Pharmacological investigation of natural compounds for therapeutic potential in neuropathic pain

The present research is based on the investigation of post treatment naturally occurring compounds berbamine (BBM), bergapten (BRG) and carveol (CAR) in relation to its therapeutic effect in neuroinflammation and chronic constriction injury induced neuropathic pain (CCI-NP). The drug-likeness of the compounds was explored by SwissADME (http://www.swissadme.ch/). Docking was performed by Auto dock, PyRx and Discovery Studio Visualiser 2016 against cyclooxygenase-2 (COX-2) (PDB ID: ICX2), tumour necrosis factor-alpha TNF-α (PDB ID: 10T7) and nuclear factor-kappa B (NF-κb) (PDB ID: INFK). Molecular dynamic simulation was performed through Desmond software. In in-vivo protocols, sciatic nerve was ligated and treatment was initiated and maintained until the 14th day. Behavioural assays (paw deformation, thermal hyperalgesia, mechanical allodynia and cold allodynia) were performed and tissues were extracted for molecular investigation. Hydrogen bonds and binding affinities of ligand target complex were determined. Berbamine showed binding against NF-κB (7.9 kcal/mol). Treatment reversed paw deformation, reduced thermal hyperalgesia, mechanical allodynia and cold allodynia. Treatment also improves the level of protective GSH and GST levels in the sciatic nerve and spinal cord and lowering the detrimental oxidative stress markers iNOS and LPO. Based on the results the aforementioned compounds correct behavioural deficit, inhibit COX-2, TNF-, and NF-κB over expression, as evidenced by Enzyme-linked immunosorbant assay (ELISA) provide neuroprotection in chronic constriction damage. Hence berbamine can be considered as neuroprotective compound.