scholarly journals Adaptogenic Properties of a Phytoecdysteroid-Rich Extract from the Leaves of Spinacia oleracea L.

Plants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2555
Author(s):  
Yuliya S. Sidorova ◽  
Vladimir A. Shipelin ◽  
Nikita A. Petrov ◽  
Sergey N. Zorin ◽  
Vladimir K. Mazo
Keyword(s):  
Emotional Stress ◽  
Spinacia Oleracea ◽  
Anxiolytic Effect ◽  
In Vivo Studies ◽  
Stress System ◽  
Nonspecific Resistance ◽  
In Vivo Models ◽  
Food Ingredients ◽  
Spinacia Oleracea L

Increasing the ability of the human body to adapt in conditions of physical or emotional stress is promising from the standpoint of the use of preventive nutrition containing functional food ingredients (FFI) with proven effectiveness in complex physiological in vivo studies. In this work, we developed FFI from spinach leaves (Spinacia oleracea L.) with a high content of polyphenols and adaptogens—phytoecdysteroids. Using in vivo models of increased physical activity and immobilization-induced emotional stress, we evaluated the nonspecific resistance of rats in response to the addition of the developed FFI to the diet. In the acute toxicity experiment, we found no signs of FFI toxicity up to 5000 mg/kg body weight. As a result of the daily 26-day consumption of FFI, we observed an anxiolytic effect in physiological studies. FFI prevented an increase in the content of biogenic amines in the blood, the main markers of the stress system, and had a positive effect on the lipid metabolism of the rats. The obtained results demonstrate a “smoothing” effect on the body’s reaction in response to induced stress conditions.

scholarly journals Site-specific serine phosphorylation of spinach leaf sucrose-phosphate synthase

1992 ◽  
Vol 283 (3) ◽  
pp. 877-882 ◽  
Author(s):  
J L A Huber ◽  
S C Huber
Keyword(s):  
Okadaic Acid ◽  
Spinacia Oleracea ◽  
Sucrose Phosphate Synthase ◽  
Serine Phosphorylation ◽  
Spinacia Oleracea L ◽  
Spinach Leaf ◽  
Sucrose Phosphate ◽  
Phosphate Synthase

We recently reported [Huber, Huber & Nielsen (1989) Arch. Biochem. Biophys. 270, 681-690] that spinach (Spinacia oleracea L.) sucrose-phosphate synthase (SPS; EC 2.4.1.14) was phosphorylated in vivo when leaves were fed [32P]Pi. In vitro the enzyme was phosphorylated and inactivated by using [gamma-32P]ATP. We now report that SPS is phosphorylated both in vivo and in vitro on serine residues. The protein is phosphorylated at multiple sites both in vivo and in vitro as indicated by two-dimensional peptide maps of the immunopurified SPS protein. After being fed with radiolabel, leaves were illuminated or given mannose (which activates the enzyme), in the presence or absence of okadaic acid. Feeding okadaic acid to leaves decreased the SPS activation state in the dark and light and in leaves fed mannose. Across all the treatments, the activation state of SPS in situ was inversely related to the labelling of two phosphopeptides (designated phosphopeptides 5 and 7). These two phosphopeptides are phosphorylated when SPS is inactivated in vitro with [gamma-32P]ATP, and thus are designated as regulatory (inhibitory) sites [Huber & Huber (1991) Biochim. Biophys. Acta 1091, 393-400]. Okadaic acid increased the total 32P-labelling of SPS and in particular increased labelling of the two regulatory sites, which explains the decline in activation state. In the presence of okadaic acid, two cryptic phosphorylation sites became labelled in vivo that were not apparent in the absence of the inhibitor. Overall, the results suggest that light/dark regulation of SPS activity occurs as a result of regulatory serine phosphorylation. Multiple sites are phosphorylated in vivo, but two sites in particular appear to regulate activity and dephosphorylation of these sites in vivo is sensitive to okadaic acid.

