scholarly journals Effect of Hydroalcoholic Extract of Satchys Lavandulifolia on Pentylenetetrazole-Induced Seizures in Male Mice: The Role of Gabaergic and Opioidergic Systems

Author(s):  
Hamid Behzad Nia ◽  
◽  
Amin Naseri ◽  
Mohammadreza Emamhadi ◽  
Shervin Ghadarjani ◽  
...  

Introduction: Epilepsy is one of the most common neurological disorders. Though there are effective medications available for treatment of epilepsy, the use of most drugs is associated with many side effects and drug interactions. Stachys lavandulifolia (SL) used in Iranian traditional medicine show anti-anxiety and sedative actions. The objective of the current study was to evaluate the anticonvulsant effect of hydroalcoholic extract of SL on the pentylenetetrazole (PTZ)-induced seizure in male mice and the role of benzodiazepine and opioid receptors. Methods: This study was conducted on 100 male mice randomly categorized into 10 groups: Normal Saline, Diazepam groups (0.025 and 0.1 mg/kg), SL extract groups (50, 100 and 200 mg/kg), Diazepam 0.025 mg/kg + SL extract 50mg/kg and three groups that pre-treated with NS, Flumazenil or Naloxone, 5 min before injection of 200 mg/kg extract. After 30 min, PTZ (80 mg/kg) was injected to animals and seizure indices were evaluated. Results: The SL extract attenuated the PTZ-induced seizures in a dose dependent manner and pre-treatment with flumazenil reversed this effect of SL extract but pre-treatment with naloxone could not reverse this effect, because seizure indices on naloxone pretreated group was still lower than normal saline group. Combination of ineffective dose of diazepam and SL extract decrease PTZ-induced seizures. Discussion: The results of our study showed the anticonvulsant properties of hydroalcoholic extract of SL. These effects might be due to the impact of the components of this extract on the central benzodiazepine system.


Drug Research ◽  
2017 ◽  
Vol 68 (04) ◽  
pp. 196-204 ◽  
Author(s):  
Marcelo Silva ◽  
Wagner Vilegas ◽  
Marcelo da Silva ◽  
Ana Paiotti ◽  
Mauricio Pastrelo ◽  
...  

AbstractThe aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 – Sham group:; G2 – TNBS group; G3, G4 –colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 – colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.



2018 ◽  
Vol 118 (02) ◽  
pp. 229-250 ◽  
Author(s):  
H. Spronk ◽  
T. Padro ◽  
J. Siland ◽  
J. Prochaska ◽  
J. Winters ◽  
...  

AbstractAtherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin–angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet–fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia–reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C–based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.



2018 ◽  
Vol 19 (12) ◽  
pp. 3711 ◽  
Author(s):  
Ovidiu Balacescu ◽  
Daniel Sur ◽  
Calin Cainap ◽  
Simona Visan ◽  
Daniel Cruceriu ◽  
...  

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial–mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.



Coatings ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1111
Author(s):  
Ladislav Reinprecht ◽  
Radovan Tiňo ◽  
Marek Šomšák

The adhesion strength between the transparent acrylic or alkyd coatings and the Norway spruce (Picea abies Karst L.) wood was determined by EN ISO 4624 and analyzed concerning four variables: (a) fungicidal pre-treatment of wood with boric acid or benzalkonium chloride, (b) cold plasma modification of wood surfaces, (c) presence of hindered amine light stabilizer (HALS) or hydroxyphenyl-benzotriazoles (BTZ) in the role of UV-additives in coatings, and (d) weathering of coated wood—lasting 1 week in Xenotest by a modified EN 927-6, or 14, 28 and 42 weeks outdoors at 45° by EN 927-3. In the un-weathered state, the adhesion strength was positively affected by the initial plasma modification of wood surfaces, more evident with the application of acrylic water-borne coatings. On the contrary, the adhesion strength was not influenced by the fungicidal pre-treatment of wood and by the UV-additive’s presence in coatings. The adhesion was negatively affected by weathering—exponentially outdoor—irrespective of the fungicidal pre-treatment of wood, the plasma modification of wood surfaces, the coating type, and the presence of UV-additive in coatings.



2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Katarzyna Szadujkis-Szadurska ◽  
Bartosz Malinowski ◽  
Małgorzata Piotrowska ◽  
Grzegorz Grześk ◽  
Michał Wiciński ◽  
...  

