scholarly journals Identification of α-Glucosidase Inhibitors from Leaf Extract of Pepper (Capsicum spp.) through Metabolomic Analysis

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 649
Author(s):  
Samuel Tilahun Assefa ◽  
Eun-Young Yang ◽  
Gelila Asamenew ◽  
Heon-Woong Kim ◽  
Myeong-Cheoul Cho ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Positive Control ◽  
Partial Least Square ◽  
Least Square ◽  
Inhibitory Potency ◽  
Glucosidase Inhibitors ◽  
Hydroxycinnamic Acid Derivatives ◽  
Capsicum Spp ◽  
Pepper Leaves

Metabolomics and in vitro α-glucosidase inhibitory (AGI) activities of pepper leaves were used to identify bioactive compounds and select genotypes for the management of type 2 diabetes mellitus (T2DM). Targeted metabolite analysis using UPLC-DAD-QToF-MS was employed and identified compounds that belong to flavone and hydroxycinnamic acid derivatives from extracts of pepper leaves. A total of 21 metabolites were detected from 155 samples and identified based on MS fragmentations, retention time, UV absorbance, and previous reports. Apigenin-O-(malonyl) hexoside, luteolin-O-(malonyl) hexoside, and chrysoeriol-O-(malonyl) hexoside were identified for the first time from pepper leaves. Pepper genotypes showed a huge variation in their inhibitory activity against α-glucosidase enzyme(AGE) ranging from 17% to 79%. Genotype GP38 with inhibitory activity of 79% was found to be more potent than the positive control acarbose (70.8%.). Orthogonal partial least square (OPLS) analyses were conducted for the prediction of the AGI activities of pepper leaves based on their metabolite composition. Compounds that contributed the most to the bioactivity prediction model (VIP >1.5), showed a strong inhibitory potency. Caffeoyl-putrescine was found to show a stronger inhibitory potency (IC50 = 145 µM) compared to acarbose (IC50 = 197 µM). The chemometric procedure combined with high-throughput AGI screening was effective in selecting polyphenols of pepper leaf for T2DM management.

Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

2020 ◽  
pp. 1-9
Author(s):  
Pınar Ercan ◽  
Sedef Nehir El
Keyword(s):  
Inhibitory Activity ◽  
Digestive Enzymes ◽  
Positive Control ◽  
Anthocyanin Content ◽  
Inhibitory Effects ◽  
Total Anthocyanin ◽  
Total Anthocyanin Content ◽  
Before And After ◽  
Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

scholarly journals Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1206
Author(s):  
Reham Hammadi ◽  
Norbert Kúsz ◽  
Csilla Zsuzsanna Dávid ◽  
Zoltán Behány ◽  
László Papp ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Cytotoxic Activity ◽  
Inhibitory Activity ◽  
High Performance ◽  
Skin Condition ◽  
Positive Control ◽  
Active Species ◽  
The European Union ◽  
Ingenol Mebutate

Ingenol mebutate, isolated from Euphorbia peplus, is an ingenane-type diterpenoid, primarily used for the topical treatment of actinic keratosis, a premalignant skin condition. The aim of our work was to investigate other Euphorbia species to find structurally similar diterpenes that can be used as alternatives to ingenol mebutate. Pharmacological investigation of Euphorbia candelabrum, Euphorbia cotinifolia, Euphorbia ramipressa, and Euphorbia trigona revealed the potent keratinocyte (HPV-Ker cell line) inhibitory activity of these spurge species. From the methanolic extract of the aerial parts of Euphorbia trigona Miller, the most active species, five ingol (1–5) and four ingenane-type diterpenoids (6–9) were isolated by various chromatographic separation techniques, including open column chromatography, vacuum liquid chromatography, thin-layer chromatography, and high-performance liquid chromatography. The structures of the compounds were determined by NMR spectroscopic analysis and by comparison of the assignations with the literature data. The cytotoxic activity of the compounds against keratinocytes was tested in vitro by using ingenol mebutate as a positive control. Among the isolated compounds, two ingenane derivatives (6 and 7) exhibited remarkably stronger cytotoxic activity (IC50 values 0.39 μM and 0.32 μM, respectively) on keratinocytes than ingenol mebutate (IC50 value 0.84 μM). These compounds could serve as starting materials for further investigations to find alternatives to Picato® (with active substance ingenol mebutate), which was withdrawn from marketing authorization in the European Union.

scholarly journals Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Huan-Hua Xu ◽  
Zhen-Hong Jiang ◽  
Cong-Shu Huang ◽  
Yu-Ting Sun ◽  
Long-Long Xu ◽  
...  
Keyword(s):  
Chemical Properties ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Practical Significance ◽  
Plasma Metabolites ◽  
Active Components ◽  
The Difference

