Exploring the anti-inflammatory, sedative, antidiabetic, and antioxidant potential in in-vitro and in-vivo models and phenolic profiling of Atractylis aristata Batt.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylis aristata batt., as an endemic plant from the Asteraceae family, holds a significant position in the Ahaggar region of southern Algeria's traditional medicine. The aerial parts of Atractylis aristata was used to cure inflammation, fever, and stomach disorders. AIM OF THE STUDY: The objective of the present investigation was to ascertain the overall bioactive components and phytochemical components and examine the antioxidant, antidiabetic, anti-inflammatory, acute toxicity, and sedative properties of the crude extract obtained from the aerial portions of Atractylis aristata (AaME). MATERIALS AND METHODS: The AaME's antioxidant activity was assessed by the use of pyrogallol autoxidation, (1,1 diphenyl-2-picrylhydrazyl) (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power (RP) techniques. 1 mg/mL of AaME was used to evaluate the antidiabetic activity by applying the enzyme α-amylase inhibitory power test. At the same time, the bovine serum albumin (BSA) denaturation method was employed to quantify the in vitro anti-inflammatory activity at different concentrations (1.5625, 0.78125, 0.390625, 0.1953125 and 0.09765625 mg/mL). In contrast, following the Organization for Economic Co-operation and Development (OECD) guideline No. 423, which covers acute oral toxicity testing protocols, the limit dosage test was employed to assess in vivo acute toxicity. At the dose of 0.08 mg/mL, the carrageenan-induced paw edema approach was used to assess the anti-inflammatory efficacy in vivo, and the sedative activity was carried out at the dose of 0.08 mg/mL using the measurement of the locomotor method. Different bioactive compounds were identified within AaME using LC-MS/MS and HPLC-UV analysis. RESULTS: The acute toxicity study showed no fatalities or noticeable neurobehavioral consequences at the limit test; this led to their classification in Globally Harmonized System (GHS) category Five, as the OECD guideline No 423 recommended. At a concentration of 0.08 mg/mL (2000 mg/kg), AaME showed apparent inhibition of paw edema and a significant (p = 0.01227) reduction in locomotor activity compared to the control animals. Our findings showed that AaME exhibited considerable antioxidant (IC50 = 0.040 ± 0.003 mg/mL (DPPH), IC50 = 0.005 ± 5.77 × 10-5 mg/mL (ABTS), AEAC = 91.15 ± 3.921 mg (RP) and IR% = 23.81 ± 4.276 (Inhibition rate of pyrogallol) and rebuts antidiabetic activities (I% = 57.6241% ± 2.81772). Our findings revealed that the maximum percentage of BSA inhibition (70.84 ± 0.10%) was obtained at 1.562.5 mg/mL. Thus, the AaME phytochemical profile performed using phytochemical screening, HPLC-UV, and LC-MS/MS analysis demonstrated that A. aristata can be a valuable source of chemicals with biological activity for pharmaceutical manufacturers. CONCLUSION: The phytochemical profiling, determined through HPLC-UV and LC-MS/MS applications, reveals this plant's therapeutic value. The aerial parts of Atractylis aristata contain bioactive molecules such as gallic acid, ascorbic acid, and quercetin, contributing to its significant antioxidant capabilities. Furthermore, identifying alizarin, the active compound responsible for its anti-inflammatory properties, could provide evidence supporting the anti-inflammatory capabilities of this subspecies.

Hypoglycemic effects of mountain caviar extract and inhibitory mechanism of saponins, including momordin Ic, on glucose absorption.

