ACYLATED FLAVONOIDS OF SPIRAEA GENUS AS α-AMYLASE INHIBITORS

Spiraea L. is a genus of deciduous shrubs of Rosaceae family widespread on the territory of Eastern Siberia. As a result of the study of six Spiraea species growing on the Baikal region, it was shown that they characterized by a high content of phenolic compounds and their extracts had an inhibitory effect on α-amylase. The use of correlation analysis made it possible to reveal the leading role of flavonoids as carriers of the biological effect of extracts. The most active was the extract of S. salicifolia leaves with an IC50 value 69,30 μg/mL After fractionation and chromatographic separation of the extractive substances, 18 compounds were isolated from the ethyl acetate fraction of S. salicifolia and fifteen of them for the first time for the species, including trifolin, 6′′-O-caffeoyl-hyperoside, 6′′-O-caffeoyl-isoquercitrin, 6′′-O-caffeoyl-astragalin, 1-O-p-hydroxybenzoyl-6-O-p-coumaroyl-β-d-glucopyranoside, 3,4,5-tri-O-caffeoylquinic acid, isoramnetinin-3-O-β-d-glucopyranoside, tiliroside, isoramnetin-3-O-α-l-rhamnopyranoside, 1-O-cis-cinnamoyl-6-O-(2′-methylene-4′-hydroxybutyroyl)-β-d-glucopyranose, 1-О-(4′′-hydroxy-3′′-methylfurane-2′′-one)-6-О-trans-cinnamoyl-β-d-glucopyranose, 1-О-(4′′-hydroxy-3′′-methylfurane-2′′-one)-6-О-cis-cinnamoyl-β-d-glucopyranose, 6-tuliposide A and tulipalin A. The most active inhibitors of α-amylase were flavonoid caffeoyl glycosides with 6′′-O-caffeoyl-hyperoside as a most effective inhibitor with IC50 value 46.18 μg/mL. Latter compound determined the total anti-α-amylase effect of S. salicifolia. The content of 6′′-O-caffeoyl-hyperoside in leaves of S. salicifolia was 0,60-10,53 mg/g and flavonoids – 12,02-23,17 mg/g. This study demonstrated the fact that the acylated flavonoids of Spiraea are effective inhibitors of α-amylase.

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Dynamics of intravital concentration of amino acid metabolites in human brain in post-traumatic period

Доклады Академии наук ◽

10.31857/s0869-56524842238-242 ◽

2019 ◽

Vol 484 (2) ◽

pp. 238-242

Author(s):

N. A. Semenova ◽

P. E. Menshchikov ◽

A. V. Manzhurtsev ◽

M. V. Ublinskiy ◽

T. A. Akhadov ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Amino Acid ◽

Human Brain ◽

Leading Role ◽

Acid Metabolites ◽

Post Traumatic ◽

First Time

Intracellular concentrations of N acetyaspartate (NAA), aspartate (Asp) and glutamate (Glu) were determined for the first time in human brain in vivo, and the effect of severe traumatic brain injury on NAA synthesis in acute and late post-traumatic period was investigated. In MRI‑negative frontal lobes one day after injury Asp and Glu levels were found to decrease by 45 and 35%, respectively, while NAA level decreased by only 16%. A negative correlation between NAA concentration and the ratio of Asp/Glu concentrations was found. In the long-term period, Glu level returned to normal, Asp level remained below normal by 60%, NAA level was reduced by 65% relative to normal, and Asp/Glu ratio significantly decreased. The obtained results revealed leading role of the neuronal aspartate-malate shuttle in violation of NAA synthesis.

