Ethyl acetate fruit fraction of tetrapleura tetraptera modulates cholinergic anti‐inflammatory pathways: an invivo and insilico study

Abstract Background Studies suggest a potential link between stroke and Alzheimer’s disease wherein stroke may serve as a trigger for the onset or acceleration of Alzheimer’s pathogenesis as damage to the brain’s blood vessels may lead to the accumulation of amyloid beta protein which is a hallmark of Alzheimer’s disease. Recent research has shown that stroke treatment may hold the key to treating Alzheimer’s disease. The anti‐inflammatory potentials of Cholinergic signaling are a novel therapeutic target in memory decline associated with Alzheimer’s. Therefore, cholinergic agonists which play a crucial role in increasing the synaptic levels of acetylcholine could in turn downregulate inflammatory mediators as well as modulate Cholinergic signaling thereby improving cognition Method Molecular docking analysis of TT‐Fruits ligand against Iba1(PDB ID: 2d58), IL‐6 (PDB ID: 1Alu), and AChE (PDB ID: 5hfa) was conducted using Pyrex, Autodock Vina option with Galantamine and minocycline (MNC) as a control drugs to evaluate the molecular interactions between the ligands present in EAFFTT and inflammatory mediators implicated in stroke pathology. In‐vivo study was conducted as follows: 50 Male adult Wistar rats (200 – 220g) were randomly distributed into five groups: Group I‐Sham, and Group II‐V were subjected to Ischemia/Reperfusion (I/R) for 30 minutes and then treated daily with H 2 O, EAFFTT 200 mg/kg, EAFFTT 100 mg/kg, or MNC 50 mg/kg respectively, orally for seven days. Following this, the brains were extracted and processed for IL‐6 and AChE ELISA and IBA 1 immunohistochemistry for reactive microglia. Result molecular docking results predicted Aridanin and Echinocystic acid as the lead ligands in EAFFTT with a higher binding affinity with the proteins (Iba1, IL‐6, and AChE) than the control drugs. In the experimental study, I/R without treatment showed a significant increase in IL‐6, AChE, and the number of activated microglia. However, a significant decrease in IL‐6, AChE, and the number of reactive microglia was observed in I/R +EAFFTT (100 and 200 mg/kg), and I/R +MNC (50 mg/kg) ‐treated groups Conclusion Tetrapleura tetraptera fruit phenolics docked well with IBA1, IL‐6 and AChE, thereby modulating their expression, as EAFFTT is a potential neurotherapeutic agent against stroke‐induced neuroinflammation