scholarly journals The Effects of Food on Cannabidiol Bioaccessibility

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3573
Author(s):  
Khadijeh Mozaffari ◽  
Stephanie Willette ◽  
Ben F. Lucker ◽  
Sarah E. Kovar ◽  
Francisco Omar Holguin ◽  
...  
Keyword(s):  
Bile Salts ◽  
Micelle Formation ◽  
Food Matrix ◽  
Fed State ◽  
Lipase Enzyme ◽  
Three Phase ◽  
The Impact ◽  
Substrate Concentrations ◽  
Fatty Acid Absorption

Cannabidiol (CBD) is a hydrophobic non-psychoactive compound with therapeutic characteristics. Animal and human studies have shown its poor oral bioavailability in vivo, and the impact of consuming lipid-soluble CBD with and without food on gut bioaccessibility has not been explored. The purpose of this research was to study the bioaccessibility of CBD after a three-phase upper digestion experiment with and without food, and to test lipase activity with different substrate concentrations. Our results showed that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may also contribute to an increase in CBD bioaccessibility. The food matrix used was a mixture of olive oil and baby food. Overall, the fed-state digestion revealed significantly higher micellarization efficiency for CBD (14.15 ± 0.6% for 10 mg and 22.67 ± 2.1% for 100 mg CBD ingested) than the fasted state digestion of CBD (0.65 ± 0.7% for 10 mg and 0.14 ± 0.1% for 100 mg CBD ingested). The increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules. In conclusion, the bioaccessibility of CBD depends on the food matrix and the presence of lipase and bile salts.

Influence of taurocholate, taurochenodeoxycholate, and taurodehydrocholate on sulfobromophthalein transport into bile.

1979 ◽  
Vol 236 (1) ◽  
pp. E10
Author(s):  
S Binet ◽  
Y Delage ◽  
S Erlinger
Keyword(s):  
Bile Salts ◽  
Mixed Micelle ◽  
Mixed Micelles ◽  
Important Determinant ◽  
Micelle Formation ◽  
Similar Increase ◽  
Mixed Micelle Formation ◽  
Series Of Experiments

To test the hypothesis that incorporation of sulfobromophthalein (BSP) into mixed micelles could account for the increase in its biliary transport maximum (Tmax) by bile salts, we have compared in hamsters the influence on BSP Tmax of taurocholate and taurochenodeoxycholate (two micelle-forming physiological bile salts) to that of taurodehydrocholate, a bile salt which, in vitro, does not form micelles. In a first series of experiments, it was observed that taurocholate and taurochenodeoxycholate increased the secretion of phospholipid (40 and 53%, respectively), and cholesterol (50 and 110%, respectively), whereas taurodehydrocholate decreased the secretion of phospholipid (-31%) and cholesterol (-43%). This result suggests that, in vivo, taurodehydrocholate or its metabolites do not form mixed micelles. In a second series of experiments, it was seen that the three bile salts induced a similar increase in BSP Tmax (63% with taurocholate, 52% with taurochenodeoxycholate, and 51% with taurodehydrocholate). These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal BSP secretion into bile.

scholarly journals In Vivo Predictive Dissolution Testing of Montelukast Sodium Formulations Administered with Drinks and Soft Foods to Infants

2020 ◽  
Vol 21 (7) ◽  
Author(s):  
J. Martir ◽  
T. Flanagan ◽  
J. Mann ◽  
N. Fotaki
Keyword(s):  
Drug Product ◽  
Drug Dissolution ◽  
Simulated Gastric Fluid ◽  
Dissolution Testing ◽  
Fed State ◽  
Fasted State ◽  
Direct Administration ◽  
The Impact

