Health Potential of Clery Strawberries: Enzymatic Inhibition and Anti-Candida Activity Evaluation

Strawberries, belonging to cultivar Clery (Fragaria × ananassa Duchesne ex Weston) and to a graft obtained by crossing Clery and Fragaria vesca L., were chosen for a study on their health potential, with regard to the prevention of chronic and degenerative diseases. Selected samples, coming from fresh and defrosted berries, submitted to different homogenization techniques combined with thermal and microwave treatments, had been previously analyzed in their polyphenolic content and antioxidant capacity. In the present work, these homogenates were evaluated in relation to their enzymatic inhibition activity towards acetylcholinesterase and butyrylcholinesterase, α-amylase, α-glucosidase and tyrosinase. All these enzymes, involved in the onset of diabetes, and neurodegenerative and other chronic diseases, were modulated by the tested samples. The inhibitory effect on tyrosinase and cholinesterase was the most valuable. Antifungal activity against Candida albicans, recently shown to play a crucial role in human gut diseases as well as diabetes, rheumatoid arthritis and Alzheimer’s disease, was also shown in vitro and confirmed by the in vivo text on Galleria mellonella. Overall, the obtained results confirm once again the health potential of strawberries; however, the efficacy is dependent on high quality products submitted to correct processing flow charts.

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Characterisation of the antimicrobial mode of action of gallium maltolate

Access Microbiology ◽

10.1099/acmi.ac2020.po0222 ◽

2020 ◽

Vol 2 (7A) ◽

Author(s):

Magdalena Piatek ◽

Darren Griffith ◽

Kevin Kavanagh

Keyword(s):

Mode Of Action ◽

Galleria Mellonella ◽

Iron Acquisition ◽

Structural Similarity ◽

Opportunistic Pathogen ◽

Inhibitory Effect ◽

Label Free ◽

Iron Storage

To human health worldwide. Existing treatments are becoming inefficacious and therefore there is an urgent need for the development of treatments with alternative modes of action. The use of gallium as an antimicrobial agent has been of interest due to its unconventional mode of action involving the inhibition of iron acquisition and metabolism. The structural similarity and inability to reduce from a trivalent to divalent form under normal physiological conditions allows gallium to act as an iron mimetic and inhibit many iron-dependent biological pathways, respectively. The antimicrobial potential of gallium maltolate (GaM), Ga(III) coordination complex of maltol, was investigated on the opportunistic pathogen Pseudomonas aeruginosa. In vitro and in vivo analyses using Galleria mellonella (greater wax moth) larvae demonstrated the potent bacteriostatic and non-toxic effect of the complex. Subsequent analysis of GaM treated P. aeruginosa via label-free quantitative proteomics provided an insight into the intrinsic mechanisms of action of GaM. Increased expression of iron-storage protein Bacterioferritin B, the HemO component of iron-sulfur clusters and several stress response proteins (Chaperone Proteins ClpB, HtpG and DnaJ) indicate cell stress in response to inhibited iron uptake. Decreased expression of LasA Protease and LasB Elastase quorum-sensing proteins and flagellar motility proteins FlgM and FlgG further demonstrate the growth inhibitory effect of GaM. These findings provide a basis for a better understanding of the mode of action of GaM, a requirement for the improvement of synthesis and efficacy of the treatment.

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787. The Addition of Avibactam Augments the Activity of Piperacillin Against Mycobacterium abscessus in vitro, and Is Effective in Treating M. abscessus Infection in a Galleria mellonella in vivo Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.794 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S281-S282

Author(s):

Michal Meir ◽

Daniel Barkan

Keyword(s):

Galleria Mellonella ◽

Inhibitory Effect ◽

Mycobacterium Abscessus ◽

In Vivo Model ◽

Great Promise ◽

Infection Model ◽

In Vivo Models ◽

Antimicrobial Treatments

Abstract Background Mycobacterium abscessus is an emerging multi-drug-resistant pathogen, harboring the β-lactamse BlaMAB. Avibactam is a non-β-lactam, β-lactamase inhibitor shown to inhibit BlaMAB and improve the efficacy of ampicillin for M. abscessus infections in in vitro and in vivo models. Whether the addition of avibactam to piperacillin enables use of the latter against M. abscessus is unknown Methods We used a recombinant, luminescent M. abscessus to measure the reduction of MIC to meropenem, ampicillin, and piperacillin induced by avibactam. We then used our previously established G. mellonella infection model (Figure 1)1 to evaluate the effect of antimicrobial treatments in vivo. Results Addition of avibactam (4 µg/mL) consistently decreased MIC of ampicillin and piperacillin by 16 and 16–32-fold, respectively, but as expected had no significant effect on meropenem MIC (Figure 2). We inoculated 60 G. mellonella larvae with luminescent M. abscessus on day 0, and treated larvae with meropenem, piperacillin, avibactam alone, or piperacillin combined with avibactam on days 2 and 3. Using IVIS® imaging, we measured infection progression in live infected larvae on day 4. Larvae treated with meropenem and piperacillin–avibactam had significantly lower infection burden compared with untreated controls (P < 0.0001 and P = 0.004, respectively). Piperacillin and avibactam alone had no significant inhibitory effect (Figure 3). Conclusion Our findings suggest that the piperacillin–avibactam combination is effective against M. abscessus infections. This novel combination may hold a great promise for patients with cystic fibrosis suffering from M. abscessus, Pseudomonas aeruginosa, and/or Staphylococcus aureus co-infections. The G. mellonella infection model may be used in future studies to assess the efficacy of various antimicrobials and antimicrobial combinations on M. abscessus, P. aeruginosa, and S. aureus co-infections. Reference 1. Meir M et al. Antimicrob Agents Chemother. 2018. Disclosures All authors: No reported disclosures.

