scholarly journals Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models

2009 ◽  
Vol 103 (7) ◽  
pp. 944-952 ◽  
Author(s):  
Aida Serra ◽  
Alba Macià ◽  
Maria-Paz Romero ◽  
Josep Valls ◽  
Cinta Bladé ◽  
...  
Keyword(s):  
Biological Effects ◽  
Oral Intake ◽  
Grape Seed ◽  
Rat Plasma ◽  
In Vivo Models ◽  
Rich Food ◽  
The Matrix ◽  
High Level

Among procyanidins (PC), monomers, such as catechin and epicatechin, have been widely studied, whereas dimer and trimer oligomers have received much less attention, despite their abundance in our diet. Recent studies have showed that as dimers and trimers could be important in determining the biological effects of procyanidin-rich food, understanding their bioavailability and metabolism is fundamental. The purpose of the present work is to study the stability of PC under digestion conditions, the metabolism and the bioavailability by using a combination of in vitro and in vivo models. Simultaneously, the matrix effect of a carbohydrate-rich food on the digestibility and bioavailability of PC is investigated. The results show a high level of stability of PC under gastric and duodenal digestion conditions. However, the pharmacokinetic study revealed limited absorption. Free forms of dimers and trimers have been detected in rat plasma, reaching the maximum concentration 1 h after oral intake of a grape seed extract.

scholarly journals Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Reiko Nakao ◽  
Weilin Shen ◽  
Yasuka Shimajiri ◽  
Kumiko Kainou ◽  
Yuki Sato ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Muscle Atrophy ◽  
Ubiquitin Ligase ◽  
Oral Intake ◽  
Rat Plasma ◽  
Cytochalasin D ◽  
Apical Side ◽  
Basolateral Side

AbstractWe previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy.

Neuroprotective effect of Chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo

2014 ◽  
Vol 92 (6) ◽  
pp. 429-437 ◽  
Author(s):  
Hyo Geun Kim ◽  
Ji-Young Kim ◽  
Wei-Wan Whang ◽  
Myung Sook Oh
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Beta ◽  
Antioxidant Activities ◽  
Neuronal Damage ◽  
Biological Effects ◽  
Neuroprotective Effect ◽  
In Vivo Models ◽  
Aβ Oligomer

Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer’s disease (AD), and has been proposed as a potential therapeutic target. Chunghyuldan (CHD; Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) possesses wide-ranging biological effects, including anti-hyperlipidemic, anti-stroke, anti-inflammatory, and antioxidant activities that could affect neurological functions. In this study, we examined the effects of CHD in in-vitro and in-vivo models of AD induced by the oligomeric form of amyloid-beta (Aβ oligomer), which acts directly on microglia-mediated neuroinflammation to result in neuronal damage and cognitive impairment. CHD at 0.1–100 μg·mL−1 significantly protected PC12 cells and rat primary hippocampal cells from Aβ oligomer1–42 toxicity. In addition, CHD at 1–10 μg·mL−1 inhibited Aβ oligomer1–42 induced production of nitric oxide, tumor necrosis factor-α, and interleukin-1β in microglial cells. In an in-vivo AD model, administration of CHD (50 mg·(kg body mass)−1, for 5 days, per oral) inhibited the activation of astrocytes and microglia in the dentate gyrus and neuronal damage in the CA1 of the ipsilateral hippocampus. Moreover, CHD ameliorated cognitive impairment induced by Aβ oligomer1–42 toxicity. These results demonstrate the neuroprotective effects of CHD through inhibition of microglia-mediated neuroinflammation in in-vitro and in-vivo AD-like models induced by Aβ oligomer1–42 toxicity.