scholarly journals Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1248
Author(s):  
Muhammad Waleed Baig ◽  
Humaira Fatima ◽  
Nosheen Akhtar ◽  
Hidayat Hussain ◽  
Mohammad K. Okla ◽  
...  
Keyword(s):  
In Silico ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Metabolic Reaction ◽  
Datura Innoxia ◽  
In Vivo Models ◽  
Immobility Time ◽  
Anti Inflammatory

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

scholarly journals Effect of Resveratrol on In Vitro and In Vivo Models of Diabetic Retinophathy: A Systematic Review

2019 ◽  
Vol 20 (14) ◽  
pp. 3503 ◽  
Author(s):  
Mario D. Toro ◽  
Katarzyna Nowomiejska ◽  
Teresio Avitabile ◽  
Robert Rejdak ◽  
Sarah Tripodi ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Risk Of Bias ◽  
In Vivo Studies ◽  
Exclusion Criteria ◽  
In Vivo Models ◽  
In Vivo Experiments ◽  
Retinal Pathology ◽  
Full Text Review

A large number of preclinical studies suggest the involvement of resveratrol in the prevention and treatment of eye diseases induced by oxidative stress and inflammation. We tested the hypothesis that resveratrol influences many pathways of in vitro and in vivo models of diabetic retinopathy through a systematic literature review of original articles. The review was conducted in accordance with the PRISMA guidelines. A literature search of all original articles published until April 2019 was performed. The terms “resveratrol” in combination with “retina”, “retinal pathology”, “diabetic retinopathy” and “eye” were searched. Possible biases were identified with the adopted SYRCLE’s tool. Eighteen articles met inclusion/exclusion criteria for full-text review. Eleven of them included in vitro experiments, 11 studies reported in vivo data and 3 studies described both in vitro and in vivo experiments. Most of the in vivo studies did not include data that would allow exclusion of bias risks, according to SYRCLE’s risk of bias tool. Both in vitro and in vivo data suggest anti-apoptotic, anti-inflammatory and anti-oxidative actions of resveratrol in models of diabetic retinopathy. However, results on its anti-angiogenic effects are contradictory and need more rigorous studies.

scholarly journals Assessment of biosafety and toxicity of hydrophilic gel for implantation in experimental in vitro and in vivo models 

2021 ◽  
Author(s):  
Natalia Bezdieniezhnykh ◽  
Alexandra Lykhova ◽  
Tamara Kozak ◽  
Taras Zadvornyi ◽  
Olena Voronina ◽  
...  
Keyword(s):  
Human Peripheral Blood ◽  
Clinical Manifestations ◽  
Peripheral Blood Lymphocytes ◽  
Model Systems ◽  
In Vivo Studies ◽  
In Vivo Models ◽  
Pharmacologically Active ◽  
Hydrophilic Gel

Abstract Background: The assessment of biosafety of pharmacologically active substances is crucial for determining the feasibility of their medical use. There are controversial issues regarding the use of substances of different origins as implants. Methods: We have conducted the comprehensive studies to determine the in vivo toxicity and in vitro genotoxicity of new generation of hydrophilic gel for implantation (production name of the substance "Activegel") to detail its characteristics and assess its biosafety. Results: In vivo studies have shown the absence of clinical manifestations of intoxication in animals and no abnormalities in their physiological condition, general and biochemical blood tests. Evaluation of the site of the gel application showed no inflammatory reaction and evidenced on normal state of tissues of animal skin. The results of the genotoxicity test indicated that the gel did not affect the parameters of DNA comets and, accordingly, had no genotoxic effect on human peripheral blood lymphocytes. When studying the effect of the gel on malignantly transformed cells in vitro, it was found that the gel for implantation did not change the proliferative activity and viability of human breast cancer cells. Conclusions: Comprehensive in vitro and in vivo study using various experimental model systems showed that the hydrophilic gel for implantation "Activegel" is non-toxic.