Mountain caviar is a fruit of Kochia scoparia that contains momordin Ic as a major saponin constituent. Its extract (MCE) has been shown to suppress blood glucose elevations in the human oral glucose tolerance test (OGTT) as well as increases in blood glucose in OGTT, gastric emptying (GE), and glucose incorporation in the small intestine in rats. However, the effects of MCE and momordin Ic on glucose absorption in mice and these action mechanisms have not been examined for more than 2 decades. Therefore, we herein investigated the effects of MCE, its saponin fraction, and momordin Ic on blood glucose elevations in mice. Mouse blood glucose elevation tests were performed on carbohydrate-loaded mice. The mountain caviar saponin fraction significantly delayed blood glucose elevations in glucose-, sucrose-, and soluble starch-loaded mice. In glucose-loaded mice, the saponin fraction, MCE, and momordin Ic significantly suppressed rapid glucose elevations after glucose loading, but not sucrose loading. A mouse GE study was performed by loading with glucose and phenolphthalein solution. Momordin Ic and MCE strongly suppressed mouse GE. Intestinal glucose absorption was evaluated by the incorporation of 2-deoxyglucose (2-DG) into Caco-2 cell layers and mouse duodenum wall vesicles. The results obtained showed that momordin Ic inhibited the incorporation of 2-DG into Caco-2 cells and mouse duodenum vesicles. Collectively, these results suggest that MCE, particularly the principal saponin, momordin Ic, preferably suppressed glucose-induced blood glucose elevations and delayed carbohydrate-induced glucose elevations in mice. The underlying mechanism was found to involve the suppression of GE and intestinal glucose absorption.

Structure-function relationship and biological activity of polysaccharides from mulberry leaves: A review.

Mulberry (Latin name "Morus alba L.") is a perennial deciduous tree in the family of Moraceae, widely distributed around the world. In China, mulberry is mainly distributed in the south and the Yangtze River basin. Its leaves can be harvested 3-6 times a year, which has a great resource advantage. Mulberry leaves are regarded as the homology of medicine and food traditional Chinese medicine (TCM). Polysaccharides, as its main active ingredients, have various effects, such as antioxidant, hypoglycemic, hepatoprotective, and immunomodulatory. This review summarizes the research progress in the extraction, purification, structural characterization, and structure-function relationship of polysaccharides from mulberry leaves in the last decade, hoping to provide a reference for the subsequent development and market application of polysaccharides from mulberry leaves.

Lipoic acid-mediated oral drug delivery system utilizing changes on cell surface thiol expression for the treatment of diabetes and inflammatory diseases.

Lipoic acid (LA), which has good safety and oral absorption, is obtained from various plant-based food sources and needs to be supplemented through human diet. Moreover, substances with a disulfide structure can enter cells through dynamic covalent disulfide exchange with thiol groups on the cell membrane surface. Based on these factors, we constructed LA-modified nanoparticles (LA NPs). Our results showed that LA NPs can be internalized into intestinal epithelial cells through surface thiols, followed by intracellular transcytosis via the endoplasmic reticulum-Golgi pathway. Further mechanistic studies indicated that disulfide bonds within the structure of LA play a critical role in this transport process. In a type I diabetes rat model, the oral administration of insulin-loaded LA NPs exhibited a more potent hypoglycemic effect, with a pharmacokinetic bioavailability of 5.42 ± 0.53%, representing a 1.6 fold enhancement compared to unmodified PEG NPs. Furthermore, a significant upregulation of surface thiols in inflammatory macrophages was reported. Thus, we turned our direction to investigate the uptake behavior of inflammatory macrophages with increased surface thiols towards LA NPs. Inflammatory macrophages showed a 2.6 fold increased uptake of LA NPs compared to non-inflammatory macrophages. Surprisingly, we also discovered that the antioxidant resveratrol facilitates the uptake of LA NPs in a concentration-dependent manner. This is mainly attributed to an increase in glutathione, which is involved in thiol uptake. Consequently, we employed LA NPs loaded with resveratrol for the treatment of colitis and observed a significant alleviation of colitis symptoms. These results suggest that leveraging the variations of thiol expression levels on cell surfaces under both healthy and diseased states through an oral drug delivery system mediated by the small-molecule nutrient LA can be employed for the treatment of diabetes and certain inflammatory diseases.

Evaluation of antioxidant, antidiabetic and antiobesity potential of phenylpropanoids (PPs): Structure-activity relationship and insight into action mechanisms against dual digestive enzymes by comprehensive technologies.

