scholarly journals Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1677
Author(s):  
Mohamed Bouhrim ◽  
Hayat Ouassou ◽  
Salima Boutahiri ◽  
Nour Elhouda Daoudi ◽  
Hamza Mechchate ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ex Vivo ◽  
Ussing Chamber ◽  
Diabetic Rats ◽  
Postprandial Hyperglycemia ◽  
Antihyperglycemic Effect ◽  
Opuntia Dillenii

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO’s effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.

scholarly journals Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells

2021 ◽  
Author(s):  
Naresh Damuka ◽  
Miranda Orr ◽  
Paul W. Czoty ◽  
Jeffrey L. Weiner ◽  
Thomas J. Martin ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ex Vivo ◽  
Neuroblastoma Cells ◽  
Proper Function ◽  
Brain Functions ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Vitro Binding

AbstractMicrotubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.

Abstract WP498: Impaired Pericyte Constriction and Cerebral Blood Flow Autoregulationin Diabetes

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yedan Liu ◽  
Shaoxun Wang ◽  
Ya Guo ◽  
Huawei Zhang ◽  
Richard Roman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Vascular Cognitive Impairment ◽  
Treated Group ◽  
Diabetic Rats ◽  
Cerebrovascular Function

Diabetes is the primary pathological factor attributed to Alzheimer’s disease and vascular cognitive impairment. Previous studies demonstrated that hyperglycemia promoted oxidative stress in the cerebral vasculature. Cerebrovascular pericytes contribute to maintaining blood-brain barrier (BBB) integrity and regulating cerebral blood flow (CBF). However, whether hyperglycemia diminishes the contractile capability of pericytes, impairs CBF autoregulation and increases BBB permeability are unclear. In the present study, we examined the role of pericytes in cerebrovascular function and cognition in diabetes using cell culture in vitro , isolated penetrating arterioles ex vivo and CBF autoregulation in vivo . Reactive oxygen species were elevated in high glucose (HG, 30 mM) treated vs. normal glucose (NG, 5.5 mM) treated pericytes. Further, mitochondrial superoxide production was increased in HG-treated vs. NG-treated group (13.24 ± 1.01 arbitrary unit (a.u.)/30min vs. 6.98 ± 0.36 a.u./30min). Mitochondrial respiration decreased in HG-treated vs. NG-treated pericytes (3718 ± 185.9 pmol/min/mg, n=10 vs. 4742 ± 284.5 pmol/min/mg, n=10) as measured by a Seahorse XFe24 analyzer. HG-treated pericytes displayed fragmented mitochondria in association with increased fission protein (DRP1) and decreased fusion protein (OPA1) expression. HG-treated pericytes displayed lower contractile capability than NG-treated cells (20.23 ± 7.15% vs. 29.46 ± 9.41%). The myogenic response was impaired in penetrating arterioles isolated from diabetic rats in comparison with non-diabetic rats. Autoregulation of CBF measured by a laser Doppler flowmeter was impaired in diabetic rats compared with non-diabetic rats. Diabetic rats exhibited greater BBB leakage than control rats. The cognitive function was examined using an eight-arm water maze. Diabetic rats took longer time to escape than the non-diabetic rats indicating learning and memory deficits. In conclusion, hyperglycemia induces pericyte dysfunction by altering mitochondrial dynamics and diminishing contractile capability, which promotes BBB leakage, decreases CBF autoregulation and contributes to diabetes-related dementia.

In-vitro, ex-vivo, and in-vivo release evaluation of in situ forming buprenorphine implants using mixture of PLGA copolymers and additives

2018 ◽  
Vol 68 (16) ◽  
pp. 965-977 ◽  
Author(s):  
Hossein Kamali ◽  
Elham Khodaverdi ◽  
Farzin Hadizadeh ◽  
Seyed Ahmad Mohajeri ◽  
Younes Kamali ◽  
...  
Keyword(s):  
Ex Vivo ◽  
In Situ Forming ◽  
In Vivo Release

scholarly journals How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 675 ◽  
Author(s):  
Mariana Amaral ◽  
Ana Sofia Martins ◽  
José Catarino ◽  
Pedro Faísca ◽  
Pradeep Kumar ◽  
...  
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Polymeric Nanoparticles ◽  
Spherical Shape ◽  
Diabetic Rats ◽  
Laser Scattering ◽  
In Vivo Models ◽  
Mean Size

Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats’ glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.

Antihyperglycemic effect of a chicken feet hydrolysateviathe incretin system: DPP-IV-inhibitory activity and GLP-1 release stimulation

2019 ◽  
Vol 10 (7) ◽  
pp. 4062-4070 ◽  
Author(s):  
Àngela Casanova-Martí ◽  
Francisca Isabel Bravo ◽  
Joan Serrano ◽  
Anna Ardévol ◽  
Montserrat Pinent ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Ex Vivo ◽  
Antihyperglycemic Effect ◽  
Dpp Iv

The potential of hydrolysates of chicken feet proteins as natural DPP-IV inhibitors was investigated. After a screening, one hydrolysate was testedin vivoand showed antihyperglicemic effect. In addition, it stimulated GLP-1in vitroandex vivo.