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Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches

Stem Cells International ◽

10.1155/2015/796215 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

T. Jazedje ◽

A. L. Ribeiro ◽

M. Pellati ◽

H. M. de Siqueira Bueno ◽

G. Nagata ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Cell Lineage ◽

Inhibitory Effect ◽

Mammary Adenocarcinoma ◽

Breast Adenocarcinoma ◽

Human Fallopian Tube ◽

Initial Stage ◽

First Time

The use of Mesenchymal Stromal Cells (MSCs) aiming to treat cancer has shown very contradictory results. In an attempt to clarify the contradictory results reported in the literature and the possible role of human fallopian tube Mesenchymal Stromal Cells (htMSCs) against breast cancer, the aim of this study was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma using two different approaches: (1) coinjections of htMSCs and 4T1 murine tumor cell lineage and (2) injections of htMSCs in mice at the initial stage of mammary adenocarcinoma development. Coinjected animals had a more severe course of the disease and a reduced survival, while tumor-bearing animals treated with 2 intraperitoneal injections of 106htMSCs showed significantly reduced tumor growth and increased lifespan as compared with control animals. Coculture of htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased VEGF production. For the first time, we show that MSCs isolated from a single source and donor when injected in the same animal model and tumor can lead to opposite results depending on the experimental protocol. Also, our results demonstrated that htMSCs can have an inhibitory effect on the development of murine mammary adenocarcinoma.

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Characterization of the secretory profile and exosomes of limbal stem cells in the canine species

PLoS ONE ◽

10.1371/journal.pone.0244327 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244327

Author(s):

Antonio J. Villatoro ◽

Cristina Alcoholado ◽

María del Carmen Martín-Astorga ◽

Gustavo Rico ◽

Viviana Fernández ◽

...

Keyword(s):

Stem Cells ◽

Ocular Surface ◽

Inhibitory Effect ◽

Proteomic Profile ◽

Limbal Stem Cells ◽

High Concentrations ◽

First Time

Limbal stem cells (LSCs) are a quiescent cell population responsible for the renewal of the corneal epithelium. Their deficiency is responsible for the conjunctivization of the cornea that is seen in different ocular pathologies, both in humans and in the canine species. The canine species represents an interesting preclinical animal model in ocular surface pathologies. However, the role of LSCs in physiological and pathological conditions in canine species is not well understood. Our objective was to characterize for the first time the soluble factors and the proteomic profile of the secretome and exosomes of canine LSCs (cLSCs). In addition, given the important role that fibroblasts play in the repair of the ocular surface, we evaluated the influence of the secretome and exosomes of cLSCs on their proliferation in vitro. Our results demonstrated a secretory profile of cLSCs with high concentrations of MCP-1, IL-8, VEGF-A, and IL-10, as well as significant production of exosomes. Regarding the proteomic profile, 646 total proteins in the secretome and 356 in exosomes were involved in different biological processes. Functionally, the cLSC secretome showed an inhibitory effect on the proliferation of fibroblasts in vitro, which the exosomes did not. These results open the door to new studies on the possible use of the cLSC secretome or some of its components to treat certain pathologies of the ocular surface in canine species.

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Dopamine Modulates Drosophila Gut Physiology, Providing New Insights for Future Gastrointestinal Pharmacotherapy

Biology ◽

10.3390/biology10100983 ◽

2021 ◽

Vol 10 (10) ◽

pp. 983

Author(s):

Samar El Kholy ◽

Kai Wang ◽

Hesham R. El-Seedi ◽

Yahya Al Naggar

Keyword(s):