Phenylpropanoids (PPs), a group of natural compounds characterized by one or more C6-C3 units, have exhibited considerable potential in addressing metabolic disease. However, the comprehensive investigation on the relationship of compound structures and involved activity, along with the action mechanisms on the drug target is absent. This study aimed to evaluate the antioxidant and inhibitory activities of 16 PPs against two digestive enzymes, including α-glucosidase and pancreatic lipase, explore the structure-activity relationships and elucidate the mechanisms underlying enzyme inhibition. The findings revealed the similarities in the rules governing antioxidant and enzyme inhibitory activities of PPs. Specifically, the introduction of hydroxyl groups generally exerted positive effects on the activities, while the further methoxylation and glycosylation were observed to be unfavorable. Among the studied PPs, esculetin exhibited the most potent antioxidant activity and dual enzymes inhibition potential, displaying IC50 values of 0.017 and 0.0428 mM for DPPH and ABTS radicals scavenging, as well as 1.36 and 6.67 mM for α-glucosidase and lipase inhibition, respectively. Quantification analysis indicated esculetin bound on both α-glucosidase and lipase successfully by a mixed-type mode. Further analyses by UV-Vis, FT-IR, fluorescence spectra, surface hydrophobicity, SEM, and molecular docking elucidated that esculetin could bind on the catalytic or non-catalytic sites of enzymes to form complex, impacting the normal spatial conformation for hydrolyzing the substrate, thus exhibiting the weakened activity. These results may shed light on the utilization value of natural PPs for the management of hyperglycemia and hyperlipemia, and afford the theoretical basis for designing drugs with stronger inhibition against the dual digestive enzymes based on esculetin.

Extraction, purification, structural modification, activities and application of polysaccharides from different parts of mulberry.

The mulberry plant is a member of the Moraceae family and belongs to the Morus genus. Its entire body is a treasure, with mulberries, mulberry leaves, and mulberry branches all suitable for medicinal use. The main active ingredient in mulberries is mulberry polysaccharide. Studies have shown that polysaccharides from different parts of mulberry exhibit antioxidant, antidiabetic, antibacterial, anti-inflammatory, and blood pressure-lowering properties. There are more studies on the biological activities, extraction methods, and structural characterization of polysaccharides from different parts of mulberry. However, the structural characterization of mulberry polysaccharides is mostly confined to the types and proportions of monosaccharides and the molecular weights of polysaccharides, and there are fewer systematic studies on polysaccharides from different parts of mulberry. In order to better understand the bioactive structure of mulberry polysaccharides, this article discusses the recent research progress in the extraction, separation, purification, bioactivity, structural modification, and application of polysaccharides from different parts of mulberry (mulberry leaves, mulberry fruits, and mulberry branches). It also delves into the pharmacological mechanisms of action of mulberry polysaccharides to provide a theoretical basis for further research on mulberry polysaccharides with a view to their deeper application in the fields of feed and nutraceuticals.

Explore the active ingredients and potential mechanism of action on Actinidia arguta leaves against T2DM by integration of serum pharmacochemistry and network pharmacology.

BACKGROUND: Actinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear. AIM OF THE STUDY: This study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action. METHODS: Firstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an "H-C-T-P-D" interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis. RESULTS: Serum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets. CONCLUSION: This study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.

Phytochemical Profiling and Assessment of Antidiabetic Activity of Curcuma Angustifolia Rhizome Methanolic Extract: An In Vitro and In Silico Analysis.

Curcuma angustifolia Roxb. is a plant with medicinal potential, traditionally used to treat different diseases. The present study aimed to determine the antidiabetic activity of C. angustifolia rhizome in vitro and in silico. The methanolic extract of C. angustifolia rhizome was analyzed by FTIR and GC-MS to determine the phytochemicals present. The antidiabetic potential of the extract was evaluated by different assays in vitro. The extract inhibited both α-amylase and α-glucosidase enzymes and the glucose diffusion through the dialysis membrane in a concentration-dependent manner with IC50 values of 530.39±0.09, 293.75±0.11, and 551.74±0.3 µg/ml respectively. The methanolic extract also improved yeast cell's ability to take up glucose across plasma membranes and the adsorption of glucose. The findings were supported by molecular docking studies. The results showed that the methanol extract of C. angustifolia rhizome has significant antidiabetic activity and thus can be also studied to isolate the potential compound with antidiabetic activities.

Evaluating the biological (antidiabetic) potential of TEM, FTIR, XRD, and UV-spectra observed berberis lyceum conjugated silver nanoparticles.

