1,3,4-Oxadiazole Derivative Attenuates Chronic Constriction Injury Induced Neuropathic Pain: A Computational, Behavioral, and Molecular Approach

Abstract

The production and up-regulation of inflammatory mediators are contributing factors for the development and maintenance of neuropathic pain. In the present study, the post-treatment of synthetic 1,3,4 oxadiazole derivative (B3) for its neuroprotective potential in chronic constriction injury-induced neuropathic pain was applied. In-silico studies were carried out through Auto Dock, PyRx, and DSV to obtain the possible binding and interactions of the ligands (B3) with COX-2, IL-6, and iNOS. The sciatic nerve of the anesthetized rat was constricted with sutures 3/0. Treatment with 1,3,4-oxadiazole derivative was started a day after surgery and continued until the 14th day. All behavioral studies were executed on day 0, 3rd, 7th, 10th, and 14th. The sciatic nerve and spinal cord were collected for further molecular analysis. The interactions in the form of hydrogen bonding stabilizes the ligand target complex. B3 showed three hydrogen bonds with IL-6. B3, in addition to correcting paw posture/deformation induced by CCI, attenuates hyperalgesia (p < 0.001) and allodynia (p < 0.001). B3 significantly raised the level of GST and GSH in both the sciatic nerve and spinal cord and reduced the LPO and iNOS (p < 0.001). B3 attenuates the pathological changes induced by nerve injury, which was confirmed by H&E staining and IHC examination. B3 down-regulates the over-expression of the inflammatory mediator IL-6 and hence provides neuroprotective effects in CCI-induced pain. The results demonstrate that B3 possess anti-nociceptive and anti-hyperalgesic effects and thus minimizes pain perception and inflammation. The possible underlying mechanism for the neuroprotective effect of B3 probably may be mediated through IL-6.

Investigation of Natural Compounds for Therapeutic Potential in Streptozotocin-induced Diabetic Neuroinflammation and Neuropathic Pain

“…An immuno-histochemical (IHC) investigation was performed according to a previously well-defined procedure with slight modifications ( Faheem et al, 2020 ). The tissue (spinal cord) was fixed in paraffin on slides, deparaffinized with xylene 100%, and rehydrated by washing with graded dilutions of ethanol (100%, 90%, 80%, and 70%).…”

Frequency of Depression in Patients with Religious Inclination

“…It is recognized by persistent low mood which is more than two weeks and also related with anhedonia or lack of concern in previously pleasurable activities. Other associated features comprise significant weight reduction when not dieting or weight gain (e.g., a alteration of more than 5 % of body weight in a month), or change in appetite nearly every day, sleeplessness or over sleepiness nearly every day, psychomotor excitement or retardation, tiredness or loss of drive, feelings of worthlessness or extreme or inappropriate guilt, reduced capability to think or concentrate, or uncertainty, recurring feelings of death 4,5 . The symptoms cause clinically important suffering or deficiency in social, occupational or other significant areas of functioning 6,7 .…”

Investigation of 1, 3, 4 Oxadiazole Derivative in PTZ-Induced Neurodegeneration: A Simulation and Molecular Approach

“…In this context the selected compound has been already reported for antioxidant, analgesic, anti-inflammatory, toxicity assessment, tumor inhibition activities and also effective in relieving chronic constriction induced painful symptoms. 10,11 The two-dimensional (2D) and three-dimensional (3D) structures of B3 are shown in Figures 1A and 2A, respectively. This study utilized the computational techniques, behavioral approach, and molecular investigation to elucidate the ameliorative effect of B3 in PTZ-induced seizures.…”

“…Nowadays docking is a preliminary step to first confirm the interaction of ligand with its respective target. 10,11 The favorable results of docking in the form of binding affinities and hydrogen bonds was the reason to perform molecular dynamics (MD) simulation for further validation interaction of B3 against GABA. MD simulation is gaining attention of researcher involved in drug discovery and development.…”

“…The agents of this class have promising anti- inflammatory, analgesic, and anti-oxidant potential. 10,11 Recently this class of active agents has been also researched for its attenuating potential of middle cerebral artery occlusion-induced stroke. 52 The agents belonging to oxadiazoles are also researched for anti-Alzheimer potential, anticancer, antimicrobial, anti-inflammatory, anti-allodynic properties, and anti-insomnia.…”