Aim of the Study.The purpose of this study was to investigate the impact of ischemia and reperfusion on the resistance of arteries to AVP (arginine vasopressin), with a particular emphasis on the role of smooth muscle cells in the action of vasopressin receptors and the role of the cGMP-associated signalling pathway.Materials and Methods.Experiment was performed on the perfunded tail arteries from male Wistar rats. The constriction triggered by AVP after 30 minutes of ischemia and 30 and 90 minutes of reperfusion was analysed. Analogous experiments were also carried out in the presence of 8Br-cGMP.Results.Ischemia reduces and reperfusion increases in a time-dependent manner the arterial reaction to AVP. The presence of 8Br-cGMP causes a significant decrease of arterial reactivity under study conditions.Conclusions.Ischemia and reperfusion modulate arterial contraction triggered by AVP. The effect of 8Br-cGMP on reactions, induced by AVP after ischemia and reperfusion, indicates that signalling pathway associated with nitric oxide (NO) and cGMP regulates the tension of the vascular smooth muscle cells.



2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Shakiba Nasiri-Boroujeni ◽  
Mohammad Rahimi-Madiseh ◽  
Zahra Lorigooini ◽  
Khadijeh Piroti ◽  
Mahmoud Rafieian-Koupaei ◽  
...  

It is necessary to seek more effective sources to design new drug against epilepsy. This study aimed to evaluate the effect of hydroalcoholic extract of Artemisia persica on pentylenetetrazole- (PTZ-) induced seizure in male mice by investigating the possible role of the NMDA receptor and antioxidative stress effect. The phenolic profile of A. persica extract was determined by HPLC-DAD analysis. Mice were treated with normal saline or A. persica extract or pentobarbital or a subeffective dose of extract plus ketamine (NMDA receptor antagonist) and/or effective dose of extract plus NMDA. PTZ (90 mg/kg) was injected intravenously for induction of seizure. The seizure threshold was measured. Then mice were euthanized and the antioxidant capacity and the level of malondialdehyde (MDA) of the prefrontal cortex and serum were measured. The gene expression of NMDA receptor subunits (Nr2a and Nr2b) was determined by real-time PCR. Findings showed that A. persica extract increased the seizure threshold, increased antioxidant capacity, and decreased MDA levels in the serum and brain samples. A. persica extract reduced the expression of NMDA receptor subunits. The result showed that ketamine potentiated the effect of the subeffective dose of extract. HPLC analysis showed that quercetin had the highest flavonoid content and also caffeic acid had the highest content of the phenolic acids. A. persica extract probably via NMDA receptor exerts anticonvulsant properties.



Author(s):  
Nitya Selvaraj ◽  
Deepa Kameswari ◽  
Ramya Gandhi ◽  
Meher Ali Raja Mohamad

Background: Emerging evidence has demonstrated the role of high-voltage -sensitive activated dihydropyridine (L-type, CaV1.x) channels in the development of epilepsy. Based on that we hypothesized that lercanidipine, a dihydropyridine calcium channel blocker, would protect against Pentylenetetrazole (PTZ) induced kindling in mice model of epilepsy.Methods: Kindling was induced in Swiss albino mice with PTZ in subconvulsive dose (30 mg/kg i.p.) thrice a week for nine weeks and the effect was scored using ‘4 point scoring system’. Rechallenging on the 3rd and 10th day with the same dose of PTZ was carried out after the last chronic dose.Results: The data of the present study demonstrated that pretreatment with lercanidipine (½ h before PTZ, in doses of 1 and 3 mg/kg i.p. daily) alone and in combination with diazepam (2mg/kg i.p.) had decreased the incidence and severity of seizure as well as prolonged the onset of kindling in a dose-dependent manner (p <0.05). On rechallenging, lercanidipine resulted in reduction of seizure score (p <0.05) and increased the seizure latency.Conclusions: The present study suggested that lercanidipine offered neuroprotection against PTZ induced kindling in mice.