Recent Progress in Oleanolic Acid: Structural Modification and Biological Activity

2021 ◽  
Vol 21 ◽  
Author(s):  
Wang Wang ◽  
Yutong Li ◽  
Yan Li ◽  
Dejuan Sun ◽  
Hua Li ◽  
...  
Keyword(s):  
Oleanolic Acid ◽  
Structural Modification ◽  
Recent Progress ◽  
Biological Activities ◽  
Biological Effects ◽  
Biologically Active ◽  
In Vivo Models ◽  
Action Mechanisms

: Natural products have been proven as the main source of biologically active compounds, which are potentially useful for drug development. As one of the most studied pentacyclic triterpenes, oleanolic acid (OA) exhibits a broad range of biological activities and serves as a good scaffold for the development of novel derivatives that could be vital in drug discovery for various ailments. Up to now, many of its derivatives with multiple bioactivities have been prepared through chemical modification. This review summarizes the recent reports of OA derivatives (2016-present) and their biological effects and action mechanisms in vitro and in vivo models, and discusses the design of novel and potent derivatives.

scholarly journals Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1932
Author(s):  
Chiara D’Angelo ◽  
Sara Franceschelli ◽  
José Luis Quiles ◽  
Lorenza Speranza
Keyword(s):  
Cardiovascular Health ◽  
Biological Effects ◽  
Low Density Lipoprotein ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
In Vivo Models ◽  
And Oxidative Stress

The growing incidence of cardiovascular disease (CVD) has promoted investigations of natural molecules that could prevent and treat CVD. Among these, hydroxytyrosol, a polyphenolic compound of olive oil, is well known for its antioxidant, anti-inflammatory, and anti-atherogenic effects. Its strong antioxidant properties are due to the scavenging of radicals and the stimulation of synthesis and activity of antioxidant enzymes (SOD, CAT, HO-1, NOS, COX-2, GSH), which also limit the lipid peroxidation of low-density lipoprotein (LDL) cholesterol, a hallmark of atherosclerosis. Lowered inflammation and oxidative stress and an improved lipid profile were also demonstrated in healthy subjects as well as in metabolic syndrome patients after hydroxytyrosol (HT) supplementation. These results might open a new therapeutic scenario through personalized supplementation of HT in CVDs. This review is the first attempt to collect together scientific literature on HT in both in vitro and in vivo models, as well as in human clinical studies, describing its potential biological effects for cardiovascular health.

A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

2015 ◽  
Vol 17 (2) ◽  
Author(s):  
Alan MacNicoll ◽  
Mick Kelly ◽  
Hatice Aksoy ◽  
Evelien Kramer ◽  
Hans Bouwmeester ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Oral Intake ◽  
In Vivo Models ◽  
Nano Titanium Dioxide

scholarly journals FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fei Xu ◽  
Jiajia Li ◽  
Mengdong Ni ◽  
Jingyi Cheng ◽  
Haiyun Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Biological Effects ◽  
Ovarian Cancer Cells ◽  
Promoting Effect ◽  
In Vivo Models ◽  
Cancer Cell Survival ◽  
Cancer Tissues

Abstract Background The tumor suppressor FBW7 is the substrate recognition component of the SCF E3-ubiquitin ligase complex that mediates proteolytic degradation of various oncogenic proteins. However, the role of FBW7 in ovarian cancer progression remains inadequately understood. Methods IP-MASS, co-IP, immunohistochemistry, and western blotting were used to identify the potential substrate of FBW7 in ovarian cancer. The biological effects of FBW7 were investigated using in vitro and in vivo models. LC/MS was used to detect the m6A levels in ovarian cancer tissues. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of YTHDF2. Results We unveil that FBW7 is markedly down-regulated in ovarian cancer tissues and its high expression is associated with favorable prognosis and elevated m6A modification levels. Consistently, ectopic FBW7 inhibits ovarian cancer cell survival and proliferation in vitro and in vivo, while ablation of FBW7 empowers propagation of ovarian cancer cells. In addition, the m6A reader protein, YTHDF2, is identified as a novel substrate for FBW7. FBW7 counteracts the tumor-promoting effect of YTHDF2 by inducing proteasomal degradation of the latter in ovarian cancer. Furthermore, YTHDF2 globally regulates the turnover of m6A-modified mRNAs, including the pro-apoptotic gene BMF. Conclusions Our study has demonstrated that FBW7 suppresses tumor growth and progression via antagonizing YTHDF2-mediated BMF mRNA decay in ovarian cancer.

