Predictive capabilities of in vitro colon bioaccessibility for estimating in vivo relative bioavailability of arsenic from contaminated soils: Arsenic speciation and gut microbiota considerations

The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the antiinflammatory potential of HT-containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products’ phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs’ bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs’ metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases.

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Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

Acta Pharmaceutica ◽

10.2478/v10007-009-0010-2 ◽

2009 ◽

Vol 59 (1) ◽

pp. 15-30 ◽

Cited By ~ 6

Author(s):

Pramod Kumar ◽

Sanjay Singh ◽

Brahmeshwar Mishra

Keyword(s):

Drug Release ◽

Extended Release ◽

Relative Bioavailability ◽

Pharmacokinetic Parameters ◽

Healthy Human ◽

Tramadol Hydrochloride ◽

Release Formulation ◽

Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

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Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

mSystems ◽

10.1128/msystems.00123-18 ◽

2018 ◽

Vol 3 (6) ◽

Cited By ~ 2

Author(s):

Jingwei Cai ◽

Robert G. Nichols ◽

Imhoi Koo ◽

Zachary A. Kalikow ◽

Limin Zhang ◽

...

Keyword(s):

Mass Spectrometry ◽

Amino Acids ◽

Flow Cytometry ◽

Free Radical ◽

Gut Microbiota ◽

Structure And Function ◽

Metabolic Phenotyping ◽

And Function

ABSTRACTThe gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combinesin vitromicrobial incubation (isolated cecal contents from mice), flow cytometry, and mass spectrometry- and1H nuclear magnetic resonance (NMR)-based metabolomics to evaluate xenobiotic-induced microbial toxicity. Tempol, a stabilized free radical scavenger known to remodel the microbial community structure and functionin vivo, was studied to assess its direct effect on the gut microbiota. The microbiota was isolated from mouse cecum and was exposed to tempol for 4 h under strict anaerobic conditions. The flow cytometry data suggested that short-term tempol exposure to the microbiota is associated with disrupted membrane physiology as well as compromised metabolic activity. Mass spectrometry and NMR metabolomics revealed that tempol exposure significantly disrupted microbial metabolic activity, specifically indicated by changes in short-chain fatty acids, branched-chain amino acids, amino acids, nucleotides, glucose, and oligosaccharides. In addition, a mouse study with tempol (5 days gavage) showed similar microbial physiologic and metabolic changes, indicating that thein vitroapproach reflectedin vivoconditions. Our results, through evaluation of microbial viability, physiology, and metabolism and a comparison ofin vitroandin vivoexposures with tempol, suggest that physiologic and metabolic phenotyping can provide unique insight into gut microbiota toxicity.IMPORTANCEThe gut microbiota is modulated physiologically, compositionally, and metabolically by xenobiotics, potentially causing metabolic consequences to the host. We recently reported that tempol, a stabilized free radical nitroxide, can exert beneficial effects on the host through modulation of the microbiome community structure and function. Here, we investigated a multiplatform phenotyping approach that combines high-throughput global metabolomics with flow cytometry to evaluate the direct effect of tempol on the microbiota. This approach may be useful in deciphering how other xenobiotics directly influence the microbiota.

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Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer

Pharmaceutics ◽

10.3390/pharmaceutics13101560 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1560

Author(s):

Amr Gamal ◽

Haitham Saeed ◽

Fatma I. Abo El-Ela ◽

Heba F. Salem

Keyword(s):

Steady State ◽

Skin Cancer ◽

Entrapment Efficiency ◽

The United States ◽

Relative Bioavailability ◽

Passive Targeting ◽

Therapeutic Benefits ◽

Steady State Flux

Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm2/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer.

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Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract

Nature Communications ◽

10.1038/s41467-021-27762-y ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Jianan Zhang ◽

Morgan E. Walker ◽

Katherine Z. Sanidad ◽

Hongna Zhang ◽

Yanshan Liang ◽

...

Keyword(s):

Gut Microbiota ◽

Molecular Mechanisms ◽

Ex Vivo ◽

Metabolic Activation ◽

Consumer Products ◽

Environmental Chemicals ◽

Intestinal Microbes ◽

Targeted Inhibition

AbstractEmerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.