Diabetes is a life-threatening disease that affects different parts of the body including the liver, kidney, and pancreas. The core root of diabetes is mainly linked to oxidative stress produced by reactive oxygen species (ROS). Berberis lyceum Royle (BLR) is the source of natural products. It comprises numerous bioactive compounds having antioxidant activities. In the current investigation, silver nanoparticles from BLR root extract were synthesized, characterized, and assessed for antidiabetic potential. UV spectrophotometry, Transmission electron microscopy (TEM), Fourier transform infra-red spectroscopy (FTIR), and x-ray diffraction (XRD) were applied for the characterization of NPs. It was evident from the morphological studies that the synthesized NPs were spherical and the average size was 11.02 nm. Results revealed that BLR-AgNPs showed higher radical scavenging activity as compared to BLR extract. Moreover, BLR-AgNPs displayed superior in vivo and in vitro antidiabetic activity in comparison to BLR extract. Glucose level (116.5 ± 5.1 mg/dL), liver function test (ALAT: 54.038 ± 6.2 IU/L; ASAT: 104.42 ± 13.9 IU/L; ALP: 192.6 ± 2.4 IU/L; bilirubin: 1.434 ± 0.14 mg/dL; total protein: 5.14 ± 0.24 mg/dL), renal function test (urea: 39.6 ± 0.63 mg/dL; uric acid: 21.4 ± 0.94 mg/dL; creatinine: 0.798 ± 0.03 mg/dL; albumin: 4.14 ± 0.2 mg/dL), lipid profile level (cholesterol: 101.62 ± 3 mg/dL; triglyceride: 110.42 ± 7 mg/dL; HDL-C: 29.7 ± 3 mg/dL; LDL-C: 47.056 ± 1 mg/dL; VLDL-C: 22.0 ± 1.3 mg/dL) and hematology (WBCs: 3.82 ± 0.24 103 /µL; RBCs: 4.78 ± 0.42 106 /µL; Hb: 12.6 ± 1.0 g/dL; Hematocrit: 39.4 ± 3.7%; MCV: 65.8 ± 3 fL; platelets: 312 ± 22.4; neutrophils: 34.8 ± 1.87; eosinophils: 3.08 ± 0.43; monocytes: 3.08 ± 0.28; lymphocytes: 75.6 ± 3.77) confirmed the significant antidiabetic potential of BLR-AgNPs. Histopathological examination authenticated that BLR-AgNPs caused a significant revival in the morphology of the liver, kidney, and pancreas. Hence, findings of the study suggested the BLR-AgNPs as a potent antidiabetic agent and could be an appropriate nanomedicine to prevent diabetes in future. RESEARCH HIGHLIGHTS: Berberis lyceum extract as a reducing, capping, and stabilization agent for the BLR-AgNPs synthesis Evaluation of α-amylase inhibition, antioxidant, and α-glucosidase inhibition potential Thorough characterization using Fourier transform infrared spectroscopy, Transmission electron microscopy, x-ray diffraction, and UV-VIS spectrophotometer, which is 1st of its kind In-vivo antidiabetic activity evaluation through multiple biomarkers.

