scholarly journals Phenolic Acids from Lycium barbarum Leaves: In Vitro and In Silico Studies of the Inhibitory Activity against Porcine Pancreatic α-Amylase

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1388
Author(s):  
Luna Pollini ◽  
Alessandra Riccio ◽  
Cristina Juan ◽  
Carmela Tringaniello ◽  
Federica Ianni ◽  
...  
Keyword(s):  
Phenolic Acids ◽  
Inhibitory Activity ◽  
Leaf Extract ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Lycium Barbarum ◽  
Plant Materials ◽  
Vitro Assay ◽  
In Silico Studies

Nowadays, bioactive compounds from vegetable food and waste are of great interest for their inhibitory potential against digestive enzymes. In the present study, the inhibitory activity of methanolic extract from Lycium barbarum leaves on porcine pancreas α-amylase has been studied. The α-amylase inhibitory activity of the constituent phenolic acids was also investigated. The leaves were extracted by ultrasound-assisted method, one of the most efficient techniques for bioactive extraction from plant materials, and then the phenolic acids were identified by Accurate-Mass Quadrupole Time-of-Flight (Q-TOF) Liquid Chromatography/Mass Spectrometry (LC/MS). Chlorogenic and salicylic acids were the most abundant phenolic acids in L. barbarum leaf extract. The inhibitory effect against α-amylase, determined for individual compounds by in vitro assay, was higher for chlorogenic, salicylic, and caffeic acids. L. barbarum leaf extract showed an appreciable α-amylase inhibitory effect in a concentration-dependent manner. Docking studies of the considered phenolic acids into the active site of α-amylase suggested a conserved binding mode that is mainly stabilized through H-bonds and π-π stacking interactions.

Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro

2016 ◽  
Vol 27 (2) ◽  
Author(s):  
Ganiyu Oboh ◽  
Veronica O. Odubanjo ◽  
Fatai Bello ◽  
Ayokunle O. Ademosun ◽  
Sunday I. Oyeleye ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Inhibitory Effect ◽  
Seed Extract ◽  
Persea Americana ◽  
Dependent Manner ◽  
Natural Treatment

AbstractAvocado pear (The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of FeThe extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID.The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

Caffeic and chlorogenic acids inhibit key enzymes linked to type 2 diabetes (in vitro): a comparative study

2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Ganiyu Oboh ◽  
Odunayo M. Agunloye ◽  
Stephen A. Adefegha ◽  
Ayodele J. Akinyemi ◽  
Adedayo O. Ademiluyi
Keyword(s):  
Type 2 Diabetes ◽  
Chlorogenic Acid ◽  
Caffeic Acid ◽  
Phenolic Acids ◽  
Quinic Acid ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Key Enzymes

AbstractChlorogenic acid is a major phenolic compound that forms a substantial part of plant foods and is an ester of caffeic acid and quinic acid. However, the effect of the structures of both chlorogenic and caffeic acids on their antioxidant and antidiabetic potentials have not been fully understood. Thus, this study sought to investigate and compare the interaction of caffeic acid and chlorogenic acid with α-amylase and α-glucosidase (key enzymes linked to type 2 diabetes) activities in vitro.The inhibitory effect of the phenolic acids on α-amylase and α-glucosidase activities was evaluated. Thereafter, their antioxidant activities as typified by their 1,1-diphenyl-2 picrylhydrazyl radical scavenging ability and ferric reducing antioxidant properties were determined.The results revealed that both phenolic acids inhibited α-amylase and α-glucosidase activities in a dose-dependent manner (2–8 μg/mL). However, caffeic acid had a significantly (p<0.05) higher inhibitory effect on α-amylase [ICThe esterification of caffeic acid with quinic acid, producing chlorogenic acid, reduces their ability to inhibit α-amylase and α-glucosidase activities. Thus, the inhibition of α-amylase and α-glucosidase activities by the phenolic acids could be part of the possible mechanism by which the phenolic acids exert their antidiabetic effects.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

184 Two types of anti-TIGIT antibodies with distinct binding epitope and functional activities

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A198-A198
Author(s):  
Tingting Zhong ◽  
Xinghua Pang ◽  
Zhaoliang Huang ◽  
Na Chen ◽  
Xiaoping Jin ◽  
...  
Keyword(s):  
T Cells ◽  
Mixed Culture ◽  
Cell Activity ◽  
Cross Reactivity ◽  
Binding Activity ◽  
Jurkat Cells ◽  
List Type ◽  
Dependent Manner ◽  
Vitro Assay