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Assessing prebiotic effects of resistant starch on modulating gut microbiota with an in vivo animal model and an in vitro semi-continuous fermentation model

10.31274/etd-180810-2954 ◽

2010 ◽

Cited By ~ 1

Author(s):

Li Li

Keyword(s):

Animal Model ◽

Gut Microbiota ◽

Resistant Starch ◽

Continuous Fermentation ◽

In Vivo Animal Model ◽

Fermentation Model

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High-Fat Diet Induced Gut Microbiota Alterations Associating With Ghrelin/Jak2/Stat3 Up-Regulation to Promote Benign Prostatic Hyperplasia Development

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.615928 ◽

2021 ◽

Vol 9 ◽

Author(s):

Meng Gu ◽

Chong Liu ◽

TianYe Yang ◽

Ming Zhan ◽

Zhikang Cai ◽

...

Keyword(s):

Cell Proliferation ◽

Benign Prostatic Hyperplasia ◽

Gut Microbiota ◽

High Fat Diet ◽

Prostatic Hyperplasia ◽

Prostate Tissue ◽

High Fat ◽

Ghrelin Receptor

The role of high-fat diet (HFD) induced gut microbiota alteration and Ghrelin as well as their correlation in benign prostatic hyperplasia (BPH) were explored in our study. The gut microbiota was analyzed by 16s rRNA sequencing. Ghrelin levels in serum, along with Ghrelin and Ghrelin receptor in prostate tissue of mice and patients with BPH were measured. The effect of Ghrelin on cell proliferation, apoptosis, and induction of BPH in mice was explored. Our results indicated that BPH mice have the highest ratio of Firmicutes and Bacteroidetes induced by HFD, as well as Ghrelin level in serum and prostate tissue was significantly increased compared with control. Elevated Ghrelin content in the serum and prostate tissue of BPH patients was also observed. Ghrelin promotes cell proliferation while inhibiting cell apoptosis of prostate cells. The effect of Ghrelin on enlargement of the prostate was found almost equivalent to that of testosterone propionate (TP) which may be attenuated by Ghrelin receptor antagonist YIL-781. Ghrelin could up-regulate Jak2/pJak2/Stat3/pStat3 expression in vitro and in vivo. Our results suggested that Gut microbiota may associate with Ghrelin which plays an important role in activation of Jak2/Stat3 in BPH development. Gut microbiota and Ghrelin might be pathogenic factors for BPH and could be used as a target for mediation.

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Lactobacillus reuteri Ameliorates Intestinal Inflammation and Modulates Gut Microbiota and Metabolic Disorders in Dextran Sulfate Sodium-Induced Colitis in Mice

Nutrients ◽

10.3390/nu12082298 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2298

Author(s):

Gang Wang ◽

Shuo Huang ◽

Shuang Cai ◽

Haitao Yu ◽

Yuming Wang ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Disorders ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Lactobacillus Reuteri ◽

Intestinal Inflammation ◽

Intestinal Bacteria ◽

Ht 29

Lactobacillus reuteri, a commensal intestinal bacteria, has various health benefits including the regulation of immunity and intestinal microbiota. We examined whether L. reuteri I5007 could protect mice against colitis in ameliorating inflammation, modulating microbiota, and metabolic composition. In vitro, HT-29 cells were cultured with L. reuteri I5007 or lipopolysaccharide treatment under three different conditions, i.e., pre-, co- (simultaneous), and posttreatment. Pretreatment with L. reuteri I5007 effectively relieves inflammation in HT-29 cells challenged with lipopolysaccharide. In vivo, mice were given L. reuteri I5007 by gavage throughout the study, starting one week prior to dextran sulfate sodium (DSS) treatment for one week followed by two days without DSS. L. reuteri I5007 improved DSS-induced colitis, which was confirmed by reduced weight loss, colon length shortening, and histopathological damage, restored the mucus layer, as well as reduced pro-inflammatory cytokines levels. Analysis of 16S rDNA sequences and metabolome demonstrates that L. reuteri I5007 significantly alters colonic microbiota and metabolic structural and functional composition. Overall, the results demonstrate that L. reuteri I5007 pretreatment could effectively alleviate intestinal inflammation by regulating immune responses and altering the composition of gut microbiota structure and function, as well as improving metabolic disorders in mice with colitis.

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