Unveiling the chemical profiling and remarkable modulation of carbohydrate metabolism by costus root, Dolomiaea costus (Falc.) in streptozotocin (STZ)-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dolomiaea costus (Falc.), formerly Saussurea costus (Falc.) Lipsch., an ayurvedic medicinal plant, has long been recognized and utilized in diverse indigenous systems of medicine for its multifaceted therapeutic properties, including anti-inflammatory, carminative, expectorant, antiarthritic, antiseptic, aphrodisiac, anodyne, and antidiabetic effects. AIM OF THE STUDY: The potential and underlying mechanisms of D. costus root as an antidiabetic agent were investigated in this study. Additionally, the quantification of phenolic and flavonoid compounds, which dominate the extracts, was of particular interest in order to elucidate their contribution to the observed effects. MATERIALS AND METHODS: High-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was employed to analyze the chemical constituents in D. costus root aqueous extract (DCA) and D. costus root ethanolic extract (DCE). Furthermore, the inhibitory potentials of DCE and its respective fractions as well as DCA against α-amylase, α-glucosidase, and lipase enzymes were assessed. Subsequently, the efficacy of DCA and DCE extracts was evaluated using an established streptozotocin (STZ)-induced diabetic animal model; this involved administering the extracts at doses of 200 and 400 mg/kg bwt. and comparing them with a positive control (glibenclamide (Glib.) at 0.6 mg/kg bwt.). After induction of diabetes (except for negative control), all animals received the treatments orally for 21 days consecutively, followed by the collection of rat serum to assess various parameters including, glycemic and lipid profiles, liver and kidney functions, antioxidant activity, glycolysis, and gluconeogenesis pathways. RESULTS: The results of HPLC-ESI-MS/MS revealed that isochlorogenic acid A (8393.64 µg/g) and chlorogenic acid (6532.65 µg/g) were the predominant compounds in DCE and DCA, respectively. Both extracts exhibited notable antidiabetic properties, as evidenced by their ability to regulate blood glycemic and lipid profiles (glucose, insulin, HBA1C; HDL, TC, TGs), liver enzymes (ALT, ALP, AST), kidney function (urea, creatinine, uric acid), oxidative stress biomarkers (MDA), antioxidant enzymes (CAT, GSH, SOD), as well as glycolysis (glucokinase) and gluconeogenesis (G-6-P, FBP1) pathways. CONCLUSIONS: Furthermore, the administration of D. costus extracts significantly mitigated STZ-induced diabetic hyperglycemia. These results can be attributed, at least partially, to the presence of several polyphenolic compounds with potent antioxidant and anti-inflammatory activities.

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization.

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and sugar production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay of extracts from diverse sugarcane byproducts and their biological attributes remains underexplored. This study focused on extracting the lipid fraction from a blend of selected sugarcane byproducts (straw, bagasse, and filter cake) using ethanol. The resulting extract underwent comprehensive characterization, including physicochemical analysis (FT-IR, DSC, particle size distribution, and color) and chemical composition assessment (GC-MS). The biological properties were evaluated through antihypertensive (ACE), anticholesterolemic (HMG-CoA reductase), and antidiabetic (alpha-glucosidase and Dipeptidyl Peptidase-IV) assays, alongside in vitro biocompatibility assessments in Caco-2 and Hep G2 cells. The phytochemicals identified, such as ß-sitosterol and 1-octacosanol, likely contribute to the extract's antidiabetic, anticholesterolemic, and antihypertensive potential, given their association with various beneficial bioactivities. The extract exhibited substantial antidiabetic effects, inhibiting α-glucosidase (5-60%) and DPP-IV activity (25-100%), anticholesterolemic potential with HMG-CoA reductase inhibition (11.4-63.2%), and antihypertensive properties through ACE inhibition (24.0-27.3%). These findings lay the groundwork for incorporating these ingredients into the development of food supplements or nutraceuticals, offering potential for preventing and managing metabolic syndrome-associated conditions.

Fructooligosaccharides from Cynoglossum tubiflorus: Effect of the molecular size on their antidiabetic activity in high-fat diet and alloxan induced diabetic rats.

The use of acetylation followed by silica gel column purification allowed the isolation of eight fructooligosaccharides (FOS) from the ethanol extract of Cynoglossum tubiflorus roots. Each FOS was identified by analyzing its FT-IR, HRMS/MS and NMR data, including 1H, 13C and 2D NMR HH COSY, HMBC and NOESY. In diabetic rats treated with a series of FOS from Glc-(Fru)3 to Glc-(Fru)7, a significant inhibition of intestinal α-amylase was observed. This activity increases proportionally with the FOS molecular size. It was found that they delay the absorption of total cholesterol (TC), ldl-cholesterol (LDL-C) and increase HDL-cholesterol (HDL-C) in a molecular size-dependent manner. This inhibitory effect on the activity of the digestive enzyme causes a significant (p < 0.05) reduction in the level of glucose in the blood as an anti-diabetic action. The ethanolic extract (E.E) exerts a significant effect against α-amylase as well as antihyperglycemic and antihyperlipidemic actions, while its acetylation suppresses these effects. Therefore, this study demonstrates for the first time that pure FOS act as an efficient agent in preventing hyperglycemia and hyperlipidemia and that this action evolves in the same manner with their molecular size.