PS02.239: SPECIFIC INHIBITION OF BONE MORPHOGENIC PROTEIN (BMP4) AS A POTENTIAL THERAPEUTIC STRATEGY FOR ESOPHAGEAL ADENOCARCINOMA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 190-190
Author(s):  
Kausilia Krishnadath ◽  
Sanne Hoefnagel ◽  
Silvia Calpe ◽  
Matthew Read ◽  
Danielle Straub ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Conflicts Of Interest ◽  
Bmp Signaling ◽  
In Vivo Studies ◽  
Tumor Xenograft ◽  
In Vivo Models ◽  
Treatment Naïve ◽  
Bmp4 Expression

Abstract Background In Western countries, the highly malignant Esophageal adenocarcinoma (EAC) have the most dramatically rising incidence of all malignancies. BMP4 is a growth factor important for carcinogenesis. We found that BMP4 is aberrantly expressed in Barret's esophagus, the pecursor lesion of EAC, and that together with CDX2 drives the intestinalization of epithelial metaplasia. However, its role in esophageal adenocarcinoma (EAC) remains uncertain. Methods Method: To elucidate whether BMP4 is involved in malignancy in EAC we used an RNA sequencing database of 56 EAC treatment naive endoscopic biopsies to investigate if there is a subgroup of cancers with high BMP signaling. We validated results by qPCR and immunohistochemistry in matching tumor samples. Next we used our recently developed effective and highly specific anti-BMP4 antibodies(1,2) to study the effect of inhibition of BMP4 on both in vitro as well as in vivo models of EAC. Results Using a gene set that was recently published for BMP signaling, we were able to distinguish a subgroup of EAC patients with increased BMP signaling. By IHC we confirmed that 70% of EAC tumors express BMP4 at the protein level. We found that patients with high levels of BMP4 expression tend to have a poorer recurrence-free survival compared to patients with low BMP4 expression, which suggests a more aggressive tumor behavior in BMP4 expressing EAC tumors. Most importantly, inhibition of BMP4 function in EAC cells by our recently developed anti-BMP4 antibodies lead to an increase in chemo-sensitivity and a decreased in invasive and migratory capabilities in vitro. Preclinical in vivo studies with a patient-derived tumor xenograft mouse model of an EAC tumor confirmed that anti-BMP4 antibodies can effectively reduce tumor growth and synergistically act with chemotherapy agents. Conclusion We identified a subgroup of EAC with increased BMP signaling. Our studies support a role of BMP4 in chemo-resistance and invasiveness in EAC, and indicate that inhibition of BMP4 with highly our specific llama-derived antibodies is an attractive therapy for improving outcomes of EAC. Disclosure All authors have declared no conflicts of interest.

Design, Synthesis and Anxiolytic Activity Evaluation of N-Acyltryptophanyl- Containing Dipeptides, Potential TSPO Ligands#

2019 ◽  
Vol 15 (4) ◽  
pp. 383-399 ◽  
Author(s):  
Tatiana A. Gudasheva ◽  
Olga A. Deeva ◽  
Grigory V. Mokrov ◽  
Alina S. Dyabina ◽  
Milada A. Yarkova ◽  
...  
Keyword(s):  
Open Field ◽  
Design Method ◽  
Anxiolytic Effect ◽  
Benzodiazepine Receptor ◽  
Anxiolytic Activity ◽  
Translocator Protein ◽  
In Vivo Studies ◽  
Inner Mitochondrial Membrane ◽  
New Compounds

