scholarly journals Structural Features of Three Hetero-Galacturonans from Passiflora foetida Fruits and Their in Vitro Immunomodulatory Effects

Polymers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 615 ◽  
Author(s):  
Ya Song ◽  
Peng Wen ◽  
Huili Hao ◽  
Minqian Zhu ◽  
Yuanming Sun ◽  
...  
Keyword(s):  
Structural Features ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Minimum Effective Concentration ◽  
Enhancing Effect ◽  
Traditional Chinese Herbal Medicine ◽  
Raw264.7 Macrophages ◽  
Pharmaceutical Industries ◽  
Passiflora Foetida

Passiflora foetida is a horticultural plant and vital traditional Chinese herbal medicine. In our previous study, the characterization and immuno-enhancing effect of fruits polysaccharide 1 (PFP1), a water-eluted hetero-mannan from wild Passiflora foetida fruits, were investigated. Herein, another three salt-eluted novel polysaccharides, namely PFP2, PFP3, and PFP4, were obtained and structurally characterized. The results showed that PFP2, PFP3, and PFP4 were three structurally similar hetero-galacturonans with different molecular weights of 6.11 × 104, 4.37 × 104, and 3.48 × 105 g/mol, respectively. All three of these hetero-galacturonans are mainly composed of galacturonic acid, galactose, arabinose (75.69%, 80.39%, and 74.30%, respectively), and other monosaccharides including mannose, fucose, glucose, ribose, xylose, and glucuronic acid (24.31%, 19.61, and 25.70%, respectively), although differences in their backbone structure exist. Additionally, immunomodulatory assay indicated that the three hetero-galacturonans possess the ability to promote the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in RAW264.7 macrophages in a concentration-dependent manner (p < 0.05). Especially, PFP3 displayed a stronger enhancing effect than PFP2 and PFP4 at the minimum effective concentration. Therefore, the results suggested that the obtained three salt-eluted hetero-galacturonans, especially PFP3, could be utilized as immunomodulatory effectivity ingredients in nutritional/pharmaceutical industries.

Lysophosphatidic acid rapidly induces protein kinase D activation through a pertussis toxin-sensitive pathway

2000 ◽  
Vol 278 (1) ◽  
pp. C33-C39 ◽  
Author(s):  
Lina Paolucci ◽  
James Sinnett-Smith ◽  
Enrique Rozengurt
Keyword(s):  
Protein Kinase ◽  
Pertussis Toxin ◽  
Lysophosphatidic Acid ◽  
Kinase Inhibitor ◽  
Structural Features ◽  
Protein Kinase D ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Swiss 3T3

Protein kinase D (PKD) is a serine-threonine protein kinase with distinct structural features and enzymological properties. Herein we demonstrate that lysophosphatidic acid (LPA) induces rapid PKD activation in mouse Swiss 3T3 and Rat-1 cells. LPA induced PKD activation in a concentration-dependent fashion with maximal stimulation (7.6-fold) achieved at 5 μM. Treatment of Swiss 3T3 cells with the protein kinase C (PKC) inhibitors GF-I, Ro-31–8220, and Gö-7874 completely abrogated PKD activation induced by LPA at concentrations that did not inhibit PKD activity when added directly to the in vitro kinase assays. PKD activation induced by LPA was attenuated markedly and selectively by prior exposure of either Swiss 3T3 or Rat-1 cells to pertussis toxin (PTx) in a concentration-dependent manner. In contrast, treatment with the protein tyrosine kinase inhibitor genistein, the MEK inhibitor PD-098059, or the phosphoinositide 3-kinase inhibitor wortmannin did not affect PKD activation in response to LPA. These results provide the first example of PTx-sensitive and PKC-dependent PKD activation and identify a novel Gi-dependent event in the action of LPA.

scholarly journals Cytotoxicity, Phytochemical, Antiparasitic Screening, and Antioxidant Activities of Mucuna pruriens (Fabaceae)

Plants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1249 ◽  
Author(s):  
Mahboob Adekilekun Jimoh ◽  
Oladayo Amed Idris ◽  
Muhali Olaide Jimoh
Keyword(s):  
Gallic Acid ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Mucuna Pruriens ◽  
Total Phenolic ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Antioxidant Power ◽  
Pharmaceutical Industries