Antioxidant and Antidiabetic Potential of Ormocarpum cochinchinense (Lour.) Merr. Leaf: An Integrated In vitro and In silico Approach.

Diabetes is a prevalent metabolic disorder associated with various complications. Inhibition of α-glucosidase and α-amylase enzymes is an effective strategy for managing non-insulin-dependent diabetes mellitus. This study aimed to investigate the antioxidant and antidiabetic potential of Ormocarpum cochinchinense leaf through in vitro and in silico approaches. The methanol extract exhibited the highest phenolic and flavonoid content over solvent extracts aqueous, acetone, hexane, and chloroform, the same has been correlating with strong antioxidant activity. Furthermore, the methanol extract demonstrated significant inhibitory effects on α-amylase and α-glucosidase enzymes, indicating its potential as an antidiabetic agent. Molecular docking analysis identified compounds, including myo-inositol, with favorable binding energies comparable to the standard drug metformin. The selected compounds displayed strong binding affinity towards α-amylase and α-glucosidase enzymes. Structural dynamics analysis revealed that myo-inositol formed a more stable complex with the enzymes. These findings suggest that O. cochinchinense leaf possesses antioxidant and antidiabetic properties, making it a potential source for developing therapeutic agents.

Investigation of Phytochemical, Antioxidant and Antidiabetic Potentials of Scabiosa L. (Caprifoliaceae) Species with Chemometric Methods.

In this research, the total phenolic and flavonoid amounts, phenolic compositions, in vitro antioxidant, antibacterial and antidiabetic properties of the methanol extracts obtained from Scabiosa L. (Caprifoliaceae) species distributed in the flora of Türkiye were investigated using chemometric methods. For this purpose, principal component (PCA) and agglomerative hierarchical clustering analysis were performed as chemometric methods. Chlorogenic acid, quinic acid and cyranoside were determined in the extracts. According to chemometric analysis, S. columbaria subsp. ochroleuca var. ochroleuca and S. triniifolia species were found to be valuable in terms of methanol extract yields, total phenolic and flavonoid contents, antioxidant and antidiabetic activities while S. columbaria subsp. ochroleuca var. webbiana species were found to be valuable in terms of phenolic composition. The methanol extracts of Scabiosa species showed high antioxidant activity, with high phenolic and flavonoid contents. Among the tested 13 bacteria, Scabiosa extracts showed only low activity against Klebsiella pneumoniae, Streptococcus pneumoniae and Pseudomonas aeruginosa. The extracts showed high α-amylase and α-glucosidase inhibitory activity. The results show that Scabiosa methanol extracts may be a source of alternative antioxidants that may be beneficial in slowing or preventing the progression of various oxidative stress-related diseases.

Hypoglycemic activity of immature persimmon (Diospyros kaki Thunb.) extracts and its inhibition mechanism for α-amylase and α-glucosidase.

Persimmon tannins, particularly in immature persimmons, haven't yet received corresponding attention to research on therapy of diabetes mellitus in spite of high hypoglycemic activity. To accurately screening key hypoglycemic components, immature persimmon extracts were isolated and identified using enzyme affinity ultrafiltration and HRLC-ESI-MS/MS. Among them, Hederagenin (IC50 = 0.077 ± 0.003 mg/mL), Ursolic acid (IC50 = 0.001 ± 0.000 mg/mL) and Quercetin dehydrate (IC50 = 0.081 ± 0.001 mg/mL) exhibited the strongest inhibitory effect on α-amylase (HSA and PPA) and α-glucosidase, respectively. And their inhibition mechanisms were analyzed using multi-spectral analysis, atomic force microscope and molecular docking, indicating the bonding with starch digestion enzymes through hydrogen bonding and hydrophobic interaction, and generating the enzyme aggregation. In vivo starch-tolerance experiment further verified that these inhibitors could improve postprandial hyperglycemia (17.18 % âˆ¼ 40.29 %), far more than acarbose. Suppressing, Hederagenin and Ursolic acid as triterpenoids appeared amazing potentiality to alleviate postprandial hyperglycemia, which suggested that IPE were comprehensive exploration values on prevention and treatment of hyperglycemia.