BackgroundTIGIT is an inhibitory receptor mainly expressed on natural killer (NK) cells, CD8+ T cells, CD4+ T cells and Treg cells. TIGIT competes with CD226 for binding with CD155. In cancers, CD155 has been reported to up-regulate on tumor cells, and TIGIT was found to increase on TILs.1 Activation of TIGIT/CD155 pathway would mediate immunosuppression in tumor; while blockade of TIGIT promotes anti-tumor immune response.MethodsAK126 and AK113 are two humanized anti-human TIGIT monoclonal antibodies developed by Akesobio. Binding activity of AK126 and AK113 to human TIGIT, and competitive binding activity with CD155 and CD112, were performed by using ELISA, Fortebio, and FACS assays. Cross-reactivity with cynomolgus monkey TIGIT and epitope binning were also tested by ELISA assay. In-vitro assay to investigate the activity to promote IL-2 secretion was performed in mixed-culture of Jurkat-TIGIT cells and THP-1 cells.ResultsAK126 and AK113 could specifically bind to human TIGIT with comparative affinity and effectively blocked the binding of human CD155 and CD112 to human TIGIT. X-ray crystal structure of TIGIT and PVR revealed the C’-C’’ loop and FG loop regions of TIGIT are the main PVR interaction regions.2 The only amino acid residue differences in these regions between human and monkey TIGIT are 70C and 73D. AK126 binds to both human and monkey TIGIT, AK113 binds only to monkey TIGIT. This suggests that these residues are required for AK113 binding to human TIGIT, but not required for AK126. Interestingly, results from cell-based assays indicated that AK126 and AK113 showed significantly different activity to induce IL-2 secretion in mixed-culture of Jurkat-TIGIT cells and THP-1 cells (figure 1A and B), in which AK126 had a comparable capacity of activity to 22G2, a leading TIGIT mAb developed by another company, to induce IL-2 secretion, while, AK113 showed a significantly higher capacity than 22G2 and AK126.Abstract 184 Figure 1Anti-TIGIT Antibodies Rescues IL-2 Production in Vitro T-Cell Activity Assay in a dose dependent manner. Jurkat-TIGIT cells (Jurkat cells engineered to over-express human TIGIT) were co-cultured with THP-1 cells, and stimulated with plate-bound anti-CD3 mAb in the presence of TIGIT ligand CD155 (A) or CD112 (B) with anti-TIGIT antibodies. After incubated for 48h at 37° C and 5.0% CO2, IL-2 levels were assessed in culture supernatants by ELISA. Data shown as mean with SEM for n = 2.ConclusionsWe discovered two distinct types of TIGIT antibodies with differences in both epitope binding and functional activity. The mechanism of action and clinical significance of these antibodies require further investigation.ReferencesSolomon BL, Garrido-Laguna I. TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother 2018;67:1659–1667.Stengel KF, Harden-Bowles K, Yu X, et al. Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell-cell adhesion and signaling mechanism that requires cis-trans receptor clustering. Proc Natl Acad Sci USA 2012;109:5399–5404.

scholarly journals Identification of Vinyl Sulfone Derivatives as EGFR Tyrosine Kinase Inhibitor: In Vitro and In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2211
Author(s):  
Thitinan Aiebchun ◽  
Panupong Mahalapbutr ◽  
Atima Auepattanapong ◽  
Onnicha Khaikate ◽  
Supaphorn Seetaha ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Kinase Inhibitor ◽  
Kinase Assay ◽  
Vinyl Sulfone ◽  
Egfr Tyrosine Kinase ◽  
In Silico Studies ◽  
Sulfone Derivatives

Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site. Afterwards, these screened compounds were tested for the inhibitory activity towards EGFR-TK using ADP-Glo™ kinase assay, and we found that only VF16 compound exhibited promising inhibitory activity against EGFR-TK with the IC50 value of 7.85 ± 0.88 nM. In addition, VF16 showed a high cytotoxicity with IC50 values of 33.52 ± 2.57, 54.63 ± 0.09, and 30.38 ± 1.37 µM against the A431, A549, and H1975 cancer cell lines, respectively. From 500-ns MD simulation, the structural stability of VF16 in complex with EGFR-TK was quite stable, suggesting that this compound could be a novel small molecule inhibitor targeting EGFR-TK.

