The effects of liquid extract of Allium sativum on the basic and speed-dependent electrophysiological properties of islolated atrioventicular nodal of rabbit

زمینه و هدف: گیاهان دارویی، به علت سهولت دسترسی، کاهش عوارض جانبی و قیمت مناسب، به عنوان جایگزین‌های شایسته داروهای شیمیایی، همواره مورد توجه بوده‌اند. مطالعات قبلی در مورد اثرات فارماکولوژیک و بیوشیمیایی گیاه سیر (Allium sativum) بیانگر اثرات کاهندگی فشارخون، اثرات آنتی آریتمیک، خاصیت اینوتروپ و کرونوتروپ منفی می باشد. هدف از این مطالعه تعیین اثرات عصاره آبی سیر بر روی خواص پایه و کارکردی گره دهلیزی بطنی می باشد. روش بررسی: در تحقیق حاضر از گستره بافتی جدا شده گره دهلیزی بطنی خرگوش (2-5/1 کیلوگرم) شامل دهلیز راست، سپتوم بین دهلیزی و دسته هیس جهت تعیین تاثیر غلظت های مختلف عصاره آبی سیر استفاده شد. پروتکل های انتخابی تحریکی (تسهیل، خستگی، ریکاوری) برای بررسی خواص گره دهلیزی – بطنی در 14 خرگوش (2 گروه) به صورت مستقل مورد استفاده قرار گرفتند. در گروه اول آزمایشی (8 خرگوش) غلظت های مختلف سیر (20، 30، 100 و 850 میلی گرم در لیتر) و در گروه دوم وراپامیل (1/0 میکرومولار) بکار برده شد. داده ها با استفاده از آزمون های آماری ویکاکسون و آنالیز واریانس تجزیه و تحلیل شد. یافته ها: نتایج این تحقیق بیانگر تاثیر معنی دار غلظت های مختلف عصاره گیاه در افزایش پارامترهای الکتروفیزیولوژیک پایه (زمان هدایت دهلیزی–بطنی، ونکباخ، زمان تحریک ناپذیری کارکردی و زمان تحریک نپذیری موثر) و همچنین میزان خستگی می باشد (05/0

Antioxidant Activity and Cardioprotective Effect of Potentilla reptans L. via Ischemic Preconditioning (IPC)

Background and objectives:  Potentilla reptans L. from Rosaceae family is used as traditional medicine in Iran and other countries. Previous investigations on Potentilla species have reported strong antioxidant activity and cardioprotective effect. In this study, antioxidant activity of aerial parts and root of Potentilla reptans, and the cardio protective role of its root on preconditioning ischemia reperfusion injury have been investigated. Methods: Antioxidant activity of aerial parts and root of this plant were measured by DPPH and FRAP methods and its total phenolics content was estimated by Folin-Ciocalteu assay. Catechin was isolated from ethyl acetate fraction by Paper chromatography. Cardioprotective role of P. reptans root were evaluated by thirty five rats in five groups.The hearts were subjected to 30 minutes of ischemia and 100 minutes of reperfusion. The ischemic preconditioning (IPC) protocol was applied before the main ischemia. The myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining. The hemodynamic parameters, arrhythmia scoring and coronary flow were measured during reperfusion. Results: Potentilla reptans root showed stronger antioxidant activity and total phenolics content compared to the aerial parts. Total extract of root significantly decreased the infarct size and increased coronary flow in a concentration-dependent manner. Conclusion: Our results showed that the protective effects of Potentilla reptans root appeared by its phenolic compounds and reactive oxygen species (ROS) inhibition mechanism