Dopamine Receptors ◽

Smooth Muscles ◽

Model Organism ◽

Inhibitory Effect ◽

Adult Males ◽

Gal4 Driver ◽

Intestinal Physiology ◽

Gut Physiology ◽

First Time

Dopamine has a variety of physiological roles in the gastrointestinal tract (GI) through binding to Drosophila dopamine D1-like receptors (DARs) and/or adrenergic receptors and has been confirmed as one of the enteric neurotransmitters. To gain new insights into what could be a potential future promise for GI pharmacology, we used Drosophila as a model organism to investigate the effects of dopamine on intestinal physiology and gut motility. GAL4/UAS system was utilized to knock down specific dopamine receptors using specialized GAL4 driver lines targeting neurons or enterocytes cells to identify which dopamine receptor controls stomach contractions. DARs (Dop1R1 and Dop1R2) were shown by immunohistochemistry to be strongly expressed in all smooth muscles in both larval and adult flies, which could explain the inhibitory effect of dopamine on GI motility. Adult males’ gut peristalsis was significantly inhibited by knocking down dopamine receptors Dop1R1, Dop1R2, and Dop2R, but female flies’ gut peristalsis was significantly repressed by knocking down only Dop1R1 and Dop1R2. Our findings also showed that dopamine drives PLC-β translocation from the cytoplasm to the plasma membrane in enterocytes for the first time. Overall, these data revealed the role of dopamine in modulating Drosophila gut physiology, offering us new insights for the future gastrointestinal pharmacotherapy of neurodegenerative diseases associated with dopamine deficiency.

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The role of mitochondria in the molecular and cellular effects of radon

BULLETIN of the L N Gumilyov Eurasian National University BIOSCIENCE Series ◽

10.32523/2616-7034-2021-135-2-71-85 ◽

2021 ◽

Vol 135 (2) ◽

pp. 71-85

Author(s):

O.V. Bulgakova ◽

◽

G.A. Toksabayeva ◽

A.A. Aripova ◽

A.Zh. Kausbekova ◽

...

Keyword(s):

Ionizing Radiation ◽

Malignant Transformation ◽

World Health ◽

Cellular Effects ◽

Leading Role ◽

The Moment ◽

Health Organization ◽

Unique Cell ◽

First Time

Mitochondria are unique cell organoids that have their own mitochondrial DNA. They are involved in the regulation of many processes, such as cell survival, apoptosis, and cellular metabolism. It has long been known that mitochondria play a leading role in the mechanism of malignant transformation in the development of many neoplasms. Radon is a radioactive inert gas, is recognized as a carcinogen and, according to the World Health Organization, it is the second cause of lung cancer after smoking. Radon is found in soil, water and air in various concentrations. Radon migrates from the soil and rocks into the surrounding air, as a result of which it accumulates in poorly ventilated or closed rooms. Such areas represent the primary environment in which people are exposed to radioactive radon radiation. Radon penetrates through cracks in the Earth's crust and accumulates in the lower layers of the atmosphere. An increase in the concentration of radon in the air is observed in regions rich in uranium deposits, as well as near uranium mines. However, at the moment, the mechanisms of malignant transformation induced by radon are still not completely clear. In this review, we consider for the first time the most modern understanding of the role of mitochondria in the molecular and cellular effects of ionizing radiation, including radon. This kind of knowledge can be of great importance for improving the antitumor effectiveness of radiation therapy, as well as for reducing damage to healthy cells exposed to ionizing radiation and protecting the population living in an area potentially dangerous for radon manifestations.

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α-Amilase Inhibitory Activity of Fraction of Ethanolic Extract of Lebui Seed (Cajanus cajan (L.) Millsp.) Grown in West Nusa Tenggara

Journal of Food and Pharmaceutical Sciences ◽

10.22146/jfps.720 ◽

2020 ◽

pp. 266-272

Author(s):

Dian Resti Setyaningrum ◽

Rumiyati ◽

Yekti Asih Purwestri ◽

Satrijo Saloko ◽

Agung Endro Nugroho ◽

...