Abstract Background OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. Methods Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. Results Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. Conclusions This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.

scholarly journals In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

2013 ◽  
Vol 49 (4) ◽  
pp. 803-809
Author(s):  
Monica Lacerda Lopes Martins ◽  
Henrique Poltronieri Pacheco ◽  
Iara Giuberti Perini ◽  
Dominik Lenz ◽  
Tadeu Uggere de Andrade ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Colorimetric Assay ◽  
Hypotensive Effect ◽  
Ace Inhibition ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Total Phenolic ◽  
Before And After

In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES), a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE) activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE) and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg), with acetylcholine (ACh) as positive control (5 µg/kg, i.v.). The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg) in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.). Captopril (30 mg/kg) was used as positive control. Bulbostylis capillaris (86.89 ± 15.20%) and ERE (74.89 ± 11.95%, ERE) were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%). ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

scholarly journals Multivariate Statistical Analysis Uncovers Spectrum–Effect Relationship between HPLC Fingerprints and Antioxidant Activity of Saffron

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Ya You ◽  
Zijin Xu ◽  
Qingrou Zhong ◽  
Lin Zhu ◽  
Susu Lin ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Quality Control ◽  
Evaluation Method ◽  
Control Method ◽  
Partial Least Square ◽  
Least Square ◽  
Crocus Sativus ◽  
Effect Relationship ◽  
Spectrum Effect

Crocus sativus L. is commonly used as functional food and medicinal herb in traditional Chinese medicine. In this study, the spectrum–effect relationship was established between HPLC fingerprints and in vitro antioxidant activity of saffron to improve the quality evaluation method of saffron. The fingerprints of 21 batches of saffron collected from different regions were assessed, and the data were further analyzed by chemometric methods, including similarity analysis, hierarchical clustering analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. The spectrum–effect relationship between fingerprints and antioxidant effect of saffron was analyzed by grey relational analysis and partial least square methods to figure out the antioxidant component of saffron. Thirteen common peaks of 21 batches of saffron were included in the analysis, and peak 3 (picrocrocin), peak 7 (crocin I), and peak 10 (crocin II) were identified as the main active components responsible for antioxidant efficacy. Besides, a multi-index quality control method was developed for simultaneous determination of these three antioxidant components in saffron. Taken together, this study provided new strategies for the quality control and the development of new bioactive products of saffron in the future.

scholarly journals Characterization of α-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2402 ◽  
Author(s):  
Suganya Murugesu ◽  
Zalikha Ibrahim ◽  
Qamar-Uddin Ahmed ◽  
Nik-Idris Nik Yusoff ◽  
Bisha-Fathamah Uzir ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Molecular Docking ◽  
Acid Methyl Ester ◽  
Docking Simulation ◽  
Partial Least Square ◽  
Least Square ◽  
Gas Chromatography Mass Spectrometry ◽  
Glucosidase Inhibitors ◽  
Clinacanthus Nutans

Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant’s therapeutic effect to manage hyperglycemia.

scholarly journals Analysis of protein glycation in human fingernail clippings with near-infrared (NIR) spectroscopy as an alternative technique for the diagnosis of diabetes mellitus

2018 ◽  
Vol 56 (9) ◽  
pp. 1551-1558 ◽  
Author(s):  
Tinne Monteyne ◽  
Renaat Coopman ◽  
Antoine S. Kishabongo ◽  
Jonas Himpe ◽  
Bruno Lapauw ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Healthy Subjects ◽  
Near Infrared ◽  
Nir Spectroscopy ◽  
Partial Least Square ◽  
Least Square ◽  
Protein Glycation ◽  
Patients With Diabetes ◽  
Diagnosis Of Diabetes Mellitus

Abstract Background: Glycated keratin allows the monitoring of average tissue glucose exposure over previous weeks. In the present study, we wanted to explore if near-infrared (NIR) spectroscopy could be used as a non-invasive diagnostic tool for assessing glycation in diabetes mellitus. Methods: A total of 52 patients with diabetes mellitus and 107 healthy subjects were enrolled in this study. A limited number (n=21) of nails of healthy subjects were glycated in vitro with 0.278 mol/L, 0.556 mol/L and 0.833 mol/L glucose solution to study the effect of glucose on the nail spectrum. Consequently, the nail clippings of the patients were analyzed using a Thermo Fisher Antaris II Near-IR Analyzer Spectrometer and near infrared (NIR) chemical imaging. Spectral classification (patients with diabetes mellitus vs. healthy subjects) was performed using partial least square discriminant analysis (PLS-DA). Results: In vitro glycation resulted in peak sharpening between 4300 and 4400 cm−1 and spectral variations at 5270 cm−1 and between 6600 and 7500 cm−1. Similar regions encountered spectral deviations during analysis of the patients’ nails. Optimization of the spectral collection parameters was necessary in order to distinguish a large dataset. Spectra had to be collected at 16 cm−1, 128 scans, region 4000–7500 cm−1. Using standard normal variate, Savitsky-Golay smoothing (7 points) and first derivative preprocessing allowed for the prediction of the test set with 100% correct assignments utilizing a PLS-DA model. Conclusions: Analysis of protein glycation in human fingernail clippings with NIR spectroscopy could be an alternative affordable technique for the diagnosis of diabetes mellitus.