This study aimed at assessing the biological activities of Mucuna pruriens seeds using cytotoxicity, phytochemical, antiparasitic screening, and antioxidant assays. Mature fruits of M. pruriens were harvested from Fort Hare University’s Research Farm located in Alice, South Africa. The collected seeds were pulverized in a standard process and taken to the laboratory for crude extraction and further treatments. Cytotoxic, antimalarial, and trypanocidal effects of crude extracts obtained from ethanol and water were tested, while the total phenolic, proanthocyanidin, and flavonoid contents of the aqueous extracts as well as their pharmacological activities were determined in vitro using 2,2-diphenyl-1-picrylhydrazyl ethanol (DPPH), ferric reducing antioxidant power (FRAP), and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Although the extracts showed mild antiparasitic (antiplasmodial and trypanocidal) effects, results from the cytotoxic experiment revealed that M. pruriens is not toxic to human cervix adenocarcinoma (HeLa) cells when tested using 50 µg/mL of extracts. It was observed that the seeds were remarkably rich in phenol (3730.1 ± 15.52 mg gallic acid equivalent (GAE)/g) compared to flavonoids (63.03 ± 1.95 mg quercetin equivalent (QE)/g) and proanthocyanidin (18.92 ± 1.09 mg catechin equivalent (CE)/g). Also, the antioxidant activities of the extracts were comparable to those of the standard antioxidant drugs (rutin and gallic acid) used, in a concentration-dependent manner. There was a direct relationship between phenolic acid content and antioxidant effects. It is therefore suggested that M. pruriens seeds be incorporated into human diets as a supplement to promote healthy living. Pharmaceutical industries with a particular interest in natural phenolic acids should consider using seeds of M. pruriens as pharmaceutical precursors.

scholarly journals Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1271 ◽  
Author(s):  
Tomas Šneideris ◽  
Lina Baranauskienė ◽  
Jonathan G. Cannon ◽  
Rasa Rutkienė ◽  
Rolandas Meškys ◽  
...  
Keyword(s):  
Beta Amyloid ◽  
Structural Features ◽  
Alpha Synuclein ◽  
Fibril Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Amyloid Fibril Formation ◽  
Flavone Derivatives ◽  
Alpha Synuclein Aggregation

A range of diseases is associated with amyloid fibril formation. Despite different proteins being responsible for each disease, all of them share similar features including beta-sheet-rich secondary structure and fibril-like protein aggregates. A number of proteins can form amyloid-like fibrilsin vitro, resembling structural features of disease-related amyloids. Given these generic structural properties of amyloid and amyloid-like fibrils, generic inhibitors of fibril formation would be of interest for treatment of amyloid diseases. Recently, we identified five outstanding inhibitors of insulin amyloid-like fibril formation among the pool of 265 commercially available flavone derivatives. Here we report testing of these five compounds and of epi-gallocatechine-3-gallate (EGCG) on aggregation of alpha-synuclein and beta-amyloid. We used a Thioflavin T (ThT) fluorescence assay, relying on halftimes of aggregation as the measure of inhibition. This method avoids large numbers of false positive results. Our data indicate that four of the five flavones and EGCG inhibit alpha-synuclein aggregation in a concentration-dependent manner. However none of these derivatives were able to increase halftimes of aggregation of beta-amyloid.

scholarly journals Microtubule bundling by MAP65-1 protects against severing by inhibiting the binding of katanin

2019 ◽  
Vol 30 (13) ◽  
pp. 1587-1597 ◽  
Author(s):  
Graham M. Burkart ◽  
Ram Dixit
Keyword(s):  
Cortical Microtubule ◽  
Structural Features ◽  
Cross Linking ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Concentration Dependent Manner ◽  
Mutant Proteins ◽  
Microtubule Severing ◽  
Biological Studies

The microtubule-severing enzyme katanin (KTN1) regulates the organization and turnover of microtubule arrays by the localized breakdown of microtubule polymers. In land plants, KTN1 activity is essential for the formation of linearly organized cortical microtubule arrays that determine the axis of cell expansion. Cell biological studies have shown that even though KTN1 binds to the sidewalls of single and bundled microtubules, severing activity is restricted to microtubule cross-over and nucleation sites, indicating that cells contain protective mechanisms to prevent indiscriminate microtubule severing. Here, we show that the microtubule-bundling protein MAP65-1 inhibits KTN1-mediated microtubule severing in vitro. Severing is inhibited at bundled microtubule segments and the severing rate of nonbundled microtubules is reduced by MAP65-1 in a concentration-dependent manner. Using various MAP65-1 mutant proteins, we demonstrate that efficient cross-linking of microtubules is crucial for this protective effect and that microtubule binding alone is not sufficient. Reduced severing due to microtubule bundling by MAP65-1 correlated to decreased binding of KTN1 to these microtubules. Taken together, our work reveals that cross-linking of microtubules by MAP65-1 confers resistance to severing by inhibiting the binding of KTN1 and identifies the structural features of MAP65-1 that are important for this activity.

scholarly journals Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial

2020 ◽  
Vol 75 (9) ◽  
pp. 2376-2380 ◽  
Author(s):  
Minh Patrick Lê ◽  
Nathan Peiffer-Smadja ◽  
Jeremie Guedj ◽  
Nadège Néant ◽  
France Mentré ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Loading Dose ◽  
Short Term ◽  
Concentration Dependent Manner ◽  
Minimum Effective Concentration ◽  
Once Daily ◽  
Target Drug ◽  
Infection Treatment ◽  
State Concentration