Abstract In vitro dissolution testing conditions that reflect and predict in vivo drug product performance are advantageous, especially for the development of paediatric medicines, as clinical testing in this population is hindered by ethical and technical considerations. The aim of this study was to develop an in vivo predictive dissolution test in order to investigate the impact of medicine co-administration with soft food and drinks on the dissolution performance of a poorly soluble compound. Relevant in vitro dissolution conditions simulating the in vivo gastrointestinal environment of infants were used to establish in vitro-in vivo relationships with corresponding in vivo data. Dissolution studies of montelukast formulations were conducted with mini-paddle apparatus on a two-stage approach: infant fasted-state simulated gastric fluid (Pi-FaSSGF; for 1 h) followed by either infant fasted-state or infant fed-state simulated intestinal fluid (FaSSIF-V2 or Pi-FeSSIF, respectively; for 3 h). The dosing scenarios tested reflected in vivo paediatric administration practices: (i.) direct administration of formulation; (ii.) formulation co-administered with vehicles (formula, milk or applesauce). Drug dissolution was significantly affected by co-administration of the formulation with vehicles compared with after direct administration of the formulation. Montelukast dissolution from the granules was significantly higher under fed-state simulated intestinal conditions in comparison with the fasted state and was predictive of the in vivo performance when the granules are co-administered with milk. This study supports the potential utility of the in vitro biorelevant dissolution approach proposed to predict in vivo formulation performance after co-administration with vehicles, in the paediatric population.

Experimental Study of the Impact of Alisma plantago-aquatica Secretions on Pathogenic Bacteria

2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay
Keyword(s):  
Pathogenic Bacteria ◽  
Initial Density ◽  
Biologically Active ◽  
Erysipelothrix Rhusiopathiae ◽  
Natural Focus ◽  
Test Species ◽  
Popula Tions ◽  
And Control ◽  
The Impact

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.

Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

2020 ◽  
Vol 23 ◽  
Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Silver Nanoparticles ◽  
Nuclear Dna ◽  
Liquid Paraffin ◽  
Tail Length ◽  
Hepatic Tissue ◽  
Tissue Destruction ◽  
Group 2 ◽  
The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems

2019 ◽  
Vol 16 (8) ◽  
pp. 688-697
Author(s):  
Ravinder Verma ◽  
Deepak Kaushik
Keyword(s):  
Drug Delivery ◽  
Ph Value ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Rapid Screening ◽  
Resonance Spectroscopy ◽  
Fed State ◽  
In Vitro Lipolysis ◽  
Ph Stat

: In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali
Keyword(s):  
Zataria Multiflora ◽  
Th2 Cytokine ◽  
Ifn Γ ◽  
The Impact

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

scholarly journals Tyrosol-Enriched Tomatoes by Diffusion across the Fruit Peel from a Chitosan Coating: A Proposal of Functional Food

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 335
Author(s):  
Silvia Tampucci ◽  
Antonella Castagna ◽  
Daniela Monti ◽  
Clementina Manera ◽  
Giuseppe Saccomanni ◽  
...  
Keyword(s):  
Tomato Fruit ◽  
Storage Period ◽  
Food Matrix ◽  
Fruit Peel ◽  
Fresh Food ◽  
In Vitro Permeation ◽  
Active Transfer

Chitosan is receiving increasing attention from the food industry for being a biodegradable, non-toxic, antimicrobial biopolymer able to extend the shelf life of, and preserve the quality of, fresh food. However, few studies have investigated the ability of chitosan-based coatings to allow the diffusion of bioactive compounds into the food matrix to improve its nutraceutical quality. This research is aimed at testing whether a hydrophilic molecule (tyrosol) could diffuse from the chitosan-tyrosol coating and cross the tomato peel. To this end, in vitro permeation tests using excised tomato peel and an in vivo application of chitosan-tyrosol coating on tomato fruit, followed by tyrosol quantification in intact fruit, peel and flesh during a seven-day storage at room temperature, were performed. Both approaches demonstrated the ability of tyrosol to permeate across the fruit peel. Along with a decreased tyrosol content in the peel, its concentration within the flesh was increased, indicating an active transfer of tyrosol into this tissue. This finding, together with the maintenance of constant tyrosol levels during the seven-day storage period, is very promising for the use of chitosan formulations to produce functional tomato fruit.

scholarly journals Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1497
Author(s):  
Pansong Zhang ◽  
Qiao Guo ◽  
Zhihua Wei ◽  
Qin Yang ◽  
Zisheng Guo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Mammalian Cells ◽  
Secretion System ◽  
Chinese Herbs ◽  
Infection Model ◽  
Lung Pathology ◽  
Promising Alternative ◽  
The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

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