Keyword(s):

Ethyl Acetate ◽

Ethyl Acetate Fraction ◽

Alpha Amylase ◽

Hexane Fraction ◽

Inhibition Activity ◽

Water Fraction ◽

Ic50 Value ◽

Bioactive Content ◽

Amylase Inhibitors

Diabetes is a metabolic syndrome characterized by high blood sugar levels or hyperglycemia.Alpha-amylase inhibitors can be used as an antidiabetic that controls postprandial hyperglycemia.Alpha-amylase inhibitors are found in plants as protein and non-protein bioactive content such as in lebuiseed. The purpose of this study was to determine the activity of alpha-amylase inhibition of the fraction ofethanol extract of lebui seed. This research was carried out by extraction of lebui seed and then fractionatedlebui extract to obtain n-hexane fraction (HF), ethyl acetate fraction (EAF), and water fraction (WF). Thefractions then tested to alpha-amylase inhibition activity in vitro by measuring the reducing sugar using3.5-dinitrosalicylic (DNS) reagent. Furthermore, the identification of the bioactive content of each fraction wascarried out using thin layer chromatography. The results of alpha-amylase inhibition activity test showed thatall fractions had the ability to inhibit alpha-amylase. The IC50 value of the n-hexane fraction, ethyl acetatefraction, and water fraction were 173.05 mg/ml, 9.98 mg/ml, and 137.19 mg/ml, respectively. Ethyl acetatefraction has the smallest IC50 value compared to other fractions. Based on the identification of the bioactivecontent, bioactive content that is only found in the ethyl acetate fraction but not in other fractions are tannins.Therefore, the chemical content in lebui seed which acts as an alpha-amylase inhibitor might be tannins.

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Discovery of a Novel ERp57 Inhibitor as Antiplatelet Agent from Danshen (Salvia miltiorrhiza)

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/9387568 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Jia Zou ◽

Yang Chen ◽

Maggie Pui Man Hoi ◽

Jun Li ◽

Tao Wang ◽

...

Keyword(s):

Platelet Aggregation ◽

Rosmarinic Acid ◽

Salvia Miltiorrhiza ◽

Antiplatelet Agent ◽

Underlying Mechanism ◽

Inhibitory Effect ◽

Inhibitory Effects ◽

Protein Disulfide ◽

First Time

Danshen (Salvia miltiorrhiza) is a well-known herb in Traditional Chinese Medicine (TCM) for treating cardiovascular diseases, but the underlying mechanism remains to be fully elucidated. Here, we showed that Danshen and its active ingredient rosmarinic acid exhibited antiplatelet effects through the inhibition of ERp57, a member of protein disulfide isomerase (PDI) with potential roles in platelet aggregation. Danshen extract (DSE) exhibited potent inhibitory effects on the platelet aggregation induced by arachidonic acid- (AA-) induced platelet aggregation and the enzymatic activity of ERp57. Rosmarinic acid was identified by virtual screening and molecular docking as one of the hit compounds for ERp57. In line with this, rosmarinic acid displayed significant inhibitory effect on ERp57 activity and inhibited AA-induced platelet aggregation. Taken together, we demonstrated for the first time that DSE and rosmarinic acid displayed inhibitory effects on the catalytic activity of ERp57, providing evidence of the regulatory role of ERp57 underlying the antiplatelet effects of Danshen.

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Optimization and Anti-Cancer Properties of Fluoromethylketones as Covalent Inhibitors for Ubiquitin C-Terminal Hydrolase L1

Molecules ◽

10.3390/molecules26051227 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1227

Author(s):

Aaron D. Krabill ◽

Hao Chen ◽

Sajjad Hussain ◽

Chad S. Hewitt ◽

Ryan D. Imhoff ◽

...

Keyword(s):

Biological Evaluation ◽

Deubiquitinating Enzyme ◽

Migration Behavior ◽

Disease States ◽

Ic50 Value ◽

Anti Cancer ◽

Covalent Inhibitors ◽

And Migration ◽

First Time

The deubiquitinating enzyme (DUB) UCHL1 is implicated in various disease states including neurodegenerative disease and cancer. However, there is a lack of quality probe molecules to gain a better understanding on UCHL1 biology. To this end a study was carried out to fully characterize and optimize the irreversible covalent UCHL1 inhibitor VAEFMK. Structure-activity relationship studies identified modifications to improve activity versus the target and a full cellular characterization was carried out for the first time with this scaffold. The studies produced a new inhibitor, 34, with an IC50 value of 7.7 µM against UCHL1 and no observable activity versus the closest related DUB UCHL3. The molecule was also capable of selectively inhibiting UCHL1 in cells and did not demonstrate any discernible off-target toxicity. Finally, the molecule was used for initial probe studies to assess the role of UCHL1 role in proliferation of myeloma cells and migration behavior in small cell lung cancer cells making 34 a new tool to be used in the biological evaluation of UCHL1.

