Computational Analysis of Ginsenoside Rb1 and Gastrodin Analogues for Neurogenesis-Related Activity in Ischaemic Stroke

Abstract

At the global stage, ischemic stroke remains a leading cause of mortality and long-term disability, with a disproportionate portion of this burden being borne by low-and-middle-income nations, and increasingly, the young productive population bracket. Ischemic stroke’s management has historically been constrained by considerable challenges in the form of narrow therapeutic windows, high treatment costs, and strict eligibility criteria for the institution of either of the only two treatment options available at the disposal of medics, with those being thrombolysis, and mechanical thrombectomy. Mounting evidence favourably positions pharmacological augmentation of endogenous neurogenesis as a compelling strategy capable of appreciably enhancing structural and functional brain repair following ischemic stroke. In this regard, a relatively unexplored source of neurorestorative agents is phytochemicals sourced from conventionally used traditional therapeutic plants. A computation-heavy framework integrating ligand-based virtual screening, target-based molecular docking, pharmacokinetic profiling, and in silico toxicology forecasting was employed in a bid to meet the study’s principal objective, which was to identify novel phytochemical analogues possessing superior neurogenic potential, and favourable pharmacokinetic and toxicological profiles to ginsenoside Rb1, and gastrodin. Ginsenoside Rb1’s structural complexity resulted in the compound only yielding 6 analogues from Swiss Similarity. For the most part, most of these analogues underperformed relative to the parent compound across critical parameters. The only parameters where some analogues managed to outperform ginsenoside Rb1 was GI (gastrointestinal) absorption, and Lipinski’s violations. Gastrodin on the other hand typified a simpler chemical structure and returned some 400 analogues, several of which posted superior results to gastrodin’s. A common challenge encountered with these analogues however was their inability to traverse the BBB (blood brain barrier). These findings highlight the potential of phytochemicals as candidates for further investigation into endogenous brain repair, though experimental validation is required before their neurorestorative relevance can be established.