Ginkgo biloba extract is an alternative medicine available as a standardized formulation, EGb 761^®, which consists of ginkgolides, bilobalide, and flavonoids. The individual constituents have varying therapeutic mechanisms that contribute to the pharmacological activity of the extract as a whole. Recent studies show anxiolytic properties of ginkgolide A, migraine with aura treatment by ginkgolide B, a reduction in ischemia-induced glutamate excitotoxicity by bilobalide, and an alternative antihypertensive property of quercetin, among others. These findings have been observed in EGb 761 as well and have led to clinical investigation into its use as a therapeutic for conditions such as cognition, dementia, cardiovascular, and cerebrovascular diseases. This review explores the therapeutic mechanisms of the individual EGb 761 constituents to explain the pharmacology as a whole and its clinical application to cardiovascular and neurological disorders, in particular ischemic stroke.

Nitrone therapeutics has been employed in the treatment of oxidative stress-related diseases such as neurodegeneration, cardiovascular disease and cancer. The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. However, the specific mechanism of nitrone bioactivity remains unclear. In this review, we present a variety of nitrone chemistry and biological activity that could be implicated for the nitrone’s pharmacological activity. The chemistries of spin trapping and spin adduct reveal insights on the possible roles of nitrones for altering cellular redox status through radical scavenging or nitric oxide donation, and their biological effects are presented. An interdisciplinary approach towards the development of novel synthetic antioxidants with improved pharmacological properties encompassing theoretical, synthetic, biochemical and in vitro/in vivo studi...

In this work, a series of α-phenyl-N-tert-butyl nitrones bearing one, two, or three substituents on the tert-butyl group was synthesized. Cyclic voltammetry (CV) was used to investigate their electrochemical properties and showed a more pronounced substituent effect for oxidation than for reduction. Rate constants of superoxide radical (O₂^•–) reactions with nitrones were determined using a UV–vis stopped-flow method, and phenyl radical (Ph^•) trapping rate constants were measured by EPR spectroscopy. The effect of N-tert-butyl substitution on the charge density and electron density localization of the nitronyl carbon as well as on the free energies of nitrone reactivity with O₂^•– and HO₂^• were computationally rationalized at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level of theory. Theoretical and experimental data showed that the rates of the reaction correlate with the nitronyl carbon charge density, suggesting a nucleophilic nature of O₂^•– and Ph^• addition to the nitronyl carbon atom. Finally, the substituent effect was investigated in cell cultures exposed to hydrogen peroxide and a correlation between the cell viability and the oxidation potential of the nitrones was observed. Through a combination of computational methodologies and experimental methods, new insights into the reactivity of free radicals with nitrone derivatives have been proposed.