In vitro and silico assessment of berbericinine, a promising drug candidate against neurodegeneration and neuroinflammation

To perform in vitro and silico assessments of berbericinine, and to assess its protective effect against neurodegeneration and neuroinflammation. Isolation and characterization of berbericinine from Tinospora cordifolia leaves followed by TLC, and HPLC studies. In vitro anti-inflammatory activity, free radical scavenging action, and choline esterase inhibitory studies were performed followed by in silico toxicity studies and docking studies. The TLC and HPLC studies compared to the standard confirmed the purity of isolated berbericinine from Tinospora cordifolia leaves. Findings of TLC with HPLC confirmed the presence of said bioactive compound with Rf of 0.4 and Rt of 20.82 min. DPPH and FRAP assays confirmed the potent antioxidant nature of berbericinine (IC₅₀ of 29.04 µg/mL and TEAC of 56.35 µMol). Further, the in vitro anti-inflammatory study revealed that extract and isolated berbericinine inhibited albumin denaturation and showed potent anti-proteinase, and anti-lipoxygenase activities. The findings indicated that isolated berbericinine showed higher anti-inflammatory activity than the extract. The in silico approach aided the identification of the possible targets of action of berbericinine in the brain. Results of docking studies suggest that berbericinine showed a high docking score of − 7.6 kcal/mol with MAP kinase (1CM8), − 7.8 kcal/mol with β-secretase (2OHM), − 7.2 kcal/mol with NF-KB (6M2D), and − 7.4 kcal/mol with EGFR (4D90) and resulted in robust binding affinities with key molecular targets. Furthermore, berbericinine revealed a potent in vitro acetylcholine esterase inhibitory effect in a dose-dependent manner. The research findings indicate that isolated berbericinine shows promising potential in interacting with and influencing critical pathways, particularly relevant in the context of neurodegenerative disorders like Alzheimer's disease.