Chemical Decellularization Methods and Its Effects on Extracellular Matrix

Background:  Extracellular matrix (ECM) produced by tissue decellularization processes as a biological scaffold due to its unique properties compared to other scaffolds for migration and implantation of stem cells have been used successfully in the field of tissue engineering and regenerative medicine in the last years. The objective of this manuscript was to provide an overview of the chemical decellularization methods, evaluation of decellularized ECM and the potential effect of the chemical decellularization agents on the biochemical composition.Methods: We searched in Google Scholar, PubMed, Scopus, and Science Direct. The literature search was done by using the following keywords: “ECM, biologic scaffold, decellularization, chemical methods, tissue engineering.” We selected articles have been published from 2000 to 2016, and 15 full texts and 97 abstracts were reviewed.Results:Employing an optimization method to minimize damage to the ECM ultrastructure as for a result of the lack of reduction in mechanical properties and also the preservation of essential proteins such as laminin, fibronectin, Glycosaminoglycans (GAGs), growth factor is required. Various methods include chemical, physical and enzymatic technics were studied. However, on each of these methods can have undesirable effects on ECM.Conclusion: It is suggested that instead of the Sodium dodecyl sulfate (SDS) which have high strength degradation, we can use zwitterionic separately or in combination with SDS. Tributyl phosphate (TBP) due to its unique properties can be used in decellularization process

Hydro-alcoholic extract of Matricaria recutita exhibited dual anti-spasmodic effect via modulation of Ca2+ channels, NO and PKA2-kinase pathway in rabbit jejunum

Objective: Several studies have shown the antispasmodic activity of Matricariarecutita without detailing the underlying mechanism(s). The present study was designed to determine whether the antispasmodic mechanisms of M. recutita extract mediated via histaminergic/cholinergic receptors, Ca2+channels, activation of PKA2 and NO release in isolated rabbit jejunum. Methods and Materials: The concentration- dependent (3 × 10-3–1.3 × 10-2 mg/ml) antispasmodic effect of the hydro-alcoholic extract of M. recutita flowers was studied in isolated rabbit jejunum. The isolated jejunum preparations were divided into seven groups, including the pharmacological probes that modulate cholinergic, histaminergic, and nitrergic receptors, as well as PKA2. Results: M. recutita inhibited spontaneous smooth muscle contractility of the jejunum in a concentration-dependent manner (3 × 10-3–1.3 × 10-2 mg/ml) and reduced both K+- and Ca2+-induced contractions, which is similar to the effect of verapamil. The antispasmodic effect of M. recutita wasinhibited by H89 (a PKA2 inhibitor). The myorelaxant effect of M. recutita increased in the presence of ACh/His and H89. Conclusion: M. recutita evoked antispasmodic and spasmolytic effects mediated through different signaling pathways. Our results have shown this dual inhibitory effect is mediated by blocking Ca2+ channels, activating His and ACh receptors, releasing NO, and activating PKA2

Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles

Glycogen synthase kinase-3 beta (GSK-3ß) regulates glycogen metabolism and many different cellulars, including apoptosis, signaling, and neural. It is a crucial therapeutic receptor in heart disease, type 2 diabetes, and Alzheimer’s. In this study, using computational methods, flavonoid compounds were investigated for potential inhibitors against GSK-3ß. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3ß receptor constructed by homology modeling. Best binding poses were discovered via in silico molecular docking simulation. We surveyed noncovalent interactions among amino acid residues involved in the active site of the modeled Protein and compounds via molecular docking and molecular dynamics (MD). Moreover, ADMET characteristics of best docking conformers have been investigated. The obtained results revealed that compound 1 containing chromenone moiety with binding energy H-bond -11.4 kcal/mol inhibited effectively binding pocket of the GSK-3ß receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3b receptor remained stable throughout 100 ns MD simulation, and also analysis of ADMET profiles revealed that selected compounds had good drug-likeness and pharmacokinetic properties. Hence, it was suggested that compounds with chromenone scaffold could potentially inhibit GSK3ß. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3ß inhibitors

chemical methods in decellularization process and its effects on extracellular matrix (ECM): narrative review