Background:The 18 kDa translocator protein (TSPO), previously known as the peripheral- type benzodiazepine receptor, plays a key role for the synthesis of neurosteroids by promoting transport of cholesterol from the outer to the inner mitochondrial membrane, which is the ratelimiting step in neurosteroid biosynthesis. Neurosteroids interact with nonbenzodiazepine site of GABAa receptor causing an anxiolytic effect without the side effects.Methods:Using the original peptide drug-based design strategy, the first putative dipeptide ligand of the TSPO N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23) was obtained. Molecular docking of GD-23 in the active pocket of the TSPO receptor using Glide software was carried out. The lead compounds GD-23 and its analogues were synthesized using activated succinimide esters coupling method. The anxiolytic activity of GD-23 and its analogues was investigated in vivo, using two validated behavioral tests, illuminated open field and elevated plus-maze.Results:he in vivo studies revealed that the following parameters are necessary for the manifestation of anxiolytic activity of new compounds: the L-configuration of tryptophan, the presence of an amide group at the C-terminus, the specific size of the N-acyl substituent at the Nterminus. Compound GD-23 (N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide) demonstrated a high anxiolytic-like effect in the doses of 0.05–1.0 mg/kg i.p. comparable with that of diazepam. Compound GD-23 was also active in the open field test when was administered orally in the doses of 0.1-5.0 mg/kg. The involvement of TSPO receptor in the mechanism of anxiolytic-like activity of new compounds was proved by the antagonism of compound GD-23 with TSPO selective inhibitor PK11195 as well as with inhibitors of enzymes which are involved in the biosynthesis of neurosteroids, trilostane and finasteride.Conclusion:A series of N-acyl-tryptophanyl-containing dipeptides were designed and synthesized as 18 kDa translocator protein (TSPO) ligands. Using a drug-based peptide design method a series of the first dipeptide TSPO ligands have been designed and synthesized and their anxiolytic activity has been evaluated. In general, some of the compounds displayed a high level of anxiolytic efficacy comparable with that of diazepam. The involvement of TSPO receptor in the mechanism of anxiolytic activity of new compounds was proved using two methods. On this basis, the N-acyl-Ltryptophanyl- isoleucine amides could potentially be a novel class of TSPO ligands with anxiolytic activity.

A Review Focused on Molecular Mechanisms of Anxiolytic Effect of Valerina officinalis L. in Connection with Its Phytochemistry through in vitro/in vivo Studies

2021 ◽  
Vol 27 ◽  
Author(s):  
Ilkay Erdogan Orhan
Keyword(s):  
Gaba Receptors ◽  
Molecular Mechanisms ◽  
Anxiolytic Effect ◽  
In Vivo Studies ◽  
Bornyl Acetate ◽  
Root Extract ◽  
Marker Compound ◽  
Valerenic Acid

: Valeriana officinalis L. (Valerianaceae) is one of the most reputed ancient medicinal plants used in modern phytotherapy and traditional medicine. Its root extract is one of the most effective herbal sedatives and tranquilizers, where the plant is also used for treatment of gastrointestinal spasms. V. officinalis has a complex phytochemistry consisting of the esterified iridoid derivatives known as valepotriates (e.g. valtrate, didrovaltrate, isovalerenic acid), sesquiterpenes (e.g. valerenic acid), flavonoids (e.g. linarin, apigenin), lignans (e.g. pinoresinol, hydroxypinoresinol), alkaloids (e.g. actinidine, valerine), triterpenes (e.g. ursolic acid), monoterpenes (e.g. borneol, bornyl acetate). Among them, valerenic acid is a marker compound for standardization of the root extracts of the plant and has been reported in many in vitro/in vivo studies to be responsible for anxiolytic action of the plant. Although modulation of gammaaminobutyric acid (GABA) receptors has been revealed to be the leading mechanism of the plant based on the existence of valerenic acid, several studies described interaction of valerenic acid with glutamergic receptors. In addition to valerenic acid; isovaleric acid, didrovaltrate, borneol, and some lignans have been also proposed to contribute to anxiolytic effect of the plant. In the current review, the data selectively scrutinized from the in vitro/in vivo studies about identifying anxiolytic molecular mechanisms of V. officinalis is focused.