scholarly journals Design, Synthesis and Pharmacological Evaluation of Novel Imidazopyridine Analogues as Proton Pump Antagonist

2020 ◽  
Vol 32 (4) ◽  
pp. 776-782
Author(s):  
Ravindra S. Sonawane ◽  
Kiran D. Patil ◽  
Avinash V. Patil
Keyword(s):  
Spectral Analysis ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Docking Studies ◽  
Design Synthesis ◽  
Standard Drug ◽  
Imidazopyridine Derivatives

A series of novel imidazopyridine derivatives as proton pump inhibitors was designed with compounds of CID data base and explored considering AZD0865 as standard. Many compounds were identified and docked in proton pump ATPase pocket (PDB ID: 4ux2). Molecular docking studies revealed that many compounds showed good proton pump ATPase inhibitory activity. The docking poses revealed the interaction of ligands with amino acid. The standard drug AZD0865 had docking score of -7.112302 and displayed interactions with Asn138 and Asp137. A series of novel imidazopyridine derivatives as proton pump inhibitors were docked, synthesized and characterized by IR, NMR, CHN and MS spectral analysis. The target imidazopyridines were prepared from substituted 2-aminonicotinic acid and 2-bromo-1-substituted ethanone. in vitro Studies explained that few compounds exhibited moderate to good proton pump ATPase inhibitory activity in comparison with the reference drugs i.e. AZD0865. Compounds 11 and 12 shown higher activities with the IC50 4.3. Compounds 1, 4, 6, 7, 8, 10 and 13 showed weak anti-ulcer activity with its IC50 5.2, 5.8, 5.5, 5.1, 4.9, 4.6 and 5.9 and positive control AZD0865 shown IC50 2.0.

scholarly journals LOWERING URIC ACID EFFICACY TEST OF THE COMBINED EXTRACT OF UNCARIA GAMBIR (HUNTER) ROXB. AND CAESALPINIA SAPPAN L. IN VIVO AND IN VITRO

2018 ◽  
Vol 11 (8) ◽  
pp. 166
Author(s):  
Sri Ningsih ◽  
Fahri Fahrudin
Keyword(s):  
Antioxidant Activity ◽  
Uric Acid ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Polyphenol Content ◽  
Caesalpinia Sappan ◽  
In Vivo Experiments ◽  
A Value

 Objective: Hyperuricemia (high uric acid levels) prevalence increased year by year. This study was aimed to elaborate the in vitro xanthine oxidase (XO) inhibitory activity and in vivo lowering hyperuricemic effect of Uncaria gambir (Hunter) Roxb) (gambir), Caesalpinia sappan L. (secang) and the combined extract of secang and gambir (formulae extract [FE]).Methods: Gambir and secang extracts were prepared by maceration with ethanol and FE was the proportioned combination of these two extracts. XO inhibitory activity was determined by measuring the formation of uric acid in the xanthine/XO system in vitro using allopurinol as a positive control at 100 ug/mL. Antioxidant activity was by 1,1-diphenyl-2-picrylhydrazyl radical reducing methods. The in vivo experiments were conducted in the oxonate-induced hyperuricemia rat model, in which FE was gavaged p.o. at the arrange dose of 75, 150, and 300 mg/kg bw for 2 weeks. Polyphenol content was measured using Folin–Ciocalteu reagent spectrophotometrically.Results: The XO inhibitory activity of FE was 80% of allopurinol, while secang and gambir were 98% and 50%, respectively. The strength was appropriate to the total polyphenol content, in which it decreased in the order of secang (99%) > FE (86%) > gambir (46%). Furthermore, FE at all tested doses was able to decrease uric acid levels. FE also demonstrated antioxidant activity with a value of 74% relative to Vitamin C at 4 ug/mL.Conclusion: These studies could be concluded that FE exhibited the ability to decrease uric acid level so that it was potential to be developed further as a uric acid-lowering agent.

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