In Situ Gels of Acylovir Nanoemulsions For Improved Delivery to The Eye

2021 ◽  
Vol 11 ◽  
Author(s):  
Manza M. Priyanka ◽  
Shinde A. Ujwala ◽  
Sheth M. Kalyani ◽  
Namita Desai
Keyword(s):  
Animal Studies ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Corneal Stroma ◽  
Class Iii ◽  
Ophthalmic Delivery ◽  
Histopathological Studies

Background: Acyclovir, BCS Class III drug is commercially available as 3 % w/w eye ointment for multiple applications. Acyclovir nanoemulsions can be proposed to reduce dose because of improved permeation characteristics. Further, the development of in situ ophthalmic gels can be advantageous to reduce the number of applications due to increased mucoadhesion and sustaining effect. Objective: The purpose of this study was the development and evaluation of nanoemulsions based in situ gels of Acyclovir (1% w/w) as potential ophthalmic delivery systems. Methods: Nanoemulsions of Acyclovir were developed by Phase Inversion Temperature method using Capmul MCM, stearyl amine and Kolliphor RH 40 as liquid lipid, charge inducer and surfactant, respectively selected on the basis of Acyclovir solubility studies in the oil phase and emulsification ability of surfactants. These nanoemulsions were further developed into in situ ophthalmic gels using gellan gum and Methocel K4M. Results: The developed gels showed a sustained effect in vitro release studies and improved goat corneal permeation in ex vivo studies when compared to marketed ointment. HET-CAM studies concluded the absence of irritation potential, while in vivo irritation study in Wistar rats showed the absence of erythema and swelling of eyes after visual inspection for 72 hours. Histopathological studies on isolated rat corneas showed no abnormalities in anterior corneal epithelium and corneal stroma without any epithelial hyperplasia. Acyclovir nanoemulsions based in situ ophthalmic gel showed increased corneal deposition and permeation in rat eyes. Conclusion: The improved potential of developed ophthalmic gels was proven due to the reduced frequency of application compared to the marketed ointment in animal studies.

scholarly journals The Progress of Intestinal Epithelial Models from Cell Lines to Gut-On-Chip

2021 ◽  
Vol 22 (24) ◽  
pp. 13472
Author(s):  
Shafaque Rahman ◽  
Mohammed Ghiboub ◽  
Joanne M. Donkers ◽  
Evita van de Steeg ◽  
Eric A. F. van Tol ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ex Vivo ◽  
Ussing Chamber ◽  
Intestinal Epithelial ◽  
The Past ◽  
Health And Disease ◽  
Conventional Models ◽  
On Chip

Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these approaches fail to fully reflect the multifactorial and complex in vivo environment (e.g., including microbiota, nutrition, and immune response) in the gut system. Although conventional models such as cell lines, Ussing chamber, and the everted sac are still used, increasingly more sophisticated intestinal models have been developed over the past years including organoids, InTESTine™ and microfluidic gut-on-chip. In this review, we gathered the most recent insights on the setup, advantages, limitations, and future perspectives of most frequently used in vitro and ex vivo models to study intestinal physiology and functions in health and disease.

scholarly journals In Situ-Forming Cellulose/Albumin-Based Injectable Hydrogels for Localized Antitumor Therapy

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4221
Author(s):  
Ying Chen ◽  
Xiaomin Wang ◽  
Yudong Huang ◽  
Peipei Kuang ◽  
Yushu Wang ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Antitumor Therapy ◽  
Injectable Hydrogels ◽  
External Temperature ◽  
Minimal Invasiveness ◽  
In Situ Forming ◽  
External Stimuli

Injectable hydrogels, which are formed in situ by changing the external stimuli, have the unique characteristics of easy handling and minimal invasiveness, thus providing the advantage of bypass surgical operation and improving patient compliance. Using external temperature stimuli to realize the sol-to-gel transition when preparing injectable hydrogel is essential since the temperature is stable in vivo and controllable during ex vivo, although the hydrogels obtained possibly have low mechanical strength and stability. In this work, we designed an in situ fast-forming injectable cellulose/albumin-based hydrogel (HPC-g-AA/BSA hydrogels) that responded to body temperature and which was a well-stabilized hydrogen-bonding network, effectively solving the problem of poor mechanical properties. The application of localized delivery of chemotherapeutic drugs of HPC-g-AA/BSA hydrogels was evaluated. In vitro and in vivo results show that HPC-g-AA/BSA hydrogels exhibited higher antitumor efficacy of reducing tumor size and seem ideal for localized antitumor therapy.

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