A New Symmetrical Thiazolidinedione Derivative: In Silico Design, Synthesis, and In Vivo Evaluation on a Streptozotocin- Induced Rat Model of Diabetes

By activating PPAR-γ, thiazolidinediones normalize glucose levels in animal models of type 2 diabetes and in patients with this pathology. The aim of the present study was to analyze 219 new derivatives in silico and select the best for synthesis, to be evaluated for acute oral toxicity in female rats and for control of diabetes-related parameters in a rat model of streptozotocin-induced diabetes. The best compound was chosen based on pharmacokinetic, pharmacodynamic, and toxicological parameters obtained in silico and binding orientation observed by docking simulations on PPAR-γ. Compound 1G was synthesized by a quick and easy Knoevenagel condensation. Acute oral toxicity was found at a dose greater than 2000 mg/Kg. Compound 1G apparently produces therapeutic effects similar to those of pioglitazone, decreasing glycaemia and triglyceride levels in diabetic animals, without liver damage. Moreover, it did not cause a significant weight gain and tended to reduce polydipsia and polyphagia, while diminishing systemic inflammation related to TNF-α and IL-6. It lowered the level of endogenous antioxidant molecules such as reduced glutathione and glutathione reductase. In conclusion, 1G may be a candidate for further testing as an euglycemic agent capable of preventing the complications of diabetes.

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Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In-Silico Modelling and In-Vivo Toxicity Evaluation

Polymers ◽

10.3390/polym13244350 ◽

2021 ◽

Vol 13 (24) ◽

pp. 4350

Author(s):

Zunaira Alvi ◽

Muhammad Akhtar ◽

Nisar U. Rahman ◽

Khaled M. Hosny ◽

Amal M. Sindi ◽

...

Keyword(s):

In Silico ◽

Sodium Tripolyphosphate ◽

Polymeric Nanoparticles ◽

Chitosan Nanoparticles ◽

Chemical Properties ◽

Aqueous Solubility ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Cross Linker

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE7 β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

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Exploring the frostbite healing potential of Hyaluronic acid based hydrogel of Manuka Honey through in-silico Antithrombotic and Anti-platelet studies of Major Phytoconstituents and in-vivo Evaluation in Wistar Rat Model

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2021.1989459 ◽

2021 ◽

pp. 1-23

Author(s):

Kumud Joshi ◽

Bhaskar Mazumder ◽

Pronobesh Chattopadhyay ◽

Danswrang Goyary ◽

Madhubanti Das ◽

...

Keyword(s):

Hyaluronic Acid ◽

Rat Model ◽

In Silico ◽

Wistar Rat ◽

Manuka Honey ◽

In Vivo Evaluation

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Acute, subacute oral toxicity and Ames test of Py-mulin: an antibacterial drug candidate

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00543-5 ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Yuan Fan ◽

Yunxing Fu ◽

Yuhang Zhou ◽

Yu Liu ◽

Baocheng Hao ◽

...

Keyword(s):

Ames Test ◽

Clinical Chemistry ◽

Toxicity Study ◽

Female Rats ◽

Drug Candidate ◽

Antibacterial Drug ◽

Acute Oral Toxicity ◽

Oral Toxicity

Abstract Background Py-mulin is a new pleuromutilin derivative with potent antibacterial activities in vitro and in vivo, suggesting this compound may lead to a promising antibacterial drug after further development. The present study is aimed to evaluate the acute and subacute oral toxicity, and the genotoxicity with the standard Ames test according to standard protocols. Methods Acute oral toxicity of Py-mulin was determined using Kunming mice. The 28-day repeated dose oral toxicity study in SD rats was performed according to OECD guideline No. 407. The bacterial reverse mutation (Ames test) was carried out using four Salmonella typhimurium (S. typhimurium) strains TA97, TA98, TA100 and TA1535 with and without S9 metabolic activation. Results The LD50 values in acute oral toxicity were 2973 mg/kg (female mice) and 3891 mg/kg (male mice) calculated by the Bliss method. In subacute toxicity study, 50 mg/kg Py-mulin did not induce any abnormality in body weight, food consumption, clinical sign, hematology, clinical chemistry, organ weight, and histopathology in all of the treatment groups. However, high doses of Py-mulin (100 and 300 mg/kg) displayed slightly hepatotoxicity to female rats. Furthermore, Py-mulin did not significantly increase the number of revertant colonies of four standard S. typhimurium strains with the doses of 0.16–1000 μg/plate in the Ames study. Conclusions Based on our findings, our study provides some information for the safety profile of Py-mulin.

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In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104458 ◽

2021 ◽

Vol 106 ◽

pp. 104458

Author(s):

Chetna Kharbanda ◽

Mohammad Sarwar Alam ◽

Hinna Hamid ◽

Yakub Ali ◽

Syed Nazreen ◽

...