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Inter-sexual multimodal communication during mating in wild geladas: the leading role of females

Current Zoology ◽

10.1093/cz/zoab093 ◽

2021 ◽

Author(s):

Anna Zanoli ◽

Marco Gamba ◽

Alban Lemasson ◽

Ivan Norscia ◽

Elisabetta Palagi

Keyword(s):

Success Probability ◽

Multimodal Communication ◽

Visual Signals ◽

Vocal Behavior ◽

Honest Signals ◽

Leading Role ◽

Mating Calls ◽

First Time ◽

Signal Exchange

Abstract Female primates can emit vocalizations associated with mating that can function as honest signals of fertility. Here, we investigated the role of mating calls and visual signals in female geladas Theropithecus gelada. Since females have a central role in the gelada society and seem to solicit sexual interactions, we answered whether they emit vocalizations in conjunction with gazing to increase mating success probability. Before and during copulations, females can emit pre-copulation calls and copulation calls. For the first time, we identified a new female vocalization emitted at the final stage of copulations (end-copulation call), possibly marking the occurrence of ejaculation. We found that longer pre-copulation call sequences were followed by both prolonged copulations and the presence of end-copulation calls thus suggesting that females use pre-copulation calls to ensure successful copula completion. Moreover, we found that different combinations of female vocal types and gazing had different effects on male vocal behavior and motivation to complete the copula. The analysis of the vocal and visual signals revealed a complex inter-sexual multimodal chattering with the leading role of females in the signal exchange. Such chattering, led by females, modulates male sexual arousal, thus increasing the probability of the copula success.

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Inhibition of pathogenicSalmonellaenteritidisgrowth mediated byEscherichia colimicrocin J25 producing strains

Canadian Journal of Microbiology ◽

10.1139/w99-106 ◽

1999 ◽

Vol 45 (12) ◽

pp. 988-994 ◽

Cited By ~ 34

Author(s):

V Portrait ◽

S Gendron-Gaillard ◽

G Cottenceau ◽

A M Pons

Keyword(s):

Salmonella Enteritidis ◽

Inhibitory Effect ◽

Biochemical Tests ◽

E Coli ◽

Relevant Role ◽

Bioreactor Experiment ◽

Intestinal Ecology ◽

First Time ◽

Microcin J25

For the first time, microcin-producing strains showing inhibitory activities against enteropathogen Salmonella enteritidis were isolated from poultry intestinal contents. Among the numerous strains isolated, two strains of Escherichia coli, named J02 and J03, showing the greatest activities against S. enteritidis, were studied. Biochemical tests and purification identified the main antagonist compound produced as microcin J25. In order to evaluate the protective potential of E. coli J02 and J03 against S. enteritidis infection, the ability of these strains to inhibit growth of S. enteritidis was investigated in mixed culture. A strong antagonist activity was obtained with a preculture phase of the active strain in minimal medium before incubation with S. enteritidis. In a bioreactor experiment simulating the chicken gastric and intestinal tract environment, a mixture of the two strains E. coli J02 and J03, provided an enhanced inhibitory effect. Microcinogenic strain activities were not affected by bile, pancreatic enzymes addition, or acidic conditions. These results suggest the relevant role of microcin-producing microorganisms in microbial intestinal ecology. To conclude, this study shows that microcin J25 strains could exert a beneficial protective effect against S. enteritidis growth in situ.Key words: microcin J25, Salmonella, mixed cultures.

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