Integrated Pharmacognostic Characterization, Molecular Docking, Pharmacological Validation, And Advanced Drug Delivery System Development Of Novel Phytoconstituents Isolated From Tinospora Cordifolia For Neuroprotective Applications

Background: Neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, represent a growing global health challenge characterized by oxidative stress, neuroinflammation, and protein misfolding. Tinospora cordifolia, a traditional Ayurvedic medicinal plant, has long been used for neurological disorders. This study aimed to integrate pharmacognostic characterization, molecular docking, in vitro and in vivo validation, and advanced drug delivery systems to evaluate its neuroprotective potential. Methods: Authentic T. cordifolia stems were collected and subjected to pharmacognostic evaluation, physicochemical analysis, and phytochemical extraction. Major phytoconstituents were isolated and structurally elucidated using HPLC, NMR, and LC-MS/MS. Molecular docking was performed against targets including AChE, BChE, MAO-B, NMDA receptor, Tau protein, and β-amyloid. In vitro neuroprotective activity was assessed via antioxidant (DPPH, ABTS, FRAP), cholinesterase inhibition, and neuronal cell protection assays (SH-SY5Y, PC12). In vivo validation employed rodent models of neurodegeneration (scopolamine, AlCl₃, rotenone), assessing behavioral, biochemical, and histopathological endpoints. Nanocarrier formulations of lead compounds were developed and evaluated for size, zeta potential, entrapment efficiency, release kinetics, and BBB penetration. Results: Pharmacognostic and phytochemical analyses confirmed the presence of bioactive alkaloids (berberine, magnoflorine, palmatine) and diterpenoid glycosides (tinosporaside). Molecular docking predicted strong binding to cholinesterases and amyloid targets, correlating with in vitro enzyme inhibition and antioxidant activity. In vivo studies demonstrated improved cognitive performance, restored oxidative markers, and preserved neuronal architecture in berberine- and magnoflorine-treated groups. Nanocarrier formulations enhanced brain delivery, sustained release, and pharmacokinetic profiles. Conclusion: Phytoconstituents from T. cordifolia exhibit multi-target neuroprotective effects, which are significantly enhanced by nanocarrier delivery systems. These findings support their potential development as safe and effective therapeutic agents for neurodegenerative disorders.