Keyword(s):

Propionic Acid ◽

In Silico ◽

In Vivo Evaluation ◽

Ppar Γ

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EVALUATION OF ANTIDIABETIC ACTIVITY OF LEUCOMERIS SPECTABILIS EXTRACT IN ALLOXAN-INDUCED DIABETIC RATS

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5.1838 ◽

2018 ◽

Vol 8 (5) ◽

pp. 273-279

Author(s):

Ved Pal Baiga ◽

Kuldeep Kumar ◽

Shivansh Yadav ◽

Prevesh Kumar ◽

Divakar Shukla ◽

...

Keyword(s):

Body Weight ◽

Serum Marker ◽

Diabetic Rats ◽

Antidiabetic Activity ◽

Acute Oral Toxicity ◽

Marker Enzymes ◽

Oral Toxicity ◽

In Vivo Evaluation ◽

Sugar Levels

The objective of the study is to investigate the hydro alcoholic leaves extract of Leucomeris spectabilis (Asteraceae) for hypoglycemic effects in normal and diabetic rats. Acute oral toxicity study indicated that HAE was safe up to a dose of 2000 mg/kg body weight of rats and screened for antidiabetic activity in alloxan (120 mg/ kg, i.p.) induced diabetic rats for 21 days along with phytochemical analyses of HAE were also carried out. In-vivo evaluation of the extracts decreased blood sugar levels with significant improvement in blood glucose level, serum marker enzymes (SGPT, SGOT and ALP) and the content at the end of 1, 2 and 3rd weeks after HAELC treatment. The results suggest of antidiabetic activity study revealed that HAE possesses significant (p < 0.05) hypoglycemic activity compared to diabetic rats group. The results showed that the hydroalcoholic leaves extract has significantly most of effect in 200mg/kg. Keywords: Leucomeris spectabilis, Leaves, Acute oral toxicity, Alloxan, Ant-diabetic activity.

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Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911521997849 ◽

2021 ◽

pp. 088391152199784

Author(s):

Loveleen Kaur ◽

Ajay Kumar Thakur ◽

Pradeep Kumar ◽

Inderbir Singh

Keyword(s):

Drug Release ◽

In Silico ◽

Ex Vivo ◽

Strong Interactions ◽

Dissolution Time ◽

Sem Images ◽

In Vivo Evaluation ◽

Release Studies

Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.

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Correction: In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model

Biomaterials Science ◽

10.1039/d0bm90110e ◽

2021 ◽

Author(s):

Xiuying Li ◽

Zhenhong Wei ◽

Binxi Li ◽

Jing Li ◽

Huiying Lv ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Rat Model ◽

Burn Injury ◽

Therapeutic Effects

Correction for ‘In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model’ by Xiuying Li et al., Biomater. Sci., 2019, 7, 2861–2872, DOI: 10.1039/C9BM00242A.

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Sub-acute oral toxicity and in vivo antioxidant properties of Oxalis cernua

South African Journal of Botany ◽

10.1016/j.sajb.2020.07.004 ◽

2020 ◽

Vol 133 ◽

pp. 91-97

Author(s):

Meriama Belghoul ◽

Abderrahmane Baghiani ◽

Seddik Khennouf ◽

Lekhmici Arrar

Keyword(s):

Antioxidant Properties ◽

Acute Oral Toxicity ◽

Oral Toxicity

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Antihyperuricemic, Anti-Inflammatory and Antihypertensive Effect of a Dry Extract from Solidago virgaurea L. (Asteraceae)

Scientia Pharmaceutica ◽

10.3390/scipharm89020027 ◽

2021 ◽

Vol 89 (2) ◽

pp. 27

Author(s):

Mircea Tămaş ◽

Oliviu Vostinaru ◽

Loredana Soran ◽

Ildiko Lung ◽

Ocsana Opris ◽

...

Keyword(s):

Blood Pressure ◽

Rat Model ◽

Antihypertensive Effect ◽

Chemical Constituents ◽

In Vivo Evaluation ◽

Dry Extract ◽

The Balkans ◽

Solidago Virgaurea ◽

Anti Inflammatory

Solidago virgaurea L. is a perennial plant used in European traditional medicine as a diuretic or a remedy for inflammatory conditions of the urinary tract but also for gout, especially in the Balkans. The present study was focused on a preclinical, in vivo evaluation of antihyperuricemic, anti-inflammatory, and antihypertensive effects of a dry extract from S. virgaurea L. (ESV). Colorimetric and HPLC–MS techniques were used to identify the main chemical constituents of ESV. Antihyperuricemic effect of ESV was assessed in a rat model of hyperuricemia induced by the administration of potassium oxonate. Antihypertensive effect of ESV was evaluated in hyperuricemic rats by monitoring systolic blood pressure with a non-invasive blood-pressure recording system. The anti-inflammatory effect of ESV was tested using a rat model of paw edema. The main chemical constituents of ESV were rutin and phenolic acids represented by chlorogenic and caffeic acid. ESV demonstrated significant antihyperuricemic effects in rats due to an uricosuric mechanism. Additionally, ESV reduced the progression of arterial hypertension in hyperuricemic rats and also showed anti-inflammatory properties slightly inferior to diclofenac. The results suggest that ESV could be a natural remedy for the treatment of gout and protection against endothelial dysfunction caused by hyperuricemia.

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