scholarly journals Sustained release and pharmacologic effects of human glucagon-like peptide-1 and liraglutide from polymeric microparticles

2018 ◽  
Author(s):  
Luis Peña Icart ◽  
Fernando Gomes de Souza ◽  
Luís Maurício T. R. Lima
Keyword(s):  
Body Weight ◽  
Sustained Release ◽  
Therapeutic Agent ◽  
Body Weight Gain ◽  
Particle Surface ◽  
Subcutaneous Administration ◽  
Double Emulsion ◽  
Polymeric Microparticles

AbstractThe GLP-1 class of peptide agonists has been shown to exert regulatory key roles in both diabetes, obesity and related complications. Given the short half-life of GLP-1 its use has been historically discouraged. We developed polymeric microparticles loaded with either human GLP-1 (7-37) or liraglutide peptides by double emulsion and solvent evaporation approach. The size distribution of all formulations was of about 30-50 μm. The in vitro kinetic release assays showed a sustained release of the peptides extending up to 30 to 40 days with varying profiles. Morphologic analysis demonstrated a more regular particle surface for those comprising polymers PLA, PLA-PEG and PLGA. In vivo evaluation in Swiss male mice demonstrated a similar extension of effect of decreasing in body weight gain for up to 25 days after a single subcutaneous administration of either hGLP-1 or liraglutide peptide-loaded microparticles (200 μg peptide / kg body weight) compared to controls. These demonstrate the effectiveness of hGLP-1 as a therapeutic agent in long-term, continuous release from peptide-load microparticles, and thus its plausibility as an unmodified therapeutic agent.

scholarly journals Bauhiniastatin-1 alleviates diet induced obesity and lipid accumulation through modulating PPAR-γ/AMPK expressions: In-vitro, in-vivo and in-silico studies.

2021 ◽  
Author(s):  
Karunakaran Reddy Sankaran ◽  
Lokanatha Oruganti ◽  
Muni Swamy Ganjayi ◽  
Venkataramaiah Chintha ◽  
Muni Kesavulu Muppuru ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Western Blot ◽  
Blot Analysis ◽  
Body Weight Gain ◽  
Liver Lipid ◽  
Ppar Γ ◽  
Diet Induced Obesity

Abstract Background: Consumption of energy dense foods and sedentary lifestyles have led to high prevalence of obesity and associated disorders. Intensive research efforts have focussed to develop effective alternative therapeutics from plant sources. Bauhiniastatins have been reported to possess antineoplastic activity. In the present study, Bauhiniastatin-1 (BSTN1) was isolated and purified from Bauhinia purpurea and evaluated for its therapeutic efficacy against adipogenesis and obesity using high fat diet (HFD)-induced obese rodent model and 3T3-L1 cells.Methods: We performed in-vitro experiments like MTT assay, Oil Red O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis in 3T3-L1 cells. In-vivo parameters like body weight gain, body composition, plasma adipokines, serum & liver lipid profiles, liver marker enzymes, western blot analysis and histopathological examination were conducted in rat model. In addition, molecular docking studies were also performed to understand interaction of BSTN1 with peroxisome proliferator-activated gamma receptor (PPAR-γ) and AMP-activated protein kinase (AMPK) which supported our experimental results.Results: BSTN1 at 20 μM significantly (p<0.001) inhibited cell differentiation and lipid accumulation of 3T3-L1 adipocytes. Mechanistic studies showed that mRNA expression of key adipogenic markers, PPAR-γ, fatty acid synthase (FAS) and sterol-regulatory element-binding protein-1 (SREBP1) were down-regulated while AMPK was up-regulated by BSTN1. Oral administration of BSTN1 (5 mg/kg. b.wt.) to HFD-induced obese rats substantially decreased body weight gain, fat mass, serum and liver lipid levels and promoted integrity of hepatic and adipose tissue architecture compared to HFD-control rats. In BSTN1 administered groups, decreased serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, decreased plasma leptin but increased adiponectin levels were noted. Western blot analysis of adipose and hepatic tissues collected from BSTN1 treated rats showed decreased expression level of PPAR-γ but increase in AMPK expression relative to the untreated group. In-silico studies showed strong binding interactions of BSTN1 against PPAR-γ and AMPK, the key molecules of adipogenesis and obesity.Conclusions: Taken together, the results suggest that BSTN1 could be promising molecule for the treatment of diet-induced obesity and non-alcoholic fatty liver disease (NAFLD).