Polysaccharides (pectin, mucilage, and fructan inulin) and their fermented products: A critical analysis of their biochemical, gut interactions, and biological functions as antidiabetic agents.

Diabetes mellitus is a globally metabolic endocrine syndrome marked by a deficiency of insulin secretion (type-1 DM) or glucose intolerance arising from insulin response impairment (type-2 DM) leading to abnormal glucose metabolism. With an increasing interest in natural dietary components for diabetes management, the identification of novel agents witnessed major discoveries. Plant-derived mucilage, pectin, and inulin are important non-starch polysaccharides that exhibit effective antidiabetic properties often termed soluble dietary fiber (SDF). SDF affects sugar metabolism through multiple mechanisms affecting glucose absorption and diffusion, modulation of carbohydrate metabolizing enzymes (α-amylase and α-glucosidase), ameliorating ß-pancreatic cell dysfunction, and improving insulin release or sensitivity. Certain SDFs inhibit dipeptidyl peptidase-4 and influence the expression levels of genes related to glucose metabolism. This review is designed to discuss holistically and critically the antidiabetic effects of major SDF and their underlying mechanisms of action. This review should aid drug discovery approaches in developing novel natural antidiabetic drugs from SDF.

Bioassay-guided discovery and identification of new potent α-glucosidase inhibitors from Morus alba L. and the interaction mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. (mulberry) is a well-known medicinal species that has been used by herbalist doctors for the treatment of diabetes for a long history, and modern ethnopharmacological studies have demonstrated the ameliorating effects of different mulberry extracts toward diabetes-related symptoms and identified a number of α-glucosidase inhibitors as hypoglycemic ingredients. AIM OF THE STUDY: The present study aims to explore new potent α-glucosidase inhibitors from the root bark of M. alba (known as Sang-Bai-Pi in traditional medicine) based on an in vivo antidiabetic evaluation of its extract fractions and further characterize the preliminary mechanism of the new active constituents. MATERIALS AND METHODS: α-Glucosidase inhibitory assay and diabetic mice model were used to locate and evaluate the active fractions from the extract. Diverse separation techniques (e.g. Sephadex LH-20 column chromatograph (CC) and HPLC) and spectroscopic methods (e.g. MS, NMR and ECD) were employed to isolate and structurally characterize the obtained constituents, respectively. Fluorescence quenching, kinetics and molecular docking experiments were conducted to investigate the enzyme inhibitory mechanism of the active compounds. RESULTS: The 80% ethanol eluate from the macroporous resin CC exerted good antidiabetic effects in the tested mice. Fifty-two flavonoids including 22 new ones were then separated and identified, and most of them showed strong inhibition against α-glucosidase with their structure-activity relationship being also discussed. The four new most active ingredients were further characterized to be mixed type of α-glucosidase inhibitors, and their binding modes with the enzyme were also explored. CONCLUSIONS: Our current work has demonstrated that the root bark of M. alba is an extremely rich source of flavonoids as potent α-glucosidase inhibitors and potential antidiabetic agents, which makes it a promising candidate species to develop new natural remedies for the prevention and treatment of diabetes.

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts.

Polygonum cognatum Meisn. (Polygonaceae) is used both as food and as a folk medicine to treat diabetes. This study aimed to evaluate the effect of the extracts, along with isolated compounds, from P. cognatum aerial parts on diabetes. In vitro studies were conducted using an α-glucosidase inhibitory assay, while in vivo antidiabetic studies were carried out on streptozotocin-induced diabetic rats. Effective extracts were subjected to isolation studies, and structures of the compounds were elucidated by spectroscopic methods. The ethyl acetate and n-butanol extracts had the highest effect in both in vitro and in vivo experiments. They also decreased aspartate transaminase, alanine transaminase and malondialdehyde levels, while increasing glutathione and superoxide dismutase activity in rats. From the active extracts, 11 phenolic compounds were isolated and characterized. Among the isolated compounds, quercetin was found to be the most active according to α-glucosidase inhibitory activity studies. This study provided scientific evidence for the traditional use of P. cognatum as a folk medicine for treating diabetes. The findings suggest that the ethyl acetate and n-butanol extracts, as well as quercetin, have the potential for development as antidiabetic agents.