The Effect of Graft Caliber Upon Wall Shear Within in Vivo Distal Vascular Anastomoses

1999 ◽  
Vol 121 (1) ◽  
pp. 79-88 ◽  
Author(s):  
R. S. Keynton ◽  
M. M. Evancho ◽  
R. L. Sims ◽  
S. E. Rittgers
Keyword(s):  
Stagnation Point ◽  
Intimal Hyperplasia ◽  
Biological Effects ◽  
Axial Position ◽  
Bypass Grafts ◽  
In Vivo Models ◽  
Measuring Device ◽  
Wall Shear

Wall shear has been widely implicated as a contributing factor in the development of intimal hyperplasia in the anastomoses of chronic arterial bypass grafts. Earlier studies have been restricted to either: (1) in vitro or computer simulation models detailing the complex hemodynamics within an anastomosis without corresponding biological responses, or (2) in vivo models that document biological effects with only approximate wall shear information. Recently, a specially designed pulse ultrasonic Doppler wall shear rate (PUDWSR) measuring device has made it possible to obtain three near-wall velocity measurements nonintrusively within 1.05 mm of the vessel luminal surface from which wall shear rates (WSRs) were derived. It was the purpose of this study to evaluate the effect of graft caliber, a surgically controllable variable, upon local hemodynamics, which, in turn, play an important role in the eventual development of anastomotic hyperplasia. Tapered (4–7 mm I.D.) 6-cm-long grafts were implanted bilaterally in an end-to-side fashion with 30 deg proximal and distal anastomoses to bypass occluded common carotid arteries of 16 canines. The bypass grafts were randomly paired in contralateral vessels and placed such that the graft-to-artery diameter ratio, DR, at the distal anastomosis was either 1.0 or 1.5. For all grafts, the average Re was 432 ± 112 and the average Womersley parameter,α, was 3.59 ± 0.39 based on artery diameter. There was a sharp skewing of flow toward the artery floor with the development of a stagnation point whose position varied with time (up to two artery diameters) and DR (generally more downstream for DR = 1.0). Mean WSRs along the artery floor for DR = 1.0 and 1.5 were found to range sharply from moderate to high retrograde values (589 s−1 and 1558 s−1, respectively) upstream to high antegrade values (2704 s−1 and 2302 s−1, respectively) immediately downstream of the stagnation point. Although there were no overall differences in mean and peak WSRs between groups, there were significant differences (p < 0.05) in oscillatory WSRs as well as in the absolute normalized mean and peak WSRs between groups. There were also significant differences (p < 0.05) in mean and peak WSRs with respect to axial position along the artery floor for both DR cases. In conclusion, WSR varies widely (1558 s−1 retrograde to 2704 s−1 antegrade) within end-to-side distal graft anastomoses, particularly along the artery floor, and may play a role in the development of intimal hyperplasia through local alteration of mass transport and mechano-signal transduction within the endothelium.

scholarly journals Nutritive Importance and Therapeutics Uses of Three Different Varieties (Murraya koenigii, Micromelum minutum, and Clausena indica) of Curry Leaves: An Updated Review

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
D. T. Abeysinghe ◽  
D. D. D. H. Alwis ◽  
K. A. H. Kumara ◽  
U. G. Chandrika
Keyword(s):  
Current Knowledge ◽  
Biological Activities ◽  
Biological Effects ◽  
Herbal Remedies ◽  
Murraya Koenigii ◽  
In Vivo Models ◽  
Treatment And Prevention ◽  
Curry Leaves

Murraya koenigii (M. koenigii), Micromelum minutum (M. minutum), and Clausena indica (C. indica) are three varieties of curry leaves in the family Rutaceae. They have been widely used in Ayurvedic medicine worldwide in the treatment and prevention of various diseases. Earlier findings provide strong evidence to support the three curry leaf species’ potent pharmaceutical and biological effects, including antioxidant, antidiabetic, anti-inflammatory, and antitumor activities. Various parts of these plants, such as leaves, seeds, flowers, and fruit, contain constituents responsible for the modulation of numerous biological processes. Leading constituents of curry leaves play a crucial role in diabetic and anticancer management by regulating various molecular pathways, including Bcl-2, Bax, NF-κB, and TNFα, according to in vitro and in vivo models established. Therefore, this review summarizes the current knowledge on research achievements made in terms of phytoconstituents, their structures, biological activities, and pharmacological actions with clinical studies of curry leaves up to date. The review also emphasizes the necessity for comprehensive research studies on the pharmacological actions and the mechanisms of selected phytochemicals of M. koenigii, M. minutum, and C. indica to validate their efficacy as potent herbal remedies for many ailments.

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

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