Objective :Extracellular matrix (ECM)produced by tissue decellularization processes As a biological scaffold Due to its unique properties compared to other scaffolds for migration and implantation of stem cells have been used successfully in the field of tissue engineering and regenerative medicine at the last years. Methods: for this review we searched in google scholar, medline, scopus, sciencedirect .we used extracellular matrix(ECM),biologic scaffold ,decellularization ,chemical methods, tissue engineering as keywords. We selected articles have been published from almost 2000 to 2016Results: 15 full texts and 97 abstract was reviewed. To obtain a intact ECM with preservation of ECM bioactivity. Employing an optimization method to minimize damage to the ECM Ultrastructure As a result of the lack of reduction in mechanical properties and also preservation of important proteins such as laminin, fibronectin, GAGs, growth factor is required. Various methods, including methods of chemical, physical and enzymatic studied and tested. But on each of these methods can have undesirable effects on ECM .Theobjective of this manuscript is to provide an overview of the chemical decellularization methods , Evaluation of decellularizad ECM and the potential affect of the chemical decellularization agents on the biochemical composition, ultrastructure, and mechanical behavior of the ECM scaffold materials.production an intact ECM with preservation of biochemical composition and mechanical behavior requires a correct choice regardingagents and techniques used in decellularization process.Conclusion: It is suggested that insted of the SDS which have high strength degradation we can use zwitterionic separately or in combination with SDS.TBP due to its unique properties can be used in decellularization process

Repurposing of monacolin K decorated BN nanoparticle on inhibition of HMG-CoA reductase: In silico approach

To identify a novel inhibitor of 3‑hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the current perspective has shifted toward a B12N12 nanocage that also has cardioprotective properties. Therefore, this study identified the bioactive complexes derived from monacolin K and BN nanoparticle and determines their potential for inhibiting HMG-CoA reductase, hypolipidemic activity, and anti-apoptotic properties via molecular docking. A molecular docking study was conducted with the Auto Dock Vina software on a complex of monacolin K and the B12N12 fullerene using an in silico docking approach. The protein structures of selective HMG-COA reductase, as well as peroxisome proliferator-activated receptor-α (PPAR-α) and others, were obtained from Protein Data Bank (PDB). The binding affinity between key residues involved in the binding mode of the targets and selective complexes is identified via in silico molecular docking. A further evaluation of the ADMET properties of the selective complexes has also been carried out. B12N12 nanoparticles and monacolin K complex (A) showed higher inhibitory potential for HMG-CoA reductase than monacolin K alone. These complexes seemed to be selective to the PPAR-α and caspase3 domains. Meanwhile, complex B had the highest binding affinity to the active site of SGK, TNF- α, NF-Kβ and AMPK receptors. Furthermore, both complex A and B could inhibit inflammatory targets more efficiently. The selective B12N12 nanoparticles were assessed for their drug-likeness and ADMET analysis, confirming that the selective B12N12 nanoparticles met the Lipinski and drug-likeness criteria. It was revealed that B12N12 fullerene and monacolin K complexes have potential inhibitory HMG-COA reductase and anti-apoptotic properties, as well as activating PPAR-α and AMPK. Consequently, these cardioprotective effects lead to improved cardiovascular health

Protective effect of levothyroxine with oxidative stress reduction mechanism in ischemic preconditioning model in rat heart

Background and Objective: A brief and short duration episode of ischemia is recorded in ischemic preconditioning (IPC). This latter condition provides a status in which large region of heart is protected when prolonged ischemia occurred. Levothyroxine play a protective role in IPC induction, and simultaneously with stress oxidative. This study was conducted to determine the protective effect of levothyroxine with oxidative stress reduction mechanism in ischemic preconditioning model in rat heart. Methods: This experimental study was performed on 30 male Wistar rats in three groups of 10, as follows. In the reperfusion ischaemia group (IR), the heart of the animal was placed in a Langendorff apparatus. In the ischemic preconditioning group (IPC), prior to major ischemia, was exposed to 4 periods of 5-minute ischemia with reperfusion. In the intraperitoneally administered group, levothyroxine at a dose of 25 microgram per 100 g of body weight, the heart was exposed to reperfusion ischemia. The area of infarct and the level of malondialdehyde in the heart tissue were measured. Results: The volume of Infarcted region in IR and IPC groups was 26.55 and 11.11 respectively. The same index for the Levothyroxine receiver was 12.56. Based on these findings it was demonstrated that Levothyroxine injection reduced the Infarcted region significantly similar with IPC (P<0.05). The MDA Levels in IR and IPC were 1328 and 777, respectively and in Levothyroxine group it was determined as 762. The size of Infarcted region in both IPC and treated with Levothyroxine groups significantly reduced in compared to IR group (P<0.05). Conclusion: Injection of levothyroxine with ischemic preconditioning reduced the effect of reperfusion maladaptive ischemia in rat heart