scholarly journals GIP receptor antagonist treatment causes weight loss in ovariectomized high fat diet-fed mice

2021 ◽  
Author(s):  
Geke Aline Boer ◽  
Jenna Hunt ◽  
Maria Gabe ◽  
Johanne Windeløv ◽  
Alexander Sparre-Ulricht ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Pharmacokinetic Profile ◽  
High Fat ◽  
Ovariectomized Mice ◽  
Gip Receptor

Background and purpose The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity but its exact role in these processes is unclear. Experimental approach We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomized mice during an 8-week treatment period. Key results mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor (GIPR) in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 hours in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomized HFD mice resulted in a reduction of body weight and fat mass. Conclusion and Implications mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomized mice. Our results support the development of GIP antagonists for the therapy of obesity.

scholarly journals Anti-obesity effect of Tamarindus indicus seed extract against a high-fat diet-induced obese model in rats

2020 ◽  
Vol 11 (2) ◽  
pp. 2083-2089
Author(s):  
Nabeel K ◽  
Asra Fathima ◽  
Farhath Khanum ◽  
Manjula S N ◽  
Mruthunjaya K ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Seed Extract ◽  
The Body ◽  
High Fat ◽  
Cell Viability Assay ◽  
Serum Triglycerides

The present study was aimed to evaluate the anti-obesity property of Tamarindus indica seed extract (TSE) on high fat-fed obese rats. TSE was prepared by cold maceration method and qualitative phytochemical studies had been carried out. In vitro cell viability assay (MTT assay) was and oil red staining for evaluating the lipid accumulation in cells was carried out using 3T3-L1 cells, and leptin levels was evaluated by ELISA. In-vivo Obesity was induced in experimental rats by administration of a high-fat diet for 04 weeks. The anti-obesity effect was screened by oral administration of TSE at two different dose levels i.e., 250 and 500mg/kg b. Wt. Along with a high-fat diet for a period of 04 weeks. The anti-obesity activity is estimated in terms of body weight gain, serum triglycerides (TG), Total cholesterol (TC). In -vitro studies revealed that the TSE has no cytotoxic effect, Administration of a high-fat diet for 04 weeks significantly increased the body weight, serum triglycerides, cholesterol. Upon treatment with TSE, a significant dose-dependent alteration in body weight, triglycerides, cholesterol levels were observed, inferring the anti-obesity property of Tamarindus seed extract.

scholarly journals Enhanced Survival in Mice Exposed to Ionizing Radiation by Combination of Gamma-Tocotrienol and Simvastatin

2019 ◽  
Vol 184 (Supplement_1) ◽  
pp. 644-651 ◽  
Author(s):  
Rupak Pathak ◽  
Vidya Prasanna Kumar ◽  
Martin Hauer-Jensen ◽  
Sanchita Purohit Ghosh
Keyword(s):  
Body Weight ◽  
Ionizing Radiation ◽  
Military Service ◽  
Protective Efficacy ◽  
Combined Treatment ◽  
Subcutaneous Administration ◽  
Cell Recovery ◽  
Gamma Tocotrienol

