Evaluation of the subunit α7 expression of nicotinic acetylcholine receptor and activation of proteins (JAK2/STAT3 and CREB) of cholinergic anti-inflammatory pathway in the offspring mice spleen with obesity induced by maternal high fat consumption

2016 ◽  
Author(s):  
JULIA DE OLIVEIRA SARTORI ◽  
Marcio Alberto Torsoni ◽  
CAMILLA M. SOUZA ◽  
PÂMELA G. LANZA ◽  
SULEYMA O. COSTA ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
High Fat ◽  
Nicotinic Acetylcholine ◽  
Inflammatory Pathway ◽  
Fat Consumption ◽  
Anti Inflammatory

Berberine Ameliorates Glucose Metabolism in Diabetic Rats through the alpha7 Nicotinic Acetylcholine Receptor-Related Cholinergic Anti-Inflammatory Pathway

Planta Medica ◽  
2021 ◽  
Author(s):  
Dingkun Wang ◽  
Yanlin Ren ◽  
Wei Sun ◽  
Jing Gong ◽  
Xin Zou ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Receptor Gene ◽  
Acetylcholinesterase Activity ◽  
Diabetic Rats ◽  
Nicotinic Acetylcholine ◽  
Inflammatory Pathway ◽  
Alpha7 Nicotinic Acetylcholine Receptor ◽  
Anti Inflammatory ◽  
Acetylcholine Receptor Gene

AbstractBerberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1β and TNF-α in the serum and downregulated nuclear factor κB expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway.

scholarly journals IN SILICO DESIGN AND MOLECULAR DOCKING STUDIES OF SOME 1, 2-BENZISOXAZOLE DERIVATIVES FOR THEIR ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY

2017 ◽  
Vol 9 (3) ◽  
pp. 133
Author(s):  
Sarath Sasi Kumar ◽  
Anjali T
Keyword(s):  
Molecular Docking ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Analgesic Activity ◽  
In Silico ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Nicotinic Acetylcholine ◽  
Cox 2 ◽  
Anti Inflammatory

Objective: In silico design and molecular docking of 1,2-benzisoxazole derivatives for their analgesic and anti-inflammatory activity using computational methods.Methods: In silico molecular properties of 1,2-benzisoxazole derivatives were predicted using various software’s such as Chemsketch, Molinspiration, PASS and Schrodinger to select compounds having optimum drug-likeness, molecular descriptors resembling those of standard drugs and not violating the ‘Lipinski rule of 5’. Molecular docking was performed on active site of nicotinic acetylcholine receptor (PDB: 2KSR) for analgesic activity and COX-2 (PDB: 6COX) for anti-inflammatory activity using Schrodinger under maestro molecular modelling environment.Results: From the results of molecular docking studies of 1,2-benzisoxazole derivatives, all the compounds showed good binding interactions with Nicotinic acetylcholine receptor and COX-2. Compounds 4a and 4c showed highest binding scores (-7.46 and-7.21 respectively) with nicotinic acetylcholine receptor and exhibited maximum analgesic activity. Compound 4a showed highest binding score (-7.8) with COX-2 and exhibited maximum anti-inflammatory activity.Conclusion: All the derivatives of 1,2-benzisoxazole showed good analgesic and anti-inflammatory activity as predicted using molecular docking on respective receptors.

scholarly journals Systemic Administration of α7-Nicotinic Acetylcholine Receptor Ligands Does Not Improve Renal Injury or Behavior in Mice With Advanced Systemic Lupus Erythematosus

2021 ◽  
Vol 8 ◽  
Author(s):  
Jessica Y. Morales ◽  
Cassandra M. Young-Stubbs ◽  
Caroline G. Shimoura ◽  
William R. Kem ◽  
Victor V. Uteshev ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Nicotinic Acetylcholine Receptor ◽  
Lupus Erythematosus ◽  
Advanced Disease ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Nicotinic Acetylcholine ◽  
Inflammatory Pathway ◽  
Α7 Nachr ◽  
Anti Inflammatory

There is a critical need for safe treatment options to control inflammation in patients with systemic lupus erythematosus (SLE) since the inflammation contributes to morbidity and mortality in advanced disease. Endogenous neuroimmune mechanisms like the cholinergic anti-inflammatory pathway can be targeted to modulate inflammation, but the ability to manipulate such pathways and reduce inflammation and end organ damage has not been fully explored in SLE. Positive allosteric modulators (PAM) are pharmacological agents that inhibit desensitization of the nicotinic acetylcholine receptor (α7-nAChR), the main anti-inflammatory feature within the cholinergic anti-inflammatory pathway, and may augment α7-dependent cholinergic tone to generate therapeutic benefits in SLE. In the current study, we hypothesize that activating the cholinergic anti-inflammatory pathway at the level of the α7-nAChR with systemic administration of a partial agonist, GTS-21, and a PAM, PNU-120596, would reduce inflammation, eliminating the associated end organ damage in a mouse model of SLE with advanced disease. Further, we hypothesize that systemic α7 ligands will have central effects and improve behavioral deficits in SLE mice. Female control (NZW) and SLE mice (NZBWF1) were administered GTS-21 or PNU-120596 subcutaneously via minipumps for 2 weeks. We found that the increased plasma dsDNA autoantibodies, splenic and renal inflammation, renal injury and hypertension usually observed in SLE mice with advanced disease at 35 weeks of age were not altered by GTS-21 or PNU-120596. The anxiety-like behavior presented in SLE mice was also not improved by GTS-21 or PNU-120596. Although no significant beneficial effects of α7 ligands were observed in SLE mice at this advanced stage, we predict that targeting this receptor earlier in the pathogenesis of the disease may prove to be efficacious and should be addressed in future studies.

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