2021 ◽  
Vol 18 (181) ◽  
pp. 20210023
Author(s):  
Duy T. Nguyen ◽  
Alexander F. Smith ◽  
Juan M. Jiménez

Stent thrombosis (ST) carries a high risk of myocardial infarction and death. Lack of endothelial coverage is an important prognostic indicator of ST after stenting. While stent strut thickness is a critical factor in ST, a mechanistic understanding of its effect is limited and the role of haemodynamics is unclear. Endothelialization was tested using a wound-healing assay and five different stent strut models ranging in height between 50 and 150 µm for circular arc (CA) and rectangular (RT) geometries and a control without struts. Under static conditions, all stent strut surfaces were completely endothelialized. Reversing pulsatile disturbed flow caused full endothelialization, except for the stent strut surfaces of the 100 and 150 µm RT geometries, while fully antegrade pulsatile undisturbed flow with a higher mean wall shear stress caused only the control and the 50 µm CA geometries to be fully endothelialized. Modest streamlining and decrease in height of the stent struts improved endothelial coverage of the peri-strut and stent strut surfaces in a haemodynamics dependent manner. This study highlights the impact of the stent strut height (thickness) and geometry (shape) on the local haemodynamics, modulating reendothelialization after stenting, an important factor in reducing the risk of stent thrombosis.



2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Kumsta ◽  
Jessica T. Chang ◽  
Reina Lee ◽  
Ee Phie Tan ◽  
Yongzhi Yang ◽  
...  

AbstractAutophagy can degrade cargos with the help of selective autophagy receptors such as p62/SQSTM1, which facilitates the degradation of ubiquitinated cargo. While the process of autophagy has been linked to aging, the impact of selective autophagy in lifespan regulation remains unclear. We have recently shown in Caenorhabditis elegans that transcript levels of sqst-1/p62 increase upon a hormetic heat shock, suggesting a role of SQST-1/p62 in stress response and aging. Here, we find that sqst-1/p62 is required for hormetic benefits of heat shock, including longevity, improved neuronal proteostasis, and autophagy induction. Furthermore, overexpression of SQST-1/p62 is sufficient to induce autophagy in distinct tissues, extend lifespan, and improve the fitness of mutants with defects in proteostasis in an autophagy-dependent manner. Collectively, these findings illustrate that increased expression of a selective autophagy receptor is sufficient to induce autophagy, enhance proteostasis and extend longevity, and demonstrate an important role for sqst-1/p62 in proteotoxic stress responses.



2020 ◽  
Vol 20 (2) ◽  
pp. 144-154
Author(s):  
Olayemi K. Wakeel ◽  
Oluropo B. Awosan ◽  
Oyetunji T. Kolawole ◽  
Akeem A. Ayankunle ◽  
Olukunle J. Onaolapo ◽  
...  

Objective: To determine the potential effect of Pyrenancantha staudtii extract on experimentally induced seizures in mice and to evaluate the role of benzodiazepines, naloxone, and serotonin within these pathways. Methods: Animal behaviours were evaluated using open field, hexobarbitone-induced sleep model, and anticonvulsant activity using picrotoxin-, or strychnine-, or isoniazid-induced convulsions. Attempt to understand the mode of action of the anticonvulsant activity of the plant, three notable antagonists (flumazenil, 3 mg/kg; naloxone 5 mg/kg, i.p., and cyproheptadine, 4 mg/kg, i.p) were used. Results: The results revealed a significant (p < 0.05) reduction in the frequency of rearing and grooming episodes compared with the control. The extract of P. staudtii potentiates the sleeping time of hexobarbitone-induced hypnosis in a dose-related manner. P. staudtii stem bark extracts significantly (p<0.05) prolonged the onset of a seizure and attenuated the duration of seizure in a dose-dependent manner in picrotoxin- and or isoniazid-induced seizures. While, P. staudtii stem bark extract at all doses (100, 200, and 400 mg kg-1) though significantly prolonged the onset of action, but did not confer any significant changes on the duration, as well as mortality in this strychnine-induced seizure model. However, the anticonvulsant activity of the methanolic extract of P. staudtii was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist) and naloxone (opioid receptor antagonist) but not cyproheptadine (5-HT2 receptor antagonist) in picrotoxin-induced convulsion. Conclusion: The data obtained suggest that methanol extract of P. staudtii possessed significant anticonvulsant effect, thereby confirming the traditional uses of P. staudtii in the treatment of epilepsy; mechanisms of which could involve the interaction with GABAergic and or opioidergic system.



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