scholarly journals Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides

2018 ◽  
Vol 19 (8) ◽  
pp. 2318 ◽  
Author(s):  
Sarka Pospisilova ◽  
Jiri Kos ◽  
Hana Michnova ◽  
Iva Kapustikova ◽  
Tomas Strharsky ◽  
...  
Keyword(s):  
Spinacia Oleracea ◽  
Biological Activities ◽  
Cell Metabolism ◽  
Photosynthetic Electron Transport ◽  
Lethal Effect ◽  
Bipolaris Sorokiniana ◽  
Spinacia Oleracea L ◽  
Inhibitor Compounds

: A series of sixteen ring-substituted N-arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra, Fusarium avenaceum, and Bipolaris sorokiniana. Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2E)-3-phenyl-N-[3-(trifluoromethyl)phenyl]prop-2-enamide showed the highest activities (MICs = 22.27 and 27.47 µM, respectively) against all four staphylococcal strains and against M. tuberculosis. These compounds showed an activity against biofilm formation of S. aureus ATCC 29213 in concentrations close to MICs and an ability to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin, and tetracycline). In time-kill studies, a decrease of CFU/mL of >99% after 8 h from the beginning of incubation was observed. (2E)-N-(3,5-Dichlorophenyl)- and (2E)-N-(3,4-dichlorophenyl)-3-phenylprop-2-enamide had a MIC = 27.38 µM against M. tuberculosis, while a significant decrease (22.65%) of mycobacterial cell metabolism determined by the MTT assay was observed for the 3,5-dichlorophenyl derivative. (2E)-N-(3-Fluorophenyl)- and (2E)-N-(3-methylphenyl)-3-phenylprop-2-enamide exhibited MICs = 16.58 and 33.71 µM, respectively, against B. sorokiniana. The screening of the cytotoxicity of the most effective antimicrobial compounds was performed using THP-1 cells, and these chosen compounds did not shown any significant lethal effect. The compounds were also evaluated for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. (2E)-N-(3,5-dichlorophenyl)-3-phenylprop-2-enamide (IC50 = 5.1 µM) was the most active PET inhibitor. Compounds with fungicide potency did not show any in vivo toxicity against Nicotiana tabacum var. Samsun. The structure–activity relationships are discussed.

scholarly journals Plasma-Conditioned Liquids as Anticancer Therapies In Vivo: Current State and Future Directions

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 452
Author(s):  
Xavi Solé-Martí ◽  
Albert Espona-Noguera ◽  
Maria-Pau Ginebra ◽  
Cristina Canal
Keyword(s):  
Anticancer Agents ◽  
Malignant Tumors ◽  
Atmospheric Plasma ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Novel Therapy ◽  
In Vivo Models ◽  
Good Path ◽  
Cold Plasmas

Plasma-conditioned liquids (PCL) are gaining increasing attention in the medical field, especially in oncology, and translation to the clinics is advancing on a good path. This emerging technology involving cold plasmas has great potential as a therapeutic approach in cancer diseases, as PCL have been shown to selectively kill cancer cells by triggering apoptotic mechanisms without damaging healthy cells. In this context, PCL can be injected near the tumor or intratumorally, thereby allowing the treatment of malignant tumors located in internal organs that are not accessible for direct cold atmospheric plasma (CAP) treatment. Therefore, PCL constitutes a very interesting and minimally invasive alternative to direct CAP treatment in cancer therapy, avoiding surgeries and allowing multiple local administrations. As the field advances, it is progressively moving to the evaluation of the therapeutic effects of PCL in in vivo scenarios. Exciting developments are pushing forward the clinical translation of this novel therapy. However, there is still room for research, as the quantification and identification of reactive oxygen and nitrogen species (RONS) in in vivo conditions is not yet clarified, dosage regimens are highly variable among studies, and other more relevant in vivo models could be used. In this context, this work aims to present a critical review of the state of the field of PCL as anticancer agents applied in in vivo studies.

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