scholarly journals Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110166
Author(s):  
Xin Yi Lim ◽  
Janice Sue Wen Chan ◽  
Terence Yew Chin Tan ◽  
Bee Ping Teh ◽  
Mohd Ridzuan Mohd Abd Razak ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Rna Binding ◽  
Symptomatic Relief ◽  
Andrographis Paniculata ◽  
Spike Protein ◽  
Rapid Review ◽  
In Silico Studies

Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

scholarly journals SAT0363 DELPHINIDIN DOSE-DEPENDENTLY DIMINISHES PERIPHERAL IL-17 AND IFN-Γ PRODUCING LYMPHOCYTES IN PSORIATIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1128.1-1129
Author(s):  
A. Mavropoulos ◽  
S. Tsiogkas ◽  
D. Skyvalidas ◽  
C. Liaskos ◽  
A. Roussaki-Schulze ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Cell Viability ◽  
Annexin V ◽  
Nkt Cells ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Research Support ◽  
Research Activities ◽  
Ifn Γ

Background:Delphinidin, a dietary anthocyanidin and powerful anti-oxidant from pigmented fruits and vegetables, has broad anti-inflammatory properties. In a human skin model of psoriasis, delphinidin reduced expression of proliferative and inflammatory markers (1).Objectives:The rationale of our study was to assess whether delphinidin can in vitro suppress IL-17 and IFN-γ production in peripheral blood mononuclear cell (PBMC) subsets from patients with psoriatic arthritis (PsA).Methods:PBMCs were obtained from 24 patients with PsA attending the outpatient clinic of the Department of Rheumatology/clinical Immunology at the University General Hospital of Larissa, Greece. 16 age- and sex-matched healthy volunteers were also included in the study. Delphinidin was supplemented at a concentration ranging from 1 to 50μg/ml, one hour prior to cell stimulation. Cell viability (Annexin V staining) and innate/adaptive lymphocyte subpopulations were assessed by flow cytometry with a panel of fluorochrome-conjugated antibodies against CD56, CD3, CD4 and CD8. Intracellular expression of IL-17 and IFN-γ was measured following PMA/ionomycin stimulation for 5 hours using standard cell permeabilization protocols and monoclonal antibodies against IL-17 and IFN-γResults:Delphinidin at concentration ≥10 μg/ml sharply diminished IL-17-production by CD4(+) T cells (Th17) and CD56(+)CD3(+) (NKT) cells from patients with psoriatic arthritis and normal controls (p≤0.05). IFN-γ producing T (CD4 and CD8) cells, as well as NK and NKT cells were also dose-dependently suppressed following delphinidin pre-incubation in both patients and healthy controls. Inhibition of IFN-γ(+) cells ranged from 27 to 69% and peaked at delphinidin concentration 20-50μg/ml. The inhibitory effect of delphinidin on IL-17 and IFN-γ producing lymphocytes was not due to compromised cell viability, as assessed by annexin V binding.Conclusion:Delphinidin exerts, in a dose-dependent manner, a profound in vitro inhibitory effect on T cell and NKT cell IL-17 and IFN-γ production in PsA, and therefore, it may be used as a dietary immunosuppressant, complementary to standard treatment.References:[1]Chamcheu JC Skin Pharmacol Physiol. 2015;28(4):177-88. doi: 10.1159/000368445Disclosure of Interests:ATHANASIOS MAVROPOULOS: None declared, Sotirios Tsiogkas: None declared, Dimitrios Skyvalidas: None declared, Christos Liaskos: None declared, Aggeliki Roussaki-Schulze Grant/research support from: Received a grant to support the educational and research activities of the department from Genesis Pharma (2018), Speakers bureau: Received honoraria from Genesis Pharma and Janssen(2017) and from Roche and Pharmaserve Lilly(2018), Efterpi Zafiriou Speakers bureau: Received honoraria from Genesis Pharma, Abbvie, Novartis, Roche, Jansses(2017) and Novartis, Abbvie(2018), Dimitrios Bogdanos: None declared, Lazaros Sakkas Grant/research support from: Received a grant to support the educational and research activities of the department from Bristol-Meyers Squib, Speakers bureau: Received honoraria from Actellion(2018), Janssen(2017), Novartis(2017), Sanofi-Aventis(2018), Abbvie(2017) and Roche(2017)

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

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