Abstract Ionizing radiation exposure is a major concern for active military service members, as well as civilian population. Considering that the exposure is not predictable, it is imperative that strategies to counteract radiation damage must be discovered. Recent in vitro studies performed in our laboratory demonstrated that the vitamin E analog gamma-tocotrienol (GT3) in combination with cholesterol-lowering drugs (Statins), synergistically induced endothelial thrombomodulin, an anticoagulant with radio-protective efficacy. It was hypothesized that the combination of treatment with both GT3 along with Statins would provide better radiation protection in vivo than each drug individually. CD2F1 mice were injected subcutaneously with either vehicle or single dose of GT3 (200 mg/kg body weight) 24 hours before irradiation followed by oral or subcutaneous administration of various doses of simvastatin (25, 50, and 100 mg/kg body weight) before exposure to lethal doses (11.5 and 12 Gy) of Cobalt-60 (60Co) gamma-irradiation. The combined treatment group exhibited enhanced radiation lethality protection substantially, accelerated white blood cell recovery, and augmented restoration of bone marrow cellularity when compared to the animals treated with either drug exclusively. This information clearly suggests that combined treatment could be used as a safeguard for military personnel from exposure to harmful ionizing radiation.

scholarly journals Immunobiological Effects of Fumonisin B1 in Experimental Subchronic Mycotoxicoses in Rats

2002 ◽  
Vol 9 (1) ◽  
pp. 149-155 ◽  
Author(s):  
M. G. Theumer ◽  
A. G. López ◽  
D. T. Masih ◽  
S. N. Chulze ◽  
H. R. Rubinstein
Keyword(s):  
Body Weight ◽  
Small Intestine ◽  
Mononuclear Cells ◽  
Body Weight Gain ◽  
Fusarium Verticillioides ◽  
Fumonisin B1 ◽  
Gibberella Fujikuroi ◽  
Interleukin 4

ABSTRACT Fumonisin B1 (FB1), the principal secondary metabolite produced by the fungus Fusarium verticillioides (Gibberella fujikuroi mating population A), is a potent toxin that can be found in fungus-contaminated corn and corn-based food products. We have investigated the immunobiological effects of subchronic dietary exposure to FB1 in male Wistar rats. Animals were fed with diets containing 0 (control) or 100 ppm of FB1 for 12 weeks. The total FB1 intake on day 90 was 810 mg/kg of body weight. Food consumption, body weight, and body weight gain on day 90 were reduced in animals exposed to FB1. Histopathologic changes consisted of histiocytic perivascular infiltrate and an increased number of Kupffer cells in the liver, necrosis and apoptosis of tubular epithelial cells in the kidney, and increased mitotic figures and lymphocytic infiltrate in the small intestine. Serum enzyme alkaline phosphatase was significantly elevated in rats fed FB1, while triglyceride levels decreased compared to controls. Treatment with FB1 in vivo or in vitro did not have a significant effect on mitogen-induced proliferation of spleen mononuclear cells. However, increased levels of interleukin-4 (IL-4) and decreased levels of IL-10 were released by these cells in culture compared to controls. FB1 in vivo or in vitro decreased the hydrogen peroxide (H2O2) released by peritoneal macrophages, while no changes in levels of superoxide anion produced by total peritoneal cells were detected. The results from the present work demonstrate that subchronic FB1 intake could affect the small intestine and alter the interleukin profile and some main functions of macrophages in antitumor activity.

scholarly journals Engineering of L-Plastin Peptide-Loaded Biodegradable Nanoparticles for Sustained Delivery and Suppression of Osteoclast Function In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sunipa Majumdar ◽  
Aniket S. Wadajkar ◽  
Hanan Aljohani ◽  
Mark A. Reynolds ◽  
Anthony J. Kim ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Sustained Release ◽  
Double Emulsion ◽  
Small Molecular Weight ◽  
Rhodamine Phalloidin ◽  
Amino Terminal ◽  
Osteoclast Function

