Linking traditional medicine to modern phytotherapy: Chemical characterization and assessment of antioxidant and anticholinesterase effects in vitro of a natural Persian remedy for dementia

Several natural remedies are used in the Traditional Persian Medicine (TPM) to prevent dementia, but their efficacy is debated. In this work, an improved “Safoof-e-Nesyān” formulation described in the “Qarābādin-e-Azam” pharmacopoeia was developed, and its chemical composition and antioxidant and anti-cholinesterase properties were assessed. The formulation contains a mixture (FM) of Cinnamomum cassia (CC), C. verum (CV), Pistacia lentiscus (PL), Rheum palmatum (RP), Syzygium aromaticum (SA), and Zingiber officinalis (ZO) powdered plants. Its total phenolic content is 110.45 mg GAE/g, while the total flavonoid content is 6.28 mg RE/g. 66 secondary metabolites (mainly tannins, flavonoids, anthraquinones, and gingerols) were identified by UPLC-QToF-MS analysis. FM exerts antioxidant effects by scavenging radicals, and by reducing and chelating metals such as Mb, Cu and Fe. The anticholinesterase activity of one gram of the FM equals that of 3.60 mg of the reference drug galantamine, on both acetyl- and butyryl-cholinesterase. Correlations between specific compounds and bioactivities were highlighted by multivariate analysis of data: lyoniresinol 9′-glucoside strongly correlates with antiradical activities on DPPH and ABTS and reducing activity on Cu, and with anti-AChE effects. Most of the identified flavonoids and the ellagic acid derivatives positively correlate with the reducing activity on Fe and Mb, and with anti-BChE effects. Finally, a tablet formulation of the FM was developed, and its physical properties were preliminarily assessed. Overall, our results indicate that the FM may be a useful natural remedy for dementia, although further safety and efficacy assessments in vivo are required.