Abstract Around the world, several dose regimens of hydroxychloroquine have been used for COVID-19 infection treatment, with the objective of identifying a short-term course. Hydroxychloroquine was found to decrease the viral replication in a concentration-dependent manner in vitro and to be more active when added prior to the viral challenge. A loading dose is used to rapidly attain a target drug concentration, which is usually considered as approximately the steady-state concentration. With a loading dose, the minimum effective concentration is reached much more rapidly than when using only the maintenance dose from the start. Thus, we propose a hydroxychloroquine sulphate dose regimen of 400 mg twice daily at Day 1 then 400 mg once daily from Day 2 to Day 10. We aim to evaluate this in the C-20-15 DisCoVeRy trial.

scholarly journals Antibacterial Activity of Licochalcone A against Spore-Forming Bacteria

2002 ◽  
Vol 46 (5) ◽  
pp. 1226-1230 ◽  
Author(s):  
Ryo-Ichi Tsukiyama ◽  
Harumi Katsura ◽  
Nozomu Tokuriki ◽  
Makio Kobayashi
Keyword(s):  
Antibacterial Activity ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Licochalcone A ◽  
Heat Treated ◽  
Pharmaceutical Industries ◽  
High Concentrations ◽  
Glycyrrhiza Inflata ◽  
High Level

ABSTRACT Licochalcone A was isolated from the roots of licorice, Glycyrrhiza inflata, which has various uses in the food and pharmaceutical industries; isolation was followed by extraction with ethanol and column chromatography with silica gel. In this study, the activities of licochalcone A against some food contaminant microorganisms were evaluated in vitro. The vegetative cell growth of Bacillus subtilis was inhibited in a licochalcone A concentration-dependent manner and was completely prevented by 3 μg of licochalcone A/ml. Licochalcone A showed a high level of resistance to heating at 80 to 121°C for 15 min. Licochalcone A did not inhibit the germination of heat-treated spores of B. subtilis induced by l-alanine. Licochalcone A showed effects against all gram-positive bacteria tested and especially was effective against all Bacillus spp. tested, with MICs of 2 to 3 μg/ml, but was not effective against gram-negative bacteria or eukaryotes at 50 μg/ml. Although the cationic antimicrobial peptides protamine and ε-poly-l-lysine resulted in the loss of antimicrobial activity in the presence of either 3% (wt/vol) NaCl or protease at 20 μg/ml, the antibacterial activity of licochalcone A was resistant to these conditions. Thus, licochalcone A could be a useful compound for the development of antibacterial agents for the preservation of foods containing high concentrations of salts and proteases, in which cationic peptides might be less effective.

scholarly journals Microtubule bundling by MAP65-1 protects against severing by inhibiting the binding of katanin

2019 ◽  
Author(s):  
Graham M Burkart ◽  
Ram Dixit
Keyword(s):  
Cortical Microtubule ◽  
Structural Features ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Concentration Dependent Manner ◽  
Mutant Proteins ◽  
Microtubule Severing ◽  
Biological Studies

ABSTRACTThe microtubule-severing enzyme katanin regulates the organization and turnover of microtubule arrays by the localized breakdown of microtubule polymers. In land plants, katanin (KTN1) activity is essential for the formation of linearly organized cortical microtubule arrays which determine the axis of cell expansion. Cell biological studies have shown that even though KTN1 binds to the sidewalls of single and bundled microtubules, severing activity is restricted to microtubule crossover and nucleation sites, indicating that cells contain protective mechanisms to prevent indiscriminate microtubule severing. Here, we show that the microtubule bundling protein MAP65-1 inhibits KTN1-mediated microtubule severing in vitro. Severing is inhibited at bundled microtubule segments and the severing rate of non-bundled microtubules is reduced by MAP65-1 in a concentration-dependent manner. Using various MAP65-1 mutant proteins, we demonstrate that efficient crosslinking of microtubules is crucial for this protective effect and that microtubule binding alone is not sufficient. Reduced severing due to microtubule bundling by MAP65-1 correlated to decreased binding of KTN1 to these microtubules. Taken together, our work reveals that crosslinking of microtubules by MAP65-1 confers resistance to severing by inhibiting the binding of katanin and identifies the structural features of MAP65-1 that are important for this activity.Highlight SummaryCortical microtubule bundles resist severing in vivo. Here, we show that crosslinking of microtubules by MAP65-1 inhibits severing in a dose-dependent manner by preventing katanin from binding to these microtubules.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells

2020 ◽  
Vol 16 (3) ◽  
pp. 358-362
Author(s):  
Renan S. Teixeira ◽  
Paulo H.D. Carvalho ◽  
Jair A.K. Aguiar ◽  
Valquíria P. Medeiros ◽  
Ademar A. Da Silva Filho ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Crude Extract ◽  
Hepg2 Cells ◽  
Liver Carcinoma ◽  
Adhesion Assay ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Arctium Lappa ◽  
Nih 3T3

Background: Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma (HepG2) and fibroblasts (NIH/3T3). Methods: Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity. Results: Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a concentration-dependent manner, when compared with control. Conclusion: These results suggest a promising pharmacological activity for arctigenin as an antiproliferative compound.

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