We have recently demonstrated that a small molecular weight amino-terminal peptide of L-plastin (10 amino acids; “MARGSVSDEE”) suppressed the phosphorylation of endogenous L-plastin. Therefore, the formation of nascent sealing zones (NSZs) and bone resorption are reduced. The aim of this study was to develop a biodegradable and biocompatible PLGA nanocarrier that could be loaded with the L-plastin peptide of interest and determine the efficacy in vitro in osteoclast cultures. L-plastin MARGSVSDEE (P1) and scrambled control (P3) peptide-loaded PLGA-PEG nanoparticles (NP1 and NP3, respectively) were synthesized by double emulsion technique. The biological effect of nanoparticles on osteoclasts was evaluated by immunoprecipitation, immunoblotting, rhodamine-phalloidin staining of actin filaments, and pit forming assays. Physical characterization of well-dispersed NP1 and NP3 demonstrated ~130-150 nm size, < 0.07 polydispersity index, ~-3 mV ζ-potential, and a sustained release of the peptide for three weeks. Biological characterization in osteoclast cultures demonstrated the following: NP1 significantly reduced (a) endogenous L-plastin phosphorylation; (b) formation of NSZs and sealing rings; (c) resorption. However, the assembly of podosomes which are critical for cell adhesion was not affected. L-plastin peptide-loaded PLGA-PEG nanocarriers have promising potential for the treatment of diseases associated with bone loss. Future studies will use this sustained release of peptide strategy to systematically suppress osteoclast bone resorption activity in vivo in mouse models demonstrating bone loss.

scholarly journals Biodegradable, bile salt microparticles for localized fat dissolution

2020 ◽  
Vol 6 (49) ◽  
pp. eabd8019 ◽  
Author(s):  
Hanieh Safari ◽  
Nicholas Kaczorowski ◽  
Michael L. Felder ◽  
Emma R. Brannon ◽  
Mita Varghese ◽  
...  
Keyword(s):  
Side Effects ◽  
Bile Salt ◽  
Subcutaneous Administration ◽  
Double Emulsion ◽  
Surface Erosion ◽  
Templating Method ◽  
Localized Delivery ◽  
Solvent Evaporation Process

Bile acids are proposed as therapeutic agents for various diseases, including liver diseases and obesity. However, oral or subcutaneous administration of a solubilized version of these drugs has limited efficacy and imposes unwanted side effects. Here, we describe a gold-templating method for fabricating stable, bile salt—cholate or deoxycholate—microparticles. The gold ions’ reduction at the oil-water interface in a double emulsion solvent evaporation process enables a gold–bile salt interaction and the formation of bile salt particles. We demonstrate that composite microparticles release cholate/deoxycholate into solution via a surface erosion process. We illustrate these particles’ capability to lyse adipocytes, both in vitro and in vivo, with minimal side effects, contrary to the Food and Drug Administration–approved salt solution that leads to severe inflammation and ulceration. Overall, particle-based cholate/deoxycholate opens opportunities for localized delivery of these salts, improving efficacy while minimizing side effects associated with oral and subcutaneous use.

scholarly journals Comparative efficacy of korolla (Momordica charantia) extract and Ivermec® pour on with their effects on certain blood parameters and body weight gain in indigenous chicken infected with Ascaridia galli

1970 ◽  
Vol 6 (2) ◽  
pp. 153-158 ◽  
Author(s):  
HM Shahadat ◽  
M Mostofa ◽  
MAA Mamum ◽  
ME Hoque ◽  
MA Awal
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Body Weight Gain ◽  
Momordica Charantia ◽  
Control Group ◽  
Ascaridia Galli ◽  
Indigenous Chicken ◽  
Group B

Comparative anthelmintics efficacy of whole korolla fruit (Momordica charantia) extract and ivermec® pour on was evaluated in vitro and in vivo on adult Ascaridia galli of indigenous chicken. The total trial chickens (60) were divided equally into 3 groups; group A as control, group B treated with ivermec® pour on @ 500 μg/kg bwt by dropper through skin absorption for single dose and group C treated with 3% aqueous extract of korolla. Freshly prepared aqueous extract of the korolla fruit was performed as wormicidal properties against adult A. galli on in vitro and in vivo study. 3% aqueous extract of korolla fruit was treated as higher efficacy against A. galli. The live body weight was increased in chicken after treatment in group B and C respectively but in control group body weight was slowly decreased. TEC (million/cu mm), Hb (gm %) and PCV (%30 minutes) were increased significantly in chickens of treated groups whereas ESR was increased in control groups. Key words: Anthelmintics efficacy, korolla, Ivermec® pour on, Ascaridia galli, indigenous chicken, haematological parameters  doi: 10.3329/bjvm.v6i2.2328 Bangl. J. Vet. Med. (2008). 6 (2): 153-158   

scholarly journals N-acetylcysteine+nimesulide: An association strategy aiming to prevent nimesulide-induced hepatotoxicity

