate that phenolic-rich walnut extracts can inhibit human α-glucosidases in vitro and therefore walnuts may contribute to slowing carbohydrate digestion in humans. As such, we plan to assess the effects of walnuts on postprandial glycaemia in vivo.

Polyphenolic profile and in vitro biological activity of Serbian orange (skin fermented white) wines

Orange wines are made from white grapes, but with prolonged skin contact during fermentation. Available data on their composition and potential health benefits are limited, so polyphenolic profile (HPLC analysis) and in vitro biological activities (enzyme inhibition, antioxidant, and anti-inflammatory) of 24 Serbian orange wines were analyzed, including the correlation between determined composition and bioactivities. The wines displayed distinct polyphenolic profiles, enabling partial differentiation based on overall polyphenol content, including dominant components (catechin, gallic and caffeic acids), along with occasional occurrences of anthocyanins. However, no discernible distinctions were noted based on grape varieties, vintage, or producer. All twenty-four orange wines showed a reasonable inhibition of digestive enzymes and lipid peroxidation, twenty-one samples reduced ROS generation in the cell-based assay, but only two suppressed both PGE2 and TXA2 production in U937 cells, implicating possible functional food properties. No significant correlation between polyphenolic profile and determined biological activities was noticed.

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway.

Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

Toxic or medicinal? New approach to the pharmacological and toxicological properties of Echinodorus macrophyllus leaves

Echinodorus macrophyllus contains some phytochemicals that can induce toxicity but are also promising as ingredients in products to promote and maintain health, improve the immune system, and prevent diseases. In this study, the aqueous and ethanolic extracts of leaves of this species were characterized by high-performance liquid chromatography, investigated in vitro regarding their modulating action on snake venom enzymes, and evaluated in digestive enzyme inhibition assays. The extracts inhibited the phospholipase activity induced by Bothrops jararacussu and B. moojeni venoms. The hemolytic activity induced by Crotalus durissus terrificus venom was potentiated by 30-73% by the ethanolic extract at the ratios analyzed. The thrombolytic activity induced by B. moojeni venom was inhibited by 51% and 34% by the aqueous and ethanolic extracts at a ratio of 1:5 (w:w), respectively. The clotting time induced by B. moojeni and Lachesis muta muta venoms was prolonged after incubation with either extract. The extracts also exerted antigenotoxic action on DNA fragmentation induced by L. muta muta venom. Both extracts lowered the enzymatic activity of α-glucosidases, and the ethanolic extract inhibited α-amylases. The inhibition of digestive enzymes suggests the extracts could decrease calorie availability from carbohydrate intake. Results confirm the potential therapeutic use of E. macrophyllus in the prevention and treatment of hemostatic changes, since the proteins of venoms inhibited by it exhibit high homology with human proteins involved in various pathophysiological processes, such as inflammatory responses and blood coagulation.