Antidiabetic Activity, Molecular Docking, and ADMET Properties of Compounds Isolated from Bioactive Ethyl Acetate Fraction of Ficus lutea Leaf Extract.

Diabetes contributes to the rising global death rate. Despite scientific advancements in understanding and managing diabetes, no single therapeutic agent has been identified to effectively treat and prevent its progression. Consequently, the exploration for new antidiabetic therapeutics continues. This study aimed to investigate the antidiabetic bioactive ethyl acetate fraction of F. lutea at the molecular level to understand the molecular interactions and ligand-protein binding. To do this, the fraction underwent column chromatography fractionation to yield five compounds: lupeol, stigmasterol, α-amyrin acetate, epicatechin, and epiafzelechin. These compounds were evaluated in vitro through α-glucosidase inhibition and glucose utilization assays in C2C12 muscle and H-4-11-E liver cells using standard methods. In silico analysis was conducted using molecular docking and ADMET studies. Epicatechin exhibited the most potent α-glucosidase inhibition (IC50 = 5.72 ± 2.7 µg/mL), while epiafzelechin stimulated superior glucose utilization in C2C12 muscle cells (33.35 ± 1.8%) and H-4-11-E liver cells (46.7 ± 1.2%) at a concentration of 250 µg/mL. The binding energies of the isolated compounds for glycogen phosphorylase (1NOI) and α-amylase (1OSE) were stronger (<-8.1) than those of the positive controls. Overall, all tested compounds exhibited characteristics indicative of their potential as antidiabetic agents; however, toxicity profiling predicted epiafzelechin and epicatechin as better alternatives. The ethyl acetate fraction and its compounds, particularly epiafzelechin, showed promise as antidiabetic agents. However, further comprehensive studies are necessary to validate these findings.

Antioxidant and antidiabetic flavonoids from the leaves of Dypsis pembana (H.E.Moore) Beentje & J.Dransf., Arecaceae: in vitro and molecular docking studies.

BACKGROUND: Oxidative stress and diabetes are medical conditions that have a growing prevalence worldwide, significantly impacting our bodies. Thus, it is essential to develop new natural antioxidant and antidiabetic agents. Dypsis pembana (H.E.Moore) Beentje & J.Dransf (DP) is an ornamental palm of the family Arecaceae. This study aimed to broaden the understanding of this plant's biological properties by evaluating its in vitro antioxidant and antidiabetic activities. METHODS: The in vitro antioxidant activities of the crude extract, fractions, and selected isolates were evaluated by DPPH method. While the in vitro antidiabetic activities of these samples were evaluated by assessing the degree of inhibition of α-glucosidase. Additionally, molecular docking analysis was performed to investigate the interactions of tested compounds with two potential targets, the cytochrome c peroxidase and alpha glucosidase. RESULTS: The crude extract displayed the highest antioxidant activity (IC50 of 11.56 µg/ml), whereas among the fractions, the EtOAc fraction was the most potent (IC50 of 14.20 µg/ml). Among tested compounds, isoquercetrin (10) demonstrated the highest potency, with an IC50 value of 3.30 µg/ml, followed by rutin (8) (IC50 of 3.61 µg/ml). Regarding antidiabetic activity, the EtOAc (IC50 of 60.4 µg/ml) and CH2Cl2 fractions (IC50 of 214.9 µg/ml) showed activity, while the other fractions did not demonstrate significant antidiabetic effects. Among tested compounds, kaempferol-3-O-neohesperidoside (9) showed the highest antidiabetic activity, with an IC50 value of 18.38 µg/ml, followed by kaempferol (4) (IC50 of 37.19 µg/ml). These experimental findings were further supported by molecular docking analysis, which revealed that isoquercetrin and kaempferol-3-O-neohesperidoside exhibited strong enzyme-binding affinities to the studied enzyme targets. This analysis provided insights into the structure-activity relationships among the investigated flavonol-O-glycosides. CONCLUSION: The biological and computational findings revealed that isoquercetrin and kaempferol-3-O-neohesperidoside have potential as lead compounds for inhibiting cytochrome c peroxidase and alpha glucosidase enzymes, respectively.