2021 ◽  
Vol 19 (2) ◽  
pp. 91-99
Author(s):  
Amanda G. Elias ◽  
Julia S. da Silva ◽  
Rafaela L. Klein ◽  
Francieli U. I. Amaral ◽  
Marcelo D. Arbo ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cell Model ◽  
Body Weight Gain ◽  
The Body ◽  
Relative Mass ◽  
Male Wistar Rats ◽  
Control Body

Introduction: Nimesulide is a potent anti-inflammatorywith rapid and long-lasting effects, but also with a high riskof hepatotoxicity. Objective: This work aimed to preventnimesulide-induced hepatotoxicity through the associationof nimesulide with a hepatoprotective agent. Materials andMethods: First, we tested three hepatoprotective agents:N-acetylcysteine, L-carnitine, and Gingko biloba extract inan in vitro hepatic cell model. Both N-acetylcysteine and G.biloba showed promisor results. We selected N-acetylcysteineto continue the studies in an animal model. In vivo study wasperformed using male Wistar rats divided in 4 groups: control,nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) +N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone(100mg/kg/day). Treatments were given by gavage, daily, for15 days. Results: Animals receiving nimesulide alone showedlower body weight gain compared to control. Body weightgain in the nimesulide + N-acetylcysteine group was higherthan nimesulide alone, evidencing lower toxicity. However,the body weight gain of the nimesulide + N-acetylcysteinegroup was still lower than the control animals. Animals treatedwith nimesulide alone presented an increased relative mass ofheart, liver, and spleen and significant hepatic damage seen inmicroscopy when compared to other groups. N-acetylcysteineco-administered with nimesulide prevented the increasedheart mass, but the same was not true with liver and spleen.Conclusions: This work evidence partial protection elicitedby the association of N-acetylcysteine and nimesulide againstnimesulide-induced hepatotoxicity.

scholarly journals Caralluma Acutangula Prevents Body Weight Gain in Rats Feed on Hyperlipidic Diet

2018 ◽  
Vol 75 (2) ◽  
pp. 168
Author(s):  
Pare DRAMANE ◽  
Hilou ADAMA ◽  
Adrian POTÂRNICHE ◽  
Mabozou KPEMISSI ◽  
Orsolya SÁRPATAKI ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Body Weight Loss ◽  
Treated Group ◽  
Total Phenolic ◽  
Control Group ◽  
Hyperlipidic Diet

Caralluma acutangula (Decne.) (CA) (Asclepiadaceae) is a medicinal plant traditionally used in Burkina Faso for the management of weight. The aim of this study was to evaluate the effect of extract of CA on body weight, food intake, blood biochemistry parameters on experimental obesity rat model. One group received CA 400 mg/kg b.w. per day and was fed on hyperlipidic diet (HD), while the control group received HD only for three weeks long. The phytochemical investigation of extract showed a high total phenolic content (36.21±1.36 mg GAE/100mg of extract) and total flavonoids (4.98 ±0.31 QE/100 mg of extract). In the end, CA-HD treated group had a body weight loss of 2%, compared to HD group who presented a body weight gain of 15%. The CA-HD treated group showed also a lower levels of plasma triglyceride (136.57±13.82 mg/dL) and glycemia (187.74±31.16 mg/dL) compared to HD (206.02±23.82 and respectively 230.96±79.07 mg/dL) (p<0.05). CA extract also showed a good anti-oxidant activity in vivo (effect on antioxydant enzyme (MDA, GPX, SOD) and in vitro (inhibition of DPPH radical, ferric ion reduction). This study showed that CA is a potential natural remedy for the control of body weight and alleviation of obesity related disease.

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