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1197. Inhibitory Effect of Ursodeoxycholic Acid on Clostridioides difficile Growth

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1382 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S621-S621

Author(s):

Faris Alnezary ◽

M Jahangir Alam ◽

Masaad Almutairi ◽

Saad Fallatah ◽

Khurshida Begum ◽

...

Keyword(s):

Ursodeoxycholic Acid ◽

Galleria Mellonella ◽

Inhibitory Effect ◽

Secondary Bile Acid ◽

In Vivo Experiments ◽

Clostridioides Difficile ◽

Colony Forming Units ◽

Germination And Growth

Abstract Background Ursodeoxycholic acid (UDCA), a secondary bile acid, inhibits germination and growth of Clostridioides difficile in vitro, but the results from in vivo experiments have been conflicting. We evaluated the effects of UDCA on C. difficile in vitro and in a wax moth, Galleria mellonella model. Methods The in vitro growth and germination effects of UDCA on C. difficile were assessed with increased concentration of UDCA (0.001, 0.01, 0.05, and 0.1%). To assess treatment effects of UDCA, C. difficile spores (approximately 1x10^6-8 colony forming units (CFU)) were force fed to G. mellonella larvae treated with UDCA (50 mg/kg/day) 24 hours prior to C. difficile inoculation. Forty G. mellonella larvae were used for each experiment, which was repeated with two distinct strains (R20291 and CD196). Larvae were housed at 37°C and monitored for the next five days for mortality. Results In vitro experiment demonstrated inhibition of C. difficile growth at 0.1% concentration (P < 0.001 vs control). Larvae treated with UDCA had a numerically higher survival rate (60% / 24/40) compared to controls (40% / 16/40) but the results were not statistically significant (p=0.14). Identical rates of survival were observed in the control arms for both strains (40%) and similar in the treatment arms (R20291: 70%; CD 196: 50%). Conclusion Overall, UDCA shows inhibitory effect of growth and germination of C. difficile in vitro. However, in our G. mellonella model, a single dose of UDCA given prior to infection did not prevent CDI. Further dose dependent, and multiday studies investigating the role of UDCA in CDI is needed to better understand this in vitro / in vivo paradox. Disclosures Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)

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The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649080 ◽

1973 ◽

Vol 30 (02) ◽

pp. 315-326

Author(s):

J. Heinz Joist ◽

Jean-Pierre Cazenave ◽

J. Fraser Mustard

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Barbituric Acid ◽

Platelet Rich Plasma ◽

Inhibitory Effect ◽

Primary Response ◽

Sodium Pentobarbital ◽

Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

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Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648055 ◽

1976 ◽

Vol 36 (02) ◽

pp. 401-410 ◽

Cited By ~ 6

Author(s):

Buichi Fujttani ◽

Toshimichi Tsuboi ◽

Kazuko Takeno ◽

Kouichi Yoshida ◽

Masanao Shimizu

Keyword(s):

Guinea Pig ◽

Acetylsalicylic Acid ◽

Guinea Pigs ◽

Glass Bead ◽

Animal Species ◽

Inhibitory Effect ◽

Rabbit Platelet ◽

Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

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Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

Current Alzheimer Research ◽

10.2174/1567205014666171128102557 ◽

2018 ◽

Vol 15 (6) ◽

pp. 531-543 ◽

Cited By ~ 4

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.

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Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

Author(s):

S Whitehead ◽

TE Peto

Keyword(s):

Plasmodium Falciparum ◽

Growth Inhibition ◽

Antimalarial Activity ◽

Clinical Malaria ◽

Inhibitory Effect ◽

Parasite Development ◽

And Control ◽

Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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A Peptide Found in Human Serum, Derived from the C-Terminus of Albumin, Shows Antifungal Activity In Vitro and In Vivo

Microorganisms ◽

10.3390/microorganisms8101627 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1627

Author(s):

Tecla Ciociola ◽

Pier Paolo Zanello ◽

Tiziana D’Adda ◽

Serena Galati ◽

Stefania Conti ◽

...

Keyword(s):

Antifungal Activity ◽

Human Serum ◽

Fungicidal Activity ◽

Galleria Mellonella ◽

Serum Proteins ◽

Morphological Alterations ◽

C Terminus ◽

Different Sources

The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597–609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources.

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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus

Biomedicines ◽

10.3390/biomedicines9070819 ◽

2021 ◽

Vol 9 (7) ◽

pp. 819

Author(s):

Nicolai Rügen ◽

Timothy P. Jenkins ◽

Natalie Wielsch ◽

Heiko Vogel ◽

Benjamin-Florian Hempel ◽

...

Keyword(s):

Biomedical Applications ◽

Galleria Mellonella ◽

Systemic Reactions ◽

Venom Composition ◽

Assassin Bug ◽

Molecular Components ◽

First Time ◽

Tissue Digestion

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.

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A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

Cell Death and Disease ◽

10.1038/s41419-021-03939-7 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Ying Liu ◽

Wenjie Liu ◽

Ziqiang Yu ◽

Yan Zhang ◽

Yinghua Li ◽

...

Keyword(s):

Bone Loss ◽

Osteoporosis Treatment ◽

Inhibitory Effect ◽

Specific Gene ◽

Actin Ring ◽

Treatment Target ◽

Significant Inhibitory Effect ◽

Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

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